Initiating cART during PHI represents a major opportunity to reduce HIV reservoirs and achieve optimal immune reconstitution.

Background We investigated whether dolutegravir (DTG) monotherapy could be used to maintain virological suppression in people living with human immunodeficiency virus (HIV) on a successful dolutegravir-based triple therapy. Methods MONCAY (MONotherapy of TiviCAY) was a 48-week, multicentric, randomized, open-label, 12% noninferiority margin trial. Patients with CD4 nadir >100/μL, plasma HIV-1 RNA <50 copies/mL for ≥12 months, and stable regimen with DTG/abacavir (ABC)/lamivudine (3TC) were 1:1 randomized to continue their regimen or to DTG monotherapy. The primary endpoint was the proportion of patients with HIV RNA <50 copies/mL at week 24 in intention-to-treat snapshot analysis. Virologic failure (VF) was defined as 2 consecutive HIV RNA >50 copies/mL within 2 weeks apart. Results Seventy-eight patients were assigned to DTG monotherapy and 80 to continue DTG/ABC/3TC. By week 24, 2 patients in the DTG group experienced VF without resistance to the integrase strand transfer inhibitor (INSTI) class; 1 patient discontinued DTG/ABC/3TC due to an adverse event. The success rate at week 24 was 73/78 (93.6%) in the DTG arm and 77/80 (96.3%) in the DTG/ABC/3TC arm (difference, 2.7%; 95% confidence interval [CI], –5.0 to 10.8). During subsequent follow-up, 5 additional VFs occurred in the DTG arm (2 of which harbored emerging resistance mutation to INSTI). The cumulative incidence of VF at week 48 was 9.7% (95% CI, 2.8 to 16.6) in the DTG arm compared with 0% in the DTG/ABC/3TC arm (P = .005 by the log-rank test). The Data Safety Monitoring Board recommended to reintensify the DTG arm with standardized triple therapy. Conclusions Because the risk of VF with resistance increases over time, we recommend avoiding DTG monotherapy as a maintenance strategy among people living with chronic HIV infection. Clinical Trials Registration NCT02596334 and EudraCT 2015-002853-36.

BackgroundDolutegravir is a powerful, well-tolerated integrase inhibitor with a high genetic barrier to resistance and may thus constitute the backbone of lightened regimens.MethodsThis was a monocentric, retrospective study. HIV-1-infected patients receiving dolutegravir as monotherapy (mDGV) or dual therapy (dDGV) were systematically identified. The primary outcome was the proportion of patients who maintained undetectable (<50 copies/mL) plasma HIV RNA [plasma viral load (PVL)].ResultsWe identified 21 patients on mDGV (50 mg/day) and 31 on dDGV (50 or 100 mg/day, with atazanavir ± ritonavir, n = 12; rilpivirine, n = 11; maraviroc, n = 3; lamivudine, n = 3; darunavir/ritonavir, n = 1; or abacavir, n = 1). All of the patients were treatment experienced and 48% had experienced at least one virological failure. The baseline characteristics were as follows (for the mDGV/dDGV patients, respectively): 5%/29% had a history of AIDS; the median (IQR) highest PVL was 4.5 (4.3–5.5)/5.3 (4.7–5.6) log copies/mL; the median (IQR) nadir CD4+ count was 310 (280–468)/199 (134–281) cells/mm3; 100% had undetectable PVL before the mDGV for a median (IQR) duration of 5.9 (3.5–9.9) years/81% had undetectable PVL before the dDGV for a median (IQR) duration of 3.7 (1.4–8.3) years; and the median (IQR) HIV DNA level was 2.7 (2.1–3.1)/2.9 (2.7–3) log copies/106 PBMCs. At the last follow-up visit, 100% and 97% of patients showed undetectable PVL following mDGV and dDGV, respectively [median (IQR) follow-up of 32 (29–45) and 50 (30–74) weeks, respectively].ConclusionsIn our experience, dolutegravir-based lightened regimens provided a high proportion of viral suppression, even in highly treatment-experienced patients.

We conducted a randomized, double-blind, placebo-controlled trial to compare a 3-day quinine-clindamycin regimen (group QC) with a 7-day quinine regimen (group Q) for the treatment of uncomplicated Plasmodium falciparum malaria in travelers returning from the tropics. A total of 55 and 53 patients in groups Q and QC were analyzed, respectively. Adverse effects were similar in both groups, although two patients in group Q had severe adverse reactions, leading to the cessation of treatment. The 28-day cure rate for the evaluated patients (per-protocol analysis) was 100% for group QC, whereas it was 96.3% for group Q (P ‫؍‬ 0.5). The 28-day cure rate in the intention-to-treat analysis was 96.2% for group QC, whereas it was 94.6% for group Q (P ‫؍‬ 1). There were no significant differences between the two regimens with regard to parasite and fever clearance times. Our study shows that the 3-day quinine-clindamycin regimen is well tolerated and compares favorably with a 7-day quinine treatment. This short-term regimen had previously been evaluated only in areas of endemicity. According to our results, the 3-day quinine-clindamycin regimen may be an alternative for the treatment of imported uncomplicated P. falciparum malaria in travelers returning from the tropics.

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ObjectivesTo assess the impact of long-term combined antiretroviral therapy (cART) on HIV-RNA and HIV-DNA levels in cervicovaginal secretions of HIV-1-infected women with sustained undetectable plasma RNA viral load (PVL); to explore factors predictive of residual viral shedding; and to evaluate the risk of heterosexual transmission.MethodsWomen with undetectable PVL (<50 copies/mL) for >6 months were included in this cross-sectional study. HIV-RNA and HIV-DNA were measured in blood and cervicovaginal lavage fluid (CVL). Women were systematically tested for genital infections. The risk of transmission to male partners during unprotected intercourse was estimated.ResultsEighty-one women composed the study population: all had HIV-RNA <40 copies/mL in CVL. HIV-DNA was detectable in CVL of 29/78 patients (37%). There was a weak positive correlation between HIV-DNA levels in PBMCs and CVL (r = 0.20; p = 0.08). In multivariate analysis, two factors were associated with HIV-DNA detection in CVL: previous AIDS-defining illnesses (OR = 11; 95%CI = 2–61) and current residual viremia (20

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