TasP - Antiretroviral Treatment as Prevention

2023

Article de revue

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  Larmarange Joseph, Bachanas Pamela, Skalland Timothy, Balzer Laura B., Iwuji Collins, Floyd Sian, Mills Lisa A., Pillay Deenan, Havlir Diane, Kamya Moses R., Ayles Helen, Wirth Kathleen, Dabis François, Hayes Richard, Petersen Maya et UT³C consortium (2023) « Population-level viremia predicts HIV incidence at the community level across the Universal Testing and Treatment Trials in eastern and southern Africa », PLOS global public health, 3 (7), p. e0002157. DOI : 10.1371/journal.pgph.0002157.
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  Résumé : Universal HIV testing and treatment (UTT) strategies aim to optimize population-level benefits of antiretroviral treatment. Between 2012 and 2018, four large community randomized trials were conducted in eastern and southern Africa. While their results were broadly consistent showing decreased population-level viremia reduces HIV incidence, it remains unclear how much HIV incidence can be reduced by increasing suppression among people living with HIV (PLHIV). We conducted a pooled analysis across the four UTT trials. Leveraging data from 105 communities in five countries, we evaluated the linear relationship between i) population-level viremia (prevalence of non-suppression-defined as plasma HIV RNA >500 or >400 copies/mL-among all adults, irrespective of HIV status) and HIV incidence; and ii) prevalence of non-suppression among PLHIV and HIV incidence, using parametric g-computation. HIV prevalence, measured in 257 929 persons, varied from 2 to 41% across the communities; prevalence of non-suppression among PLHIV, measured in 31 377 persons, from 3 to 70%; population-level viremia, derived from HIV prevalence and non-suppression, from < 1% to 25%; and HIV incidence, measured over 345 844 person-years (PY), from 0.03/100PY to 3.46/100PY. Decreases in population-level viremia were strongly associated with decreased HIV incidence in all trials (between 0.45/100PY and 1.88/100PY decline in HIV incidence per 10 percentage points decline in viremia). Decreases in non-suppression among PLHIV were also associated with decreased HIV incidence in all trials (between 0.06/100PY and 0.17/100PY decline in HIV incidence per 10 percentage points decline in non-suppression). Our results support both the utility of population-level viremia as a predictor of incidence, and thus a tool for targeting prevention interventions, and the ability of UTT approaches to reduce HIV incidence by increasing viral suppression. Implementation of universal HIV testing approaches, coupled with interventions to leverage linkage to treatment, adapted to local contexts, can reduce HIV acquisition at population level.

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  Plazy Mélanie, Diallo Adama, Hlabisa Thabile, Okesola Nonhlanhla, Iwuji Collins, Herbst Kobus, Boyer Sylvie, Lert France, McGrath Nuala, Pillay Deenan, Dabis François, Larmarange Joseph, Orne-Gliemann Joanna et for the ANRS TasP Study Group (2023) « Implementation and effectiveness of a linkage to HIV care intervention in rural South Africa (ANRS 12249 TasP trial) », PLOS ONE, 18 (1) (janvier 20), p. e0280479. DOI : 10.1371/journal.pone.0280479. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0280479.
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  Résumé : Background Timely linkage to care and ART initiation is critical to decrease the risks of HIV-related morbidity, mortality and HIV transmission, but is often challenging. We report on the implementation and effectiveness of a linkage-to-care intervention in rural KwaZulu-Natal, South Africa. Methods In the ANRS 12249 TasP trial on Universal Testing and Treatment (UTT) implemented between 2012–2016, resident individuals ≥16 years were offered home-based HIV testing every six months. Those ascertained to be HIV-positive were referred to trial clinics. Starting May 2013, a linkage-to-care intervention was implemented in both trial arms, consisting of tracking through phone calls and/or home visits to “re-refer” people who had not linked to care to trial clinics within three months of the first home-based referral. Fidelity in implementing the planned intervention was described using Kaplan-Meier estimation to compute conditional probabilities of being tracked and of being re-referred by the linkage-to-care team. Effect of the intervention on time to linkage-to-care was analysed using a Cox regression model censored for death, migration, and end of data follow-up. Results Among the 2,837 individuals (73.7% female) included in the analysis, 904 (32%) were tracked at least once, and 573 of them (63.4%) were re-referred. Probabilities of being re-referred was 17% within six months of first referral and 31% within twelve months. Compared to individuals not re-referred by the intervention, linkage-to-care was significantly higher among those with at least one re-referral through phone call (adjusted hazard ratio [aHR] = 1.82; 95% confidence interval [95% CI] = 1.47–2.25), and among those with re-referral through both phone call and home visit (aHR = 3.94; 95% CI = 2.07–7.48). Conclusions Phone calls and home visits following HIV testing were challenging to implement, but appeared effective in improving linkage-to-care amongst those receiving the intervention. Such patient-centred strategies should be part of UTT programs to achieve the UNAIDS 95-95-95 targets.

  Mots-clés : Antiretroviral therapy, Educational attainment, HIV, HIV diagnosis and management, HIV epidemiology, Schools, Viral load, Virus testing.

  Plazy et al. - 2023 - Implementation and effectiveness of a linkage to H.pdf 1.2 Mio (source)

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2022

Article de revue

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  Baisley Kathy, Orne-Gliemann Joanna, Larmarange Joseph, Plazy Melanie, Collier Dami, Dreyer Jaco, Mngomezulu Thobeka, Herbst Kobus, Hanekom Willem, Dabis Francois, Siedner Mark J. et Iwuji Collins (2022) « Early HIV treatment and survival over six years of observation in the ANRS 12249 Treatment as Prevention Trial », HIV Medicine, 23 (8) (février 26), p. 922-928. DOI : 10.1111/hiv.13263. https://onlinelibrary.wiley.com/doi/abs/10.1111/hiv.13263.
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  Résumé : Objectives Population-based universal test and treat (UTT) trials have shown an impact on population-level virological suppression. We followed the ANRS 12249 TasP trial population for 6 years to determine whether the intervention had longer-term survival benefits. Methods The TasP trial was a cluster-randomized trial in South Africa from 2012 to 2016. All households were offered 6-monthly home-based HIV testing. Immediate antiretroviral therapy (ART) was offered through trial clinics to all people living with HIV (PLHIV) in intervention clusters and according to national guidelines in control clusters. After the trial, individuals attending the trial clinics were transferred to the public ART programme. Deaths were ascertained through annual demographic surveillance. Random-effects Poisson regression was used to estimate the effect of trial arm on mortality among (i) all PLHIV; (ii) PLHIV aware of their status and not on ART at trial entry; and (iii) PHLIV who started ART during the trial. Results Mortality rates among PLHIV were 9.3/1000 and 10.4/1000 person-years in the control and intervention arms, respectively. There was no evidence that the intervention decreased mortality among all PLHIV [adjusted rate ratio (aRR) = 1.10, 95% confidence interval (CI) = 0.85–1.43, p = 0.46] or among PLHIV who were aware of their status but not on ART. Among individuals who initiated ART, the intervention decreased mortality during the trial (aRR = 0.49, 95% CI = 0.28–0.85, p = 0.01), but not after the trial ended. Conclusions The ‘treat all’ strategy reduced mortality among individuals who started ART but not among all PLHIV. To achieve maximum benefit of immediate ART, barriers to ART uptake and retention in care need to be addressed.

  Mots-clés : HIV, immediate antiretroviral therapy, mortality, South Africa, test and treat.

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  Bousmah Marwân-al-Qays, Iwuji Collins, Okesola Nonhlanhla, Orne-Gliemann Joanna, Pillay Deenan, Dabis François, Larmarange Joseph et Boyer Sylvie (2022) « Costs and economies of scale in repeated home-based HIV counselling and testing: Evidence from the ANRS 12249 treatment as prevention trial in South Africa », Social Science & Medicine, 305 (juillet 1), p. 115068. DOI : 10.1016/j.socscimed.2022.115068. https://www.sciencedirect.com/science/article/pii/S0277953622003744.
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  Résumé : Universal HIV testing is now recommended in generalised HIV epidemic settings. Although home-based HIV counselling and testing (HB-HCT) has been shown to be effective in achieving high levels of HIV status awareness, little is still known about the cost implications of universal and repeated HB-HCT. We estimated the costs of repeated HB-HCT and the scale economies that can be obtained when increasing the population coverage of the intervention. We used primary data from the ANRS 12249 Treatment as Prevention (TasP) trial in rural South Africa (2012–2016), whose testing component included six-monthly repeated HB-HCT. We relied on the dynamic system generalised method of moments (GMM) approach to produce unbiased short- and long-run estimates of economies of scale, using the number of contacts made by HIV counsellors for HB-HCT as the scale variable. We also estimated the mediating effect of the contact quality – measured as the proportion of HIV tests performed among all contacts eligible for an HIV test – on scale economies. The mean cost (standard deviation) of universal and repeated HB-HCT was $24.2 (13.7) per contact, $1694.3 (1527.8) per new HIV diagnosis, and $269.2 (279.0) per appropriate referral to HIV care. The GMM estimations revealed the presence of economies of scale, with a 1% increase in the number of contacts for HB-HCT leading to a 0.27% decrease in the mean cost. Our results also suggested a significant long-run relationship between mean cost and scale, with a 1% increase in the scale leading to a 0.36% decrease in mean cost in the long run. Overall, we showed that significant cost savings can be made from increasing population coverage. Nevertheless, there is a risk that this gain is made at the expense of quality: the higher the quality of HB-HCT activities, the lower the economies of scale.

  Mots-clés : AIDS/HIV, Clinical trials, Cost of care, Economies of scale, Interventions, Prevention, South Africa.

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  Bousmah et al. - 2022 - Costs and economies of scale in repeated home-base.pdf 1.2 Mio (source)

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  Sabapathy K., Balzer L., Larmarange Joseph, Block L., Floyd S., Iwuji C., Wirth K., Ayles H., Fidler S., Kamya M., Petersen M., Havlir D., Dabis F., Moore J. et Hayes R. (2022) « Achieving the UNAIDS 90–90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa », BMC Public Health, 22 (1) (décembre 13), p. 2333. DOI : 10.1186/s12889-022-14713-5. https://doi.org/10.1186/s12889-022-14713-5.
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  Résumé : Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012–2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90–90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90–90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90–90-90 targets.

  Mots-clés : Antiretroviral treatment, HIV, Treatment as Prevention, UNAIDS 90-90-90, Universal Testing and Treatment.

  Sabapathy et al. - 2022 - Achieving the UNAIDS 90–90-90 targets a comparati.pdf 2.1 Mio (source)

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2021

Article de revue

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  Fiorentino Marion, Nishimwe Marie, Protopopescu Camelia, Iwuji Collins, Okesola Nonhlanhla, Spire Bruno, Orne-Gliemann Joanna, McGrath Nuala, Pillay Deenan, Dabis François, Larmarange Joseph, Boyer Sylvie et for the ANRS 12249 TaSP Study Group (2021) « Early ART Initiation Improves HIV Status Disclosure and Social Support in People Living with HIV, Linked to Care Within a Universal Test and Treat Program in Rural South Africa (ANRS 12249 TasP Trial) », AIDS and Behavior, 25 (4) (avril), p. 1306-1322. DOI : 10.1007/s10461-020-03101-y. https://doi.org/10.1007/s10461-020-03101-y.
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  Résumé : We investigated the effect of early antiretroviral treatment (ART) initiation on HIV status disclosure and social support in a cluster-randomized, treatment-as-prevention (TasP) trial in rural South Africa. Individuals identified HIV-positive after home-based testing were referred to trial clinics where they were invited to initiate ART immediately irrespective of CD4 count (intervention arm) or following national guidelines (control arm). We used Poisson mixed effects models to assess the independent effects of (a) time since baseline clinical visit, (b) trial arm, and (c) ART initiation on HIV disclosure (n = 182) and social support (n = 152) among participants with a CD4 count > 500 cells/mm3 at baseline. Disclosure and social support significantly improved over follow-up in both arms. Disclosure was higher (incidence rate ratio [95% confidence interval]: 1.24 [1.04; 1.48]), and social support increased faster (1.22 [1.02; 1.46]) in the intervention arm than in the control arm. ART initiation improved both disclosure and social support (1.50 [1.28; 1.75] and 1.34 [1.12; 1.61], respectively), a stronger effect being seen in the intervention arm for social support (1.50 [1.12; 2.01]). Besides clinical benefits, early ART initiation may also improve psychosocial outcomes. This should further encourage countries to implement universal test-and-treat strategies.

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Article de colloque

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  Iwuji Collins, Baisley Kathy, Orne-Gliemann Joanna, Larmarange Joseph, Plazy Mélanie, Collier Dami, Dreyer Jaco, Mngomezulu T, Herbst Kobus, Hanekom W, Dabis François et Siedner Mark (2021) « Long-term survival among people living with HIV in rural South Africa: results from 6 years of observation in the ANRS 12249 treatment as prevention trial » (poster PEC279), présenté à 11th IAS Conference on HIV Science, Berlin. https://theprogramme.ias2021.org/Abstract/Abstract/2085.
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  Résumé : BACKGROUND: Universal test-and-treat trials increased population-level virological suppression across trial sites in sub-Saharan Africa. We followed the ANRS 12249 TasP trial population for 6 years to determine whether the intervention had longer-term survival benefits. METHODS: The TasP trial was a cluster-randomised trial implemented in 22 communities in rural South Africa, from 2012'2016. Households were offered six-monthly home-based HIV testing. Immediate antiretroviral therapy (ART) was offered in trial clinics to all people living with HIV (PLHIV) in the intervention clusters and according to national guidelines in the control clusters. At trial end, individuals attending the intervention clinics were transferred to the public ART programme, with a 'treat-all' strategy adopted in September 2016. Deaths during and two years after trial end were ascertained through annual demographic surveillance. Random effects Poisson regression was used to estimate rate ratios (RR) and 95%CI for the effect of trial arm on mortality among i) all PLHIV regardless of serostatus awareness, ii) PLHIV aware of their status, iii) those not on ART at entry to trial clinics. An interaction term between period and treatment arm was included, to allow the effect of trial arm to differ between periods. RESULTS: Amongst all PLHIV and those aware of their serostatus, there was no effect of immediate ART on mortality (Table). Among individuals who started ART during the trial, there was evidence that the intervention decreased mortality (aRR=0.69, 95%CI=0.45-1.04, p=0.08), although the effect was primarily during the trial (aRR=0.49, 95%CI=0.28-0.85, p=0.01), but not after the trial ended (aRR=1.15, 95%CI=0.59-2.21, p=0.69). CONCLUSIONS: The 'treat-all' strategy resulted in a mortality benefit amongst individuals who started ART within the trial but not in all PLHIV over 6 years of follow-up. To achieve maximum benefit of immediate ART in South Africa, barriers to ART uptake and retention in care need to be addressed.

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2020

Article de revue

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  Havlir Diane, Lockman Shahin, Ayles Helen, Larmarange Joseph, Chamie Gabriel, Gaolathe Tendani, Iwuji Collins, Fidler Sarah, Kamya Moses, Floyd Sian, Moore Janet, Hayes Richard, Petersen Maya et Dabis Francois (2020) « What do the Universal Test and Treat trials tell us about the path to HIV epidemic control? », Journal of the International AIDS Society, 23 (2) (février 24), p. e25455. DOI : 10.1002/jia2.25455. https://onlinelibrary.wiley.com/doi/abs/10.1002/jia2.25455.
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  Résumé : Introduction Achieving HIV epidemic control globally will require new strategies to accelerate reductions in HIV incidence and mortality. Universal test and treat (UTT) was evaluated in four randomized population-based trials (BCPP/Ya Tsie, HPTN 071/PopART, SEARCH, ANRS 12249/TasP) conducted in sub-Saharan Africa (SSA) during expanded antiretroviral treatment (ART) eligibility by World Health Organization guidelines and the UNAIDS 90-90-90 campaign. Discussion These three-year studies were conducted in Botswana, Zambia, Uganda, Kenya and South Africa in settings with baseline HIV prevalence from 4% to 30%. Key observations across studies were: (1) Universal testing (implemented via a variety of home and community-based testing approaches) achieved >90% coverage in all studies. (2) When coupled with robust linkage to HIV care, rapid ART start and patient-centred care, UTT achieved among the highest reported population levels of viral suppression in SSA. Significant gains in population-level viral suppression were made in regions with both low and high baseline population viral load; however, viral suppression gains were not uniform across all sub-populations and were lower among youth. (3) UTT resulted in marked reductions in community HIV incidence when universal testing and robust linkage were present. However, HIV elimination targets were not reached. In BCPP and HPTN 071, annualized HIV incidence was approximately 20% to 30% lower in the intervention (which included universal testing) compared to control arms (no universal testing). In SEARCH (where both arms had universal testing), incidence declined 32% over three years. (4) UTT reduced HIV associated mortality by 23% in the intervention versus control communities in SEARCH, a study in which mortality was comprehensively measured. Conclusions These trials provide strong evidence that UTT inclusive of universal testing increases population-level viral suppression and decreases HIV incidence and mortality faster than the status quo in SSA and should be adapted at a sub-country level as a public health strategy. However, more is needed, including integration of new prevention interventions into UTT, in order to reach UNAIDS HIV elimination targets.

  Mots-clés : antiretroviral therapy, HIV care continuum, HIV elimination, HIV prevention, HIV testing, public health, universal access.

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  Iwuji Collins, Chimukuche Rujeko Samanthia, Zuma Thembelihle, Plazy Melanie, Larmarange Joseph, Orne-Gliemann Joanna, Siedner Mark, Shahmanesh Maryam et Seeley Janet (2020) « Test but not treat: Community members’ experiences with barriers and facilitators to universal antiretroviral therapy uptake in rural KwaZulu-Natal, South Africa », PLOS ONE, 15 (9) (septembre 24), p. e0239513. DOI : 10.1371/journal.pone.0239513. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239513.
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  Résumé : Introduction Antiretroviral therapy (ART) has revolutionised the care of HIV-positive individuals resulting in marked decreases in morbidity and mortality, and markedly reduced transmission to sexual partners. However, these benefits can only be realised if individuals are aware of their HIV-positive status, initiated and retained on suppressive lifelong ART. Framed using the socio-ecological model, the present study explores factors contributing to poor ART uptake among community members despite high acceptance of HIV-testing within a Treatment as Prevention (TasP) trial. In this paper we identify barriers and facilitators to treatment across different levels of the socio-ecological framework covering individual, community and health system components. Methods This research was embedded within a cluster-randomised trial (ClinicalTrials.gov, number NCT01509508) of HIV treatment as Prevention in rural KwaZulu-Natal, South Africa. Data were collected between January 2013 and July 2014 from resident community members. Ten participants contributed to repeat in-depth interviews whilst 42 participants took part in repeat focus group discussions. Data from individual interviews and focus group discussions were triangulated using community walks to give insights into community members’ perception of the barriers and facilitators of ART uptake. We used thematic analysis guided by a socio-ecological framework to analyse participants’ narratives from both individual interviews and focus group discussions. Results Barriers and facilitators operating at the individual, community and health system levels influence ART uptake. Stigma was an over-arching barrier, across all three levels and expressed variably as fear of HIV disclosure, concerns about segregated HIV clinical services and negative community religious perceptions. Other barriers were individual (substance misuse, fear of ART side effects), community (alternative health beliefs). Facilitators cited by participants included individual (expectations of improved health and longer life expectancy following ART, single tablet regimens), community (availability of ART in the community through mobile trial facilities) and health system factors (fast and efficient service provided by friendly staff). Discussion We identified multiple barriers to achieving universal ART uptake. To enhance uptake in HIV care services, and achieve the full benefits of ART requires interventions that tackle persistent HIV stigma, and offer people with HIV respectful, convenient and efficient services. These interventions require evaluation in appropriately designed studies.

  Mots-clés : Antiretroviral therapy, Health care facilities, HIV, HIV diagnosis and management, HIV prevention, Religion, South Africa, Virus testing.

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Article de colloque

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  Petersen Maya, Larmarange Joseph, Wirth Kathleen E, Skalland Timothy, Ayles Helen, Kamya Moses, Lockman Shahin, Iwuji Collins, Dabis François, Makhema Joseph, Havlir Diane, Floyd Sian, Hayes Richard et UT3C Consortium (2020) « Population-level Viremia Predicts HIV Incidence across the Universal Test and Treat Studies » (communication orale), présenté à Conference on Retroviruses and Opportunitic Infections (CROI), Boston. http://www.croiconference.org/sessions/population-level-viremia-predicts-hiv-incidence-across-universal-test-treat-studies.
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  Résumé : Improved understanding of the extent to which increased population-level viral suppression will reduce HIV incidence is needed. Using data from four large Universal Test and Treat Trials, we evaluated the relationship between viremia and incidence and its consistency across epidemic contexts. We analyzed data from 105 communities in the PopART (21 communities in South Africa and Zambia, ~ 25,000 adults each), BCPP (30 communities in Botswana, ~3,600 adults each), ANRS 12249 TasP (22 communities in South Africa, ~1,300 adults each) and SEARCH (32 communities in Uganda and Kenya, ~5,000 adults each) studies. Communities ranged from rural to urban and varied in the mobility of their populations and their sex ratio (~30% to 50% male). HIV incidence was measured via repeat testing between 2012-2018. Population viremia ­– % of all adults (HIV+ or HIV-) with HIV viremia – was estimated at midpoint of follow-up based on HIV prevalence and non-suppression among HIV+, with adjustment for differences between the measurement cohort and underlying population. Community-level regression, adjusted for study, was used to quantify the association between HIV incidence and viremia and to evaluate cross-study heterogeneity. HIV prevalence (measured in 257,929 total persons, PopART: 37,006; BCPP: 12,570; TasP: 20,978; SEARCH: 187,375), ranged from 2% to 40% by community. Non-suppression among HIV+ (measured in 39,928 persons, PopART: 6,233; BCPP: 2,318; TasP: 6,617; SEARCH: 16,209) ranged from 3% to 70%. HIV incidence (measured over 345,844 person-years, PopART: 39,702; BCPP: 8,551; TasP: 26,832; SEARCH: 270,759) ranged from 0.03 to 3.4 per 100PY. Population-level viremia was strongly associated with HIV incidence; pooling across studies, HIV incidence decreased by 0.07/100PY (95% CI: 0.05,0.10, p<0.001) for each 1% absolute decrease in viremia. Incidence was significantly associated with viremia in each study; however, both strength of the incidence-viremia relationship (slope) and projected incidence at 0% viremia (intercept) differed (Figure). Lower population-level HIV viremia was associated with lower HIV incidence in all four Universal Test and Treat Studies, conducted in a wide range of epidemic contexts in sub-Saharan Africa. Differences in external infection rate (due to variation in community size, mobility, and sex ratio) may have contributed to heterogeneity between studies.

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2019

Article de revue

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  Gosset Andréa, Protopopescu Camelia, Larmarange Joseph, Orne-Gliemann Joanna, McGrath Nuala, Pillay Deenan, Dabis François, Iwuji Collins et Boyer Sylvie (2019) « Retention in Care Trajectories of HIV-Positive Individuals Participating in a Universal Test-and-Treat Program in Rural South Africa (ANRS 12249 TasP Trial) », JAIDS Journal of Acquired Immune Deficiency Syndromes, 80 (4) (avril 1), p. 375. DOI : 10.1097/qai.0000000000001938. https://journals.lww.com/jaids/Fulltext/2019/04010/Retention_in_Care_Trajectories_of_HIV_Positive.2.aspx.
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  Résumé : Objective: To study retention in care (RIC) trajectories and associated factors in patients eligible for antiretroviral therapy (ART) in a universal test-and-treat setting (TasP trial, South Africa, 2012–2016). Design: A cluster-randomized trial whereby individuals identified HIV positive after home-based testing were invited to initiate ART immediately (intervention) or following national guidelines (control). Methods: Exiting care was defined as ≥3 months late for a clinic appointment, transferring elsewhere, or death. Group-based trajectory modeling was performed to estimate RIC trajectories over 18 months and associated factors in 777 ART-eligible patients. Results: Four RIC trajectory groups were identified: (1) group 1 “remained” in care (reference, n = 554, 71.3%), (2) group 2 exited care then “returned” after [median (interquartile range)] 4 (3–9) months (n = 40, 5.2%), (3) group 3 “exited care rapidly” [after 4 (4–6) months, n = 98, 12.6%], and (4) group 4 “exited care later” [after 11 (9–13) months, n = 85, 10.9%]. Group 2 patients were less likely to have initiated ART within 1 month and more likely to be male, young (<29 years), without a regular partner, and to have a CD4 count >350 cells/mm3. Group 3 patients were more likely to be women without social support, newly diagnosed, young, and less likely to have initiated ART within 1 month. Group 4 patients were more likely to be newly diagnosed and aged 39 years or younger. Conclusions: High CD4 counts at care initiation were not associated with a higher risk of exiting care. Prompt ART initiation and special support for young and newly diagnosed patients with HIV are needed to maximize RIC.

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  Larmarange Joseph, Diallo Mamadou H, McGrath Nuala, Iwuji Collins, Plazy Mélanie, Thiébaut Rodolphe, Tanser Frank, Bärnighausen Till, Orne-Gliemann Joanna, Pillay Deenan, Dabis François et ANRS 12249 TasP Study Group (2019) « Temporal trends of population viral suppression in the context of Universal Test and Treat: the ANRS 12249 TasP trial in rural South Africa », Journal of the International AIDS Society, 22 (10) (octobre 22), p. e25402. DOI : 10.1002/jia2.25402. https://onlinelibrary.wiley.com/doi/full/10.1002/jia2.25402.
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  Résumé : Abstract Introduction The universal test-and-treat (UTT) strategy aims to maximize population viral suppression (PVS), that is, the proportion of all people living with HIV (PLHIV) on antiretroviral treatment (ART) and virally suppressed, with the goal of reducing HIV transmission at the population level. This article explores the extent to which temporal changes in PVS explain the observed lack of association between universal treatment and cumulative HIV incidence seen in the ANRS 12249 TasP trial conducted in rural South Africa. Methods The TasP cluster-randomized trial (2012 to 2016) implemented six-monthly repeat home-based HIV counselling and testing (RHBCT) and referral of PLHIV to local HIV clinics in 2 ? 11 clusters opened sequentially. ART was initiated according to national guidelines in control clusters and regardless of CD4 count in intervention clusters. We measured residency status, HIV status, and HIV care status for each participant on a daily basis. PVS was computed per cluster among all resident PLHIV (≥16, including those not in care) at cluster opening and daily thereafter. We used a mixed linear model to explore time patterns in PVS, adjusting for sociodemographic changes at the cluster level. Results 8563 PLHIV were followed. During the course of the trial, PVS increased significantly in both arms (23.5% to 46.2% in intervention, +22.8, p < 0.001; 26.0% to 44.6% in control, +18.6, p?

  Mots-clés : antiretroviral therapy, HIV, population health, retention in care, South Africa, sustained viral suppression.

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  Rolland Matthieu, McGrath Nuala, Tiendrebeogo Thierry, Larmarange Joseph, Pillay Deenan, Dabis François, Orne-Gliemann Joanna et Group for the ANRS 12249 TasP study (2019) « No effect of test and treat on sexual behaviours at population level in rural South Africa », AIDS, 33 (4) (mars 15), p. 709. DOI : 10.1097/qad.0000000000002104. https://journals.lww.com/aidsonline/Abstract/2019/03150/No_effect_of_test_and_treat_on_sexual_behaviours.14.aspx.
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  Résumé : Context: Within the community-randomized ANRS 12249 Treatment-as-Prevention trial conducted in rural South Africa, we analysed sexual behaviours stratified by sex over time, comparing immediate antiretroviral therapy irrespective of CD4+ cell count vs. CD4+-guided antiretroviral therapy (start at CD4+ cell count > 350 cells/μl then >500 cells/μl) arms. Methods: As part of the 6-monthly home-based trial rounds, a sexual behaviour individual questionnaire was administered to all residents at least 16 years. We considered seven indicators: sexual intercourse in the past month; at least one regular sexual partner in the past 6 months; at least one casual sexual partner in the past 6 months and more than one sexual partner in the past 6 months; condom use at last sex (CLS) with regular partner, CLS with casual partner, and point prevalence estimate of concurrency. We conducted repeated cross-sectional analyses, stratified by sex. Generalized Estimating Equations models were used, including trial arm, trial time, calendar time and interaction between trial arm and trial time. Results: CLS with regular partner varied between 29–51% and 23–46% for men and women, respectively, with significantly lower odds among women in the control vs. intervention arm by trial end (P < 0.001). CLS with casual partner among men showed a significant interaction between arm and trial round, with no consistent pattern. Women declared more than one partner in the past 6 months in less than 1% of individual questionnaires; among men, rates varied between 5–12%, and odds significantly and continuously declined between calendar rounds 1 and 7 [odds ratio = 4.2 (3.24–5.45)]. Conclusion: Universal Test and Treat was not associated with increased sexual risk behaviours.

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2018

Article de revue

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  Iwuji Collins C, Orne-Gliemann Joanna, Larmarange Joseph, Balestre Eric, Thiebaut Rodolphe, Tanser Frank, Okesola Nonhlanhla, Makowa Thembisa, Dreyer Jaco, Herbst Kobus, McGrath Nuala, Bärnighausen Till, Boyer Sylvie, De Oliveira Tulio, Rekacewicz Claire, Bazin Brigitte, Newell Marie-Louise, Pillay Deenan et Dabis François (2018) « Universal test and treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial », The Lancet HIV, 5 (3) (mars 1), p. e116-e125. DOI : 10.1016/S2352-3018(17)30205-9. http://www.sciencedirect.com/science/article/pii/S2352301817302059.
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  Résumé : Summary Background Universal antiretroviral therapy (ART), as per the 2015 WHO recommendations, might reduce population HIV incidence. We investigated the effect of universal test and treat on HIV acquisition at population level in a high prevalence rural region of South Africa. Methods We did a phase 4, open-label, cluster randomised trial of 22 communities in rural KwaZulu-Natal, South Africa. We included individuals residing in the communities who were aged 16 years or older. The clusters were composed of aggregated local areas (neighbourhoods) that had been identified in a previous study in the Hlabisa subdistrict. The study statisticians randomly assigned clusters (1:1) with MapInfo Pro (version 11.0) to either the control or intervention communities, stratified on the basis of antenatal HIV prevalence. We offered residents repeated rapid HIV testing during home-based visits every 6 months for about 4 years in four clusters, 3 years in six clusters, and 2 years in 12 clusters (58 cluster-years) and referred HIV-positive participants to trial clinics for ART (fixed-dose combination of tenofovir, emtricitabine, and efavirenz) regardless of CD4 cell count (intervention) or according to national guidelines (initially ≤350 cells per μL and <500 cells per μL from January, 2015; control). Participants and investigators were not masked to treatment allocation. We used dried blood spots once every 6 months provided by participants who were HIV negative at baseline to estimate the primary outcome of HIV incidence with cluster-adjusted Poisson generalised estimated equations in the intention-to-treat population after 58 cluster-years of follow-up. This study is registered with ClinicalTrials.gov, number NCT01509508, and the South African National Clinical Trials Register, number DOH-27-0512-3974. Findings Between March 9, 2012, and June 30, 2016, we contacted 26 518 (93%) of 28 419 eligible individuals. Of 17 808 (67%) individuals with a first negative dried blood spot test, 14 223 (80%) had subsequent dried blood spot tests, of whom 503 seroconverted after follow-up of 22 891 person-years. Estimated HIV incidence was 2·11 per 100 person-years (95% CI 1·84–2·39) in the intervention group and 2·27 per 100 person-years (2·00–2·54) in the control group (adjusted hazard ratio 1·01, 95% CI 0·87–1·17; p=0·89). We documented one case of suicidal attempt in a woman following HIV seroconversion. 128 patients on ART had 189 life-threatening or grade 4 clinical events: 69 (4%) of 1652 in the control group and 59 (4%) of 1367 in the intervention group (p=0·83). Interpretation The absence of a lowering of HIV incidence in universal test and treat clusters most likely resulted from poor linkage to care. Policy change to HIV universal test and treat without innovation to improve health access is unlikely to reduce HIV incidence. Funding ANRS, GiZ, and 3ie.

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  Larmarange Joseph, Diallo Mamadou Hassimiou, McGrath Nuala, Iwuji Collins, Plazy Mélanie, Thiébaut Rodolphe, Tanser Frank, Bärnighausen Till, Pillay Deenan, Dabis François et Orne-Gliemann Joanna (2018) « The impact of population dynamics on the population HIV care cascade: results from the ANRS 12249 Treatment as Prevention trial in rural KwaZulu-Natal (South Africa) », Journal of the International AIDS Society, 21 (S4) (juillet 20), p. e25128. DOI : 10.1002/jia2.25128. https://onlinelibrary.wiley.com/doi/abs/10.1002/jia2.25128.
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  Résumé : Introduction The universal test and treat strategy (UTT) was developed to maximize the proportion of all HIV-positive individuals on antiretroviral treatment (ART) and virally suppressed, assuming that it will lead to a reduction in HIV incidence at the population level. The evolution over time of the cross-sectional HIV care cascade is determined by individual longitudinal trajectories through the HIV care continuum and underlying population dynamics. The purpose of this paper is to quantify the contribution of each component of population change (in- and out-migration, HIV seroconversion, ageing into the cohort and definitive exit such as death) on the HIV care cascade in the context of the ANRS 12249 Treatment as Prevention (TasP) cluster-randomized trial, investigating UTT in rural KwaZulu-Natal, South Africa, between 2012 and 2016. Methods HIV test results and information on clinic visits, ART prescriptions, viral load and CD4 count, migration and deaths were used to calculate residency status, HIV status and HIV care status for each individual on a daily basis. Position within the HIV care continuum was considered as a score ranging from 0 (undiagnosed) to 4 (virally suppressed). We compared the cascade score of each individual joining or leaving the population of resident adults living with HIV with the average score of their cluster at the time of entry or exit. Then, we computed the contribution of each entry or exit on the average cascade score and their annualized total contribution, by component of change. Results While the average cascade score increased over time in all clusters, that increase was constrained by population dynamics. Permanent exits and ageing into the people living with HIV cohort had a marginal effect. Both in-migrants and out-migrants were less likely to be retained at each step of the HIV care continuum. However, their overall impact on the cross-sectional cascade was limited as the effect of in- and out-migration balanced each other. The contribution of HIV seroconversions was negative in all clusters. Conclusions In a context of high HIV incidence, the continuous flow of newly infected individuals slows down the efforts to increase ART coverage and population viral suppression, ultimately attenuating any population-level impact on HIV incidence. Clinical Trial Number NCT01509508 (clinicalTrials.gov)/DOH-27-0512-3974 (South African National Clinical Trials Register).

  Mots-clés : Cross-sectional cascade, HIV care continuum, Migration, Population dynamics, Public health, Rural South Africa, Structural drivers.

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Article de colloque

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  Larmarange Joseph (2018) « Mobility in Africa: human rights and the HIV care cascade » (communication orale TUSA1802), présenté à 22nd International AIDS Conference, Amsterdam. http://programme.aids2018.org/Programme/Session/221.
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  Larmarange Joseph, Diallo Mamadou Hassimiou, McGrath Nuala, Iwuji Collins, Plazy Mélanie, Thiébaut Rodolphe, Tanser Frank, Bärnighausen Till, Orne-Gliemann Joanna, Pillay Deenan, Dabis François et ANRS 12249 TasP Study Group (2018) « Temporal trends of population viral suppression in the context of Universal Test and Treat: results from the ANRS 12249 TasP trial in rural South Africa » (communication orale TUAC0103), présenté à 22nd International AIDS Conference, Amsterdam. http://programme.aids2018.org/Programme/Session/105.
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  Résumé : Background: The universal test-and-treat strategy (UTT) aims to maximize the proportion of all people living with HIV (PLWHIV) on antiretroviral treatment (ART) and virally suppressed in a community, i.e. to reach population viral suppression (PVS). The ANRS 12249 TasP trial did not demonstrate an impact of universal ART on HIV incidence at population level (Lancet HIV 2017). Here, we investigated whether PVS improved during the course of the trial: differentially by arm, according to trial interventions or contextual changes. Methods: The TasP cluster-randomized trial (2012-2016) implemented six-monthly repeated home-based HIV counselling and testing (RHBCT) and referral of PLWHIV to local HIV clinics in 2×11 clusters opened sequentially. ART was initiated according to national guidelines in control clusters vs. regardless of CD4 count in intervention clusters. Test results, clinic visits, ART prescriptions, viral loads, CD4 counts, migrations and deaths were used to produce information on residency status, HIV status and HIV care status for each participant. PVS was computed daily and per cluster among all resident PLWHIV (≥16, including those not in care). We used a mixed linear model to explore the relation between PVS with calendar time, time since cluster opening, trial arm and interaction between arm and time since cluster opening, adjusting on sociodemographic changes at cluster level. Results: 8,646 PLWHIV were observed. Between January 1st, 2013 and January 1st, 2016, PVS increased significantly in both arms (intervention: 29.0% to 46.2%, +17.2, p< 0.001; control: 32.4% to 44.6%, +12.2, p < 0.001), but difference in temporal variation (+5.0%) was not significant (p=0.175). According to adjusted model (figure) this increase was mainly attributable to RHBCT (measured by time since cluster opening). They were also some effect due to contextual changes (measured by calendar time). The effect attributable to universal ART (interaction term) was limited. Conclusions: Although suboptimal, the UTT strategy implemented in TasP trial improved PVS over time. As it was mainly due to RHBCT rather than universal ART, it did not induce differences between arms, explaining the null effect observed on cumulative incidence, the main trial finding. Changes in ART initiation guidelines alone are not enough to significantly increase PVS.

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• Larmarange Joseph, Diallo Mamadou Hassimiou, McGrath Nuala, Iwuji Collins, Thiébaut Rodolphe, Tanser Frank, Bärnighausen Till, Pillay Deenan, Dabis François, Orne-Gliemann Joanna et ANRS 12249 TasP Study Group (2018) « From individual care trajectories to HIV care cascade at population level in rural KwaZulu-Natal (South Africa): the impact of population dynamics » (communication orale), présenté à Life History Research Society Conference, Paris.
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  Résumé : Introduction The universal test-and-treat strategy (UTT) was developed to maximize the proportion of all HIV-positive individuals on antiretroviral and virally suppressed, assuming that it leads to reduction in HIV incidence. The evolution over time of the cross-sectional population HIV care cascade is determined by longitudinal individual trajectories through the HIV care continuum and the underlying HIV population dynamics. This structural effect could dilute the impact observed at population level of a UTT strategy RT: either add impact on what (incidence) or delete sentence. The purpose of this paper is to quantify the contribution of each component of population change on the population HIV care cascade in the context of UTT. Sample We used prospective individual-level longitudinal data from the ANRS 12249 cluster-randomized trial which was implemented in rural KwaZulu-Natal, South Africa between 2012 and 2016 to test such an approach. Methods HIV tests results and information on clinic visits, ART prescription, viral load and CD4 count, migration and deaths were used to calculate residency status, HIV status and HIV care status for each individual on a daily basis. Position within the HIV care continuum was considered as a score ranging from 0 (undiagnosed) to 4 (virally suppressed). We compared the cascade score of each individual joining or leaving the HIV population with the average score of their cluster at the time of entry or exit. Then, we computed the contribution of each event on the average cascade score and the annualised total contribution of all events, considering 5 components of HIV population change: aging into the cohort, HIV seroconversions, in-migrations, out-migrations, and permanent exits (including deaths). Results While the average cascade score increased over time in all clusters, that increase was limited due to population dynamics, the total contribution of all population entries and exits being negative. Permanent exits and individuals already infected when reaching the age of 16 had a marginal effect. Although migrants had a lower position than the rest of the population, their overall impact on the cross-sectional population cascade remained limited as in- and out-migration compensated each other. Conclusions In a context of high HIV incidence, the continuous flow of newly infected individuals slows down the efforts to increase ART coverage and population viral suppression.

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• Nishimwe Marie, Protopopescu Camelia, Iwuji Collins, Okesola Nonhlanhla, Spire Bruno, Orne-Gliemann Joanna, McGrath Nuala, Pillay Deenan, Dabis François, Larmarange Joseph et Boyer Sylvie (2018) « Effet du traitement antirétroviral précoce sur la révélation du statut sérologique du VIH et le soutien social dans un programme de dépistage et traitement universel en Afrique du Sud (essai TasP ANRS 12249) » (communication orale S17.05), présenté à 9e Conférence Internationale Francophone sur le VIH et les Hépatites Virales (AFRAVIH 2018), Bordeaux.
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  Résumé : Objectif La révélation du statut VIH et le soutien social sont associés à une meilleure observance au traitement antirétroviral (TARV) et à de bons résultats cliniques. Cette analyse a pour but d’évaluer l’effet de l’initiation précoce du TARV sur la révélation du statut VIH et le soutien social dans un essai de dépistage et traitement universel (UTT) conduit en zone rurale en Afrique du Sud. Méthodes Dans cet essai randomisé en clusters (2012-2016), un dépistage universel était proposé à domicile. Les personnes VIH+ orientées vers les cliniques de l’essai pouvaient recevoir le TARV immédiatement dans le bras intervention (I) ou selon les recommandations nationales (CD4≤350 jusqu’au 31/12/2014 puis ≤500) dans le bras contrôle (C). Cette analyse a inclus les patients non traités à la 1ère visite (baseline), ayant des CD4>500 et au moins 2 visites de suivi. Un index de révélation (0-5) et un index de soutien social (0-4) ont été estimés à baseline puis tous les 6 mois : un point a été attribué lorsque le patient déclarait avoir révélé son statut VIH à (ou recevoir du soutien social de) au moins un des membres des groupes suivants : partenaire régulier, famille, amis, voisins, autres. Des modèles de Poisson à effets mixtes ont été utilisés pour étudier, après ajustement sur les facteurs individuels, l’effet sur les 2 index : 1) du temps depuis baseline, du bras de randomisation et de leur terme d’interaction statistique; 2) de l’initiation du TARV (variable dépendante du temps); 3) du terme d’interaction statistique entre initiation du TARV et bras. Résultats Sur 3019 patients suivis dans les cliniques de l’essai, 1597 étaient non traités à baseline, dont 473 ayant des CD4>500 et 182 au moins 2 visites (93 dans le bras I et 89 dans le bras C). Le suivi médian [écart interquartile (EIQ)] était de 13,2[7,0-18,5] mois. À 6 mois, 97% étaient sous TARV dans le bras I et 22% dans le bras C. À baseline, la médiane [EIQ] de l’index de révélation était de 2[1-2] versus 1[1-2] dans les bras I et C (p=0,72) et celle de l’index de soutien social de 1[1-2] versus 2[1-3] (p=0,12). Les valeurs des deux index ont augmenté au cours du temps, avec une hausse significativement plus rapide dans le bras I pour le soutien social (ratio du taux d’incidence (RTI) [IC95%]=1,2[1,0;1,5] par an versus le bras C) et une évolution similaire entre les bras pour l’index de révélation. L’initiation du TARV était positivement associée aux 2 index (RTI [IC95%]=1,5[1,3;1,7]) et 1,3[1,1;1,6], respectivement). Pour la révélation du statut, l’initiation du TARV annulait l’effet du bras, alors que pour le soutien social l’effet de l’initiation du TARV était plus important dans le bras I (RTI [IC95%]=1,5[1,1;2,0]). Conclusion Nos résultats obtenus en milieu rural sud-africain suggèrent que l’initiation précoce du TARV impacterait positivement la révélation du statut VIH et le soutien social. Ces résultats sont encourageants pour les pays qui ont fait le choix de mettre en œuvre des stratégies UTT.

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• Perriat Delphine, Diallo Mamadou Hassimiou, Dabis François, Pillay Deenan, Orne-Gliemann Joanna, Larmarange Joseph et ANRS 12249 TasP Study Group (2018) « From home-based HIV testing to viral suppression : HIV care trajectories in the context of Universal Test-and-Treat in rural South Africa » (communication orale), présenté à Life History Research Society Conference, Paris.
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  Résumé : Background : In order for people living with HIV to achieve an undetectable viral load, and thus live longer and healthier, they need access to a continuum of services. There are numerous reports of “leaks” at all steps of the HIV care cascade. We described the timing and sequencing of individual HIV care statuses from care referral to viral suppression, by identifying groups of individuals with similar trajectories and factors associated. Sample : We used prospective individual-level longitudinal data from the ANRS 12249 TasP cluster-randomized trial, which investigated the impact of universal antiretroviral treatment (ART) on HIV incidence in rural South Africa (2012-2016). We included trial participants >16 years, identified HIV+, not in care at referral and followed-up for ≥18 months. Method : The care status of all study participants was classified for each calendar day as : not in care, in care but not on ART, on ART but not virally suppressed, virally suppressed. We used state sequence data analysis to identify homogeneous care trajectories groups. A multinomial logistic regression was used to identify the profile of each group in terms of individual and cluster characteristics. Results : 1,816 participants were included. Median age was 34 years [IQR 27-45], 74% were female. We identified four care trajectories groups : (i) participants who mostly did not enter care (55%), (ii) participants with inconstant care, visiting a clinic occasionally but leaving care thereafter (median time to exit care : 10 m. [5.2-13]) (12%), (iii) participants who took extensive time at each step of the care continuum (median time between referral and ART : 8.0 m. [6.4-9.7]) (12%) and (iv) participants who rapidly progressed towards continuous care (median time between referral and ART : 1.2 m. [0.6-2.7]) (21%). Participants younger than 50 years, newly diagnosed at referral, living further than a kilometre from a trial clinic, and living in a cluster were immediate ART was not offered, were more likely to present with incomplete, inconstant and slow care trajectories. Conclusions : A longitudinal and person-specific approach to the study of HIV care patterns contributed to highlight the heterogeneity in care trajectories, in terms of speed and care utilization behaviours. Differentiated and personalised care and support should be scaled-up, especially between diagnosis and ART initiation, which constitutes the main bottleneck of HIV programs in this South African rural study area.

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2017

Article de revue

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  Ruzagira Eugene, Baisley Kathy, Kamali Anatoli, Biraro Samuel, Grosskurth Heiner et Working Group on Linkage to HIV Care (2017) « Linkage to HIV care after home-based HIV counselling and testing in sub-Saharan Africa: a systematic review », Tropical medicine & international health: TM & IH, 22 (7) (juillet), p. 807-821. DOI : 10.1111/tmi.12888.
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  Résumé : BACKGROUND: Home-based HIV counselling and testing (HBHCT) has the potential to increase HIV testing uptake in sub-Saharan Africa (SSA), but data on linkage to HIV care after HBHCT are scarce. We conducted a systematic review of linkage to care after HBHCT in SSA. METHODS: Five databases were searched for studies published between 1st January 2000 and 19th August 2016 that reported on linkage to care among adults newly identified with HIV infection through HBHCT. Eligible studies were reviewed, assessed for risk of bias and findings summarised using the PRISMA guidelines. RESULTS: A total of 14 studies from six countries met the eligibility criteria; nine used specific strategies (point-of-care CD4 count testing, follow-up counselling, provision of transport funds to clinic and counsellor facilitation of HIV clinic visit) in addition to routine referral to facilitate linkage to care. Time intervals for ascertaining linkage ranged from 1 week to 12 months post-HBHCT. Linkage ranged from 8.2% [95% confidence interval (CI), 6.8-9.8%] to 99.1% (95% CI, 96.9-99.9%). Linkage was generally lower (<33%) if HBHCT was followed by referral only, and higher (>80%) if additional strategies were used. Only one study assessed linkage by means of a randomised trial. Five studies had data on cotrimoxazole (CTX) prophylaxis and 12 on ART eligibility and initiation. CTX uptake among those eligible ranged from 0% to 100%. The proportion of persons eligible for ART ranged from 16.5% (95% CI, 12.1-21.8) to 77.8% (95% CI, 40.0-97.2). ART initiation among those eligible ranged from 14.3% (95% CI, 0.36-57.9%) to 94.9% (95% CI, 91.3-97.4%). Additional linkage strategies, whilst seeming to increase linkage, were not associated with higher uptake of CTX and/or ART. Most of the studies were susceptible to risk of outcome ascertainment bias. A pooled analysis was not performed because of heterogeneity across studies with regard to design, setting and the key variable definitions. CONCLUSION: Only few studies from SSA investigated linkage to care among adults newly diagnosed with HIV through HBHCT. Linkage was often low after routine referral but higher if additional interventions were used to facilitate it. The effectiveness of linkage strategies should be confirmed through randomised controlled trials.

  Mots-clés : aconsejamiento y prueba del VIH en el hogar, conseil et dépistage du VIH à domicile, HIV/AIDS, home-based HIV counselling and testing, liaison avec les soins, linkage to care, Ouganda, Uganda, VIH/SIDA, vinculación a la atención sanitaria.

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Article de colloque

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  Gosset Andréa, Protopopescu Camelia, Okesola Nonhlanhla, Spire Bruno, Larmarange Joseph, Orne-Gliemann Joanna, McGrath Nuala, Pillay Deenan, Dabis François, Iwuji Collins et Boyer Sylvie (2017) « Care trajectories among people living with HIV and followed within a universal test and treat programme in rural South Africa (ANRS 12249 TasP trial) » (poster WEPED1454), présenté à 9th IAS Conference on HIV Science (IAS 2017), Paris. http://programme.ias2017.org/Abstract/Abstract/3791.
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  Résumé : Background: Retention in care is essential to optimize antiretroviral treatment (ART) impact on viral suppression and ensure the success of the universal test and treat (UTT) strategy. We aimed to identify care trajectories and associated factors among ART-eligible patients within the UTT cluster-randomized TasP trial. Methods: Following home-based HIV testing, HIV-positive individuals were referred to TasP clinics and offered immediate ART (intervention arm) or according to national guidelines (control arm). This analysis included all patients ART-eligible at their first clinic visit ≥18 months before the trial end. Monthly clinical follow-up was offered in TasP clinics. A patient was considered exiting care if ≥3 months late for the last appointment, transferred-out or dead. Care trajectories, assessed over 18 months of follow-up, and their associated factors were identified using a group-based trajectory model (Nagin, 2005, Harvard University Press).   Results: Among the 787 ART-eligible patients who attended TasP clinics, four trajectory groups were identified: 70.5% remained in care throughout the entire follow-up period (group 1), 13.6% exited care rapidly (median 4 [IQR 4-6] months after first visit) (group 2), 10.6% exited care latter (11 [9-13] months) (group 3) and 5.2% exited care then returned after 4 [3-9] months (group 4) (Figure 1). The risk of exiting care (groups 2&3) was higher in newly diagnosed patients and those <29 years. The “returning group” members (group 4) were more likely male, with CD4 >350 cells/mm3 at first visit, living in high HIV prevalence clusters (>34%) with the lower nurse-patient ratio, and less likely to have initiated ART. Conclusions: Although most patients remained in care over the 18-month period, a significant proportion exited care at different follow-up times. Particular attention should be paid to men, young and newly diagnosed patients, and those with CD4>350 in order to improve retention in care and maximize the effect of UTT strategies. (Figure)

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  Larmarange Joseph, Diallo Mamadou Hassimiou, Iwuji Collins, Orne-Gliemann Joanna, McGrath Nuala, Plazy Mélanie, Tanser Frank, Thiebaut Rodolphe, Pillay Deenan et Dabis François (2017) « Cascade of Care of HIV Seroconverters in the Context of Universal "Test and Treat" » (communication orale et poster 1018), présenté à Conference on Retroviruses and Opportunistic Infections (CROI) 2017, Seattle. http://www.croiconference.org/sessions/cascade-care-hiv-seroconverters-context-universal-%E2%80%9Ctest-and-treat%E2%80%9D-0.
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  Résumé : The ANRS 12249 TasP cluster-randomized trial aimed at evaluating the impact of a Universal Test and Treat (UTT) approach on population-based HIV incidence in rural KwaZulu Natal, South Africa. Previous results showed low rates of early linkage to HIV care and treatment and did not identify any incidence reduction. To optimize the impact of UTT, time to ART initiation and viral suppression must be shorten significantly, in particular among newly infected individuals. We describe here the longitudinal cascade of care for those seroconverting during the course of the TasP trial. Every six months between March 2012 and June 2016, resident members aged ≥16 years old were offered rapid HIV testing at home and asked independently to provide dried blood spot (DBS) samples. Those testing positive or who self-reported their positive status were referred to local trial clinics for ART initiation, regardless of their CD4 count (intervention) or according to national guidelines (control). Cases of HIV seroconversion were identified using multiple sources: repeat DBS, repeat rapid tests, HIV+ self-reports and clinic visits. Date of seroconversion was estimated using a random point approach. The HIV care status, for each day following seroconversion (M0), was computed using additional data collected on CD4 count, ART prescription, viral load and migration out of the trial area. Follow-up was right-censored by dates of death or trial closure if alive. We observed 565 individuals acquiring HIV (244 in intervention arm; 321 in control arm). Among them, one year after seroconversion (M12), 22% out-migrated from the trial area. 57% were diagnosed (aware of their HIV status), 27% were actively in HIV care, 12% were on ART, and were 10% virally suppressed. The cascade was comparable in both trial arms, except for ART coverage, higher in the intervention arm (15%) than in the control arm (9%). The observed cascade of care was suboptimal in seroconverters despite the introduction of UTT services and a trial environment. This poor outcome was aggravated in this rural setting by out-migration considered here as loss to the cascade. Newly HIV-infected individuals need time to (re)test, initiate ART and reach viral suppression. This is one of the plausible explanations of the lack of effect of the UTT strategy on HIV incidence in our setting. For a UTT approach to be effective, innovative strategies to identify seroconverters and support them to engage in ART care promptly are required.

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  Nishimwe Marie, Protopopescu Camelia, Iwuji Collins, Okesola Nonhlanhla, Spire Bruno, Orne-Gliemann Joanna, McGrath Nuala, Pillay Deenan, Dabis François, Larmarange Joseph et Boyer Sylvie (2017) « The impact of early ART initiation on HIV disclosure and social support among people living with HIV and followed within a universal test and treat programme in rural South Africa (ANRS 12249 TasP trial) » (communication orale), présenté à AIDS Impact 13th International Conference, Cape Town. http://www.aidsimpact.com/abstracts/-KohAV6cKhSNCJEku24i.
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  Résumé : Aim HIV status disclosure and social support have been associated with increased antiretroviral treatment (ART) adherence and better clinical outcomes. We aimed to investigate the impact of early ART initiation on HIV status disclosure and social support among patients in care within the universal test and treat (UTT) cluster-randomized TasP trial conducted in rural South Africa between 2012 and 2016. Method/Issue Following home-based HIV testing, HIV-positive individuals were referred to trial clinics and offered ART regardless of CD4 in intervention arm or according to national guidelines (CD4≤350 cells/mm3 until December 2014, then ≤500 cells/mm3) in control arm. This analysis included patients not ART-treated at baseline (i.e. first clinic visit) and with CD4>500 cells/mm3 who attended at least two clinic visits. HIV disclosure and social support indexes (0-5) were estimated every 6 months: one point was attributed when HIV status was disclosed to - or when the patient reported social support from - at least one member of the following groups: regular partner, family, friends, neighbours, others. We used Poisson mixed effects models, adjusted on individual factors, exploring (i) the impact of time since baseline clinic visit, trial arm and interaction between arm and time; (ii) the impact of ART initiation (time-dependent); and (iii) interaction between arm and ART initiation. Results/Comments Of 3019 patients entering in care in trial clinics, 1597 were not on ART at baseline, 477 had CD4>500 cells/mm3 and 182 had at least two visits (93 in intervention, 89 in control arm). The 182 participants had a median [interquartile range (IQR)] follow-up duration of 13.2 [7.0-18.5] months. After 6 months, 22% had initiated ART in control arm versus 97% in intervention arm, while after 12 months they were 29% and 98% respectively. At baseline, median [IQR] HIV disclosure index was 2 [1;2] versus 1 [1;2] in intervention and control arms, respectively (p=0.361) and median [IQR] social support index was 1 [0;2] versus 2 [1;3] (p=0.053). Both outcomes significantly improved over time. The social support increased significantly faster in intervention arm (Incidence Rate Ratio (IRR) [95% Confidence Interval (CI)]=1.25 [1.04;1.49] per year for the interaction). HIV disclosure was higher in intervention arm (IRR (95% CI)=1.23 [1.10;1.38]), with a similar increase over time between arms. When introducing ART initiation, treatment appeared positively associated with both outcomes (IRR [95% CI]=1.39 [1.17;1.65] for HIV disclosure and 1.36 [1.13;1.63] for social support). For HIV disclosure, differences in ART initiation between arms explained the higher disclosure observed in intervention arm, the effect of arm not being significant anymore. Initiating ART was also associated to increased social support, and this effect was stronger in intervention arm (IRR [95% CI] =1.51 [1.13;2.01] for the interaction). Discussion Our findings suggest that, besides clinical benefits, early ART initiation at high CD4 cell count may also positively influence HIV disclosure and social support. For this second outcome, a longer time of follow-up may however be required to observe this benefit. These findings are encouraging for countries that made the choice of implementing UTT strategies.

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  Orne-Gliemann Joanna, Rolland Matthieu, Tiendrebeogo Thierry, Larmarange Joseph, Pillay Deenan, Dabis François, McGrath Nuala et ANRS 12249 TasP Study Group (2017) « Is there an effect of universal ART on sexual behaviours in rural KwaZulu-Natal, South Africa? ANRS 12249 treatment-as-prevention (TasP) trial » (poster WEPEC0968), présenté à 9th IAS Conference on HIV Science (IAS 2017), Paris. http://programme.ias2017.org/Abstract/Abstract/2390.
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  Résumé : Background: There are concerns that the implementation of Universal Test and Treat (UTT) could increase populationlevel sexual risk behaviours. We analysed the effect of universal ART vs CD4-guided ART (start at CD4≥350 then ≥500) on sexual behaviours over time, in the context of the cluster-randomised TasP trial. Methods: As part of the 6-monthly home-based survey rounds conducted in 11x2 clusters, a sexual behaviour questionnaire was administered to all residents ≥16 years. We used GEE modelling stratified by gender, to compare reported condom use at last sex (CLS), and multi-partnership (≥2 sexual partners) among those sexually-active in the previous six months across trial arms. We tested whether the sexual behaviours changed over time differently in each arm by inclusion of an interaction term between survey round and arm, using the Quasi-likelihood Independence Criterion (QIC) statistic to compare models. Results: The analysis included 43,106 reports of partnerships (22,974 control, 20,132 intervention) across 7 survey rounds (SR), between 03/2012 and 06/2016. There were no consistent or substantive changes in CLS over time neither by gender nor by arm (fig 1a, 1b); inclusion of an interaction term improved the model fit, reflecting small differences between arms in CLS over time. Less than 1.5% of women reported multiple partnerships at any SR, too few for modelling (fig 1d). The proportion of men reporting multiple partnerships decreased significantly during the study (aOR 0.79, 95% CI 0.75, 0.83), p< 0.001), similarly for each arm (interaction not significant), with overall a small, but significant higher proportion reported in the universal ART arm (13.7%) vs CD4-guided ART (12.1%) (OR=1.15, 95% CI (1.03, 1.27), p=0.02 (fig 1c). [Figure 1] Conclusions: There is no evidence of increased unprotected sex with universal ART in this South African population. Continued monitoring of population-level sexual behaviour indicators, in particular multiple partnerships, is needed as the UTT strategy is rolled out.

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  Plazy Mélanie, Diallo A, Iwuji Collins, Orne-Gliemann Joanna, Okesola Nonhlanhla, Hlabisa T, Pillay Deenan, Dabis François, Larmarange Joseph et ANRS 12249 TasP Study Group (2017) « Enhancing referral to increase linkage to HIV care in rural South Africa: example from the ANRS 12249 TasP trial » (poster TUPED1308), présenté à 9th IAS Conference on HIV Science (IAS 2017), Paris. http://programme.ias2017.org/Abstract/Abstract/2405.
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  Résumé : Background: Timely linkage to care following an HIV diagnosis is critical for people living with HIV to initiate antiretroviral treatment as early as possible and thus decrease the risks of HIV-related morbidity, mortality and HIV transmission. Linkage to HIV care is however often challenging and innovative strategies are required to help people accessing HIV care. We aimed at evaluating the effect of phone calls and home visits following an initial referral on time to linkage to care in the context of a Universal HIV Testing and Treatment (UTT) trial in rural KwaZulu-Natal, South Africa. Methods: The ANRS 12249 TasP trial was conducted from March 2012 to June 2016 with the aim to evaluate the effect of UTT on HIV incidence. Individuals ≥16 years were offered home-based HIV testing; those identified HIV-positive were referred to nearby TasP trial clinics to receive care and treatment. Starting April 2013, an enhancement strategy combining phone calls and home visits was implemented to re-refer people who did not link to care within three months of first referral. Effect of this strategy on time to linkage to care was studied as a time-varying variable among individuals not in care at first referral using a Cox regression model censored for death, migration and end of study observation. Results: Among the 7,643 individuals identified HIV-positive at home and referred to TasP clinics, 2,254 (72% female) were not in care at referral and did not link to care within three months of first referral. Among them, 451 (20%) individuals were contacted through phone calls or home visits before migration or death. Probability of linkage to care was significantly higher mong individuals re-referred to care compared to those not re-referred (Hazard Ratio 2.25; 95% Confidence Interval 1.83-2.78); significant positive effects were also observed for both genders and all age categories (< 30; 30-39; 40-49; ≥50 years old) after stratification. Conclusions: Phone calls and home visits aiming at re-referring people to HIV care appear effective in improving linkage to care. Patient-centered strategies should be part of UTT programs in order to achieve the 90-90-90 UNAIDS targets.

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2016

Article de revue

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  Boyer Sylvie, Iwuji Collins, Gosset Andréa, Protopopescu Camelia, Okesola Nonhlanhla, Plazy Mélanie, Spire Bruno, Orne-Gliemann Joanna, McGrath Nuala, Pillay Deenan, Dabis François, Larmarange Joseph et group on behalf of the ANRS 12249 TasP study (2016) « Factors associated with antiretroviral treatment initiation amongst HIV-positive individuals linked to care within a universal test and treat programme: early findings of the ANRS 12249 TasP trial in rural South Africa », AIDS Care, 28 (sup3) (juin 2), p. 39-51. DOI : 10.1080/09540121.2016.1164808. http://dx.doi.org/10.1080/09540121.2016.1164808.
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  Résumé : Prompt uptake of antiretroviral treatment (ART) is essential to ensure the success of universal test and treat (UTT) strategies to prevent HIV transmission in high-prevalence settings. We describe ART initiation rates and associated factors within an ongoing UTT cluster-randomized trial in rural South Africa. HIV-positive individuals were offered immediate ART in the intervention arm vs. national guidelines recommended initiation (CD4≤350 cells/mm3) in the control arm. We used data collected up to July 2015 among the ART-eligible individuals linked to TasP clinics before January 2015. ART initiation rates at one (M1), three (M3) and six months (M6) from baseline visit were described by cluster and CD4 count strata (cells/mm3) and other eligibility criteria: ≤100; 100–200; 200–350; CD4>350 with WHO stage 3/4 or pregnancy; CD4>350 without WHO stage 3/4 or pregnancy. A Cox model accounting for covariate effect changes over time was used to assess factors associated with ART initiation. The 514 participants had a median [interquartile range] follow-up duration of 1.08 [0.69; 2.07] months until ART initiation or last visit. ART initiation rates at M1 varied substantially (36.9% in the group CD4>350 without WHO stage 3/4 or pregnancy, and 55.2–71.8% in the three groups with CD4≤350) but less at M6 (from 85.3% in the first group to 96.1–98.3% in the three other groups). Factors associated with lower ART initiation at M1 were a higher CD4 count and attending clinics with both high patient load and higher cluster HIV prevalence. After M1, having a regular partner was the only factor associated with higher likelihood of ART initiation. These findings suggest good ART uptake within a UTT setting, even among individuals with high CD4 count. However, inadequate staffing and healthcare professional practices could result in prioritizing ART initiation in patients with the lowest CD4 counts.

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  Camlin Carol S., Seeley Janet, Viljoen Lario, Vernooij Eva, Simwinga Musonda, Reynolds Lindsey, Reis Ria, Plank Rebeca, Orne-Gliemann Joanna, McGrath Nuala, Larmarange Joseph, Hoddinott Graeme, Getahun Monica, Charlebois Edwin D. et Bond Virginia (2016) « Strengthening universal HIV ‘test-and-treat’ approaches with social science research: », AIDS, 30 (6), p. 969-970. DOI : 10.1097/QAD.0000000000001008. http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00002030-201603270-00019.
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  Chikovore Jeremiah, Gillespie Natasha, McGrath Nuala, Orne-Gliemann Joanna, Zuma Thembelihle et Group On Behalf of the ANRS 12249 TasP Study (2016) « Men, masculinity, and engagement with treatment as prevention in KwaZulu-Natal, South Africa », AIDS Care, 28 (sup3) (juin 2), p. 74-82. DOI : 10.1080/09540121.2016.1178953. http://dx.doi.org/10.1080/09540121.2016.1178953.
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  Résumé : Men’s poorer engagement with healthcare generally and HIV care specifically, compared to women, is well-described. Within the HIV public health domain, interest is growing in universal test and treat (UTT) strategies. UTT strategies refer to the expansion of antiretroviral therapy (ART) in order to reduce onward transmission and incidence of HIV in a population, through a “treatment as prevention” (TasP). This paper focuses on how masculinity influences engagement with HIV care in the context of an on-going TasP trial. Data were collected in January–November 2013 using 20 in-depth interviews, 10 of them repeated thrice, and 4 focus group discussions, each repeated four times. Analysis combined inductive and deductive approaches for coding and the review and consolidation of emerging themes. The accounts detailed men’s unwillingness to engage with HIV testing and care, seemingly tied to their pursuit of valued masculinity constructs such as having strength and control, being sexually competent, and earning income. Articulated through fears regarding getting an HIV-positive diagnosis, observations that men preferred traditional medicine and that primary health centres were not welcoming to men, descriptions that men used lay measures to ascertain HIV status, and insinuations by men that they were removed from HIV risk, the indisposition to HIV care contrasted markedly with an apparent readiness to test among women. Gendered tensions thus emerged which were amplified in the context where valued masculinity representations were constantly threatened. Amid the tensions, men struggled with disclosing their HIV status, and used various strategies to avoid or postpone disclosing, or disclose indirectly, while women’s ability to access care readily, use condoms, or communicate about HIV appeared similarly curtailed. UTT and TasP promotion should heed and incorporate into policy and health service delivery models the intrapersonal tensions, and the conflict, and poor and indirect communication at the micro-relational levels of couples and families.

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  Iwuji Collins C., Orne-Gliemann Joanna, Larmarange Joseph, Okesola Nonhlanhla, Tanser Frank, Thiebaut Rodolphe, Rekacewicz Claire, Newell Marie-Louise, Dabis Francois et Group ANRS 12249 TasP trial (2016) « Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about ART in Rural KwaZulu-Natal, South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial », PLOS Med, 13 (8) (août 9), p. e1002107. DOI : 10.1371/journal.pmed.1002107. http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002107.
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  Résumé : Collins Iwuji and colleagues report implementation indicators and early health outcomes from the first phase of a cluster-randomized trial of immediate antiretroviral therapy to all HIV-positive individuals in rural KwaZulu-Natal, South Africa.

  Mots-clés : antiretroviral therapy, Cluster trials, HIV, HIV diagnosis and management, HIV epidemiology, HIV prevention, Questionnaires, South Africa.

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  Moshabela Mosa, Zuma Thembelihle, Orne-Gliemann Joanna, Iwuji Collins, Larmarange Joseph, McGrath Nuala et Group on behalf of the ANRS 12249 TasP Study (2016) « “It is better to die”: experiences of traditional health practitioners within the HIV treatment as prevention trial communities in rural South Africa (ANRS 12249 TasP trial) », AIDS Care, 28 (sup3) (juin 2), p. 24-32. DOI : 10.1080/09540121.2016.1181296. http://dx.doi.org/10.1080/09540121.2016.1181296.
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  Résumé : The ANRS 12249 Treatment-as-Prevention (TasP) cluster-randomized trial in rural South Africa uses a “test and treat” approach. Home-based testing services and antiretroviral treatment initiation satellite clinics were implemented in every cluster as part of the trial. A social science research agenda was nested within TasP with the aim of understanding the social, economic and contextual factors that affect individuals, households, communities and health systems with respect to TasP. Considering the rural nature of the trial setting, we sought to understand community perceptions and experiences of the TasP Trial interventions as seen through the eyes of traditional health practitioners (THPs). A qualitative study design was adopted using four repeat focus group discussions conducted with nine THPs, combined with community walks and photo-voice techniques, over a period of 18 months. A descriptive, interpretive and explanatory approach to analysis was adopted. Findings indicate that THPs engaged with the home-based testing services and HIV clinics established for TasP. Specifically, home-based testing services were perceived as relatively successful in increasing access to HIV testing. A major gap observed by THPs was linkage to HIV clinics. Most of their clients, and some of the THPs themselves, found it difficult to use HIV clinics due to fear of labelling, stigma and discrimination, and the ensuing personal implications of unsolicited disclosure. On the one hand, a growing number of patients diagnosed with HIV have found sanctuary with THPs as alternatives to clinics. On the other hand, THPs in turn have been struggling to channel patients suspected of HIV into clinics through referrals. Therefore, acceptability of the TasP test and treat approach by THPs is a major boost to the intervention, but further success can be achieved through strengthened ties with communities to combat stigma and effectively link patients into HIV care, including partnerships with THPs themselves.

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  Orne-Gliemann Joanna, Zuma Thembelihle, Chikovore Jeremiah, Gillespie Natasha, Grant Merridy, Iwuji Collins, Larmarange Joseph, McGrath Nuala, Lert France, Imrie John et Group On Behalf of the TasP Study (2016) « Community perceptions of repeat HIV-testing: experiences of the ANRS 12249 Treatment as Prevention trial in rural South Africa », AIDS Care, 28 (sup3) (juin 2), p. 14-23. DOI : 10.1080/09540121.2016.1164805. http://dx.doi.org/10.1080/09540121.2016.1164805.
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  Résumé : In the context of the ANRS 12249 Treatment as Prevention (TasP) trial, we investigated perceptions of regular and repeat HIV-testing in rural KwaZulu-Natal (South Africa), an area of very high HIV prevalence and incidence. We conducted two qualitative studies, before (2010) and during the early implementation stages of the trial (2013–2014), to appreciate the evolution in community perceptions of repeat HIV-testing over this period of rapid changes in HIV-testing and treatment approaches. Repeated focus group discussions were organized with young adults, older adults and mixed groups. Repeat and regular HIV-testing was overall well perceived before, and well received during, trial implementation. Yet community members were not able to articulate reasons why people might want to test regularly or repeatedly, apart from individual sexual risk-taking. Repeat home-based HIV-testing was considered as feasible and convenient, and described as more acceptable than clinic-based HIV-testing, mostly because of privacy and confidentiality. However, socially regulated discourses around appropriate sexual behaviour and perceptions of stigma and prejudice regarding HIV and sexual risk-taking were consistently reported. This study suggests several avenues to improve HIV-testing acceptability, including implementing diverse and personalised approaches to HIV-testing and care, and providing opportunities for antiretroviral therapy initiation and care at home.

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  Plazy Mélanie, Farouki Kamal El, Iwuji Collins, Okesola Nonhlanhla, Orne-Gliemann Joanna, Larmarange Joseph, Lert France, Newell Marie-Louise, Dabis François et Dray-Spira Rosemary (2016) « Access to HIV care in the context of universal test and treat: challenges within the ANRS 12249 TasP cluster-randomized trial in rural South Africa », Journal of the International AIDS Society, 19 (1) (juin 1). DOI : 10.7448/IAS.19.1.20913. http://www.jiasociety.org/index.php/jias/article/view/20913.
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Article de colloque

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  Iwuji Collins, Orne-Gliemann Joanna, Balestre Eric, Larmarange Joseph, Thiébaut Rodolphe, Tanser Frank, Okesola Nonhlanhla, Makowa Thembisa, Dreyer Jaco, Herbst Kobus, McGrath Nuala, Bärnighausen Till, Boyer Sylvie, de Oliveira Tulio, Rekacewicz Claire, Bazin Brigitte, Newell Marie-Louise, Pillay Deenan, Dabis François et ANRS 12249 TasP Study Group (2016) « The impact of universal test and treat on HIV incidence in a rural South African population: ANRS 12249 TasP trial, 2012-2016 » (communication orale n°FRAC0105LB), présenté à 21st International AIDS Conference (AIDS 2016), Durban. http://programme.aids2016.org/Abstract/Abstract/10537.
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  Résumé : Background: The population impact of universal test and treat (UTT) on HIV transmission has not yet been evaluated. Methods: A cluster-randomized trial was implemented in 2x11 rural communities in KwaZulu-Natal, South Africa. All residents ≥16 years were offered rapid HIV testing and provided dried blood spots (DBS) during 6-monthly home-based survey rounds. HIV-positive participants were referred to cluster-based trial clinics to receive ART regardless of CD4 count (intervention arm) or according to national guidelines (control arm). Standard of care ART was also available in the Department of Health clinics. HIV incidence was estimated on repeat DBS using cluster-adjusted Poisson regression. Results: Between 03/2012 and 04/2016, 13,239 and 14,916 individuals (63% women, median age 30 years) were registered in the intervention and control arms. Contact frequency per round among registered individuals ranged from 64% to 83%, HIV ascertainment from 74% to 85%. Baseline HIV prevalence was 29.4%(95%CI 28.8-30.0), with 7,578 individuals identified as HIV-positive. 1,513(36%) of 4,172 HIV-positive individuals not previously in care linked to trial clinics within 6 months of referral. ART initiation in trial clinics at 3 months was 90.9%(576/634) and 52.3%(332/635) in the intervention and control arms; viral suppression (< 400 copies/mL) 12 months after ART initiation was 94.9%(300/316) and 94.2%(194/206), respectively. Overall ART coverage at entry was 31% and 36% in the intervention and control arms, reaching 41% in both arms by closing date. Repeat DBS tests were available for 13,693 individuals HIV-negative at baseline, yielding 461 seroconversions in 20,833 person-years (PY). HIV incidence was 2.16 per 100 PY (1.88-2.45) in the intervention arm and 2.26 (1.98-2.54) in the control arm (adjusted relative risk: 0.95 [0.82-1.10]). Severe adverse events rates were 3.4%(45/1,323) and 3.5%(57/1,604) in the intervention and control arms. Follow-up will be completed by 06/2016. Conclusions: Our trial shows high acceptance of home-based HIV testing and high levels of viral suppression among individuals on ART. However overall linkage to care remains poor. No reduction in HIV incidence was demonstrated. Several factors are being investigated, including determinants of poor linkage, change in national ART guidelines, migration and geography of sexual networks. (Funded by ANRS, GiZ and 3ie; Clinical Trials registration NCT00332878).

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  Larmarange Joseph, Iwuji Collins, Orne-Gliemann Joanna, McGrath Nuala, Plazy Mélanie, Baisley Kathy, Bärnighausen Till, Dabis François, Pillay Deenan et ANRS 12249 TasP Study Group (2016) « Measuring the Impact of Test and Treat on the HIV Cascade: the Challenge of Mobility » (communication orale), présenté à Conference on Retroviruses and Opportunistic Infections (CROI), Boston. http://www.croiwebcasts.org/console/player/29736.
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  Résumé : Background Universal test and treat (UTT) could substantially improve the HIV care cascade at population level (i.e. the proportion of all HIV-infected people being diagnosed, on ART and virally suppressed at a given date) and thus reduce HIV incidence. Several trials are currently exploring this hypothesis. Due to demographic change, the study population of HIV-infected individuals is composed of people with various degrees of exposure to the trial interventions. This structural effect could potentially dilute the impact observed at population level of a UTT strategy. Here, we describe a dynamic cascade according to both calendar (population) and exposure (individual) time approaches, using preliminary data from the ANRS 12249 TasP cluster-randomized trial ongoing in rural KwaZulu-Natal (South Africa). Methods Analysis was conducted within a subgroup of 4 clusters with the longest follow-up time where five six-monthly rounds of home-based HIV testing had been conducted between March 2012 and July 2015. Resident members 16 years and above were offered rapid HIV testing and asked to provide dried blood spots (DBS) each time. Those ascertained HIV-positive were referred to local trial clinics for ART initiation and follow-up. HIV tests results and information on clinic visits, ART prescription, viral load and CD4 count, migration and death were used to calculate residency status, HIV status and HIV care status for each individual on each calendar day. This calendar cascade was then compared to the exposure cascade, where each status was recalculated for individuals at any given date with exposure time defined as the duration since trial registration. Results Figure 1 - CROI Abstract According to calendar time, the overall cascade improved rapidly during the first 15 months of the trial (from 25 to 40% virally suppressed), but more slowly thereafter (Fig a). Although the target population size of HIV-infected people remained rather stable over time ( 665 individuals, Fig b), population turnover was high (Fig c). According to exposure time, with a decreasing sample size over time (Fig e), the cascade improved continuously between M0 and M30, from 20% to 50% virally suppressed (Fig. d). Conclusions Population mobility dilutes the observed impact of UTT interventions on the cascade at population level. These preliminary findings also suggest that the impact of a UTT approach could be maximized as long as there is a coordination to facilitate continued access to care when people move.

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  Orne-Gliemann Joanna, Zuma Thembelihle, Larmarange Joseph et ANRS 12249 TasP Study Group (2016) « Home-based HIV testing and linkage to care : lessons learned from the ANRS 12249 TasP trial » (communication orale (MOSA4402), présenté à 21st International AIDS Conference (AIDS 2016), Durban. http://programme.aids2016.org/Programme/Session/126.
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2015

Article de revue

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  Orne-Gliemann Joanna, Larmarange Joseph, Boyer Sylvie, Iwuji Collins, McGrath Nuala, Bärnighausen Till, Zuma Thembelihle, Dray-Spira Rosemary, Spire Bruno, Rochat Tamsen, Lert France, Imrie John et ANRS 12249 TasP Study Group (2015) « Addressing social issues in a universal HIV test and treat intervention trial (ANRS 12249 TasP) in South Africa: methods for appraisal », BMC Public Health, 15 (1) (mars 1), p. 209. DOI : 10.1186/s12889-015-1344-y. http://www.biomedcentral.com/1471-2458/15/209/abstract.
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  Mots-clés : Antiretroviral treatment, Behaviour, Community, Cost, HIV care, HIV Infections, HIV testing, Social, South Africa.

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Article de colloque

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  Iwuji Collins, Dray-Spira Rosemary, Calmy Alexandra, Larmarange Joseph, Orne-Gliemann Joanna, Dabis François, Pillay Deenan et Porter Kholoud (2015) « Does a universal test and treat strategy impact ART adherence in rural South Africa? ANRS 12249 TasP cluster-randomized trial » (communication orale n°MOAC0104), présenté à 8th IAS Conference on HIV Pathogeneis, Treatment & Prevention, Vancouver. DOI : 10.7448/IAS.18.5.20340.
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  Résumé : Background: HIV treatment guidelines are recommending ART at increasingly higher CD4 counts for maximizing individual and population benefits. However, the expansion of ART use may be at the expense of optimal adherence. We report on adherence and virological suppression when initiating ART at different CD4 thresholds within the Treatment as Prevention (ANRS 12249) trial of universal home-based testing and immediate ART initiation in rural KwaZulu-Natal. Methods: Using data of a cluster-randomised trial of immediate ART vs. initiation according to current national guidelines (CD4≤350cells/mm3), we compared adherence levels (≥95% vs. < 95%) measured using a visual analogue scale (VAS) and pill count (PC) and virological suppression at 6 months (< 400 c/mL) according to CD4 count at ART initiation through logistic regression models, adjusting for possible confounders (age, sex, marital status, education and employment). Results: During March 2012-May 2014, 601 participants who were not on ART entered care in trial clinics; 382 initiated ART; 254 have completed ≥6 months on ART, 227 of whom had 6 months HIV RNA data and were included in analyses. 169 were women; median (IQR) age and CD4 at ART initiation were 35 years (28, 46) and 313cells/mm3 (206, 513). Adherence ≥95% at 6 months was high (88% and 83% by PC and VAS, respectively) with no evidence that this was associated with CD4 at initiation (aOR=0.97 per 100 cells/mm3 higher, 95%-CI: 0.83-1.12, p=0.65 for VAS; aOR 1.13 per 100cells/mm3 higher, 0.98-1.31, p=0.09 for PC). Male sex was independently associated with < 95% adherence (2.58, 1.24-5.35, p= 0.01; ref. females). 83% (183/227) of those who started ART achieved HIV suppression by 6 months with no association with CD4 at initiation (1.13 per 100cells/mm3 higher, 0.96-1.33, p=0.40). Compared to those with ≥95% adherence by VAS, individuals with < 95% adherence were somewhat less likely to suppress (0.44, 0.19-1.03, p=0.06). Conclusions: We found no evidence that, among people newly entering HIV care, higher CD4 at ART initiation was associated with reduced adherence or poorer virological suppression, at least in the short-term. In this rural South African setting, motivation to adhere to ART may be independent of the presence of symptomatic HIV disease.

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  Larmarange Joseph (2015) « Treatment as Prevention (TasP) studies: the challenge of CD4 count treatment eligibility changes in Africa. Perspectives from the TasP ANRS 12249 trial » (communication orale), présenté à 9th INTEREST Workshop, Harare. http://www.virology-education.com/online-program-9th-interest/.
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  Plazy Mélanie, El Farouki Kamal, Iwuji Collins, Okesola Nonhlanhla, Orne-Gliemann Joanna, Larmarange Joseph, Newell Marie-Louise, Pillay Deenan, Dabis François, Dray-Spira Rosemary et ANRS 12249 TasP Study Group (2015) « Entry into care following universal home-based HIV testing in rural KwaZulu-Natal, South Africa: the ANRS TasP 12249 cluster-randomised trial » (communication orale n°WEAD0103), présenté à 8th IAS Conference on HIV Pathogeneis, Treatment & Prevention, Vancouver. DOI : 10.7448/IAS.18.5.20409.
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  Résumé : Background: In a Universal Test and Treat (UTT) strategy, entry into care soon after HIV diagnosis is crucial to achieve optimal population-antiretroviral treatment (ART) coverage. We evaluated the rate of, and factors associated with, entry into care following home-based HIV testing in a cluster-randomised trial of the effect of immediate ART on HIV incidence in rural KwaZulu-Natal, South Africa. Methods: From March 2012 to May 2014, individuals ≥16 years in ten (2 x 5) clusters were offered home-based HIV testing; those ascertained HIV-positive were referred to TasP trial clinics and were offered universal and immediate ART (intervention clusters) or according to national guidelines (control clusters). Entry into care was defined as attending a TasP clinic within three months of referral among adults not actively in HIV care (no visit to local HIV programme within past 13 months). Associated factors were identified separately by sex, using multivariable logistic regression. Results: Overall, 1,205 adults (72.6% women) not actively in HIV care were referred to a TasP clinic. Of these, 405 (33.6%) attended a TasP clinic within three months (no difference between trial arms): 32.5% of women, 36.7% of men. Participants who ever visited the local HIV programme (n=360) were more likely to enter into care than those who didn''t (women: adjusted Odd-Ratio (aOR) 1.76, 95% Confidence Interval [1.26-2.45]; men: 2.07 [1.18-3.64]). In women (n=875), those less likely to attend a TasP clinic within three months had completed some secondary school (0.51 [0.33-0.79]) or at least secondary school (0.47 [0.29-0.76]) versus below primary school; were living 1-2 km from a TasP clinic (0.43 [0.30-0.62]) or 2-5 km (0.40 [0.27-0.61]) versus < 1 km; didn''t know anyone HIV+ within their family (0.60 [0.43-0.81]) and didn''t agree that it is good to initiate ART as soon as possible if infected (0.47 [0.26-0.85]); among men (n=330), none of the factors examined was significantly associated with entry into care. Conclusions: Only one-third of HIV-positive adults referred after home-based HIV testing entered into care within three months in this rural South African community with a 30% HIV prevalence. Innovative interventions should be considered to ensure the success of a UTT strategy.

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2014

Article de revue

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  Larmarange Joseph, Balestre Eric, Orne-Gliemann Joanna, Iwuji Collins, Okesola N., Newell M.L., Dabis François et Lert France (2014) « HIV ascertainment through repeat home-based testing in the context of a treatment as prevention trial (ANRS 12249 TasP) in rural South Africa », AIDS Research and Human Retroviruses, 30 (Suppl. 1), p. A287. DOI : 10.1089/aid.2014.5650.abstract. http://www.documentation.ird.fr/hor/fdi:010063442.
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Article de colloque

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  Iwuji Collins, Orne-Gliemann Joanna, Tanser Frank, Thiébaut Rodolphe, Larmarange Joseph, Okesola Nonhlanhla, Newell Marie-Louise et Dabis François (2014) « Feasibility and acceptability of an antiretroviral treatment as prevention (TasP) intervention in rural South Africa: results from the ANRS 12249 TasP cluster-randomised trial » (communication orale n°WEAC0105LB), présenté à 20th International AIDS Conference, Melbourne. http://pag.aids2014.org/session.aspx?s=1118.
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  Larmarange Joseph, Orne-Gliemann Joanna, Balestre Eric, Iwuji Collins, Okesola Nonhlanhla, Newell Marie-Louise, Dabis François, Lert France et TasP ANRS 12249 Study Group (2014) « HIV ascertainment through repeat home-based testing in the context of a Treatment as Prevention trial (ANRS 12249 TasP) in rural South Africa » (poster P52.05), présenté à HIV Research for Prevention, Cape Town. DOI : 10.1089/aid.2014.5650.abstract.
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  Résumé : Background The ANRS 12249 TasP cluster-randomised trial evaluates whether HIV testing of all members of a community, followed by immediate antiretroviral treatment (ART) for infected people, will prevent onward sexual transmission and reduce HIV incidence at population level. Ascertaining the HIV status of a high proportion of the population regularly and repeatedly is key to the success of any universal test and treat strategy, as the first step of the HIV cascade. Methods Between March 2012 and March 2014, we implemented three six-monthly rounds of home-based HIV counselling and testing in ten local communities (clusters). At each home visit, individual questionnaires were administered and a rapid HIV test offered to all trial participants. We report early results on rates of HIV ascertainment, defined as undergoing a rapid HIV test or HIV-positive self-report. Results Of 12,911 eligible individuals (resident in the trial area and ≥16 years), 10,007 were successfully contacted at least once. At first contact, HIV status was ascertained for 7,628 (76.2% [95% CI: 75.4-77.1]) individuals. At second contact, among the 5,885 individuals contacted a second time, HIV status was ascertained for 2,829 (85.0% [95% CI: 83.7-86.2]) of the 3,328 tested negative at first contact and for 543 (45.7% [95% CI: 42.9-48.6]) of the 1,188 who refused a rapid test at first contact. Overall, HIV ascertainment rate was 89.0% (5,239/5,885 [95% CI: 88.2-89.8]) among trial participants contacted twice. Conclusions Repeat home-based HIV testing is acceptable and feasible in this rural area. Socio-demographic characteristics, behaviours, attitudes, household characteristics and experience of HIV infection and ART in the household will be explored for their association with HIV ascertainment uptake. This will inform whether this intervention reaches the individuals at higher risk in a rural South African region.

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2013

Article de revue

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  Iwuji Collins C, Orne-Gliemann Joanna, Tanser Frank, Boyer Sylvie, Lessells Richard J, Lert France, Imrie John, Bärnighausen Till, Rekacewicz Claire, Bazin Brigitte, Newell Marie-Louise, Dabis François et ANRS 12249 TasP study group (2013) « Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial », Trials, 14 (1), p. 230. DOI : 10.1186/1745-6215-14-230. http://clinicaltrials.gov/ct2/show/NCT01509508?term=anrs+12249&rank=1.
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  Résumé : BACKGROUND: Antiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial's secondary outcomes. METHODS/DESIGN: A cluster-randomised trial in 34 (2 × 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 × 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/μL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters. DISCUSSION: We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974.

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Article de colloque

• Imrie John, Larmarange Joseph, Orne-Gliemann Joanna, Iwuji Collins, Lert France et ANRS 12249 TasP Study Group (2013) « Issues emerging from universal test and treat (UTT) intervention trials » (communication orale n°CS20#2), présenté à 2nd International Conference for the Social Sciences and Humanities in HIV, Paris.
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  Résumé : Universal repeat testing and early antiretroviral treatment (UTT) strategies to reduce onward sexual transmission are major social, as well as biomedical interventions. Several UTT trials are underway or being prepared. This paper discusses some emerging issues arguing extensive social science within UTT trials needs complementary enquiry to guide public health and operational decisions beyond the trials themselves. The issues fall under three broad headings: 1) Social and behavioural consequences of large numbers of people knowing their HIV-status and potentially beginning treatment early. Will the impacts on sexual behaviour, disclosure and stigma all be positive? Harmful? 2) Normative changes at individual and community levels. What normative changes occur in communities exposed to prolonged, intense research around unspoken or socially taboo subjects? Does seeing more healthy people attending clinics alter community perceptions of disease and care? Can salient positive changes be identified and replicated? 3) Operational and ethical implications of transforming research interventions into routine care. Who should lead? Requirements for sustainability. Impacts of institutions ‘knowing’ about individuals’ HIV status and care uptake, especially in contexts of criminalisation and marginalised or vulnerable populations? UTT strategies have potentially great social consequences that need to be explored alongside the actual trials, to guide and inform future decisions and policy.

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• Imrie John, Larmarange Joseph, Orne-Gliemann Joanna, Lert France et ANRS 12249 TasP Study Group (2013) « Taking test and treat interventions to the next level – Beginning to think what additional information needs to guide public health and operational decisions? » (poster n°2289118), présenté à 6th South African AIDS Conference, Durban.
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  Résumé : Background The proposition universal repeat HIV testing and early initiation of antiretroviral treatment for all HIV-positives (UTT) can lead to reduced HIV incidence is being, or will be, tested in several studies. UTT interventions are major social, as well as biomedical interventions, for individuals and target communities. Implementing UTT trial (ANRS 12249 TasP Trial) provoked thinking about what is needed for public health and operational decisions to move to the next level if UTT efficacy is demonstrated. Methods In ANRS 12249 Tasp Trial innovative social science tools are implemented at each UTT stage to ensure a comprehensive understanding of the social determinants of intervention uptake at the individual and community-level and the impacts at individual, household and community level. But these alone cannot guide such a decision. Results Additional questions requiring answers: Social and Behavioural consequences of UTT: What are the long-term social and behavioural consequences of large numbers of people knowing their HIV-status and starting treatment early? Will impacts on sexual behaviour, disclosure and stigma necessarily be positive, now and in the long term? Changes in individual and community norms: Will community perceptions of HIV and healthcare be changed seeing healthy people going to clinics? How are community norms around testing and treatment, stigma and discrimination affected by prolonged, intense research? Can salient positive changes be identified and replicated? Operational and ethical implications of moving UTT into routine care: Who should lead? What are the sustainability requirements? What ethical issues are there in authorities ‘knowing’ individuals’ HIV status and care uptake? Conclusions UTT strategies have potentially great social consequences for the individuals and populations involved. Questions emerging from UTT trials need further enquiry before public health and operational decisions to move beyond the trials are made.

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• Larmarange Joseph, Imrie John, Orne-Gliemann Joanna, Iwuji Collins, Lert France et ANRS 12249 TasP Study Group (2013) « Socio-economic issues investigated in an HIV Treatment as Prevention (TasP) trial in rural KwaZulu-Natal: research questions, implementation and progress » (poster n°2288617), présenté à 6th South African AIDS Conference, Durban.
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  Résumé : Background HIV testing of all adult members of a community, followed by immediate antiretroviral treatment (ART) initiation of HIV-infected participants, regardless of immunological or clinical staging, could prevent onward transmission and reduce HIV incidence. The community cluster-randomized ANRS 12249 Treatment as Prevention (TasP) trial has been designed to test acceptability, feasibility and efficacy of this strategy in Hlabisa sub-district, KwaZulu-Natal. In addition to epidemiological, clinical and operational challenges, TasP raises unprecedented social challenges at individual and population levels. Methods The trial began in March 2012. Innovative research tools are being implemented at each stage of the TasP intervention: repeat home-based questionnaires with household heads and individual household members; specific questionnaires for the HIV-infected individuals attending trial clinics and for those who choose not enter HIV care; combined with in-depth semi-structured individual qualitative interviews, repeat focus groups discussions (consumer panels) using participatory methods. Results We will be able to describe precisely participation in the trial and to understand the social determinants of uptake in terms of repeat HIV testing, linkage to and retention in HIV care; the impact of this TasP strategy on quality of life; the economic impact on households and the healthcare system; and consequences for people’s life in terms of HIV disclosure, stigma, sexual behaviours, social support, treatment experience and adherence. Conclusions TasP is not just a biomedical intervention. Understanding the consequences of implementing universal HIV testing and ART on individual behaviour changes and community social norms is crucial to explain any observe impact on HIV incidence.

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• Larmarange Joseph, Imrie John, Orne-Gliemann Joanna, Iwuji Collins, Lert France et ANRS 12249 TasP Study Group (2013) « Addressing social science in a HIV Treatment as Prevention trial in South Africa » (communication orale n°CS12#1), présenté à 2nd International Conference for the Social Sciences and Humanities in HIV, Paris.
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  Résumé : Models show that universal HIV testing and early antiretroviral treatment (ART) could lead to reduced HIV incidence and potential eradication under assumptions that have yet to be observed in real life – high coverage and frequent repeat HIV testing, high levels of linkage and retention in care. ANRS 12249 Treatment as Prevention (TasP) trial in rural KwaZulu-Natal aims to evaluate acceptability, feasibility and efficacy of this strategy. It has two components: home-based testing of all ≥16 years every six months with immediate versus standard ART initiation for HIV-infected individuals (HIV+). TasP is a biomedical intervention raising unprecedented social challenges. Relationships between individual and community factors, their interactions and implications are all being investigated using innovative quantitative and qualitative tools. Key issues addressed include: Who accepts repeat testing/immediate ART and why? What are the obstacles? How TasP impacts on people’s lives in terms of quality of life; HIV disclosure; stigmatisation, relationships; sexual behaviours; perceptions; social support; treatment experience and adherence? Economic impact for households and health care systems? What are the changes at community level during TasP implementation and influences on individual behaviours? These are investigated in three groups: the general population; HIV+ attending clinics; and those who do not entre care, for a comprehensive understanding of the determinants of uptake.

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• Larmarange Joseph, Orne-Gliemann Joanna, Iwuji Collins, Imrie John, Lert France, Dabis François, Newell Marie-Louise et ANRS 12249 TasP Study Group (2013) « Acceptability and Uptake of Repeat Home-based HIV Counselling and Testing in Rural South Africa. Preliminary Data of the ANRS 12249 TasP Trial » (poster n°2406992), présenté à 17th International Conference on AIDS and STIs in Africa (ICASA), Cape Town.
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  Résumé : Background: The ANRS 12249 Treatment as Prevention (TasP) trial is assessing whether HIV testing of all members of a community, followed by immediate ART initiation of all HIV-infected individuals, regardless of immunological or clinical staging, will prevent onward sexual transmission and reduce HIV incidence in the same population. The implementation of universal and repeat home-based HIV testing is not documented yet in a high HIV incidence and prevalence context. Methods: A cluster-randomised trial is implemented using a phased-approach in the Hlabisa sub-district (KwaZulu Natal, South Africa) where more than 20% of adults are living with HIV. The trial started in March 2012; ten clusters are implemented in the first phase to assess the feasibility and acceptability of the two consecutive interventions (test then treat). The HIV testing strategy consists in a large range of community and clinic HIV testing options including the implementation of 6-monthly rounds of home-based HIV counselling and testing by dedicated counsellors. At each home visit, trial participants are administered individual questionnaires and offered a rapid HIV test. Results: As of April 30, 2013, 6 907 eligible subjects (16 years or above) were registered in six clusters and 5 122 (74%) were contacted. HIV status of 3 923 (76.5% of those contacted) was ascertained, 3 256 accepting the rapid HIV test at home and 667 being already aware of their HIV-positive status. We will present updated data from the first four trial clusters, where all eligible members of the community will have been offered three rounds of home-based HIV testing within 18 months. Uptake of HIV testing at each round will be reported. Uptake of repeat HIV testing will be measured among those testing HIV-negative at first round and who accept repeat HIV testing at rounds 2 and 3. We will also describe the reasons for HIV test refusal. Finally, we will present participants' attitudes regarding repeat HIV testing, and changes between rounds 1 and 3. Conclusions: Acceptance of regular and frequent HIV testing is key to the community-based efficacy of treatment as prevention initiatives in settings with very high incidence. Our data will provide first indications of whether repeat home-based HIV testing is acceptable and feasible in such a rural South African region.

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