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Background: UNAIDS models use data from the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration in setting assumptions about mortality rates after antiretroviral treatment (ART) initiation. This study aims to update these assumptions with new data, to quantify the extent of regional variation in ART mortality and to assess trends in ART mortality., Methods: Adult ART patients from Africa, Asia and the Americas were included if they had a known date of ART initiation during 2001-2017 and a baseline CD4 cell count. In cohorts that relied only on passive follow-up (no patient tracing or linkage to vital registration systems), mortality outcomes were imputed in patients lost to follow-up based on a meta-analysis of tracing study data. Poisson regression models were fitted to the mortality data., Results: 464 048 ART patients were included. In multivariable analysis, mortality rates were lowest in Asia and highest in Africa, with no significant differences between African regions. Adjusted mortality rates varied significantly between programmes within regions. Mortality rates in the first 12 months after ART initiation were significantly higher during 2001-2006 than during 2010-2014, although the difference was more substantial in Asia and the Americas [adjusted incidence rate ratio (aIRR) 1.43, 95% CI: 1.22-1.66] than in Africa (aIRR 1.07, 95% CI: 1.04-1.11)., Conclusion: There is substantial variation in ART mortality between and within regions, even after controlling for differences in mortality by age, sex, baseline CD4 category and calendar period. ART mortality rates have declined substantially over time, although declines have been slower in Africa.

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.

Purpose of Review: People living with HIV-2 infected usually initiate antiretroviral therapy (ART) at an advanced period in the course of their infection after a long asymptomatic period characterized by high CD4 cell count and thus at a relatively advanced age. In the new international context of early and universal ART initiation, the aim was to review survival patterns among HIV-2 infected patients, either on ART or not., Recent Findings: Very few reports were published on mortality in people living with HIV-2 during the last 5 years. People living with HIV-2 experience high mortality rates although lower than people living with HIV-1 before ART initiation. They seem to survive longer regardless of the conditions of ART use. Mortality is associated with late presentation, male sex, CD4 cell count less than 500 cell/μl, high plasma viral load, hemoglobin rate less than 8 g/dl and body mass index less than 18 kg/m., Summary: People living with HIV-2 initiate ART later than HIV-1 and HIV duals, resulting in higher disease progression and mortality rate. The clinical management of HIV-2 infected patients should now include early diagnosis and treatment initiation as per international guidelines. Further research needs to explore the 'what to start' question and document specific causes of death in people living with HIV-2 and enrolled in care in Africa., Competing Interests: The authors have no conflict of interest to declare.

Objective: To assess the virological response, genotypic resistance profiles, and antiretroviral plasma concentrations in HIV-2 antiretroviral-treated (antiretroviral therapy, ART) patients in Côte d'Ivoire., Methods: A cross-sectional survey was conducted among HIV-2 patients receiving ART. Plasma HIV-2 viral load was performed using the Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS) assay. Protease and reverse transcriptase sequencing was performed using in-house methods and antiretroviral plasma concentrations were assessed using ultra performance liquid chromatography combined with tandem mass spectrometry., Results: One hundred and forty-five HIV-2-treated patients were enrolled with a median CD4 cell count of 360 cells/μl (interquartile range, IQR = 215-528). Median duration of ART was 4 years (IQR = 2-7) and 74% of patients displayed viral load less than 50 copies/ml. Median plasma HIV-2 RNA among patients with viral load more than 50 copies/ml was 3016 copies/ml (IQR = 436-5156). Most patients (84%) received a lopinavir/ritonavir-based regimen. HIV-2 resistance mutations to nucleoside reverse transcriptase inhibitors and protease inhibitors were detected in 21 of 25 (84%) and 20 of 29 (69%) samples, respectively. The most prevalent nucleoside reverse transcriptase inhibitor resistance mutations were M184I/V (90%), Q151M (24%), and S215F/Y (24%). The most prevalent protease inhibitor resistance mutations were V47A (60%) and I54M (30%). Median CD4 cell counts were 434 cells/μl (292-573) and 204 cells/μl (122-281) in patients with viral load less than 50 copies/ml and those exhibiting virological failure (P < 0.0001), respectively. The proportions of patients with adequate antiretroviral plasma concentrations were 81 and 93% in patients displaying virological failure and in those with viral load less than 50 copies/ml, respectively (P = 0.046), suggesting good treatment adherence., Conclusion: We observed adequate drug plasma concentrations and virological suppression in a high proportion of HIV-2-infected patients. However, in cases of virological failure, the limited HIV-2 therapeutic arsenal and cross-resistance dramatically reduced treatment options.

Objective: To assess the effect of aging on the immunological response to antiretroviral therapy (ART) in the West African context., Methods: The change in CD4 T-cell count was analysed according to age at the time of ART initiation among HIV-infected patients enrolled in the International epidemiological Database to Evaluate AIDS (IeDEA) Collaboration in the West African region. CD4 gain over 12 months of ART was estimated using linear mixed models. Models were adjusted for baseline CD4 cell count, sex, baseline clinical stage, calendar period and ART regimen., Results: The total number of patients included was 24,107, contributing for 50,893 measures of CD4 cell count in the first year of ART. The baseline median CD4 cell count was 144 cells/μl [interquartile range (IQR) 61-235]; median CD4 cell count reached 310 cells/μl (IQR 204-443) after 1 year of ART. The median age at treatment initiation was 36.3 years (10th-90th percentiles = 26.5-50.1). In adjusted analysis, the mean CD4 gain was significantly higher in younger patients (P < 0.0001). At 12 months, patients below 30 years recovered an additional 22 cells/μl on average [95% confidence interval (CI) 2-43] compared to patients at least 50 years., Conclusion: Among HIV-infected adults in West Africa, the immunological response after 12 months of ART was significantly poorer in elderly patients. As the population of treated patients is likely to get older, the impact of this age effect on immunological response to ART may increase over time.

Purpose of Review: In this review, we describe the challenges faced by using clinical cohorts to perform Monitoring and Evaluation (M&E) and the possible solutions for increasing and strengthening health systems in low-income and middle-income countries., Recent Findings: HIV scale-up has facilitated the transition from paper-based medical records to electronic medical records at hundreds of sites in most of the countries in sub-Saharan Africa and the implementation of national HIV databases. However, National M&E systems in resource-limited settings tend to be chronically challenged by persistently incomplete reporting and inaccurate data, which undermines their usefulness. In low-income and middle-income countries, new information technologies such as Web-based systems and mobile phone networks are expanding rapidly. Their use will improve data quality and, therefore, reduce participant dropout and improve reporting rates. These systems have the potential to allow real time access to summary reports and to integrate data from other settings such as maternal and infant health clinics., Summary: The efforts to address the AIDS pandemic in sub-Saharan Africa will require enhanced information systems. Stronger systems are needed to deliver primary healthcare for those with and without HIV, and it is also essential to build and take advantage of synergies across health information systems.

Objective: To compare the lymphocyte T CD4+ (CD4) response to combinations of antiretroviral therapy (ART) in HIV-1, HIV-2 and dually positive patients in West Africa., Design and Setting: Collaboration of 12 prospective cohorts of HIV-infected adults followed in Senegal (2), Gambia (1), Mali (2), Benin (1) and Côte d'Ivoire (6)., Subjects: Nine thousand, four hundred and eighty-two patients infected by HIV-1 only, 270 by HIV-2 only and 321 dually positive, who initiated an ART., Outcome Measures: CD4 change over a 12-month period., Results: Observed CD4 cell counts at treatment initiation were similar in the three groups [overall median 155, interquartile range (IQR) 68; 249 cells/microl). In HIV-1 patients, the most common ART regimen was two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI; N = 7714) as well as for dually positive patients (N = 135). HIV-2 patients were most often treated with a protease inhibitor-based regimen (N = 193) but 45 of them were treated with an NNRTI-containing ART. In those treated with a NNRTI-containing regimen, the estimated mean CD4 change between 3 and 12 months was significantly lower in HIV-2 (-41 cells/microl per year) and dually positive patients (+12 cells/microl per year) compared to HIV-1 patients (+69 cells/microl per year, overall P value 0.01). The response in HIV-2 and dually positive patients treated by another regimen (triple NRTIs or protease inhibitor-containing ART) was not significantly different than the response obtained in HIV-1-only patients (all P values >0.30)., Conclusion: An optimal CD4 response to ART in West Africa requires determining HIV type prior to initiation of antiretroviral drugs. NNRTIs are the mainstay of first-line ART in West Africa but are not adapted to the treatment of HIV-2 and dually positive patients.

Background: Pregnancy outcomes in women receiving highly active antiretroviral treatment (HAART) in Africa are not well described., Methods: HIV-1-infected pregnant women in the ANRS Ditrame Plus and the MTCT-Plus projects were included. Between March 2001 and July 2003, when HAART was not yet available, women eligible for HAART received a short-course antiretroviral regimen, zidovudine (ZDV) or (ZDV + lamivudine) and single dose of nevirapine for preventing mother-to-child transmission (PMTCT group). Between August 2003 and August 2007, eligible women for HAART received it (HAART group). The frequencies of low birth weight (LBW) (<2500 g), stillbirth and infant mortality are reported. Risk factors associated with LBW were investigated using a logistic regression model., Results: Of the 326 HIV-infected pregnant women, 175 women received short-course antiretroviral (median CD4 cell count 177 cells/microl) and 151 received HAART (median CD4 cell count 182 cells/microl). At 12 months, three paediatric infections (2.3%) occurred in the HAART group vs. 25 (16.1%) in the PMTCT group (P < 0.001). The rate of LBW was 22.3% in the HAART group and 12.4% in the PMTCT group (P = 0.02). In multivariable analysis (n = 309), after adjustment on maternal CD4 cell count, WHO stage, age and maternal BMI, HAART initiated before pregnancy [adjusted odds ratio (OR) 2.88, 95% confidence interval (CI) 1.10-7.51] and during pregnancy (adjusted OR 2.12, 95% CI 1.15-4.65) and maternal BMI at delivery (adjusted OR 2.43, 95% CI 1.20-4.91) were associated with LBW., Conclusion: HAART in pregnant African women with advanced HIV disease substantially reduced mother-to-child transmission, but was associated with LBW.

Objectives: In Africa, single-dose nevirapine (NVPsd), short regimens of zidovudine (ZDV) or ZDV + lamivudine (3TC) are recommended to prevent peripartum mother-to-child HIV transmission (PMTCT). We evaluated the 6-week field efficacy of two more PMTCT drug combinations., Design: An open-label intervention cohort in Abidjan., Methods: In 2001-2002, consenting women started oral ZDV 300 mg twice daily (bid) at > or =36 weeks of gestation, with 600 mg of ZDV + 200 mg NVPsd orally at beginning of labour. In 2002-2003, the antepartum regimen at > or =32 weeks comprised ZDV as previously + 3TC 150 mg bid; the labour dose comprised ZDV + NVPsd as previously + 300 mg 3TC orally. Neonates received ZDV syrup (2 mg/kg per 6 h) for 7 days + NVPsd syrup (2 mg/kg) on day 2 in both periods. Each woman was assisted to either use breast milk substitutes or breastfeed exclusively. Paediatric HIV infection was diagnosed by plasma HIV RNA viral load at 4 weeks, confirmed at 6 weeks. The reference group was a cohort receiving a short regimen of ZDV > or = 36-38 weeks in 1995-2000 in the same population., Results: A total of 1144 HIV-infected pregnant women were included: 351 with ZDV, 420 with ZDV + NVPsd and 373 with ZDV + 3TC + NVPsd; 1010 livebirths were eligible for analysis; 79 children were HIV-infected peripartum. Six-week transmission probability was 6.5% [95% confidence interval (CI), 3.9-9.1%) with ZDV + NVPsd, a 72% reduction compared with ZDV alone (95% CI, 52-88%; P = 0.0002 adjusted on maternal CD4, clinical stage and breastfeeding). It was 4.7% (95% CI, 2.4-7.0%) with ZDV + 3TC + NVPsd (P = 0.34 compared with ZDV + NVPsd)., Conclusions: A short-course of ZDV + NVPsd prevents most peripartum HIV transmission in Africa. This regimen could be added to international guidelines.