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Background Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis (TB), particularly in sub-Saharan Africa. Current anti-TB treatment is poorly effective since TBM mortality reaches 40% in HIV-negative patients and up to 70% in HIV-co-infected patients. To reduce TBM-induced morbidity and mortality, the INTENSE-TBM trial evaluates two interventions in both HIV-infected and uninfected patients: an anti-TB treatment intensification using oral high-dose rifampicin (35 mg/kg daily) and linezolid (1200 mg daily and then 600 mg daily) during the first 8 weeks of the anti-TB treatment and the use of adjunctive aspirin (200 mg daily). Methods This is a randomized controlled, phase III, multicenter, 2 × 2 factorial plan superiority trial. The trial has four arms, combining the two experimental treatments (intensified TBM regimen and aspirin) with the two reference treatments (WHO standard TB treatment and placebo), and is open-label for anti-TB treatment and double-blind placebo-controlled for aspirin treatment. This trial is conducted in adults or adolescents of age ≥15 years with TBM defined as “definite,” “probable,” or “possible” using Tuberculosis Meningitis International Research Consortium criteria, in four African countries: Ivory Coast, Madagascar, Uganda, and South Africa. The primary outcome is all-cause death between inclusion and week 40. Discussion The INTENSE-TBM trial represents a key opportunity to enhance TBM treatment with widely available existing drugs notably in high-incidence settings of both TB and HIV. The trial design is pragmatic and the results will permit early and effective applications in TBM patient care, in both HIV and TB high-incidence countries. Trial registration ClinicalTrials.gov NCT04145258. Registered on October 30, 2019.

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.

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.

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.

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.

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

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.

International audience; Whether risk compensation could offset the preventive effect of early initiation of antiretroviral therapy (ART) on human immunodeficiency virus (HIV) transmission remains unknown. Using virological and behavioral data collected 12 months after inclusion in the TEMPRANO randomized trial of early ART (Abidjan, Côte d'Ivoire, 2009–2012), we estimated the risk of HIV transmission and compared it between the intervention (early ART; n = 490) and control (deferred ART; n = 467) groups. We then simulated increases in various sexual risk behaviors in the intervention group and estimated the resulting preventive effect. On the basis of reported values of sexual behaviors, we estimated that early ART had an 89% (95% confidence interval: 81, 95) preventive effect on the cumulative risk of HIV transmission over a 1-month period. This preventive effect remained significant for a wide range of parameter combinations and was offset (i.e., nonsignificant) only for dramatic increases in different sexual behaviors simulated simultaneously. For example, when considering a 2-fold increase in serodiscordance and the frequency of sexual intercourse together with a 33% decrease in condom use, the resulting preventive effect was 47% (95% confidence interval: −3, 74). An important reduction of HIV transmission may thus be expected from the scale-up of early ART, even in the context of behavioral change.

Background Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care. Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies. Methods and Findings Inclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in “cycle threshold” [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A “target value” of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis. Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%–32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%–91.1%) in Group A Ct < 20. Both mortality 95% CIs included the predefined target value (30% and 85%, respectively). Baseline serum creatinine was ≥110 μmol/l in 48% of patients in Group A Ct ≥ 20 (≥300 μmol/l in 14%) and in 90% of patients in Group A Ct < 20 (≥300 μmol/l in 44%). In Group A Ct ≥ 20, 17% of patients with baseline creatinine ≥110 μmol/l died, versus 97% in Group A Ct < 20. In patients who survived, the mean decrease in viral load was 0.33 log10 copies/ml per day of follow-up. RNA viral load values and mortality were not significantly different between adults starting favipiravir within, In the context the recent Ebola outbreak, Xavier Anglaret and colleagues test an experimental treatment, favipiravir, for Ebola virus disease in a multicenter non-randomized trial., Editors' Summary Background In 2014 and 2015, an Ebola virus outbreak larger than any known before occurred in West Africa. Ebola virus disease (EVD) is highly contagious, and many infected people die. Central to the emergency response to the recent outbreak were local Ebola treatment centers where patients were diagnosed, were isolated, and received supportive care. With thousands of patients dying and many health workers contracting the disease, fear was ubiquitous and distrust abundant. While conducting research in this environment was extremely challenging, the urgent need for treatments and the opportunity to conduct studies that could bring such treatments closer to reality was also recognized. In September 2014, WHO released a short list of existing drugs that were candidates for clinical trials among patients infected in the outbreak. Favipiravir, an antiviral drug developed in Japan for patients with severe influenza, was on the list. Why Was This Study Done? Because of the urgent need to find drugs that could reduce deaths caused by Ebola, the researchers decided to conduct a clinical trial using favipiravir in patients with EVD in Guinea. In view of the circumstances, they decided against a randomized controlled trial and instead designed a study where all participants would receive the same treatment. In randomized controlled trials only some participants receive the treatment in addition to standard care, while others serve as a control group and receive standard care only, or standard care plus a placebo. Such studies allow stronger conclusions to be drawn about whether a treatment is safe and whether it works or not. The researchers had two main reasons for this decision. First, patients from the same family or village often sought EVD treatment at the same time, and the researchers felt that it was ethically unacceptable to randomize such groups, with only some of them receiving the experimental drug. Second, the strict isolation procedures imposed to interrupt virus transmission had intensified fear in affected communities and fueled rumors of illicit drug experimentation and organ theft at the treatment centers. In this context, the researchers worried that a randomized study might increase distrust among the community and the reluctance of patients to seek care. Rather than seeking definitive answers about the safety and efficacy of favipiravir in patients with EVD, the objectives of the study as it was designed were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak and to learn lessons from the experience. In addition, the researchers planned to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD in the hope that their preliminary findings could improve the design of subsequent trials and the chance to provide conclusive answers. What Did the Researchers Do and Find? After 13 weeks of preparation, the trial took place from December 2014 to April 2015 at four separate Ebola treatment centers, three in rural areas and one in an urban setting. In addition to standard care (which included rehydration, antimalarial and antibacterial therapies, and medication to reduce fever, pain, and nausea), all participants were given favipiravir by mouth for ten days, at doses substantially higher than those recommended for patients with influenza. Outcomes measured were mortality, viral load changes over time (based on blood samples), and adverse events. EVD was confirmed with an assay that used patient blood and provided an estimate of the viral load, that is, of how much virus the blood contained. Because viral load was known to influence the course of EVD, the researchers analyzed the participants in two groups, namely, those with a viral load estimate above a certain threshold and those with viral load estimate below the threshold. They also used existing data from Guinean patients diagnosed with Ebola earlier in the outbreak who had received only standard care and calculated an expected mortality rate for patients above and below the viral load threshold. The researchers were able to enroll 126 participants in the trial. Of these, 111 were included in the final analysis. Of 99 adult and adolescent participants 13 years and older, 55 were in the lower viral load group and 44 in the higher viral load group. Mortality was 20% in the former and 91% in the latter. Neither mortality rate was significantly different from that of earlier patients who had received only standard care. The researchers also found that favipiravir was well tolerated. None of the patients stopped the course of treatment, vomiting following drug intake was rare, and no severe adverse events were attributed to the drug. The researchers did not see a difference in mortality between patients who reported onset of symptoms less than three days before the start of treatment and those whose symptoms had started more than three days the start of treatment. What Do these Findings Mean? The report shows that it is possible to conduct an emergency trial during an outbreak in a low-resource setting. In fact, at the time of its acceptance, this paper reported on an Ebola treatment trial larger than any other yet published. The experience described should be useful for similar undertakings in the future. The following conditions contributed to the success of the trial: close collaboration between researchers, local health officials, and affected communities on one hand, and flexibility in design, conduct, and analysis based on close monitoring and interim assessments on the other. Besides using interim results to influence the conduct and analysis of their own trial, the researchers also shared these results with the scientific community in real time, and this feedback influenced other research during the outbreak. The trial could not answer definitively whether favipiravir treatment was safe or reduced mortality in patients with EVD. The results suggest that the drug is unlikely to be beneficial for patients with very high viral loads, at least when given by itself. They also suggest that favipiravir is safe in patients with lower viral loads, and that in such patients additional efficacy studies are warranted. Intermediate analysis of various measurements in trial participants showed that the estimate of viral load from the field EVD diagnosis test is a good proxy for the actual viral load (determined after the samples were shipped to and analyzed in a reference laboratory in France) and suitable as a surrogate marker. The results also confirm that viral load is a strong predictor of mortality. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001967. The World Health Organization has pages on Ebola virus disease, trials of Ebola treatments and vaccines, and the current update of the list of suitable drugs for testing or use in patients infected with Ebola (originally compiled in September 2014) US Centers for Disease Control and Prevention has information on the Ebola outbreak in West Africa The European Centre for Disease Prevention and Control also has information on the Ebola outbreak in West Africa

BACKGROUND: The effect of early initiation of antiretroviral therapy (ART; ie, at CD4(+) T-cell counts >350 cells/mm(3)) on sexual behaviors and human immunodeficiency virus type 1 (HIV) transmission risk has not been documented in populations other than HIV-serodiscordant couples in stable relationships. METHODS: On the basis of data from a behavioral study nested in a randomized, controlled trial (Temprano-ANRS12136) of early ART, we compared proportions of risky sex (ie, unprotected sex with a partner of negative/unknown HIV status) reported 12 months after inclusion between participants randomly assigned to initiate ART immediately (hereafter, "early ART") or according to ongoing World Health Organization criteria. Group-specific HIV transmission rates were estimated on the basis of sexual behaviors and viral load-specific per-act HIV transmission probabilities. The ratio of transmission rates was computed to estimate the protective effect of early ART. RESULTS: Among 957 participants (baseline median CD4(+) T-cell count, 478 cells/mm(3)), 46.0% reported sexual activity in the past month; of these 46.0%, sexual activity for 41.5% involved noncohabiting partners. The proportion of subjects who engaged in risky sex was 10.0% in the early ART group, compared with 12.8% in the standard ART group (P = .17). After accounting for sexual behaviors and viral load, we estimated that the protective effect of early ART was 90% (95% confidence interval, 81%-95%). CONCLUSION: Twelve months after inclusion, patients in the early and standard ART groups reported similar sexual behaviors. Early ART decreased the estimated risk of HIV transmission by 90%, suggesting a major prevention benefit among seronegative sex partners in stable or casual relationships with seropositive individuals.

Background Few data are available on antiretroviral therapy (ART) response among HIV-2 infected patients. We conducted a systematic review on treatment outcomes among HIV-2 infected patients on ART, focusing on the immunological and virological responses in adults. Methods Data were extracted from articles that were selected after screening of PubMed/MEDLINE up to November 2012 and abstracts of the 1996–2012 international conferences. Observational cohorts, clinical trials and program reports were eligible as long as they reported data on ART response (clinical, immunological or virological) among HIV-2 infected patients. The determinants investigated included patients’ demographic characteristics, CD4 cell count at baseline and ART received. Results Seventeen reports (involving 976 HIV-2 only and 454 HIV1&2 dually reactive patients) were included in the final review, and the analysis presented in this report are related to HIV-2 infected patients only. There was no randomized controlled trial and only two cohorts had enrolled more than 100 HIV-2 only infected patients. The median CD4 count at ART initiation was 165 cells/mm3, [IQR; 137–201] and the median age at ART initiation was 44 years (IQR: 42–48 years). Ten studies included 103 patients treated with three nucleoside reverse transcriptase inhibitors (NRTI). Protease inhibitor (PI) based regimens were reported by 16 studies. Before 2009, the most frequent PIs used were Nelfinavir and Indinavir, whereas it was Lopinavir/ritonavir thereafter. The immunological response at month-12 was reported in six studies and the mean CD4 cell count increase was +118 cells/μL (min-max: 45–200 cells/μL). Conclusion Overall, clinical and immuno-virologic outcomes in HIV-2 infected individuals treated with ART are suboptimal. There is a need of randomized controlled trials to improve the management and outcomes of people living with HIV-2 infection. Electronic supplementary material The online version of this article (doi:10.1186/1471-2334-14-461) contains supplementary material, which is available to authorized users.

International audience; BACKGROUND: In resource-limited settings, scaling-up antiretroviral treatment (ART) has required the involvement of decentralized health facilities with limited equipment. We estimated the incidence of serious morbidity among HIV-infected adults receiving ART in one of these HIV routine care center in sub-Saharan Africa. METHODS: We conducted a prospective study at the Centre Medical de Suivi des Donneurs de Sang (CMSDS), which is affiliated with the National Centre for Blood Transfusion in Abidjan, Cote d'Ivoire. Adult patients infected with HIV-1 or HIV-1/HIV-2 who initiated ART between January 2003 and December 2008 were eligible for the study. Standardized clinical data were collected at each visit. Serious morbidity was defined as a new episode of malaria, WHO stage 3-4 event, ANRS grade 3-4 adverse event, or any event leading to death or to hospitalization. RESULTS: 1008 adults, 67% women, with a median age of 35 years, and a median pre-ART CD4 count of 186/mm3 started ART and were followed for a median of 17.3 months. The overall incidences of loss to follow-up, death, and attrition were 6.2/100 person-years (PY) [95% CI 5.1-7.2], 2.3/100 PY [95% CI 1.6-2.9], and 8.1/100 PY [95% CI 7.0-9.4], respectively. The incidence of first serious event was 11.5/100 PY overall, 15.9/100 PY within the first year and 8.3/100 PY thereafter. The most frequently documented specific diagnoses were malaria, tuberculosis, bacterial septicemia and bacterial pneumonia. CONCLUSION: Among HIV-infected adults followed in routine conditions in a West African primary care clinic, we recorded a high incidence of serious morbidity during the first year on ART. Providing care centers with diagnostic tools and standardizing data collection are necessary steps to improve the quality of care in primary care facilities in sub-Saharan Africa.

International audience; n.a