Striking differences in weight gain after cART initiation depending on early or advanced presentation: results from the ANRS CO4 FHDH cohort.

BACKGROUND: Many studies have reported weight gain in ART-naive people living with HIV (PWH) initiating an integrase strand-transfer inhibitor-based regimen. We studied the impact of early or advanced presentation and that of individual drugs in PWH initiating combined ART (cART) between 2012 and 2018. METHODS: From the French Hospital Database HIV cohort, we assessed factors associated with a weight gain  ≥10%, weight change after cART initiation or BMI increase  ≥5 kg/m2 up to 30 months. The analyses were conducted overall, and among PWH with early (primary infection or CD4 >350/mm3 and viral load  <100 000 copies/mL, without AIDS) and advanced presentation (AIDS or CD4 <200/mm3, not during primary infection). RESULTS: At 30 months, 34.5% (95% CI: 33.5-35.6) of the 12 773 PWH had a weight gain ≥10%, with 20.9% (95% CI: 19.6-22.2) among the 5794 with early presentation and 63.1% (95% CI: 60.9-65.3) among the 3106 with advanced presentation. Weight gain was 2.8 kg (95% CI: 2.0-3.7) for those with early presentation and 9.7 kg (95% CI: 8.4-11.1) for those with advanced presentation. Most weight gain occurred in the first 12 months. Underweight and obese PWH were at significantly higher risk of a BMI increase  ≥5 kg/m2 than normal-weight PWH. Results differed within classes and by outcome. Raltegravir and dolutegravir were consistently associated with greater weight gain than the other third agents. Tenofovir alafenamide was also associated with higher weight gain than tenofovir disoproxil or abacavir. CONCLUSIONS: After initiating cART, PWH with early presentation exhibited a small weight gain, whereas it was large among those with advanced presentation. The choice of ART should account for the risk of weight gain, especially for PWH who present with advanced disease and/or are obese.

Minority resistant variants are also present in HIV-2-infected antiretroviral-naive patients.

Objectives: To assess the prevalence of minority resistant variants (MRV) and X4-tropic minority variants in ART-naive HIV-2-infected patients. Patients and methods: ART-naive HIV-2-infected patients with detectable plasma viral load (>100 copies/mL) included in the ANRS HIV-2 CO5 Cohort were assessed. We performed ultra-deep sequencing (UDS) of protease, RT, integrase and gp105 regions. Only mutations in the HIV-2 ANRS list >1% were considered. HIV-2 tropism was assessed by V3 loop region UDS, and each read was interpreted with determinants of CXCR4-coreceptor use. Results: Among the 47 patients assessed, three displayed plasma viruses with a resistance-associated mutation (RAM) above the 20% detection threshold, all in RT, resulting in a prevalence of transmitted drug resistance for NRTI of 7.9% (95% CI 0.0%-16.5%). No RAM above the 20% detection threshold was found in protease or integrase. At the 1% detection threshold the transmitted drug resistance prevalence was 9.8% (95% CI 0.6%-19.0%), 13.2% (95% CI 3.5%-22.9%) and 4.5% (95% CI 0%-17.5%) for PI, NRTI and integrase inhibitors. The most prevalent MRV was the PI RAM I50V detected in three samples. Tropism analysis showed that 21% of patients (4 of 19) exhibited X4-tropic viruses: two in majority proportion and two in minority proportions (1.5% and 1.9%). Conclusions: In this first study assessing the prevalence of MRV in HIV-2 infection among ART-naive patients, we observed a 2-3-fold higher prevalence of RAM when a 1% detection threshold of mutations was used compared with a 20% threshold. Similarly, the proportion of patients with X4-tropic viruses was twice as high when UDS was used.

No perinatal HIV-1 transmission from women with effective antiretroviral therapy starting before conception.

BACKGROUND: The efficacy of preventing perinatal transmission (PT) of human immunodeficiency virus type 1 (HIV-1) depends on both viral load (VL) and treatment duration. The objective of this study was to determine whether initiating highly active antiretroviral therapy (ART) before conception has the potential to eliminate PT. METHODS: A total of 8075 HIV-infected mother/infant pairs included from 2000 to 2011 in the national prospective multicenter French Perinatal Cohort (ANRS-EPF) received ART, delivered live-born children with determined HIV infection status, and did not breastfeed. PT was analyzed according to maternal VL at delivery and timing of ART initiation. RESULTS: The overall rate of PT was 0.7% (56 of 8075). No transmission occurred among 2651 infants born to women who were receiving ART before conception, continued ART throughout the pregnancy, and delivered with a plasma VL <50 copies/mL (upper 95% confidence interval [CI], 0.1%). VL and timing of ART initiation were independently associated with PT in logistic regression. Regardless of VL, the PT rate increased from 0.2% (6 of 3505) for women starting ART before conception to 0.4% (3 of 709), 0.9% (24 of 2810), and 2.2% (23 of 1051) for those starting during the first, second, or third trimester (P < .001). Regardless of when ART was initiated, the PT rate was higher for women with VLs of 50-400 copies/mL near delivery than for those with <50 copies/mL (adjusted odds ratio, 4.0; 95% CI, 1.9-8.2). CONCLUSIONS: Perinatal HIV-1 transmission is virtually zero in mothers who start ART before conception and maintain suppression of plasma VL.

"Real life" use of raltegravir during pregnancy in France: The Coferal-IMEA048 cohort study.

INTRODUCTION: Limited "real life" data on raltegravir (RAL) use during pregnancy are available. Thus, we aimed at describing effectiveness and safety of RAL-based combined antiretroviral therapy (cART) in this setting. METHODS: HIV-1-infected women receiving RAL during pregnancy between 2008 and 2014 in ten French centers were retrospectively analysed for: (1) proportion of women receiving RAL anytime during pregnancy who achieved a plasma HIV-RNA (pVL) < 50 copies/mL at delivery, and (2) description of demographics, immuno-virological parameters and safety in women and new-borns. RESULTS: We included 94 women (median age, 33 years) of which 85% originated from Sub-Saharan Africa and 16% did not have regular health insurance coverage. Sixteen women were cART-naïve (median HIV diagnosis at 30 weeks of gestation), whereas 78 were already on cART before pregnancy (40% with pVL < 50 copies/mL). RAL was initiated before pregnancy (n = 33), during the second trimester (n = 11) and the third trimester of pregnancy (n = 50). No RAL discontinuations due to adverse events were observed. Overall, at the time of delivery, pVL was < 50 copies/mL in 70% and < 400 copies/mL in 84% of women. Specifically, pVL at delivery was < 50 copies/mL in 82%, 55% and 56% of cases when RAL was started before pregnancy, during the second or third trimester of pregnancy, respectively. Median term was 38 weeks of gestation, no defect was reported and all new-borns were HIV non-infected at Month 6. CONCLUSIONS: RAL appears safe and effective in this "real-life" study. No defect and no HIV transmission was reported in new-borns.

Sleeve gastrectomy is a safe and efficient procedure in HIV patients with morbid obesity: a case series with results in weight loss, comorbidity evolution, CD4 count, and viral load.

BACKGROUND: The efficacy and safety of bariatric surgery have been poorly studied in patients affected with HIV. Although sleeve gastrectomy (SG) is the most widely used procedure in many countries, most of the published literature reported results with the gastric bypass (GBP) procedure on morbidly obese HIV patients. METHODS: We have evaluated retrospectively, in eight consecutive patients who underwent a SG, its effect in weight loss and its impact on the treatment and on the markers of HIV infection. RESULTS: Seven out of eight patients were females. The mean age was 46 years, with a median preoperative BMI of 42 kg/m(2). The mean duration of HIV infection and CD4 cell count were 13.4 years and 457 cells/mm(3), respectively. The mean weight loss was 37 kg in 20 months, the excess BMI loss was 80.8 ± 30.9 %, and the excess weight loss is 81.5 ± 28.9 % with one minor complication. CD4 counts were unchanged. Three patients had therapy modifications that were unrelated to bariatric surgery. Two patients had a therapeutic drug monitoring before and after the intervention. Plasma concentrations remained in therapeutic levels after the SG. Most comorbidities disappeared postoperatively, decreasing the cardiovascular risk. CONCLUSIONS: The sleeve gastrectomy was safe and effective with no consequences on CD4 counts and viral load in HIV-affected obese patients. It should be considered as a part of the treatment in morbidly obese HIV patients.

Visiting one's native country: the risks of nonadherence in HIV-infected sub-Saharan migrants--ANRS VIHVO study.

The aim of this study was to evaluate to what extent travel-related factors may cause adherence failure to antiretroviral therapy (ART) in otherwise adherent migrants when traveling back to Africa. HIV-infected sub-Saharian migrants living in France with a plasma HIV viral load < 200 copies/mL, with no change in ART for ≥3 months and who were about to visit their native country for between 2 weeks and 6 months were enrolled for the study. Patients completed a self-administered adherence questionnaire both at enrollment and during the week following their return to France. Adherence failure occurred in 23 (11.5%) of 200 patients. Negative perception about ART effectiveness (adjusted odds ratio = 4.3; 95% confidence interval = 1.3-13.7), unexpected traumatic events during their stay in their native country (7.8; 2.3-26.1), and a prolongation of their stay (5.2; 1.4-20.4) were independently associated with a higher likelihood of adherence failure. Owning/renting one's house in France (0.30; 0.10-0.96), singlehood (0.23; 0.05-1.00), and HIV status disclosure (0.19; 0.05-0.76) were correlates of sustained adherence during traveling.