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Objective: We aimed to assess the frequency of tenofovir (TDF) resistance in people failing tenofovir/lamivudine or emtricitabine (XTC)/nonnucleotide reverse-transcriptase inhibitor-based first-line antiretroviral treatment (ART) using data from 15 nationally representative surveys of HIV drug resistance conducted between 2014 and 2018 in Cameroon, Guatemala, Honduras, Nicaragua, Senegal, Uganda, Vietnam and Zambia. Methods: Prevalence of nucleoside reverse-transcriptase inhibitor resistance among participants with virological nonsuppression (viral load >= 1000 copies/ml) who had received TDF-based ART for 12-24 months (early ART group) and at least 40 months (long-term ART group) was assessed using Sanger sequencing and resistance was interpreted using the Stanford HIVdb algorithm. For each group, we estimated a pooled prevalence using random effect meta-analysis. Results: Of 4677 participants enrolled in the surveys, 640 (13.7%) had virological nonsuppression, 431 (67.3%) were successfully genotyped and were included in the analysis; of those, 60.3% (260) were participants in the early ART group. Overall, 39.1, 57.9, 38.5 and 3.6% patients in the early ART group and 42.9, 69.3, 42.9 and 10.0% patients on long-term ART had resistance to TDF, XTC, TDF + XTC and TDF + XTC + zizidovudine, respectively. Overall, tenofovir resistance was mainly due to K65R or K70E/G/N/A/S/T/Y115F mutations (79%) but also due to thymidine analogue mutations (21%) which arise from exposure to thymidine analogues but causing cross-resistance to TDF. Conclusion: Dual resistance to TDF + XTC occurred in more than 40% of the people with viral nonsuppression receiving tenofovir-based first-line ART, supporting WHO recommendation to optimize the nucleoside backbone in second-line treatment and cautioning against single drug substitutions in people with unsuppressed viral load.

Background: Pretreatment HIV drug resistance (PDR) has the potential to affect treatment outcome and mortality. We present here the first nationally representative PDR study conducted in Cameroon. Methods: From February to July 2015, HIV-infected ART initiators were recruited from 24 randomly selected clinics situated in both urban and rural regions. Dried blood spot specimens were collected from study participants at these clinics and centralized in a reference laboratory in Yaounde, Cameroon, for drug resistance testing. HIV drug resistance mutations were identified using the Stanford algorithm. Results: Overall, from the 379 participants recruited, 321 pol sequences were successfully interpreted. Two hundred and five sequences were from patients attending urban ART clinics and 116 from patients seen at rural facilities. Nine percent of sequences (29/321) were from participants reporting previous exposure to antiretrovirals. PDR prevalence among all initiators was 10.4% (95% CI 5.4%-19.1%), with 14.2% (95% CI 6.6%-27.9%) reported in urban areas and 4.3%(95% CI 1.2%-14.3%) in rural areas. Among participants with no prior exposure to antiretrovirals, PDR prevalence was 10.4% (95% CI 4.7%-21.5%) overall, with 13.5% (95% CI 5.1%-31.5%) and 5.3% (95% CI 1.4%-17.5%) reported in urban and rural areas, respectively. Conclusions: Our findings indicate that at least 10% of patients initiating ART in Cameroon carry viruses with PDR and may be at risk of premature ART failure. The high level of NNRTI-associated resistance is of particular concern and supports introduction of drugs with a higher genetic barrier to resistance.

Background: To investigate change in renal function in African patients initiating second-line antiretroviral therapy (ART) including ritonavir-boosted protease inhibitor (PI/r) with or without tenofovir disoproxil fumarate (TDF). Methods: HIV-1-positive adults, failing standard first-line ART were randomized to either TDF/emtricitabine (FTC)+LPV/r, abacavir + didanosine +LPV/r or TDF/FTC+darunavir (DRV)/r and followed for 18 months. Patients with an estimated glomerular filtration rate (eGFR) >= 60 ml/min/1.73 m(2) at baseline were included in this analysis. Results: Data from 438 out of 454 randomized patients were analysed. Median age was 38 years and 72% were women. Initiation of PI/r-based second-line regimen induced a marked eGFR decline of -10.5 ml/min/1.73 m2 at week 4 in all treatment groups with a greater decrease in TDF/FTC+LPV/r arm (-15.1 ml/min/1.73 m(2)). At month 18, mean eGFR in the non-TDF containing regimen recovered its baseline level and was significantly greater than eGFR 18-month levels in the TDF-containing regimens that experienced only partial recovery (difference: -10.7; CI -16.8, -4.6; P=0.001 in TDF/FTC+LPV/r and -6.4; CI -12.5, -0.3; P=0.04 in TDF/FTC+DRV/r). At 18 months, prevalence of stage 3 chronic kidney disease was low (60 ml/ml/1.73 m(2) at baseline. They also support the recommendation of reassessing renal function 1 month after initiation of treatment including ritonavir to account for the ritonavir-related artefactual decrease of eGFR and determine the new reference baseline value.

Background: Early feeding patternsmay affect the growth of HIV-exposed children and thus their subsequent health and cognition. Objective: We assessed the association of infant feeding (IF) mode with length-for-age z score (LAZ) and stunting fromage 2 d to 18 mo in HIV-exposed African childrenwithin a controlled randomized trial, which evaluated triple antiretrovirals initiated during pregnancy and continued for 6 mo postpartum to prevent HIV transmission. Methods: HIV-infected pregnant women with CD4 + counts of 200-500 cells/mm(3) from Burkina Faso, Kenya, and South Africa were advised to exclusively breastfeed for up to 6 mo or to formula-feed from birth. Factors associated with LAZ were investigated in all uninfected children by using mixed-effects linear models; those associated with stunting (LAZ < 22) at 6 or 12 mo were assessed in multiple logistic regression after exclusion of children stunted at age 2 d. Independent variables were IF mode: formula feeding (FF), exclusive breastfeeding (EBF) < 3 mo, or EBF $ 3 mo (reference); sex; trial arm; maternal characteristics; and site. Results: Among 728 children, FF was associated with a greater increase in LAZ from 2 d to 6 mo (+ 0.07 z score/mo, P < 0.001). Between 6 and 18 mo, FF and EBF < 3mowere both associated with greatermean LAZ than was EBF$ 3mo (+ 0.52z scores and + 0.43 z scores, respectively, P < 0.001). Among children not stunted at 2 d, FF was independently associatedwith a reduced risk of stunting at 6mo (OR: 0.24; 95% CI: 0.07, 0.81; P = 0.021), whereas EBF < 3 mo was not (OR: 0.49; 95% CI: 0.22, 1.10; P= 0.09). Conclusions: In this observational study of HIV-exposed uninfected infants, growth in length in the first 6mo of lifewas faster in formula-fed infants than in exclusively breastfed infants. The plausibility of

International audience; Background: UNAIDS recently defined the 90-90-90 target as a way to end the HIV epidemic. However, the proportion of virological success following antiretroviral therapy (ART) may not be as high as the anticipated 90%, and may in fact be highly heterogeneous. We aimed to describe the proportion of virological success in sub-Saharan Africa and to identify factors associated with the proportion of virological success. Methods: We performed a systematic review and meta-analysis focusing on the proportion of patients in sub-Saharan Africa who demonstrate virological success at 12 and 24 months since ART initiation, as well as at 6 and 36 months, where possible. Programme factors associated with the proportion of virological success were identified using meta-regression. Analyses were conducted using both on-treatment (OT) and intention-to-treat (ITT) approaches. Results: Eighty-five articles were included in the meta-analysis, corresponding to 125 independent study populations. Using an on-treatment approach, the proportions (95% confidence interval (CI)) of virological success at 12 (n = 64) and at 24 (n = 32) months since ART initiation were 87.7% (81.3-91.0) and 83.7% (79.8-87.6), respectively. Univariate analysis indicated that the proportion of virological success was not different by study design. Multivariate analysis at 24 months showed that the proportion of virological success was significantly larger in studies conducted in public sector sites than in other sites (p = 0.045). Using an ITT approach, the proportions (95% CI) of virological success at 12 (n = 50) and at 24 (n = 20) months were 65.4% (61.8-69.1) and 56.8% (51.3-62.4), respectively. At 12 months, multivariate analysis showed that the proportion of success was significantly lower in cohort studies than in trials (63.0% vs. 71.1%; p = 0.017). At 24 months, univariate analysis demonstrated that the proportion of success was also lower in cohorts. Discussion: Regardless of the time following ART initiation, and of the threshold, proportions of virological success were highly variable. Evidence from this review suggests that the new international target of 90% of patients controlled is not yet being achieved, and that in order to improve the virological outcome, efforts should be made to improve retention in care.

Objective: To assess the frequency of glomerular and tubular proteinuria in a cohort of HIV-infected patients, and to determine the factors associated with each type of injury. Design: Cross-sectional study of 1210 consecutive HIV-infected adults followed in HIV outpatient unit (Montpellier/France). Methods: Spot urine protein to creatinine (uPCR), albumin to creatinine (uACR) and albumin to protein (uAPR) ratios were assessed. Glomerular injury was defined as uACR at least 30 mg/g or uPCR at least 200 mg/g with uAPR at least 0.4. Tubular injury was defined as uPCR 200 mg/g or more with uAPR less than 0.4. Multivariate logistic regression identified independent factors of each type of proteinuria, in the 1158 patients with estimated glomerular filtration rate (eGFR) at least 60 ml/min per 1.73 m(2), using re-expressed modification of diet in renal disease equation. Results: Frequency of proteinuria was 18.2% among patients with eGFR at least 60 ml/min per 1.73 m(2) consisting in tubular proteinuria for 50.7% of them. Factors associated with glomerular proteinuria were age [OR 1.34/10-year increment (95% CI: 1.08-1.66)], diabetes [OR 3.37 (95% CI: 1.53-7.44)], and arterial hypertension [OR 2.52 (95% CI: 1.36-4.66)]. Factors associated with tubular proteinuria were age [OR 1.43 (95% CI: 1.14-1.79)], current tenofovir use [OR 3.52 (95% CI: 1.86-6.65)], hepatitis C co-infection [OR 1.62 (95% CI: 1.00-2.65)], AIDS stage [OR 1.83 (95% CI: 1.18-2.82)], CD4 cell count less than 200 per mu l [OR 2.48 (95% CI: 1.31-4.70)]. Conclusion: This study distinguished risk factors for tubular injury, mainly related to HIV disease and its treatment (tenofovir), and glomerular injury, linked to non HIV-related variables (age, diabetes, hypertension). Measuring uPCR, uACR and uAPR may help with the detection and specific management of early chronic kidney disease in HIV-infected patients having normal or sub-normal eGFR.

Background. Antiretroviral (ARV) prophylaxis effectively reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV). However, it is unclear whether stopping ARVs after breastfeeding cessation affects maternal HIV disease progression. We assessed 18-24-month postpartum disease progression risk among women in a randomized trial assessing efficacy and safety of prophylactic maternal ARVs. Methods. From 2005 to 2008, HIV-infected pregnant women with CD4(+) counts of 200-500/mm(3) were randomized to receive either triple ARV (zidovudine, lamivudine, and lopinavir/ritonavir during pregnancy and breastfeeding) or AZT/sdNVP (zidovudine until delivery with single-dose nevirapine without postpartum prophylaxis). Maternal disease progression was defined as the combined endpoint of death, World Health Organization clinical stage 4 disease, or CD4(+) counts of = 350/mm(3) progressed. Conclusions. Interrupting prolonged triple ARV prophylaxis had no effect on HIV progression following cessation (compared with AZT/sdNVP). However, women on triple ARV prophylaxis had lower progression risk during the time on triple ARV. Given the high rate of progression among women with CD4(+) cells of

In a WHO coordinated, mother-to-child HIV transmission (MTCT) prevention trial in Burkina Faso, HIV-1 nfected mothers were adv sed to either stop breast-feeding oy 6 mo or totally avoid it. Participants were prov ded with cereal-based, infant fortified mix (IFM) from 6 to 12 mo postpartum along with infant feeding counseling. Our objective was to describe ronbreast-fed infants food consumption and adecuacy of nutrient intake. A 1-d weighed food record and one 24 h dietary recall were performed in 68 nonbreast-fed, non-HIV infected 6- to 11-mo-old infants. Mean food enemy density and feeding frequency were satisfactory n 6-8 mo ods [0.8 +/- 0.2 kcal/g (3.3 +/- 0.9 kJ/g) and 7.2 +/- 1.6 times/c] and n 9-11 moods [0.9 +/- 0.2 kcal/lg (3.6 +/- 0.8 kJ/g) and 7.7 +/- 2 1 times/d]. Median energy intake was 523 Kcal [range 82-1053 (2187 kJ, range: 345-4401)] in 6-8- and 811 kcal [range: 34-1543 (3392 kJ, range: 144-6452)] n 9-11-mo-old infants, respectively. Approximately 75% of their energy intake was provided by subsidized foods (milk that mothers obta ned from support networks and IFM). One-has of the infants had intakes < 80 kcal/kg (

Aim. - The aim of this study was to analyze the relationship between anthropometric characteristics and cardiometabolic risk factors in urban-dwelling adults in Senegal to evaluate future threats to the public health in terms of chronic diseases. Methods. - Age- and gender-matched control subjects for a study on the prevalence of lipodystrophy in HIV+ patients were selected between June and September 2006 from the general population through systematic home visits guided by area of residence of cases. After consenting to participate, these subjects underwent anthropometric, clinical and biological examinations in their homes. Results. - The sample included 60 men and 106 women, mean age of 43.2 +/- 9.4 years. Although the prevalence of overweight and obesity was much higher in women (30.2 and 29.2%, respectively) vs. 23.3 and 3.4%, respectively, in men (P < 0.001), the women had lower waist-to-hip ratios (mean [95% CI]: 0.78 [0.77-0.80] vs. 0.86 [0.84-0.88] in men; P < 10(-4)) and better systolic blood pressure, triglyceride and high-density lipoprotein (HDL)-cholesterol levels. However, their insulin levels were significantly higher (32.1 [28.2-36.5] pmol/l vs. 25.5 [21.0-30.8] in men; P < 0.04). Principal component analysis showed that glucose and insulin correlated with subcutaneous fat, whereas blood pressure correlated with central fat distribution. Lipids were distributed between these two factors. Conclusion. - Obesity still appears to be rare in Senegalese urban-dwelling men, whereas women, despite their overweight, have no untoward cardiometabolic profiles. However, the observed correlations between cardiometabolic risk factors and the amount and/or distribution of body fat suggest that obesity prevention should not be overlooked in the public health agenda for sub-Saharan Africa.

In Burkina Faso, prolonged breastfeeding with introduction of ritual fluids from birth is a deep-seated norm. We explored HIV-infected mothers' views and experiences of the acceptability and feasibility of the World Health Organization's recommended infant-feeding options within a mother-to-child-transmission prevention trial. A qualitative study was conducted on 17 formula-feeding and 19 breastfeeding mothers, from a larger cohort of 51 eligible HIV-infected women, consenting to participate in separate focus group discussions in early post-partum. Mothers opted for breastfeeding essentially out of fear of family rejection. Most of them were afraid of denigration for disrespecting tradition if they formula-fed or being suspected of HIV infection. Achieving exclusive breastfeeding remained a difficult challenge as they engaged in a continuous struggle with close elders to avoid fluid feeding. Additional stress and fatigue were fed by their perception of a high transmission risk through breast milk. Exclusive formula-feeding seemed easier to implement, especially as formula was provided free of charge. Formula-feeding mothers more frequently had a supportive partner, a strong personality and lived in better socio-economic conditions than breastfeeding mothers (76% had education and electricity supply vs. 42%, respectively). Exclusive breastfeeding for the first 6 months remains the most appropriate option for many HIV-infected mothers in sub-Saharan Africa. Its acceptability and feasibility urgently need to be improved by promoting it as the best feeding option for all infants. Other crucial interventions are the promotion of voluntary counselling and testing for couples, and greater partner involvement in infant-feeding counselling.