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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

BACKGROUND: In patients co-infected with HIV and tuberculosis, antiretroviral therapy options are limited due to drug—drug interactions with rifampicin. A previous phase 2 trial indicated that raltegravir 400 mg twice a day or efavirenz 600 mg once a day might have similar virological efficacy in patients given rifampicin. In this phase 3 trial, we assessed the non-inferiority of raltegravir to efavirenz. METHODS: We did a multicentre, open-label, non-inferiority, randomised, phase 3 trial at six sites in Côte d'Ivoire, Brazil, France, Mozambique, and Vietnam. We included antiretroviral therapy (ART)-naive adults (aged ≥18 years) with confirmed HIV-1 infection and bacteriologically confirmed or clinically diagnosed tuberculosis who had initiated rifampicin-containing tuberculosis treatment within the past 8 weeks. Using computerised random numbers, we randomly assigned participants (1:1; stratified by country) to receive raltegravir 400 mg twice daily or efavirenz 600 mg once daily, both in combination with tenofovir and lamivudine. The primary outcome was the proportion of patients with virological suppression at week 48 (defined as plasma HIV RNA concentration

BACKGROUND: It is unknown how past and active hepatitis B virus (HBV) infection affect immunorecovery and mortality in people with HIV who initiate tenofovir-based anti-retroviral therapy (ART). METHODS: Using data collected between 2008– 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 ≥2000 IU/mL; HBsAg-positive with HBV DNA

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 + 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 3.

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 CD42052 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 CD4At baseline, 190 (9%) were HBsAg-positive [135 (71%) with HBV DNA2000 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 CD4Despite no effect of HBV-infection on CD4

International audience; The West and Central African region (WCAR) still registers some of the highest rates of new HIV infections worldwide (16%) despite a low prevalence of HIV (1.9%). In this region, only 48% of people living with HIV are aware of their HIV status. To fill this gap, HIV Self testing (HIVST) could potentially be an additional approach to overcome the barriers to diagnose HIV infected patients, therefore being one of the keys to unlock the first 90 as recommended by the World Health Organization (WHO) since 2016. However, many challenges remain for the adoption of HIVST in routine clinical practice in low prevalence settings and need to be contextualized to WCAR settings. We report in this paper some of the challenges and discuss opportunities for a successful implementation of HIVST in the WCAR.

BackgroundThe presence of the human leukocyte antigen HLA-B*57:01 is associated with the development of a hypersensitivity reaction to abacavir (ABC). Limited data exist on HLA-B*57:01 prevalence in individuals with HIV-1 in Africa. This study aimed to estimate HLA-B*57:01 prevalence in individuals with HIV-1 in West and Central Africa.MethodsA cross-sectional study was conducted in four countries in West and central Africa (Burkina-Faso, Côte d’Ivoire, Gabon, and Togo) from January 2016 to February 2020 to determine the status of HLA-B*57:01 in adults with HIV-1. The presence of HLA-B*57:01 was determined by using Single Specific Primer-Polymerase Chain Reaction (SSP-PCR) in blood samples. Prevalence rates were stratified based on country.ResultsA total of 4016 (69.8% women) individuals with HIV were enrolled. Their median age was 45, and the interquartile range was 38–52. We included 500 (12.4%) patients in Burkina-Faso, 1453 (36.2%) in Côte d’Ivoire, 951 (23.7%) in Gabon, and 1112 (27.7%) in Togo. The overall HLA-B*57:01 prevalence was 0.1% [95% CI: 0.0–0.2%]. The prevalence of HLA-B*57:01 was similar according to the four countries. Only one case was reported in each country except Togo, with no cases.ConclusionsHLA-B*57:01 prevalence is low in individuals with HIV in West and central Africa, and there is no difference among countries. This study does not confirm the utility of HLA-B*57:01 allele testing for abacavir use in this region.

Background: With success and effective long-term antiretroviral treatment (ART), HIV-infected patients live longer and frequently developed non-communicable diseases (NCDs). Few studies have been conducted in low-income countries, particularly in West Africa. Methods: We carried out a cross-sectional study in the referral HIV centre of the Service des Maladies Infectieuses et Tropicales (SMIT) in Abidjan. From April to September 2015, we consecutively included HIV-1 infected patients aged 18 years and older, and on ART for a minimum of 12 months. Data were collected using a structured questionnaire, and entered into the centre’s computerised HIV database. Clinical assessment, laboratory tests, electrocardiogram, transthoracic echocardiography and vascular Doppler ultrasound were performed. The main outcome was the prevalence of patients with severe cardiovascular abnormalities (SCA). Univariate and multivariate logistic regressions were used to identify factors associated with SCA. Results: Out of 278 patients (median age 46 years, interquartile range [IQR: 41–52]), 74.5% were female. Overall, the median duration of ART was 84 months (IQR: 54–126). One hundred and ninety-nine (71.6%) patients were on first-line ART regimen and 229 (82.4%) were virologically suppressed with a median CD4 count of 511 cells/mm 3 (IQR: 347–529). Basically, cardiovascular abnormalities were mainly non-obstructive carotid plaques (19.1%) followed with left ventricular diastolic dysfunction (16.5%). The overall prevalence of SCA in the study population was 7.6% (95% Confidence Interval [95% CI]: 4.7–11.3). The prevalence of SCA 7.6% (95% Confidence Interval [95% CI]: 4.7–11.3). In multivariate analysis, age > 50 years and nadir CD4 count > 200 cells/mm 3 were significant predictors of SCA. Conclusion: The prevalence of SCA is high in West African HIV-treated patients. Given the high mortality associated with cardiovascular diseases in the general population, refining disease preventive strategies in HIV-positive subjects is essential to continue prolonging their life.

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.

Summary Background Isoniazid preventive therapy prevents active tuberculosis in people with HIV, but previous studies have found no evidence of benefit in people with HIV who had a negative tuberculin skin test, and a non-significant effect on mortality. We aimed to estimate the effect of isoniazid preventive therapy given with antiretroviral therapy (ART) for the prevention of tuberculosis and death among people with HIV across population subgroups. Methods We searched PubMed, Embase, the Cochrane database, and conference abstracts from database inception to Jan 15, 2019, to identify potentially eligible randomised trials. Eligible studies were trials that enrolled HIV-positive adults (age ≥15 years) taking ART who were randomly assigned to either daily isoniazid preventive therapy plus ART or ART alone and followed up longitudinally for outcomes of incident tuberculosis and mortality. We approached all authors of included trials and requested individual participant data: coprimary outcomes were relative risk of incident tuberculosis and all-cause mortality. We did a single-stage meta-analysis of individual participant data using stratified Cox-proportional hazards models. We did prespecified subgroup analyses by sex, CD4 cell count, and evidence of immune sensitisation to tuberculosis (indicated by tuberculin skin test or interferon-γ release assays [IGRAs]). We also assessed the relative risk of liver injury in an additional prespecified analysis. This study is registered with PROSPERO, CRD42019121400. Findings Of 838 records, we included three trials with data for 2611 participants and 8584·8 person-years of follow-up for the outcome of incident tuberculosis, and a subset of 2362 participants with 8631·6 person-years of follow-up for the coprimary outcome of all-cause mortality. Risk for tuberculosis was lower in participants given isoniazid preventive therapy and ART than participants given ART alone (hazard ratio [HR] 0·68, 95% CI 0·49–0·95, p=0·02). Risk of all-cause mortality was lower in participants given isoniazid preventive therapy and ART than participants given ART alone, but this difference was non-significant (HR 0·69, 95% CI 0·43–1·10, p=0·12). Participants with baseline CD4 counts of less than 500 cells per μL had increased risk of tuberculosis, but there was no significant difference in the benefit of isoniazid preventive therapy with ART by sex, baseline CD4 count, or results of tuberculin skin test or IGRAs. 65 (2·5%) of 2611 participants had raised alanine aminotransferase, but data were insufficient to calculate an HR. Interpretation Isoniazid preventive therapy with ART prevents tuberculosis across demographic and HIV-specific and tuberculosis-specific subgroups, which supports efforts to further increase use of isoniazid preventive therapy with ART broadly among people living with HIV. Funding National Institutes of Health and National Institute of Allergy and Infectious Diseases.

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.

The novel severe acute respiratory syndrome-coronavirus-2 pandemic has spread to Africa, where nearly all countries have reported laboratory-confirmed cases of novel coronavirus disease (COVID-19). Although there are ongoing clinical trials of repurposed and investigational antiviral and immune-based therapies, there are as yet no scientifically proven, clinically effective pharmacological treatments for COVID-19. Among the repurposed drugs, the commonly used antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) have become the focus of global scientific, media, and political attention despite a lack of randomized clinical trials supporting their efficacy. Chloroquine has been used worldwide for about 75 years and is listed by the WHO as an essential medicine to treat malaria. Hydroxychloroquine is mainly used as a therapy for autoimmune diseases. However, the efficacy and safety of CQ/HCQ for the treatment of COVID-19 remains to be defined. Indiscriminate promotion and widespread use of CQ/HCQ have led to extensive shortages, self-treatment, and fatal overdoses. Shortages and increased market prices leave all countries vulnerable to substandard and falsified medical products, and safety issues are especially concerning for Africa because of its healthcare system limitations. Much needed in Africa is a cross-continental collaborative network for coordinated production, distribution, and post-marketing surveillance aligned to low-cost distribution of any approved COVID-19 drug; this would ideally be piggybacked on existing global aid efforts. Meanwhile, African countries should strongly consider implementing prescription monitoring schemes to ensure that any off-label CQ/HCQ use is appropriate and beneficial during this pandemic.

Summary Background The novel coronavirus disease 2019 (COVID-19) epidemic has spread from China to 25 countries. Local cycles of transmission have already occurred in 12 countries after case importation. In Africa, Egypt has so far confirmed one case. The management and control of COVID-19 importations heavily rely on a country's health capacity. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of COVID-19. Methods We used data on the volume of air travel departing from airports in the infected provinces in China and directed to Africa to estimate the risk of importation per country. We determined the country's capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulations Monitoring and Evaluation Framework; and vulnerability, using the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing most to their risk. Findings Countries with the highest importation risk (ie, Egypt, Algeria, and South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (ie, Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya) have variable capacity and high vulnerability. We identified three clusters of countries that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and the city of Beijing, respectively. Interpretation Many countries in Africa are stepping up their preparedness to detect and cope with COVID-19 importations. Resources, intensified surveillance, and capacity building should be urgently prioritised in countries with moderate risk that might be ill-prepared to detect imported cases and to limit onward transmission. Funding EU Framework Programme for Research and Innovation Horizon 2020, Agence Nationale de la Recherche.

BackgroundThe novel coronavirus (2019-nCoV) epidemic has spread to 23 countries from China. Local cycles of transmission already occurred in 7 countries following case importation. No African country has reported cases yet. The management and control of 2019-nCoV introductions heavily relies on country’s health capacity. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of 2019-nCoV.MethodsWe used data on air travel volumes departing from airports in the infected provinces in China and directed to Africa to estimate the risk of introduction per country. We determined the country’s capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulation Monitoring and Evaluation Framework; and vulnerability, with the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing the most to their risk.FindingsCountries at the highest importation risk (Egypt, Algeria, Republic of South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, Kenya) have variable capacity and high vulnerability. Three clusters of countries are identified that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and Beijing, respectively.InterpretationSeveral countries in Africa are stepping up their preparedness to detect and cope with 2019-nCoV importations. Resources and intensified surveillance and capacity capacity should be urgently prioritized towards countries at moderate risk that may be ill-prepared to face the importation and to limit onward transmission.FundingThis study was partially supported by the ANR project DATAREDUX (ANR-19-CE46-0008-03) to VC; the EU grant MOOD (H2020-874850) to MG, CP, MK, PYB, VC.

IntroductionThe long-term prognosis of HIV-2-infected patients receiving antiretroviral therapy (ART) is still challenging, due to the intrinsic resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) and the suboptimal response to some protease inhibitors (PI). The objective was to describe the 5-years outcomes among HIV-2 patients harboring drug-resistant viruses.MethodsA clinic-based cohort of HIV-2-patients experiencing virologic failure, with at least one drug resistance mutation was followed from January 2012 to August 2017 in Côte d'Ivoire. Follow-up data included death, lost to follow-up (LTFU), immuno-virological responses. The Kaplan-Meier curve was used to estimate survival rates.ResultsA total of 31 HIV-2 patients with virologic failure and with at least one drug resistance mutation were included. Two-third of them were men, 28(90.3%) were on PI-based ART-regimen at enrolment and the median age was 50 years (IQR = 46-54). The median baseline CD4 count and viral load were 456 cells/mm3 and 3.7 log10 c/mL respectively, and the participants have been followed-up in median 57 months (IQR = 24-60). During this period, 21 (67.7%) patients switched at least one antiretroviral drug, including two (6.5%) and three (9.7%) who switched to a PI-based and an integrase inhibitor-based regimen respectively. A total of 10(32.3%) patients died and 4(12.9%) were LTFU. The 36 and 60-months survival rates were 68.5% and 64.9%, respectively. Among the 17 patients remaining in care, six(35.3%) had an undetectable viral load (2.ConclusionsThe 36-months survival rate among ART-experienced HIV-2 patients with drug-resistant viruses is below 70%,lower than in HIV-1. There is urgent need to improve access to second-line ART for patients living with HIV-2 in West Africa.

Background: Several biomarkers of inflammation and coagulation were reported to be associated with HIV disease progression in different settings. Here we report the association between eleven biomarkers and medium-term mortality in HIV-infected adults who participated in a trial of early antiretroviral therapy (ART) in West Africa (Temprano ANRS 12136). Methods: In Temprano, ART-naive HIV-infected adults with high CD4 counts were randomly assigned either to start ART immediately or defer ART until the WHO criteria were met. Participants who completed the 30-month trial follow-up were invited to participate in a post-trial phase (PTP). The PTP endpoint was all-cause death. We used multivariate Cox proportional models to analyze the association between baseline plasma biomarkers (IL-1ra, IL-6, sVCAM-1, sCD14, D-dimer, Fibrinogen, IP-10, sCD163, albumin, hsCRP, 16S rDNA) and all-cause death in the Temprano participants randomized to defer ART. Findings: 477 patients (median age 35, 78% women) were randomly assigned to defer starting ART until the WHO criteria were met. At baseline, the median CD4 count was 379 cells/mm3, the median plasma HIV-1 RNA level 4·6 log10 copies/mL and the median PBMC HIV-1 DNA level 3·0 log10 copies per million PBMC. 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, PBMC HIV-1 DNA and ART, the risk of death was significantly associated with baseline sVCAM-1 (≥ 1458 vs. < 1458: adjusted hazard ratio [aHR] 2·57, 95% CI 1·13-5·82) and sCD14 (≥ 2187 vs. < 2187: aHR 2·79, IQR 1·29-6·02) levels. Interpretation: In these sub-Saharan African adults with high CD4 counts, pre-ART plasma sVCAM-1 and sCD14 levels were independently associated with mortality. Trial Registration: Registered at Clinical Trials.gov (NCT00495651). Funding Statement: French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, ANRS 12224, ANRS 12253). Declaration of Interests: All authors report no conflict of interest. Ethics Approval Statement: The Temprano protocol, which included the post-trial phase, was approved by the Cote d'Ivoire National Ethics Committee for Health Research. All patients gave written informed consent.

Introduction Cotrimoxazole (CTX) should be given to all HIV-infected adults with mild or severe HIV disease or those with CD4 counts below 350/mm3 according to 2006 WHO guidelines. We assessed the impact of CTX prophylaxis on the risk of malaria episodes in HIV-1 infected adults from four West African countries with different patterns of malaria transmission. Method Multicentric cohort study, conducted between September 2007 and March 2010 in four West African cities. Antiretroviral therapy (ART) naive HIV-infected adults started CTX at enrollment (CTX group) if they had CD4

Resume Objectif Evaluer l’utilisation de fortes doses de fluconazole en monotherapie (1200 mg ou 800 mg) dans le traitement de la cryptococcose neuromeningee au cours du sida. Patients et methodes Etude retrospective menee d’aout 2008 a aout 2011 a partir des dossiers de patients atteints de cryptococcose neuromeningee dans le service des maladies infectieuses et tropicales d’Abidjan. La letalite et les facteurs associes ont ete analyses. Resultats Quarante-six cas de cryptococcose neuromeningee (2,5 % des hospitalisations) ont ete inclus. Le sex-ratio etait de 1,2. L’âge median etait de 40,5 [35–47] ans. La symptomatologie etait subaigue (93,5 %). Les principaux symptomes cliniques etaient le syndrome meninge pur (65 %), la fievre (100 %) ; 35 % des patients presentaient une meningo-encephalite. Vingt et un patients (45,7 %) etaient naifs d’antiretroviraux. Le fluconazole 1200 mg a ete prescrit chez 29 (63 %) patients. La ponction lombaire soustractive a ete effectuee chez 42 (91,3 %) patients. La letalite etait de 50 %. Les facteurs predictifs de la mortalite etaient la meningo-encephalite et les ponctions lombaires soustractives. Conclusion La letalite de la cryptococcose neuromeningee reste elevee malgre l’utilisation de fortes doses de fluconazole en monotherapie. Les ponctions lombaires soustractives contribuent a l’amelioration du pronostic.

The underpinning theme of the 2016 INTEREST Conference held in Yaoundé, Cameroon, 3–6 May 2016 was ending AIDS as a public health threat by 2030. Focused primarily on HIV treatment, pathogenesis and prevention research in resource-limited settings, the conference attracted 369 active delegates from 34 countries, of which 22 were in Africa. Presentations on treatment optimization, acquired drug resistance, care of children and adolescents, laboratory monitoring and diagnostics, implementation challenges, HIV prevention, key populations, vaccine and cure, hepatitis C, mHealth, financing the HIV response and emerging pathogens, were accompanied by oral, mini-oral and poster presentations. Spirited plenary debates on the UNAIDS 90-90-90 treatment cascade goal and on antiretroviral pre-exposure prophylaxis took place. Joep Lange career guidance sessions and grantspersonship sessions attracted early career researchers. At the closing ceremony, the Yaoundé Declaration called on African governments; UNAIDS; development, bilateral, and multilateral partners; and civil society to adopt urgent and sustained approaches to end HIV by 2030.

OBJECTIVES HIV-2-infected individuals usually initiate antiretroviral therapy (ART) at an advanced age compared with HIV-1 patients, with a potential impact on treatment outcomes. This study aimed to investigate the effect of sex and age on mortality and loss to follow-up (LTFU) among HIV-2-infected individuals initiating ART. METHODS Analyses were conducted using the database of the International Epidemiological Databases to Evaluate AIDS's collaboration in West Africa. LTFU was considered if the interval between the last visit and the closing date for this analysis was more than 180 days. Probability of death and LTFU were estimated with Kaplan-Meier methods. A Cox regression model was used to identify factors associated with death and LTFU over the first 24 months on ART. RESULTS A total of 1825 HIV-2-infected individuals, including 60% women were considered for this analysis. The median age, baseline CD4 cell count, and follow-up duration were 45 years [interquartile range (IQR; 38-52)], 185 cells/μl [IQR (95-297)], and 28.8 months [IQR (9.8-58.9)], respectively. Over the first 24 months, the mortality rate was 5.2/100 person-years of observation [95% confidence interval (CI; 4.4-6.1)] and 469 (25.7%) were LTFU. Male sex [hazard ratio (HR) = 1.9; 95% CI (1.4; 2.8)], baseline CD4 cell count less than 100 cell/μl [HR = 4.4 95% CI (1.7; 11.1); ref at least 350 cell/μl], haemoglobin 7.5-10 g/dl [HR = 2.4 95% CI (1.3; 4.4); ref at least 12 g/dl], and BMI less than 18 kg/m [HR = 2.1 95% CI (1.3; 3.4); ref = 18-25 kg/m] were associated with higher mortality over the first 24 months. Similar associations were found for LTFU. CONCLUSION Mortality and LTFU are high among ART-receiving HIV-2-infected individuals and higher in men than in women. There is a critical need to further determine the causes of poor retention and implement sex-specific solutions that improve outcomes in HIV-2 ART programmes.

International audience; AimIn West Africa, most countries have mixed HIV epidemics; new tools such as pre-exposure prophylaxis (PrEP) should target in priority most affected populations, particularly female sex workers (FSWs). This paper describes sexual and reproductive health (SRH) needs of FSWs in Côte d’Ivoire to inform the future implementation of PrEP in this population.Method/IssueThe ANRS 12361 PrEP-CI cross-sectional and mixed-methods study was designed and implemented with two Ivorian community-based organizations. 1000 FSWs completed a standardized questionnaire assessing women’s sociodemographic characteristics, sexual practices and behaviors, use of community health services, a priori acceptability of PrEP. Twenty-two in-depth interviews and eight focus group discussions were conducted at prostitution sites. FSWs were interviewed about risky practices and sexual behaviors, experiences with violence and discrimination, attitudes regarding HIV and sexually transmitted infections (STIs), and barriers to SRH services.Results/CommentsThe quantitative and qualitative results showed that FSWs were highly exposed to HIV despite their use of condoms with clients. 91% did not use condoms with their regular partner, despite their acknowledged concurrent sexual partnerships. 23% accepted condomless sexual intercourse for a large sum of money, especially when they had had few previous clients. Moreover, FSWs faced many unmet needs regarding SRH beyond HIV prevention and treatment. Inconsistent condom use exposed FSWs to STIs and undesired pregnancies. However, the prevalence of contraceptive use was low (40%) due to fear of contraception causing sterility. FSWs faced obstacles in accessing SRH care and preferred advice from their peers or self-medication.DiscussionImplementing PrEP among FSWs in West Africa, such as in Côte d’Ivoire, constitutes an opportunity to consider the chronic 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 practicing 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: The decision about whether to switch to third-line antiretroviral therapy (ART) in patients with treatment failure on second-line therapy is difficult in settings with little access to genotypic resistance testing. In this study, we used a standardised algorithm including a wide range of adherence-enhancing interventions followed by a new viral load measurement to decide whether to switch to third-line therapy in this situation. The decision, made on the basis of effectiveness of the adherence reinforcement to drive viral resuppression, did not use genotypic resistance testing. METHODS: In this prospective cohort study, adults in four west African countries with treatment failure of a boosted protease inhibitor ART regimen were offered nine adherence reinforcement interventions, and followed up for 64 weeks. We measured viral load at week 12 and used the results to decide ART treatment at week 16: if successful resuppression (plasma HIV-1 RNA /=2 log10 copies per mL compared with baseline), patients continued the same second-line regimen; otherwise they switched to a third-line regimen based on ritonavir-boosted darunavir and raltegravir. The primary endpoint was virological success at week 64 (plasma HIV-1 RNA

Background and Aim In Sub-Saharan Africa, seroclearance of hepatitis B surface antigen (HBsAg) and hepatitis B “e” antigen (HBeAg), including their quantifiable markers, have rarely been evaluated during long-term antiviral treatment among patients coinfected with HIV and hepatitis B virus (HBV). Methods In this prospective cohort study from two randomized-control trials in Cote d'Ivoire, 161 antiretroviral-naive HIV-HBV coinfected patients starting lamivudine (n = 76) or tenofovir/emtricitabine (n = 85) containing antiretroviral therapy were included. HBV DNA was quantified using an in-house assay (detection limit = 12 copies/mL) and HBsAg quantification (qHBsAg) using the Elecsys assay. Results Overall, 33 (20.5%) patients were HBeAg positive, 121 (75.2%) had detectable HBV DNA, and 92/93 (98.9%) harbored HBV genotype E. Median treatment duration was 35.5 months (interquartile range: 24.3–36.4). Among HBeAg-positive patients, cumulative proportion with HBeAg seroclearance was 46.3% (n = 14). Overall, cumulative proportion of HBsAg seroclearance was 6.6% (n = 10). Lower baseline qHBsAg levels and strong 12-month declines in qHBsAg were significantly associated with HBsAg seroclearance for both HBeAg-negative and HBeAg-positive patients. When taken at certain levels, these determinants provided moderate sensitivity (Se) and specificity (Sp) in predicting HBsAg seroclearance at month 36 (≤ 1000 IU/mL at baseline, Se = 0.80, Sp = 0.80; ≥ 1.0 log10 IU/mL drop at month 12, Se = 0.57, Sp = 1.00). Instead, qHBsAg levels ≤ 100 or ≤ 10 IU/mL at month 12 were optimal (both Se = 0.90 and Sp = 1.00). Detectable HBV-DNA provided fairly high Se and Sp when evaluated at baseline (Se = 1.00, Sp = 0.80), but not at month 12 (Se = 0.80, Sp = 0.40). Conclusions HBsAg seroclearance rates are not common in patients from Sub-Saharan Africa treated with anti-HBV containing antiretroviral therapy. qHBsAg levels at 12 months of treatment may accurately predict HBsAg seroclearance.

Most research in sub-Saharan Africa establishes hepatitis B infection via one-time hepatitis B surface antigen (HBsAg) testing. Of 237 HIV-infected patients from two clinical trials testing HBsAg positive (MiniVidas®), 206 (86.9%) had validated serological tests using another assay (Architect). Discrepancies could be due to inactive infection, highlighting the importance of assessing hepatitis B virus infection phase.

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. Results: 2,019 patients were followed for 9,253 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 2.9log10 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. Conclusions: 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. Trial Registration: Clinical Trials.gov (NCT00495651). Funding Statement: This trial was supported by grants from the French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, ANRS 12224, ANRS 12253. Declaration of Interests: All authors report no conflict of interest. Ethics Approval Statement: The Temprano protocol, which included the post-trial phase, was approved by the Cote d'Ivoire National Ethics Committee for Health Research.

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 (p4.0 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.

Author(s): Bekker, Linda-Gail; Alleyne, George; Baral, Stefan; Cepeda, Javier; Daskalakis, Demetre; Dowdy, David; Dybul, Mark; Eholie, Serge; Esom, Kene; Garnett, Geoff; Grimsrud, Anna; Hakim, James; Havlir, Diane; Isbell, Michael T; Johnson, Leigh; Kamarulzaman, Adeeba; Kasaie, Parastu; Kazatchkine, Michel; Kilonzo, Nduku; Klag, Michael; Klein, Marina; Lewin, Sharon R; Luo, Chewe; Makofane, Keletso; Martin, Natasha K; Mayer, Kenneth; Millett, Gregorio; Ntusi, Ntobeko; Pace, Loyce; Pike, Carey; Piot, Peter; Pozniak, Anton; Quinn, Thomas C; Rockstroh, Jurgen; Ratevosian, Jirair; Ryan, Owen; Sippel, Serra; Spire, Bruno; Soucat, Agnes; Starrs, Ann; Strathdee, Steffanie A; Thomson, Nicholas; Vella, Stefano; Schechter, Mauro; Vickerman, Peter; Weir, Brian; Beyrer, Chris

International audience; ContexteBien que les travailleuses du sexe (TS) constituent une population particulièrement à risque du VIH, la compréhension du fardeau du VIH reste limitée dans cette population en Afrique subsaharienne. Le projet PrEP-CI ANRS 12361 comportait une estimation de l’incidence de l’infection VIH chez des TS en Côte d’Ivoire à l’aide de tests d’infection récente.MéthodesL’étude a été conduite entre septembre 2016 et mars 2017 auprès de TS âgées de 18 ans et plus à Abidjan et à San Pedro, en mobilisant une méthodologie mixte :(i) des entretiens qualitatifs individuels et des focus groupes auprès de 60 TS,(ii) un questionnaire sociodémographique standardisé ainsi qu’un dépistage du VIH par deux tests rapides (Determine®, Alere et Vikia®, bio Mérieux) administrés par des paires éducatrices sur les sites prostitutionnels auprès de 1000 TS. En cas de positivité, un prélèvement sur DBS a été réalisé pour déterminer la fenêtre d’infection à l’aide d’un test d’infection récente (EIA-RI) adapté au contexte ivoirien.Résultats1000 TS (400 à San Pedro, 600 à Abidjan) avec un âge médian de 25 ans [Intervalle Interquartile = 21-29] ont été incluses dans l’étude et ont été dépistées pour le VIH. Parmi elles, 39 ont été diagnostiquées VIH+, dont 7 infectées récemment (durée moyenne de la durée d’infection de 113 jours), correspondant à une incidence du VIH de 2,2%.L’incidence est plus élevée à San Pedro (3,2%) qu’à Abidjan (1,5%). Ces résultats sont à mettre en regard des données qualitatives : les TS de San Pedro ont témoigné de difficultés (distance, horaires, coûts …) à accéder aux soins de santé et aux moyens de prévention, notamment le préservatif. L’infection à VIH est également associée à la vulnérabilité : l’incidence est plus élevée chez celles qui pratiquent des passes ≤ 2000 CFA (3,1% vs. 0,7%) ; chez celles qui exercent sur les trottoirs (5,1%) et dans les hôtels (3,8%) ; et chez celles qui ne travaillent qu’une fois par semaine (2,9% vs. 0 cas incident observé chez celles qui travaillent tous les jours). Les TS travaillant occasionnellement sont plus difficilement identifiées par les paires éducatrices et ont moins accès à la prévention. Enfin, les TS de moins de 25 ans sont plus à risque d’infection (2,6%) que celles de plus âgées (1,6%) et l’incidence du VIH est associée aux autres IST (2,3% chez celles ayant eu ≥1 IST au cours des 12 derniers mois vs 1,8%).ConclusionCette étude est l’une des premières à estimer l’incidence du VIH en Côte d’Ivoire chez les TS. Cette population est beaucoup plus exposée que le reste de la population générale (2,2% vs. 0,06% estimé par l’Onusida). Les nouvelles infections se concentrent chez les TS plus jeunes, en situation précaire et travaillant dans des zones reculées, en particulier dans la région de San Pedro. Ces sous-groupes vulnérables doivent donc être visés en priorité par les programmes de prévention et devraient se voir proposer une prophylaxie préexposition (PrEP) selon les recommandations de l’OMS.

When taken properly, Tenofovir-based oral preexposure prophylaxis (PrEP) has been proven to be efficient to prevent HIV acquisition [1–5]. Since 2015, PrEP is recommended by the WHO for populations at ‘substantial risk’ of HIV [6]. However, WHO points out the need for additional research on PrEP in

Immunorecovery could be attenuated in HIV-hepatitis B virus (HBV) coinfection versus HIV monoinfection during antiretroviral therapy (ART), yet, whether it also occurs in individuals from sub-Saharan Africa without severe comorbidities is unknown. In this study, 808 HIV-infected patients in Côte d'Ivoire initiating continuous ART were included. Six-month CD4+ count trajectories and the proportion reaching CD4+ T cell counts350/mm

SETTING: TEMPRANO was a multicentre, open-label trial in which human immunodeficiency virus (HIV) infected adults with high CD4 counts were randomised into early or deferred antiretroviral therapy (ART) arms with or without 6-month isoniazid preventive therapy (IPT) in a setting where the World Health Organization (WHO) recommends IPT in HIV-infected patients. Despite the WHO recommendation, IPT coverage remains low due to fear of the presence of undiagnosed active TB before prescribing IPT, and the related risk of drug resistance.OBJECTIVE: To report the frequency of undiagnosed TB in patients enrolled for IPT and describe the results of a 1-month buffer period to avoid prescribing IPT for active TB cases.DESIGN: Patients were screened using a clinical algorithm and chest X-ray at Day 0 and started on isoniazid at Month 1 if no sign/symptom suggestive of TB appeared between Day 0 and Month 1.RESULTS: Of 1030 patients randomised into IPT arms. 10% never started IPT at Month 1. Of these, 23 had active TB, including 16 with prevalent TB. Among the 927 patients who started IPT, 6 had active TB, including 1 with prevalent TB. Only 1 patient with active TB received IPT due to the 1-month buffer period between Day 0 and IPT initiation.CONCLUSION: In this study, 1.6% of adults considered free of active TB based on clinical screening at pre-inclusion actually had active TB.

Charlotte Bernard,1,2 Eric Balestre,1,2 Patrick A Coffie,3–5 Serge Paul Eholie,3,4 Eugène Messou,3–6 Viviane Kwaghe,7 Benson Okwara,8 Adrien Sawadogo,9 Yao Abo,10 François Dabis,1,2 Nathalie de Rekeneire1,2 On behalf of the International Epidemiological Database to evaluate Aids (IeDEA) West Africa Collaboration 1INSERM, Centre INSERM U1219-Epidémiologie-Biostatistique, Bordeaux, France; 2University of Bordeaux, School of Public Health (ISPED), Bordeaux, France; 3Département de Dermatologie et d’Infectiologie, UFR des Sciences Médicales, Université Félix Houphouët Boigny, Abidjan, Côte d’Ivoire; 4Unit of Infectious and Tropical Diseases, Treichville University Teaching Hospital, Abidjan, Côte d’Ivoire; 5Programme PAC-CI, Treichville University Teaching Hospital, Abidjan, Ivory Coast; 6Center of Care, Research and Training (CePReF), Yopougon-Attié Hospital, Abidjan, Ivory Coast; 7University of Abuja Teaching Hospital, Abuja, Nigeria; 8University of Benin City Teaching Hospital, Benin City, Nigeria; 9Institut Supérieur des Sciences de la Santé (INSSA), Bobo-Dioulasso Polytechnic University, Bobo-Dioulasso, Burkina Faso; 10National Blood Transfusion Center (CNTS), Abidjan, Ivory Coast Background: Reporting mortality and lost to follow-up (LTFU) by age is essential as older HIV-positive patients might be at risk of long-term effects of living with HIV and/or taking antiretroviral therapy (ART). As age effects might not be linear and might impact HIV outcomes in the oldest more severely, people living with HIV (PLHIV) aged 50–59 years and PLHIV aged >60 years were considered separately.Setting: Seventeen adult HIV/AIDS clinics spread over nine countries in West Africa.Methods: Data were collected within the International Epidemiological Databases to Evaluate AIDS West Africa Collaboration. ART-naïve PLHIV-1 adults aged >16 years initiating ART and attending ≥2 clinic visits were included (N=73,525). Age was divided into five groups: 16–29/30–39/40–49/50–59/≥60 years. The age effect on mortality and LTFU was evaluated with Kaplan–Meier curves and multivariable Cox proportional hazard regressions.Results: At month 36, 5.9% of the patients had died and 47.3% were LTFU. Patients aged ≥60 (N=1,736) and between 50–59 years old (N=6,792) had an increased risk of death in the first 36 months on ART (adjusted hazard ratio=1.66; 95% CI: 1.36–2.03 and adjusted hazard ratio=1.31; 95% CI: 1.15–1.49, respectively; reference: 50 years old should not be considered as a unique group irrespective of their age. Tailored programs focusing on improving the care services for older PLHIV in Sub-Saharan Africa are clearly needed to improve basic program outcomes. Keywords: HIV, aging, ART, mortality, lost to follow-up, Sub-Saharan Africa

Little is known on the impact of HIV-2 infection on HCV viral replication. The aim of the study was to compare HCV prevalence and viral replication based on HIV types in West Africa. A cross-sectional survey was conducted within the IeDEA HIV-2 West Africa cohort from March to December 2012. All HIVinfected adult patients who attended participating HIV clinics during the study period were included. Blood samples were collected and re-tested for HIV type discrimination, HCV serology and viral load. A total of 767 patients were enrolled: 186 HIV-1, 431 HIV-2 and 150 HIV-1&2 dually reactive. At time of sampling, 531 (69.2%) were on ART and median CD4+ cell count was 472/mm3. Thirty (3.9%, 95% CI 2.7-5.5) patients were anti-HCV positive (4.3% in HIV-1, 4.0% in HIV-1&2 dually reactive and 3.7% in HIV-2; p=0.91). Detectable HCV RNA was identified in 21 (70.0%) patients (100% in HIV-1 and HIV- 1&2 dually reactive vs. 43.8% in HIV-2; p=0.003). Systematic screening should be promoted and performed in this population, since HCV is now potentially curable in sub- Saharan Africa.

In HIV-infected patients thromboembolic disease is a complication linked to heightened risk. In Ivory Coast no study has been conducted on HIV-infected patients treated in HIV Services. The aim of our study is to describe HIV-associated thromboembolic manifestations in patients treated or untreated with antiretroviral drugs whose data were collected in the Infectious and Tropical Diseases Service (ITDS). We conducted a retrospective study by reviewing the medical records of HIV-infected patients hospitalized with deep vein thrombosis (DVT), arterial thrombosis and/or pulmonary embolism over the period January 2005-July 2015. Diagnosis was based on Doppler ultrasound of vessels and/or on thoracic angioscanner. Diagnostic, therapeutic and evolutionary features of thromboembolic manifestations in these patients were analyzed. The medical records of 36 patients, including 23 women (64%), with a sex-ratio M/F of 0.57 and an average age of 43±12 years were selected. Deep venous thrombosis (DVT) was found in 26 (72.2%) patients, pulmonary embolism (PE) in 9 (25%) patients and arterial thrombosis in 1 patient (2.8%). DVT was unilateral in 81% of cases and predominantly left-sided in 77% of cases. PE was unilateral and right-sided in 100% of cases while arterial thrombosis was bilateral in 2.7% of cases. In patients with DVT, the femoral vein (39%) and the popliteal vein (35%) were most commonly affected by thrombosis. PE involved the pulmonary arteries in 77.8% of cases while arterial thrombosis involved the left and right internal carotid. The majority of patients was under antiretroviral treatment (69%). The most commonly associated opportunistic infections included oral candidiasis (31%) and tuberculosis (33%). Nine patients died (25%). This study highlights high rates of DVT in HIV-infected patients. Other studies are necessary to better understand the role of HIV in the occurrence of thromboembolic disease.

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)-naive human immunodeficiency virus (HIV)-HBV co-infected patients from Cote 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.

With the introduction of more efficient treatments for hepatitis C virus (HCV), improved epidemiological information is required at the country level to allow evidence-based policymaking for elaboration of national strategies and HCV resources planning. We present a systematic review with meta-analysis of HCV seroprevalence data in adults in African countries. We conducted a systematic review of all HCV seroprevalence estimates reported in African countries from 2000 to 2014 in MEDLINE, AJOL and grey literature. We assessed studies performed in the general population and among blood donors, pregnant women and HIV-positive patients. A meta-regression analysis was used to provide adjusted estimates of HCV seroprevalence in the general adult population in each country, accounting for the heterogeneity in sample age structure and population types in the included studies. We identified 775 national-level estimations, among which 184 were included. Estimates of HCV seroprevalence were produced for 38 countries, in addition to the results from nationwide representative surveys available in Egypt and Libya. Next to Egypt, which clearly stands out, the highest levels of seroprevalence were found in Middle Africa (e.g. Cameroon, Gabon and Angola) and some West African countries (e.g. Burkina Faso, Benin), and the largest absolute numbers of infected adults were found in Nigeria, Ethiopia and Democratic Republic of Congo. This study exposes the diversity of HCV epidemiology among African countries. Egypt and several countries of West and Middle Africa present a HCV burden that will require strong governmental commitment to promote efficient preventive and curative interventions.

Summary Background Morbidity associated with HIV infection is poorly characterised, so we aimed to investigate the contribution of different comorbidities to hospital admission and in-hospital mortality in adults and children living with HIV worldwide. Methods Using a broad search strategy combining terms for hospital admission and HIV infection, we searched MEDLINE via PubMed, Embase, Web of Science, LILACS, AIM, IMEMR and WPIMR from inception to Jan 31, 2015, to identify studies reporting cause of hospital admission in people living with HIV. We focused on data reported after 2007, the period in which access to antiretroviral therapy started to become widespread. We estimated pooled proportions of hospital admissions and deaths per disease category by use of random-effects models. We stratified data by geographical region and age. Findings We obtained data from 106 cohorts, with reported causes of hospital admission for 313 006 adults and 6182 children living with HIV. For adults, AIDS-related illnesses (25 119 patients, 46%, 95% CI 40–53) and bacterial infections (14 034 patients, 31%, 20–42) were the leading causes of hospital admission. These two categories were the most common causes of hospital admission for adults in all geographical regions and the most common causes of mortality. Common region-specific causes of hospital admission included malnutrition and wasting, parasitic infections, and haematological disorders in the Africa region; respiratory disease, psychiatric disorders, renal disorders, cardiovascular disorders, and liver disease in Europe; haematological disorders in North America; and respiratory, neurological, digestive and liver-related conditions, viral infections, and drug toxicity in South and Central America. For children, AIDS-related illnesses (783 patients, 27%, 95% CI 19–34) and bacterial infections (1190 patients, 41%, 26–56) were the leading causes of hospital admission, followed by malnutrition and wasting, haematological disorders, and, in the African region, malaria. Mortality in individuals admitted to hospital was 20% (95% CI 18–23, 12 902 deaths) for adults and 14% (10–19, 643 deaths) for children. Interpretation This review shows the importance of prompt HIV diagnosis and treatment, and the need to reinforce existing recommendations to provide chemoprophylaxis and vaccination against major preventable infectious diseases to people living with HIV to reduce serious AIDS and non-AIDS morbidity. Funding None.

In a cohort of HIV-infected patients of sub-Saharan origin we describe the incidence of metabolic syndrome, insulin resistance, and lipodystrophy after 3 years of combined antiretroviral therapy, and model the 10-year risk of cardiovascular diseases, while taking into account environmental factors. This is a multinational, prospective cohort study conducted in HIV outpatient clinics from four tertiary care centers set in France and Côte d'Ivoire. The participants were HIV-infected, treatment-naive patients eligible to start antiretroviral treatment and were of sub-Saharan African origin. The main outcome measures were the incidence of metabolic syndrome, insulin resistance, and lipodystrophy, and the assessment of the 10-year risk of cardiovascular diseases using Framingham risk prediction, D.A.D. Cardiovascular Disease Risk, and WHO/ISH prediction charts. Of 245 patients followed for up to 3 years, the incidence of metabolic syndrome, insulin resistance, and lipodystrophy was 5.5, 8.5, and 6.8 per 100 person-years of follow-up (cumulative incidence: 14.4%, 19.2%, and 18.1%, respectively). Living in France as well as female gender and being overweight were risk factors for metabolic disorders as whole and only first generation protease inhibitors were marginally associated with metabolic syndrome. Cardiovascular risk as modeled through the three equations was high in all patients with the synergistic and deleterious effect of living in France compared to Côte d'Ivoire. This cohort study shows how the synergy between HIV, antiretroviral (ARV) exposure, and westernization of life style in a cohort of HIV-infected patients of sub-Saharan origin leads to a progressive increase in the risk of lipodystrophy, as well as metabolic syndrome and insulin resistance, all associated with increased cardiovascular risk.

In HIV-HBV-coinfected patients from sub-Saharan Africa, incidence of antiviral resistant HBV-mutations after initiating long-term antiretroviral therapy (ART) has only been evaluated in limited patient populations.In this nested, prospective cohort study from two randomized controlled trials in Côte d'Ivoire, 168 ART-naive HIV-HBV-coinfected patients, starting lamivudine (LAM, n=82) or tenofovir/emtricitabine (TDF/FTC, n=86) containing ART were included. HBV DNA viral load (VL) was quantified using an in-house assay (detection limit:12 copies/ml) while pol and preS/S regions of positive samples were sequenced.At ART-initiation, 39 (23.2%) were hepatitis B e antigen-positive, 53 (31.5%) had alanine or aspartate aminotransferase levels40 IU/ml and 98/100 (98.0%) harboured genotype E. Among the 127 (75.6%) patients with detectable baseline HBV VL (median 4.27 log10 copies/ml, IQR 3.14-7.64), cumulative percentage achieving undetectable HBV DNA was 74.2% for patients undergoing LAM-containing ART and 94.2% for TDF/FTC-containing ART after a median 35.5 months (IQR 24.3-36.5). No baseline antiviral resistance mutations were observed. Among 28/127 (22.1%) patients with low-level persistent viraemia (last HBV VL: between 12 to10(5) copies/ml), no incident amino acid changes associated with antiviral resistance were observed. Among 11/127 (8.7%) patients with high-level persistent viraemia (last HBV VL: ≥10(5) copies/ml), only two harboured incident LAM-resistance mutations at positions rtV173L+rtL180M+rtM204V with no patient exhibiting TDF/FTC-resistance. Two patients had transaminase flares120 IU/ml (incidence rate =0.5/100 person-years).Antiviral resistance, particularly to LAM, was remarkably rare in this cohort of HIV-HBV-coinfected patients. Further research is needed to determine which coinfected populations might benefit from LAM-containing ART with low risk of resistance.

Resource-limited nations must consider their response to potential contractions in international support for HIV programs.To evaluate the clinical, epidemiologic, and budgetary consequences of alternative HIV program scale-back strategies in 2 recipient nations, the Republic of South Africa (RSA) and Côte d'Ivoire (CI).Model-based comparison between current standard (CD4 count at presentation of 0.260 × 109 cells/L, universal antiretroviral therapy [ART] eligibility, and 5-year retention rate of 84%) and scale-back alternatives, including reduced HIV detection, no ART or delayed initiation (when CD4 count is0.350 × 109 cells/L), reduced investment in retention, and no viral load monitoring or second-line ART.Published RSA- and CI-specific estimates of the HIV care continuum, ART efficacy, and HIV-related costs.HIV-infected persons, including future incident cases.5 and 10 years.Modified societal perspective, excluding time and productivity costs.HIV transmissions and deaths, years of life, and budgetary outlays (2015 U.S. dollars).At 10 years, scale-back strategies increase projected HIV transmissions by 0.5% to 19.4% and deaths by 0.6% to 39.1%. Strategies can produce budgetary savings of up to 30% but no more. Compared with the current standard, nearly every scale-back strategy produces proportionally more HIV deaths (and transmissions, in RSA) than savings. When the least harmful and most efficient alternatives for achieving budget cuts of 10% to 20% are applied, every year of life lost will save roughly $900 in HIV-related outlays in RSA and $600 to $900 in CI.Scale-back programs, when combined, may result in clinical and budgetary synergies and offsets.The magnitude and details of budget cuts are not yet known, nor is the degree to which other international partners might step in to restore budget shortfalls.Scaling back international aid to HIV programs will have severe adverse clinical consequences; for similar economic savings, certain programmatic scale-back choices result in less harm than others.National Institutes of Health and Steve and Deborah Gorlin MGH Research Scholars Award.

Background In West Africa where HIV-1 and HIV-2 co-circulate, the co-infection with hepatitis B virus (HBV) and hepatitis Delta virus (HDV) is not well described. This study aimed at estimating the prevalence of HBV and HBV/HDV co-infection according to HIV types and risk factors for HBV infection among West African HIV-infected patients. Method A cross-sectional survey was conducted within the IeDEA West Africa cohort from March to December 2012 in Côte d’Ivoire (three sites), Burkina Faso and Mali (one site each). All HIV-infected adult patients on antiretroviral therapy (ART) or not who attended one of the participating HIV clinics during the study period and agreed to participate were included. Blood samples were collected and re-tested for HIV type discrimination, HBV and HDV serology as well as HBV viral load. Logistic regression was used to identify risk factors for HBV infection. Results A total of 791 patients were included: 192 HIV-1, 447 HIV-2 and 152 HIV-1&2 dually reactive. At time of sampling, 555 (70.2%) were on ART and median CD4+ cell count was 472/mm3 (inter-quartile range [IQR]: IQR: 294–644). Sixty-seven (8.5%, 95% CI 6.6–10.6) patients were HBsAg positive without any difference according to HIV type (7.9% in HIV-1, 7.2% in HIV-1&2 dually reactive and 9.4% in HIV-2; p = 0.61). In multivariate logistic analysis, age ≤ 30 years old (adjusted odds ratio [aOR] 5.00, 95% CI 1.96–12.76), age between 31 and 49 years old (aOR 1.78, 95% CI 1.00–2.21) and male gender (aOR 2.15, 95% CI 1.25–3.69) were associated with HBsAg positivity. HBV DNA testing was performed in 36 patients with blood sample available (25 on ART) and 8 (22.2%) had detectable HBV DNA. Among the HBsAg-positive individuals, 14.9% (95% CI 7.4–25.7) were also positive for anti-HDV antibody without any difference according to HIV type (28.6% in HIV-1, 14.3% in HIV-2 and 0.0% in HIV-1&2 dually reactive; p = 0.15). Conclusion HBV and HBV/HDV co-infection are common in West Africa, irrespective of HIV type. Therefore, screening for both viruses should be systematically performed to allow a better management of HIV-infected patients. Follow-up studies are necessary to determine the impact of these two viruses on HIV infection.

Supplemental Digital Content is available in the text, Objective: Use of zidovudine (ZDV) in antiretroviral therapy is limited by toxicity and twice daily (b.i.d.) dosing. Fozivudine (FZD) is a ZDV prodrug, which is activated intracellularly to ZDV-monophosphate especially in mononuclear cells but not in bone marrow cells. FZD promises improved myelotoxicity and once daily (o.d.) dosing. Design: Randomized clinical trial. Methods: We conducted an open-label, phase II, proof-of-concept trial investigating three different FZD doses (800 mg o.d., 600 mg b.i.d., 1200 mg o.d.) versus ZDV (300 mg b.i.d.) in combination with lamivudine and efavirenz in HIV-infected, ART-naive patients from Tanzania and Côte d’Ivoire. The primary objective was to demonstrate virological efficacy after 24 weeks in intent-to treat and per-protocol analysis. Secondary endpoints included safety and pharmacokinetic outcomes. Results: Of 119 participants included in the intent-to treat analysis, HIV RNA less than 50 copies/ml at 24 weeks was observed in 64 of 88 (73%) patients in the combined FZD arms versus 24 of 31 (77%) in the ZDV arm (RR 0.94, 95% confidence interval 0.75–1.18). In the per-protocol analysis, responses were 64 of 77 (87%) versus 23 of 29 (79%), respectively (RR 1.09, 95% confidence interval 0.89–1.34). Outcomes were similar between FZD arms. Overall, treatments were well tolerated. Severe or worse anaemia occurred in two cases (one related to FZD, one to ZDV), grade III/IV neutropenia was less frequent in FZD compared with ZDV arms (22 versus 42%, P = 0.035). Pharmacokinetic analysis supported o.d. administration of FZD. Conclusion: Virological 24-week efficacy was demonstrated in b.i.d. and o.d. administered FZD-based regimens. Reduced myelotoxicity of FZD needs to be confirmed in a larger trial.