Access to Hepatis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multi-country open-label trial TAC ANRS 12311 allowed assessing the feasibility, safety, efficacy of a specific care model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure. The primary outcome was sustained virological response at 12 weeks after end of treatment (SVR12). Secondary outcomes included treatment adherence, safety and SVR12 in patients who were retreated due to non-response to first-line treatment. The model of care relied on both viral load assessment and educational sessions to increase patient awareness, adherence and health literacy. The study recruited 120 participants, 36 HIV-co-infected, and 14 cirrhotic. Only one patient discontinued treatment because of return to home country. Neither death nor severe adverse event occurred. SVR12 was reached in 107 patients (89%): (90%) in genotype 1 or 2, and 88% in GT-4. All retreated patients (n = 13) reached SVR12. HCV treatment is highly acceptable, safe and effective under this model of care. Implementation research is now needed to scale up point-of-care HCV testing and SVR assessment, along with community involvement in patient education, to achieve HCV elimination in Sub-Saharan Africa.

Background Access to direct-acting antivirals for chronic hepatitis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multicenter open-label trial TAC ANRS 12311 was conducted to assess the feasibility, effectiveness and safety of an implementation model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Methods Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure. The primary outcome was sustained virological response at 12 weeks after end of treatment (SVR12). Secondary outcomes included treatment adherence, safety and SVR12 in patients who were retreated due to non-response to first-line treatment. Results The study recruited 120 participants, 36 HIV-co-infected, and 14 cirrhotic. Only one patient discontinued treatment because of return to home country. Neither death nor severe adverse event occurred. SVR12 was reached in 107 patients (89%): (90%) in genotype 1 or 2, and 88% in GT-4. All retreated patients (n = 13) reached SVR12. Conclusions This model implemented for access to HCV treatment and retreatment of viral failures appeared to be feasible, safe and effective. With the expanded access to HCV generic drugs, scaling up of HCV test-and-treat strategies should now be considered a priority for HCV elimination in Sub-Saharan Africa.

OBJECTIVE:Measuring access and preferences to Men who have Sex with Men focused community-based HIV testing sites (MSM-CBTS) in Côte d'Ivoire.DESIGN:A respondent-driven sampling telephone survey.SETTING:National survey conducted in 2018 in Côte d'Ivoire.PARTICIPANTS:518 MSM aged over 18 years old.PRIMARY AND SECONDARY OUTCOME MEASURES:Knowledge, practices, satisfaction and preferences regarding MSM-CBTS. Factors associated with MSM-CTBS access or knowledge and with HIV testing venue preferences were examined.RESULTS:Only half of the respondents (47%) reported knowing of an MSM-CBTS. Of these, 79% had already attended one. Both knowing of and ever visiting an MSM-CBTS were significantly associated with a higher number of HIV tests performed in the past 12 months and having disclosed sexual orientation to one family member.In terms of preferences, 37% of respondents said they preferred undifferentiated HIV testing sites (ie, 'all patients' HIV testing sites), 34% preferred MSM-CBTS and 29% had no preference.Those who reported being sexually attracted to women, being bisexual and those who did not know an MSM non-governmental organisation were less likely to prefer MSM-CBTS. MSM who preferred undifferentiated HIV testing sites mentioned the lack of discretion and anonymity of community-based sites and the desire to avoid the gaze of others.CONCLUSION:Community-based HIV testing is well suited for MSM who identify as homosexual and those close to the MSM community, while maintaining undifferentiated HIV testing is essential for others. Both types of activities need to be maintained and developed. Healthcare professionals in undifferentiated HIV testing sites need to be properly trained in the non-judgemental reception of MSM.

We report the association between pre‐antiretroviral therapy (pre‐ART) soluble vascular cell adhesion molecule‐1 (sVCAM‐1) levels and long‐term mortality in HIV‐infected West African adults participating in a trial of early ART in West Africa (Temprano ANRS 12136 trial).

Background: Data on HIV-1 controllers in Africa are scarce. We report the proportion of HIV-1 controllers in a group of adults prospectively monitored with frequent viral load measurements as part of a clinical trial in West Africa. Methods: For the Temprano trial, antiretroviral therapy (ART)-naive HIV-1 infected adults with no criteria for starting ART were randomized to start ART immediately or defer ART until the WHO starting criteria were met. Plasma viral load was measured every 6 months. The trial follow-up was 30 months. We considered all Temprano participants randomized to defer ART. Patients with all semestrial viral <2000 copies/ml and still off ART at month 30 were defined as HIV-1 controllers. Controllers with all viral loads <50 copies/ml were defined as elite controllers, the rest as viremic controllers. Results: Of the 1023 HIV-1-infected adults randomized in the Temprano deferred-ART group, 18 (1.8%) met the criteria for classification as HIV controllers, of whom seven (0.7%) were elite controllers and 11 (1.1%) viremic controllers. The HIV-1 controllers had low peripheral blood mononuclear cell HIV-1 DNA and low inflammatory marker levels. They maintained high CD4(+) cell count and percentages and had a low morbidity rate. Discussion: HIV controllers exist in Africa at a proportion close to that reported elsewhere. They represent a small fraction of all HIV-1-infected patients but raise important questions. Further studies should assess whether starting ART might represent more risk than benefit for some controllers, and where it does, how to identify these patients before they start ART.

BACKGROUND:Asymptomatic HIV-infected people who start ART early may feel less motivated and neglect compliance. This might promote the emergence of resistance.METHODS:In the Temprano trial, ART-naive HIV-infected adults with high CD4 counts were randomly assigned to start ART immediately (immediate group) or defer ART until the WHO criteria were met (deferred group). All participants were monitored for 30 months. Those in the deferred group who started ART were monitored for longer, until they had completed 30 months on ART. We compared the rate of virological failure and drug resistance between the immediate and deferred groups 30 months after ART initiation.RESULTS:Of the 2056 participants in Temprano, 1033 were assigned to start ART immediately and 1023 to defer ART. Of the latter, 488 started ART during trial follow-up. Patients in the deferred group who started ART had a lower median CD4 count (280 versus 465 cells/mm3) and a higher median plasma HIV-1 RNA (5.1 versus 4.7 log10 copies/mL) at baseline. During follow-up, participants in both groups had similar antiretroviral drug exposure. Thirty months after ART initiation, patients in the deferred group had a higher rate of virological failure (35.3% versus 29.9%, P = 0.04) and a lower genotypic susceptibility score (P = 0.04).CONCLUSIONS:Starting ART early decreases the risk of virological failure and drug resistance in the medium term. This benefit is of particular importance in countries where access to viral load monitoring and the number of antiretroviral drug lines is limited.

Background Hepatitis B virus (HBV) co-infection in human immunodeficiency virus (HIV)-positive individuals increases the risk of overall mortality, especially when HBV DNA levels are high. The role of CD4+ cell counts in this association is poorly defined. We aimed to determine whether HIV–HBV co-infection influences changes in CD4+ cell count before and during antiretroviral therapy and whether it affects mortality risk at levels of CD4+. Methods 2052 HIV-positive participants from Côte d’Ivoire in a randomized-control trial assessing early or deferred ART were included. HBV-status was determined by hepatitis B surface antigen (HBsAg). Changes in CD4+ cell levels were estimated using a mixed-effect linear model. The incidence rates of all-cause mortality were estimated at CD4+ counts ≤350, 351–500, >500/mm3 and were compared between HBV-status groups as incidence rate ratios (IRR). Results At baseline, 190 (9%) were HBsAg-positive [135 (71%) with HBV DNA <2000 IU/mL, 55 (29%) ≥2000 IU/mL]. Follow-up was a median 58 months (IQR = 40–69). Between co-infection groups, there were no differences in CD4+ decline before ART initiation and no differences in CD4+ increase after ART initiation. After adjusting for sex, age, baseline HIV RNA level, and early/deferred ART arm, mortality rates were not significantly different between HBsAg-positive versus HBsAg-negative participants across strata of CD4+ levels. However, HBsAg-positive individuals with HBV-DNA ≥2000 IU/mL versus HBsAg-negative individuals had increased mortality rates at ≤350/mm3 (adjusted-IRR = 3.82, 95% CI = 1.11–9.70) and 351–500/mm3 (adjusted-IRR = 4.37, 95% CI = 0.98–13.02), but not >500/mm3 (adjusted-IRR = 1.07, 95% CI = 0.01–4.91). Conclusion Despite no effect of HBV-infection on CD4+ levels, HIV-HBV co-infected individuals with high HBV replication are at higher risk of mortality when CD4+ is <500/mm3.

Background: Several biomarkers of inflammation and coagulation were reported to be associated with HIV disease progression in different settings. In this article, we report the association between 11 biomarkers and medium-term mortality in HIV-infected West African adults. Methods: In Temprano ANRS 12136, antiretroviral therapy (ART)-naive HIV-infected adults with high CD4 counts were randomly assigned either to start ART immediately or defer ART until the World Health Organization criteria were met. Participants who completed the 30-month trial follow-up were invited to participate in a posttrial phase. The posttrial phase end point was all-cause death. We used multivariate Cox proportional models to analyze the association between baseline plasma biomarkers [IL-1ra, IL-6, soluble vascular cell adhesion molecule 1 (sVCAM-1), sCD14, D-dimer, fibrinogen, IP-10, sCD163, albumin, high-sensitivity C-reactive protein, and 16S rDNA] and all-cause death in the Temprano participants randomized to defer ART. Results: Four hundred seventy-seven patients (median age 35 years, 78% women, and median CD4 count: 379 cells/mm(3)) were randomly assigned to defer starting ART until the World Health Organization criteria were met. The participants were followed for 2646 person-years (median 5.8 years). In the follow-up, 89% of participants started ART and 30 died. In the multivariate analysis adjusted for the study center, sex, baseline CD4 count, isoniazid preventive therapy, plasma HIV-1 RNA, peripheral blood mononuclear cell HIV-1 DNA, and ART, the risk of death was significantly associated with baseline sVCAM-1 (>= 1458 vs. <1458: adjusted hazard ratio 2.57, 95% confidence interval: 1.13 to 5.82) and sCD14 (>= 2187 vs. <2187: adjusted hazard ratio 2.79, interquartile range 1.29-6.02) levels. Conclusions: In these sub-Saharan African adults with high CD4 counts, pre-ART plasma sVCAM-1 and sCD14 levels were independently associated with mortality.

It is unknown how past and active hepatitis B virus (HBV) infection affect immunorecovery and mortality in people with HIV who initiate tenofovir‐based antiretroviral therapy (ART). Using data collected between 2008 and 2015, we studied people with HIV in sub‐Saharan Africa initiating immediate ART in the Temprano randomized control trial. We classified participants into HBV groups at ART initiation: hepatitis B surface antigen (HBsAg)‐positive with HBV DNA ≥ 2,000 IU/ml; HBsAg‐positive with HBV DNA < 2,000 IU/ml; isolated HBcAb‐positive; resolved infection (HBsAb‐positive/HBcAb‐positive); and HBV non‐immune/vaccinated (HBcAb‐negative). We compared square‐root CD4‐cell count increases using mixed‐effect, non‐linear regression adjusted for age, sex, baseline CD4 cell count, and HIV RNA. We compared all‐cause mortality using Bayesian parametric survival regression. Among 879 participants, 24 (2.7%) had HBsAg with high HBV DNA, 76 (8.6%) HBsAg with low HBV DNA, 325 (37.0%) isolated anti‐HBcAb, 226 (25.7%) resolved HBV infection and 228 (25.9%) HBV non‐immune/vaccinated. We found no significant difference in CD4 cell increases between HBV‐infection groups after adjustment ( p = 0.16). Participants with HBsAg and high HBV DNA had the highest incidence of all‐cause mortality (1.9/100 person‐years, 95% Credibile Interval [CrI] = 1.0–3.4). By comparison, incidence rates of mortality were reduced by 57% (95%CrI = −79%, −13%), 60% (95%CrI = −82%, −12%) and 66% (95%CrI = −84%, −23%) in those who had isolated anti‐HBcAb‐positive, resolved HBV infection and HBV non‐immune/vaccinated, respectively. In conclusion, individuals with HIV and past HBV infection or isolated anti‐HBcAb‐positive serology, much like HBV non‐immune/vaccinated, experience lower mortality than those with HBsAg and high HBV DNA. Additional HBV‐related management would not be necessary for these individuals.

BACKGROUNDOutreach HIV testing strategies have significantly contributed to the increase in the number of people knowing their HIV status in sub-Saharan Africa. This article analyzes the articulation of donor and field constraints on the implementation of outreach HIV testing strategies in Côte d'Ivoire.METHODSQualitative research was conducted in three health districts (Man, Cocody-Bingerville and Aboisso) in Côte d'Ivoire in 2015-2016, through in-depth interviews with community providers, local leaders and people tested and through observation of outreach HIV testing activities.RESULTSImplementing organizations feel "under pressure" to meet donors' objectives that are deemed unattainable, as well as the lack of training and funding. As a result, providers do not observe systematically the rules of the "three Cs" (counselling, informed consent, confidentiality), and propose testing to individuals who are "off-target" (in terms of locations and populations).DISCUSSIONImplementing NGOs experience two types of constraints those resulting from the functioning of international aid (inadequate funding compared to actual costs, objectives too high, the important chain of intermediaries) and those related to the local context (spaces not adapted to guarantee confidentiality and the professional activity of target populations).CONCLUSIONThe pressure that is exerted at different levels on implementing NGOs is detrimental to the quality of HIV testing. It is now essential to develop a more qualitative approach in defining strategies and evaluation criteria.

Background: Outreach HIV testing strategies have significantly contributed to the increase in the number of people knowing their HIV status in sub-Saharan Africa. This article analyzes the articulation of donor and field constraints on the implementation of outreach HIV testing strategies in Cote d'lvoire. Methods: Qualitative research was conducted in three health districts (Man, Cocody-Bingerville and Aboisso) in Cote d'lvoire in 2015-2016, through in-depth interviews with community providers, local leaders and people tested and through observation of outreach HIV testing activities. Results: Implementing organizations feel "under pressure" to meet donors' objectives that are deemed unattainable, as well as the lack of training and funding. As a result, providers do not observe systematically the rules of the "three Cs" (counselling, informed consent, confidentiality), and propose testing to individuals who are "off-target" (in terms of locations and populations). Discussion: Implementing NGOs experience two types of constraints those resulting from the functioning of international aid (inadequate funding compared to actual costs, objectives too high, the important chain of intermediaries) and those related to the local context (spaces not adapted to guarantee confidentiality and the professional activity of target populations). Conclusion: The pressure that is exerted at different levels on implementing NGOs is detrimental to the quality of HIV testing. It is now essential to develop a more qualitative approach in defining strategies and evaluation criteria.

BackgroundHigh HIV-1 DNA levels in peripheral blood mononuclear cells (PBMC) were associated with a higher risk of severe morbidity and a faster decline in CD4 count in ART-naive patients. We report the association between HIV-1 DNA and mortality in HIV-infected adults in a trial of early ART in West Africa.MethodsIn the Temprano trial, HIV-infected adults were randomly assigned to start ART immediately or defer ART. After trial termination, HIV-1 DNA was measured in whole blood samples frozen at baseline. We analyzed the association between baseline PBMC HIV-1 DNA and long-term mortality.Findings2019 patients were followed for 9253 patient-years (median 4.9 years). At baseline, the median CD4 count was 462/mm3 [IQR 368–571], the median plasma HIV-1 RNA 4.7 log10 copies/ml [IQR 4.0–5.2], and the median HIV-1 DNA 2.9 log10 copies/million PBMC [IQR 2.5–3.3]. During follow-up, 86 participants died. In univariate analysis, the hazard ratio [HR] of death was 2.67 (95% CI, 1.68–4.22) for patients with HIV-1 DNA ≥3 log10 copies/million PBMC vs. others, and 2.10 (95% CI, 1.38–3.21) for patients with HIV-1 RNA ≥5 log10 copies/ml vs. others. In multivariate Cox regression analysis, HIV-1 DNA levels ≥3 log10 copies/million PBMC were strongly associated mortality (adjusted HR = 2.09, 95% CI 1.24–3.52, p= 0.005) while the association between baseline plasma HIV-1 RNA and mortality was not significant.InterpretationIn these African adults who started ART with high CD4 counts, HIV-1 DNA was a strong independent predictor of death. The HIV reservoir still plays a prognostic role in the early ART era.FundingThis trial was supported by the French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, 12224 and 12253)

ObjectiveTo 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 settingThe ANRS 12361 PrEP-CI cross-sectional and mixed-methods study was designed and implemented with two community-based organisations in Côte d’Ivoire.ParticipantsA 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.ResultsAlthough 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.ConclusionsDespite 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.

Background Despite the implementation of Provider Initiated Testing and Counselling (PITC) in 2009, PITC coverage remains low in Cote d'Ivoire. The purpose of this study is to determine whether an human immunodeficiency virus (HIV) test was offered and performed at specific life events where PITC is recommended by national guidelines. Methods In 2017, a cross-sectional telephone survey was conducted among a representative sample of 3,867 adults from the general population in Côte d'Ivoire. The occurrences of the following events over the past 5 years were documented: pregnancy (event A) or partner's pregnancy (event B) of the last child, sexually transmitted infection (event C) and marriage (event D). For each of these events, participants were asked (i) if they consulted a health care professional, (ii) if they were offered an HIV test during that consultation and (iii) if they accepted it. Results Consulting a health care provider was reported by 94.9%, 58.3%, 70.3% and 19.1% of those who reported events A, B, C and D respectively. In case of medical consultations following events A, B, C and D, respectively 70.1%, 33.1%, 28.1%, and 78.8% of individuals were offered an HIV test. The testing acceptance was high regardless of the event. Overall, testing coverage was 63.7%, 16.9%, 13.4% and 14.5% for events A, B, C and D respectively. Conclusions Increasing HIV testing coverage in Côte d'Ivoire requires (i) facilitating attendance to health services in case of sexually transmitted infections, marriage and pregnancy—for men—and (ii) strengthening routine testing offer on these occasions.

BACKGROUND In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infected patients from sub-Saharan Africa with hepatitis B e antigen (HBeAg)-negative status, data are limited on the evolution of HBV activity when antiretroviral treatment (ART) is absent. METHODS A total of 43 HBeAg-negative co-infected patients not indicated for ART (per concomitant World Health Organization recommendations) were followed during participation in a randomized controlled trial in Côte d'Ivoire. Chronic HBeAg-negative phases were classified at yearly visits and defined as 'infection' (HBV DNA ≤10 000 copies/mL and normal alanine aminotransferase [ALT]) or 'hepatitis' (HBV DNA >10 000 copies/mL and/or above normal ALT). Dispersion in HBV DNA and ALT levels during follow-up was assessed using interquartile range (IQR) regression. RESULTS During a median 25 months (IQR 19-31), 17 (40%) patients consistently had 'infection', 5 (12%) consistently had 'hepatitis' and 21 (48%) fluctuated between phases. Wider dispersion in HBV DNA over time was associated with higher baseline HIV RNA (p=0.02) and higher baseline HBV DNA levels (p=0.008), while wider dispersion in ALT was associated with higher baseline HIV RNA (p<0.001), higher baseline ALT levels (p=0.02) and baseline hepatitis surface antigen >4.0 log10 IU/mL (p=0.02). CONCLUSIONS HBV activity is common with HBeAg-negative status, whose variation is partly linked to HIV replication. Fluctuations in disease phase make it difficult to assess the risk of morbidity and mortality after ART initiation.