Early HIV treatment and survival over six years of observation in the ANRS 12249 Treatment as Prevention Trial.

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.

A community-based healthcare package combining testing and prevention tools, including pre-exposure prophylaxis (PrEP), immediate HIV treatment, management of hepatitis B virus, and sexual and reproductive health (SRH), targeting female sex workers (FSWs) in Côte d'Ivoire: the ANRS 12381 PRINCESSE project.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is recommended by the WHO for HIV prevention among female sex workers (FSWs). A study conducted in 2016-2017 in Côte d'Ivoire showed that if PrEP is acceptable, FSWs also have many uncovered sexual health needs. Based on this evidence, the ANRS 12381 PRINCESSE project was developed in collaboration with a community-based organization. The main objective is to develop, document, and analyze a comprehensive sexual and reproductive healthcare package among FSWs in Côte d'Ivoire. METHODS: PRINCESSE is an open, single-arm interventional cohort of 500 FSWs in San Pedro (Côte d'Ivoire) and its surroundings. Recruitment started on November 26th, 2019 and is ongoing; the cohort is planned to last at least 30 months. The healthcare package (including HIV, hepatitis B, and sexually transmitted infection management, pregnancy screening, and contraception) is available both at mobile clinics organized for a quarterly follow-up (10 intervention sites, each site being visited every two weeks) and at a fixed clinic. Four waves of data collection were implemented: (i) clinical and safety data; (ii) socio-behavioral questionnaires; (iii) biological data; and (iv) in-depth interviews with female participants. Four additional waves of data collection are scheduled outside the cohort itself: (i) the medical and activity records of Aprosam for the PRINCESSE participants; (ii) the medical records of HIV+ FSW patients not participating in the PRINCESSE cohort, and routinely examined by Aprosam; (iii) in-depth interviews with key informants in the FSW community; and (iv) in-depth interviews with PRINCESSE follow-up actors. DISCUSSION: The PRINCESSE project is one of the first interventions offering HIV oral PrEP as part of a more global sexual healthcare package targeting both HIV- and HIV+ women. Second, STIs and viral hepatitis B care were offered to all participants, regardless of their willingness to use PrEP. Another innovation is the implementation of mobile clinics for chronic/quarterly care. In terms of research, PRINCESSE is a comprehensive, interdisciplinary project combining clinical, biological, epidemiological, and social specific objectives and outcomes to document the operational challenges of a multidisease program in real-life conditions. TRIAL REGISTRATION: The PRINCESSE project was registered on the Clinicaltrial.gov website ( NCT03985085 ) on June 13, 2019.

Couples HIV counselling and couple relationships in India, Georgia and the Dominican Republic.

BACKGROUND: Couples HIV counseling and testing is essential for combination HIV prevention, but its uptake remains very low. We aimed to evaluate factors associated with couples HIV counseling uptake in India, Georgia and the Dominican Republic, as part of the ANRS 12127 Prenahtest intervention trial. METHODS: Pregnant women ≥15 years, attending their first antenatal care (ANC) session between March and September 2009, self-reporting a stable partner, and having received couple-oriented post-test HIV counseling (trial intervention) were included. Individuals and couple characteristics associated with the acceptability of couples HIV counseling were assessed using multivariable logistic regression for each study site. RESULTS: Among 711 women included (232, 240 and 239 in the Dominican Republic, Georgia and India, respectively), the uptake of couples HIV counseling was 9.1% in the Dominican Republic, 13.8% in Georgia and 36.8% in India. The uptake of couples HIV counseling was associated with women having been accompanied by their partner to ANC, and never having used a condom with their partner in the Dominican Republic; with women having been accompanied by their partner to ANC in India; with women having a higher educational level than their partner and having ever discussed HIV with their partner in Georgia. CONCLUSION: Couple HIV counseling uptake was overall low. Strategies adapted to local socio-cultural contexts, aiming at improving women's education level, or tackling gender norms to facilitate the presence of men in reproductive health services, should be considered. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01494961 . Registered December 15, 2011. (Retrospectively registered).

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.

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/mm(3)) 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/mm(3)) 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.

Change of treatment guidelines and evolution of ART initiation in rural South Africa: data of a large HIV care and treatment programme.

BACKGROUND: While WHO recommendations are to treat people earlier and earlier, it will considerably increase the number of HIV infected people eligible for antiretroviral therapy (ART). In South Africa, a country which carries one of the highest HIV burden worldwide, very few studies are available on the impact of the ART guidelines on time to ART initiation in both individuals with low CD4 count and those newly eligible for ART. We thus aimed to describe ART initiation percentages in a large HIV programme in rural KwaZulu-Natal, South Africa, according to the temporal changes of national ART eligibility guidelines from 2007 to 2012. METHODS: Adults who accessed the decentralized Hlabisa HIV treatment programme in 2007-2012 were included. Three periods following the temporal change of ART eligibility guidelines were defined (Period 1: until April 2010; Period 2: April 2010 - July 2011; Period 3: from August 2011). Percentages of ART initiation within three months of programme entry were estimated in men, in women of childbearing age (<40 years old) and in older women, and stratifying by CD4 count. Trend tests and logistic regression models were used to study the effects of change of guidelines on ART initiation percentages. RESULTS: In individuals with CD4 count ≤200 cells/µL (N = 5709 men, N = 6743 women <40 years old and N = 2017 older women), percentages of ART initiation did not differ over time (p trend = 0.25; 0.28; and 0.14, respectively). In individuals with CD4 count = 201-350 cells/µL (N = 2680 men, N = 6086 women <40 years old and N = 1415 older women), percentages of ART initiation significantly increased over time (p trend <0.01 for the three groups): from 6 % in Period 1 to 20 % in Period 2 to 40 % in Period 3 in women of childbearing age, and from 7 % to 8-10 % to 42 % in men and in older women. CONCLUSIONS: As temporal changes of guidelines, percentages of ART initiation significantly increased in newly ART eligible people and did not decrease in individuals with very low CD4 counts. It will be crucial to continue verifying the evolution of these percentages of ART initiation with future recommendations reaching near-to-universal access to ART, to ensure that individuals most in need of ART receive it.

Continuum in HIV care from entry to ART initiation in rural KwaZulu-Natal, South Africa.

OBJECTIVE: To quantify time from entry in HIV care until Antiretroviral therapy (ART) initiation and identify factors associated with ART initiation in rural KwaZulu-Natal, South Africa. METHODS: Adults ≥16 years entering the decentralised Hlabisa ART programme between 2007 and 2011 were followed until June 2013. Median survival times to ART initiation from date of programme entry and from date of ART eligibility were estimated with Kaplan-Meier methods. Associated factors were evaluated in Cox regressions, censoring for deaths. RESULTS: Of 37 749 adults (71.6% female), 17 638 (46.7%) initiated ART. Nearly half (46.9%) met the CD4 criteria for treatment eligibility at programme entry. Among the 20 039 individuals not yet ART-eligible at entry, only 62.5% were retained in care with at least one further CD4 measurement, of whom 6688 subsequently became ART-eligible. Overall, 65.5% of the 24 398 ART-eligible individuals initiated ART over the study period. ART initiation was more likely in women (P < 0.001), in individuals ≥ 25 years old (P < 0.001) and in patients with low CD4 count (P < 0.001). Patients who became eligible during follow up were significantly more likely to initiate ART than those eligible at programme entry (72.6% vs. 62.9%, Adjusted Hazard Ratio = 1.46; 95% Confidence Interval [1.41-1.51]), adjusting for sex, age, year and CD4 count at eligibility. CONCLUSIONS: In this rural programme, continuation of care remains challenging, especially in men and younger adults. ART initiation is more likely in those engaged prior eligibility than in those entering HIV care only late in their HIV disease.

Implementation and effectiveness of a linkage to HIV care intervention in rural South Africa (ANRS 12249 TasP trial).

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.

Acceptability and feasibility of home and hospital follow-up in Burkina Faso and Guinea: A mixed-method study among patients of the COVID-19 Coverage-Africa clinical trial.

Patient experiences and perspectives on trial participation and follow-up may influence their compliance with research procedures or negatively impact their well-being. We aimed to explore the acceptability and feasibility of home-based and hospital-based follow-up modalities among COVID-19 patients enrolled in the ANTICOV ANRS COV33 Coverage-Africa trial in Burkina Faso and Guinea. The trial (2021-2022) evaluated the efficacy of treatments to prevent clinical worsening among COVID-19 patients with mild to moderate symptoms. Patients were either based at home or hospitalized, as per national recommendations, and followed-up through face-to-face visits and phone calls. We conducted a mixed-methods sub-study administering a questionnaire to all consenting participants and individually interviewing purposively selected participants. We performed descriptive analyses of Likert scale questions for the questionnaires and thematic analysis for the interviews. We conducted framework analysis and interpretation. Of the 400 trial patients, 220 completed the questionnaire (n = 182 in Burkina Faso, n = 38 in Guinea) and 24 were interviewed (n = 16 and n = 8, respectively). Participants were mostly followed-up at home in Burkina Faso; all patients from Guinea were first hospitalized, then followed-up at home. Over 90% of participants were satisfied with follow-up. Home follow-up was considered acceptable if (i) participants perceived they were not severely ill, (ii) it was combined with telemedicine, and (iii) the risk of stigma could be avoided. Hospital-based follow-up was viewed as a way to prevent contamination of family members, but could be badly experienced when mandatory and conflicting with family responsibilities and commitments. Phone calls were seen as reassuring and as a way to ensure continuity of care. These overall positive findings support the development of home-based follow-up for mildly ill patients in West-Africa, provided that both emotional and cognitive factors at individual, familial/inter-relational, healthcare and national levels be addressed when planning the implementation of a trial, or developing any public health strategy.

Implementing an outpatient clinical trial on COVID-19 treatment in an emergency epidemic context: a mixed methods study among operational and research stakeholders within the Coverage trial, Bordeaux (France).

BACKGROUND: The emergency set-up and implementation of outpatient clinical trials on epidemic emerging infectious diseases such as COVID-19 raise many issues in terms of research structuration, regulations, and health systems organization. We aimed to describe the experience and points of view of different stakeholders involved in a French home-based outpatient trial on COVID-19 and to identify the early barriers and facilitators to the trial implementation. METHODS: We conducted a mixed-methods study in July 2020. A self-administered questionnaire was emailed to 213 clinical, operational and research stakeholders involved in the Coverage trial; individual semi-directed interviews were conducted among 14 stakeholders. Questionnaire data and written interview notes are presented together by key theme. RESULTS: One hundred fifty six stakeholders responded to the questionnaire. 53.4% did not have prior experience in clinical research. The motivation of most stakeholders to participate in the Coverage trial was to feel useful during the pandemic. 87.9% agreed that the trial had an unusual set-up timeframe, and many regretted a certain lack of regulatory flexibility. Mobile medical teams and specific professional skills were perceived as instrumental for outpatient research. CONCLUSIONS: The implementation of a home-based outpatient clinical trial on COVID-19 was perceived as relevant and innovative although requiring important adaptations of usual professional responsibilities and standard research procedures. Lessons learned from the Coverage trial underline the need for improved networks between hospital and community medicine, and call for a dedicated and reactive outpatient research platform on emerging or threatening infectious diseases.

Incidence of HIV infection and associated factors among female sex workers in Côte d'Ivoire, results of the ANRS 12361 PrEP-CI study using recent infection assays.

BACKGROUND: This study aimed to estimate, using an HIV Recent Infection Testing Algorithm (RITA), the HIV incidence and its associated factors among female sex workers (FSW) in Côte d'Ivoire. METHODS: A cross-sectional study was conducted in 2016-2017 in Abidjan and San Pedro's region among FSW aged ≥ 18 years. In addition, a sociodemographic questionnaire, HIV screening was carried out by two rapid tests. In the event of a positive result, a dried blood spot sample was taken to determine, using a RITA adapted to the Ivorian context, if it was a recent HIV infection. RESULTS: A total of 1000 FSW were surveyed with a median age of 25 years (interquartile range: 21-29 years). 39 (3.9%) tested positive for HIV. The incidence of HIV was estimated to be 2.3 per 100 person-years, with higher incidence rates among those 24 years old or less (3.0% vs. 1.9%), non-Ivorian FSW (3.2% vs. 1.9%) and those with the lowest education level (4.6% in FSW who never went to school vs. 2.6%). The incidence seemed to be associated with the sex work practice conditions: higher incidence among FSW whose usual price was less than 3.50$ (4.3% vs.1.0%), FSW who had a larger number of clients on the last day of work (6.1% in those with 7 clients or more vs. 1.8%), FSW who reported not always using condoms with their clients (8.5% vs. 1.5%) and FSW who reported agreeing to sex without a condom in exchange for a large sum of money (10.1% vs. 1.2%). CONCLUSION: This study confirms that FSW remain highly exposed to HIV infection. Exposure to HIV is also clearly associated with certain sex-work factors and the material conditions of sex work. Efforts in the fight against HIV infection must be intensified to reduce new infections among FSW.

Perceptions of COVID-19 among communities of Conakry (Guinea): a qualitative study exploring the context of the ANRS COV33 Coverage-Africa therapeutic trial.

OBJECTIVES: To explore communities' perceptions about COVID-19 in the context of the ANRS COV33 Coverage-Africa clinical trial evaluating the efficacy of treatments in preventing clinical worsening of COVID-19. DESIGN: Descriptive qualitative study using semistructured in-depth individual interviews conducted by telephone in French and Soussou between May and September 2021. Data were transcribed, translated in French when applicable and analysed with the thematic analysis method. SETTING: The eight neighbourhoods most affected by COVID-19 in Conakry's urban context, capital of Guinea. PARTICIPANTS: 4 community leaders acting as key informants-providing insights regarding population's opinions-and six community members, who were exposed to an information session conducted as part of Coverage-Africa. RESULTS: According to participants, community members have heterogeneous viewpoints about COVID-19: it exists and is dangerous; it is benign ('bad cold'); or it is fictitious (eg, government conspiracy). The fear of stigmatisation and social isolation of those sick or cured of COVID-19 was largely reported by participants, with illustrations of distressing situations for the victims. To avoid stigma, many patients seem to adopt strategies of discretion (eg, lying/hiding about the disease). Although community attitudes were reported to have evolved since the beginning of the epidemic, stigma remained a pervasive concern for many people. CONCLUSIONS: Community perceptions about COVID-19 in Conakry may be partly explained by the Guinean context of Ebola history and of sociopolitical tensions. Stigmatisation of COVID+ people seems to be aimed at protecting others against contamination. However, social avoidance can greatly affect the morale of stigmatised people, especially in collectivist cultures like Guinea. Further investigating stigma, including its role on seeking COVID-19 screening and treatment services, and its consequences on mental health among affected/exposed people, would contribute to identifying improved prevention and care interventions in preparation for future health threats, and to promoting participation in health research. TRIAL REGISTRATION NUMBER: NCT04920838 (Pre-results stage).

Test but not treat: Community members' experiences with barriers and facilitators to universal antiretroviral therapy uptake in rural KwaZulu-Natal, South Africa.

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.

Sexual health needs of female sex workers in Côte d'Ivoire: a mixed-methods study to prepare the future implementation of pre-exposure prophylaxis (PrEP) for HIV prevention.

OBJECTIVE: To describe sexual and reproductive health (SRH) needs of female sex workers (FSWs) to inform the future implementation of pre-exposure prophylaxis (PrEP) for HIV prevention in this population. DESIGN AND SETTING: The ANRS 12361 PrEP-CI cross-sectional and mixed-methods study was designed and implemented with two community-based organisations in Côte d'Ivoire. PARTICIPANTS: A convenience sample of 1000 FSWs aged ≥18, not known as HIV-positive, completed a standardised questionnaire assessing sociodemographic characteristics, sexual practices, use of community health services and a priori acceptability of PrEP. Twenty-two indepth interviews and eight focus group discussions were also conducted to document FSWs' risky practices and sexual behaviours, experiences with violence and discrimination, attitudes regarding HIV and sexually transmitted infections (STIs), and barriers to SRH services. RESULTS: Although 87% described consistent condom use with clients, more than 22% declared accepting condomless sexual intercourse for a large sum of money. Furthermore, condom use with their steady partner and knowledge of their partner's HIV status were low despite their acknowledged concurrent sexual partnerships. While inconsistent condom use exposed FSWs to STIs and undesired pregnancies, the prevalence of contraceptive strategies other than condoms was low (39%) due to fear of contraception causing sterility. FSWs faced obstacles to accessing SRH care and preferred advice from their peers or self-medication. CONCLUSIONS: Despite adoption of preventive behaviour in most cases, FSWs are still highly exposed to HIV. Furthermore, FSWs seem to face several barriers to accessing SRH. Implementing PrEP among FSWs in West Africa, such as in Côte d'Ivoire, constitutes an opportunity to consider the regular follow-up of HIV-negative FSWs. PrEP initiation should not condition access to SRH services; conversely, SRH services could be a way to attract FSWs into HIV prevention. Our results highlight the importance of developing a people-focused approach that integrates all SRH needs when transitioning from PrEP efficacy trials to implementation.

Temporal trends of population viral suppression in the context of Universal Test and Treat: the ANRS 12249 TasP trial in rural South Africa.

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 < 0.001). That increase was similar in both arms (p = 0.514). In the final adjusted model, PVS increase was most associated with increased RHBCT and the implementation of local trial clinics (measured by time since cluster opening). Contextual changes (measured by calendar time) also contributed slightly. The effect of universal ART (trial arm) was positive but limited. CONCLUSIONS: PVS was improved significantly but similarly in both trial arms, explaining partly the null effect observed in terms of cumulative HIV incidence between arms. The PVS gains due to changes in ART-initiation guidelines alone are relatively small compared to gains obtained by strategies to maximize testing and linkage to care. The achievement of the 90-90-90 targets will not be met if the operational and implementational challenges limiting access to care and treatment, often context-specific, are not properly addressed. Clinical trial number: NCT01509508 (clinicalTrials.gov)/DOH-27-0512-3974 (South African National Clinical Trials Register).

"If you are here at the clinic, you do not know how many people need help in the community": Perspectives of home-based HIV services from health care workers in rural KwaZulu-Natal, South Africa in the era of universal test-and-treat.

BACKGROUND: Limited engagement in clinic-based care is affecting the HIV response. We explored the field experiences and perceptions of local health care workers regarding home-based strategies as opportunities to improve the cascade of care of people living with HIV in rural South Africa as part of a Universal Test-and-Treat approach. METHODS: In Hlabisa sub-district, home-based HIV services, including rapid HIV testing and counselling, and support for linkage to and retention in clinic-based HIV care, were implemented by health care workers within the ANRS 12249 Treatment-as-Prevention (TasP) trial. From April to July 2016, we conducted a mixed-methods study among health care workers from the TasP trial and from local government clinics, using self-administrated questionnaires (n = 90 in the TasP trial, n = 56 in government clinics), semi-structured interviews (n = 13 in the TasP trial, n = 5 in government clinics) and three focus group discussions (n = 6-10 health care workers of the TasP trial per group). Descriptive statistics were used for quantitative data and qualitative data were analysed thematically. RESULTS: More than 90% of health care workers assessed home-based testing and support for linkage to care as feasible and acceptable by the population they serve. Many health care workers underlined how home visits could facilitate reaching people who had slipped through the cracks of the clinic-based health care system and encourage them to successfully access care. Health care workers however expressed concerns about the ability of home-based services to answer the HIV care needs of all community members, including people working outside their home during the day or those who fear HIV-related stigmatization. Overall, health care workers encouraged policy-makers to more formally integrate home-based services in the local health system. They promoted reshaping the disease-specific and care-oriented services towards more comprehensive goals. CONCLUSION: Because home-based services allow identification of people early during their infection and encourage them to take actions leading to viral suppression, HCWs assessed them as valuable components within the panel of UTT interventions, aiming to reach the 90-90-90 UNAIDS targets, especially in the rural Southern African region. TRIAL REGISTRATION: The registration number of the ANRS 12249 TasP trial on ClinicalTrials.gov is NCT01509508.

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).

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).

Implementing universal HIV treatment in a high HIV prevalence and rural South African setting - Field experiences and recommendations of health care providers.

BACKGROUND: We aimed to describe the field experiences and recommendations of clinic-based health care providers (HCP) regarding the implementation of universal antiretroviral therapy (ART) in rural KwaZulu-Natal, South Africa. METHODS: In Hlabisa sub-district, the local HIV programme of the Department of Health (DoH) is decentralized in 18 clinics, where ART was offered at a CD4 count ≤500 cells/µL from January 2015 to September 2016. Within the ANRS 12249 TasP trial, implemented in part of the sub-district, universal ART (no eligibility criteria) was offered in 11 mobile clinics between March 2012 and June 2016. A cross-sectional qualitative survey was conducted in April-July 2016 among clinic-based nurses and counsellors providing HIV care in the DoH and TasP trial clinics. In total, 13 individual interviews and two focus groups discussions (including 6 and 7 participants) were conducted, audio-recorded, transcribed, and thematically analyzed. RESULTS: All HCPs reported an overall good experience of delivering ART early in the course of HIV infection, with most patients willing to initiate ART before being symptomatic. Yet, HCPs underlined that not feeling sick could challenge early ART initiation and adherence, and thus highlighted the need to take time for counselling as an important component to achieve universal ART. HCPs also foresaw logistical challenges of universal ART, and were especially concerned about increasing workload and ART shortage. HCPs finally recommended the need to strengthen the existing model of care to facilitate access to ART, e.g., community-based and integrated HIV services. CONCLUSIONS: The provision of universal ART is feasible and acceptable according to HCPs in this rural South-African area. However their experiences suggest that universal ART, and more generally the 90-90-90 UNAIDS targets, will be difficult to achieve without the implementation of new models of health service delivery.

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.

INTRODUCTION: We aimed to quantify and identify associated factors of linkage to HIV care following home-based HIV counselling and testing (HBHCT) in the ongoing ANRS 12249 treatment-as-prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. METHODS: Individuals ≥16 years were offered HBHCT; those who were identified HIV positive were referred to cluster-based TasP clinics and offered antiretroviral treatment (ART) immediately (five clusters) or according to national guidelines (five clusters). HIV care was also available in the local Department of Health (DoH) clinics. Linkage to HIV care was defined as TasP or DoH clinic attendance within three months of referral among adults not in HIV care at referral. Associated factors were identified using multivariable logistic regression adjusted for trial arm. RESULTS: Overall, 1323 HIV-positive adults (72.9% women) not in HIV care at referral were included, of whom 36.9% (n=488) linked to care <3 months of referral (similar by sex). In adjusted analyses (n=1222), individuals who had never been in HIV care before referral were significantly less likely to link to care than those who had previously been in care (<33% vs. >42%, p<0.001). Linkage to care was lower in students (adjusted odds-ratio [aOR]=0.47; 95% confidence interval [CI] 0.24-0.92) than in employed adults, in adults who completed secondary school (aOR=0.68; CI 0.49-0.96) or at least some secondary school (aOR=0.59; CI 0.41-0.84) versus ≤ primary school, in those who lived at 1 to 2 km (aOR=0.58; CI 0.44-0.78) or 2-5 km from the nearest TasP clinic (aOR=0.57; CI 0.41-0.77) versus <1 km, and in those who were referred to clinic after ≥2 contacts (aOR=0.75; CI 0.58-0.97) versus those referred at the first contact. Linkage to care was higher in adults who reported knowing an HIV-positive family member (aOR=1.45; CI 1.12-1.86) versus not, and in those who said that they would take ART as soon as possible if they were diagnosed HIV positive (aOR=2.16; CI 1.13-4.10) versus not. CONCLUSIONS: Fewer than 40% of HIV-positive adults not in care at referral were linked to HIV care within three months of HBHCT in the TasP trial. Achieving universal test and treat coverage will require innovative interventions to support linkage to HIV care.

Retention in care prior to antiretroviral treatment eligibility in sub-Saharan Africa: a systematic review of the literature.

OBJECTIVE: We aimed at summarising rates and factors associated with retention in HIV care prior to antiretroviral treatment (ART) eligibility in sub-Saharan Africa. DESIGN: We conducted a systematic literature review (2002-2014). We searched Medline/Pubmed, Scopus and Web of Science, as well as proceedings of conferences. We included all original research studies published in peer-reviewed journals, which used quantitative indicators of retention in care prior to ART eligibility. PARTICIPANTS: People not yet eligible for ART. PRIMARY AND SECONDARY OUTCOMES: Rate of retention in HIV care prior to ART eligibility and associated factors. RESULTS: 10 papers and 2 abstracts were included. Most studies were conducted in Southern and Eastern Africa between 2004 and 2011 and reported retention rates in pre-ART care up to the second CD4 measurement. Definition of retention in HIV care prior to ART eligibility differed substantially across studies. Retention rates ranged between 23% and 88% based on series ranging from 112 to 10,314 individuals; retention was higher in women, individuals aged >25 years, those with low CD4 count, high body mass index or co-infected with tuberculosis, and in settings with free cotrimoxazole use. CONCLUSIONS: Retention in HIV care prior to ART eligibility in sub-Saharan Africa has been insufficiently described so far leaving major research gaps, especially regarding long-term retention rates and sociodemographic, economic, clinical and programmatic logistic determinants. The prospective follow-up of newly diagnosed individuals is required to better evaluate attrition prior to ART eligibility among HIV-infected people.