Feasibility, safety, efficacy and potential scaling-up of sofosbuvir-based HCV treatment in Central and West Africa: (TAC ANRS 12311 trial).

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.

Preferences and access to community-based HIV testing sites among men who have sex with men (MSM) in Côte d'Ivoire.

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.

Association of cellular HIV-1 DNA and virological success of antiretroviral treatment in HIV-infected sub-Saharan African adults.

BACKGROUND: HIV-1 DNA persists in infected cells, forming viral reservoirs. Pre-antiretroviral treatment (ART) HIV-1 DNA load was reported to predict ART success in European severely immunocompromised patients. The aim of this study was to determine whether HIV-1 DNA levels are associated with virological success in less severely immunocompromised patients who receive early ART in sub-Saharan Africa. METHODS: The association between pre-ART HIV-1 DNA and the virological response after 30 months on ART was studied in multivariate logistic regression in patients randomised to immediate ART groups in the Temprano trial, which assessed the benefits of early ART in HIV-infected adults in Côte d'Ivoire. HIV-1 DNA was quantified in peripheral blood mononuclear cell (PBMC) using real-time PCR. RESULTS: HIV-1 DNA levels were measured in 1013 patients. Their medians [IQR] of pre-ART CD4 count, HIV-1 RNA and HIV-1 DNA levels were 465 [379-578]/mm3, 4.7 [4.0-5.3] log10 copies/ml and 2.9 [2.5-3.2] log10 copies/million PBMC, respectively. Pre-ART HIV-1 DNA was significantly correlated with pre-ART HIV-1 RNA (R = 0.59, p < 0.0001). In multivariate analysis, HIV-1 DNA < 3 log10 copies/million PBMC was significantly associated with virological success at M30 after adjustment for other key variables (ART regimen, IPT, sex, age, WHO clinical stage, CD4 and HIV-1 RNA; aOR 1.57; 95% CI 1.08-2.30; p = 0.02). CONCLUSION: Low HIV-1 DNA was statistically associated with virological success in this population of sub-Saharan African adults who started treatment with a median pre-ART CD4 count at 465/mm3. HIV-1 DNA could become a useful tool for guiding some therapeutic decisions in the test-and-treat era. Trial registration TEMPRANO ANRS 12136 ClinicalTrials.gov, number NCT00495651, date of registration 03/07/2007.

Plasma sVCAM-1, antiretroviral therapy and mortality in HIV-1-infected West African adults.

OBJECTIVES: 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). METHODS: The ART-naïve HIV-infected adults were randomly assigned to start ART immediately or defer ART until the WHO criteria were met. Participants who completed the trial follow-up were invited to participate in a post-trial phase (PTP). The PTP end-point was all-cause death. We used multivariable Cox proportional models to analyse the association between baseline sVCAM-1 and all-cause death, adjusting for ART strategy, sex, CD4 count, plasma HIV-1 RNA and peripheral blood mononuclear cell HIV-1 DNA levels. RESULTS: In all, 954 adults (77% women, median CD4 count of 387 cells/µL) were randomly assigned to start ART immediately (n = 477) or to defer initiation of ART (n = 477). They were followed for a median of 5.8 years [interquartile range (IQR): 5.2-6.3]. In multivariable analysis, the risk of death was significantly associated with baseline sVCAM-1 [≥1458 vs. < 1458 ng/mL; adjusted hazard ratio = 2.86, 95% confidence interval (CI): 1.60-5.11]. The 6-year probability of death rates were 14.4% (95%CI: 9.1-22.6) and 9.4% (5.4-16.1) in patients with baseline sVCAM-1 ≥ 1458 ng/mL randomized to deferred and immediate ART, respectively, and 3.8% (2.2-6.5) and 3.5% (1.9-6.3) in patients with baseline sVCAM-1 < 1458 ng/mL randomized to deferred and immediate ART. The median difference between pre-ART and 12-month sVCAM-1 levels in patients randomized to immediate ART was -252 (IQR: -587 to -61). CONCLUSIONS: Pre-ART sVCAM-1 levels were significantly associated with mortality, independently of whether ART was started immediately or deferred, but they significantly decreased after 12 months of ART.

Elite and viremic HIV-1 controllers in West Africa.

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.

Virological failure and drug resistance in West African HIV-infected adults who started ART immediately or deferred ART initiation.

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.

Telephone peer recruitment and interviewing during a respondent-driven sampling (RDS) survey: feasibility and field experience from the first phone-based RDS survey among men who have sex with men in Côte d'Ivoire.

BACKGROUND: Many respondent-driven sampling (RDS) methodologies have been employed to investigate hard-to-reach populations; however, these methodologies present some limits. We describe a minimally investigated RDS methodology in which peer recruitment and interviewing are phone-based. The feasibility of the methodology, field experiences, validity of RDS assumptions and characteristics of the sample obtained are discussed. METHODS: We conducted a phone-based RDS survey among men who have sex with men (MSM) aged 18 or above and living in Côte d'Ivoire. Eight initial MSM across Côte d'Ivoire were selected. Participants were asked to call a hotline to be registered and interviewed by phone. After the participants completed the questionnaire, they were asked to recruit a maximum of 3 MSM from their acquaintances. RESULTS: During the 9 months of the survey, 576 individuals called the hotline, and 518 MSM completed the questionnaire. The median delay between the invitation to participate and the completion of the questionnaire by peer-recruited MSM was 4 days [IQR: 1-12]. The recruitment process was not constant, with high variation in the number of people who called the hotline during the survey period. RDS chain convergence to equilibrium was reached within 6 waves for most of the selected variables. For the network size estimation assumption, participants who incorrectly estimated their network size were observed. Regarding the sample obtained, MSM were recruited from all the regions of Côte d'Ivoire with frequent interregional recruitment; 23.5% of MSM were recruited by someone who does not live in the same region. Compared to the MSM who participated in two other surveys in Côte d'Ivoire, the MSM in our sample were less likely to know about an MSM non-governmental organisation. However, MSM aged 30 years old and above and those with a low level of education were underrepresented in our sample. CONCLUSION: We show that phone-based RDS surveys among MSM are feasible in the context of sub-Saharan Africa. Compared to other classical RDS survey methodologies, the phone-based RDS methodology seems to reduce selection bias based on geography and proximity with the MSM community. However, similar to other methodologies, phone-based RDS fails to reach older and less-educated MSM.

Higher risk of mortality in HIV-HBV co-infected patients from sub-Saharan Africa is observed at lower CD4+ cell counts.

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.

Association of Plasma Soluble Vascular Cell Adhesion Molecule-1 and sCD14 With Mortality in HIV-1-Infected West African Adults With High CD4 Counts.

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) 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.

Mortality in relation to hepatitis B virus (HBV) infection status among HIV-HBV co-infected patients in sub-Saharan Africa after immediate initiation of antiretroviral therapy.

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.

[Outreach strategies of HIV testing in Côte d'Ivoire: community providers under pressure] / Dépistage du VIH hors les murs en Côte d'Ivoire : des prestataires communautaires sous pression.

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 Côte d’Ivoire. METHODS: Qualitative 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. 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.

Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts.

BACKGROUND: High 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. METHODS: In 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. FINDINGS: 2019 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. INTERPRETATION: In 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. FUNDING: This trial was supported by the French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, 12224 and 12253).

Practices and Obstacles to Provider-Initiated HIV Testing and Counseling (PITC) Among Healthcare Providers in Côte d'Ivoire.

Practices of Provider-Initiated HIV Testing and Counseling (PITC) remains suboptimal in Côte d'Ivoire. The aim of this survey was to identify the practices and obstacles to PITC among healthcare professionals in Côte d'Ivoire. A nationally representative cross-sectional survey was conducted in 2018 by telephone among three separate samples of midwives, nurses and physicians practicing in Côte d'Ivoire. The number of HIV tests proposed during consultation in the month preceding the survey was collected for each professional. Factors associated with the number of proposed tests were identified through ordinal logistic regression models. A total of 298 midwives, 308 nurses and 289 physicians were interviewed. Midwives proposed the test more frequently, followed by nurses and physicians. Among midwives, a higher number of proposed tests was associated with the perception that HIV testing does not require specific consent compared to other diseases (aOR 4.00 [95% CI 1.37-14.29]). Among nurses, having received HIV training and the presence of community HIV counselors were associated with a higher number of proposed tests (aOR 2.01 [1.31-3.09] and aOR 1.75 [1.14-2.70], respectively). For physicians, the presence of a voluntary testing center was associated with a higher number of proposed tests (aOR 1.69 [1.01-2.86]). PITC practices and barriers differed across professions. Beyond improving environmental opportunities such as dedicated staff or services, strengthening the motivations and capabilities of healthcare professionals to propose testing could improve PITC coverage.

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.

Dépistage du VIH hors les murs en Côte d'Ivoire : des prestataires communautaires sous pression.

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 Côte d'Ivoire. METHODS: Qualitative 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. 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.

Cascade of Provider-Initiated Human Immunodeficiency Virus Testing and Counselling at Specific Life Events (Pregnancy, Sexually Transmitted Infections, Marriage) in Côte d'Ivoire.

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.

Hepatitis B virus activity in untreated hepatitis B e antigen-negative human immunodeficiency virus-hepatitis B virus co-infected patients from sub-Saharan Africa.

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.

Cost-effectiveness and budget impact of immediate antiretroviral therapy initiation for treatment of HIV infection in Côte d'Ivoire: A model-based analysis.

INTRODUCTION: The Temprano and START trials provided evidence to support early ART initiation recommendations. We projected long-term clinical and economic outcomes of immediate ART initiation in Côte d'Ivoire. METHODS: We used a mathematical model to compare three potential ART initiation criteria: 1) CD4 <350/µL (ART<350/µL); 2) CD4 <500/µL (ART<500/µL); and 3) ART at presentation (Immediate ART). Outcomes from the model included life expectancy, 10-year medical resource use, incremental cost-effectiveness ratios (ICERs) in $/year of life saved (YLS), and 5-year budget impact. We simulated people with HIV (PWH) in care (mean CD4: 259/µL, SD 198/µL) and transmitted cases. Key input parameters to the analysis included first-line ART efficacy (80% suppression at 6 months) and ART cost ($90/person-year). We assessed cost-effectiveness relative to Côte d'Ivoire's 2017 per capita annual gross domestic product ($1,600). RESULTS: Immediate ART increased life expectancy by 0.34 years compared to ART<350/µL and 0.17 years compared to ART<500/µL. Immediate ART resulted in 4,500 fewer 10-year transmissions per 170,000 PWH compared to ART<350/µL. In cost-effectiveness analysis, Immediate ART had a 10-year ICER of $680/YLS compared to ART<350/µL, ranging from cost-saving to an ICER of $1,440/YLS as transmission rates varied. ART<500/µL was "dominated" (an inefficient use of resources), compared with Immediate ART. Immediate ART increased the 5-year HIV care budget from $801.9M to $812.6M compared to ART<350/µL. CONCLUSIONS: In Côte d'Ivoire, immediate compared to later ART initiation will increase life expectancy, decrease HIV transmission, and be cost-effective over the long-term, with modest budget impact. Immediate ART initiation is an appropriate, high-value standard of care in Côte d'Ivoire and similar settings.

Effect of hepatitis B virus (HBV) surface-gene variability on markers of replication during treated human immunodeficiency virus-HBV infection in Western Africa.

BACKGROUND & AIMS: Replication markers exhibit substantial variation during chronic hepatitis B virus (HBV) infection, part of which can be explained by mutations on the surface (S) gene. We aimed to identify S-gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa. METHODS: Seventy-three antiretroviral treatment (ART)-naïve human immunodeficiency virus (HIV)-HBV co-infected patients from Côte d'Ivoire, initiating anti-HBV-containing ART, had available HBV S-gene sequences. S-gene MUPIQHs were screened at ART initiation based on lower HBV-DNA or HBsAg quantification (qHBsAg) compared to wildtype. Their association with HBV virological response and qHBsAg slope during treatment was evaluated. RESULTS: Genotype E was predominant (95.9%). At ART initiation, median HBV-DNA was 7.27 log10 copies/mL (IQR = 5.26-8.33) and qHBsAg 4.08 log10 IU/mL (IQR = 3.49-4.61). Twelve S-gene MUPIQHs were identified among 21 patients (28.8%): sS140L (n = 4), sD144A (n = 1), sS167L (n = 2), sS174N (n = 6), sP178Q (n = 2), sG185L (n = 2), sW191L (n = 2), sP203Q/R (n = 2), sS204N/I/R/K/T/G (n = 7), sN207T (n = 2), sF212C (n = 1) and sV224A/Y (n = 7). MUPIQHs at positions s185+s191+s224 and s178+s204 were within highly covarying networks of S-gene mutations. Older age (P = 0.02), elevated transaminases (P = 0.03) and anti-hepatitis B "e" antibody-positive serology (P = 0.009) were significantly associated with prevalent MUPIQHs at ART initiation. During treatment, baseline MUPIQHs were not associated with time-to-undetectable HBV-DNA (P = 0.7) and qHBsAg levels decreased at similar rates between those with vs without MUPIQHs (P = 0.5). CONCLUSION: Several novel S-gene mutations were associated with reductions in replication markers among West African co-infected patients. These mutations, however, do not affect response during antiviral treatment. Their diagnostic and clinical consequences need clarification.