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HIV-1 reservoir size and dynamics are promising parameters to ensure the safe prescription of simplified maintenance antiretroviral therapy in chronically HIV-1 infected patients. In the SIMPL’HIV trial, HIV-1 DNA was quantified in peripheral blood mononuclear cells obtained at baseline and week 48 to investigate changes over time and evidence of a predictive relationship to maintain HIV-1 RNA

Background Dolutegravir (DTG)–based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL’HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricitabine (FTC). We present the 48-week efficacy and safety data on DTG + FTC versus cART. Methods and findings SIMPL’HIV was a multicenter, open-label, non-inferiority randomized trial with a factorial design among treatment-experienced people with HIV in Switzerland. Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART, and 1:1 to simplified patient-centered monitoring versus standard monitoring. The primary endpoint was the proportion of patients virologically suppressed with, Delphine Sculier and co-workers study switching to dual antiretroviral therapy including dolutegravir in virologically-suppressed patients with HIV infection., Author summary Why was the study done? Treatment simplification among people with HIV has been tested worldwide and includes reducing the number and/or dosage of antiretroviral drugs, and simplifying monitoring, but without compromising adherence and quality of life. We evaluated the combination of dolutegravir (DTG) + emtricitabine (FTC) as an alternative to standard therapy combinations in an HIV population highly representative of routine clinical conditions. Simplified patient-centered monitoring was also evaluated, to allow patients to receive care outside the hospital as is usual in Switzerland. What did the researchers do and find? We conducted the SIMPL’HIV study, a randomized trial with a factorial design, to permit patients with a suppressed viral load to receive a simplified treatment of DTG + FTC and/or simplified patient-centered monitoring. Efficacy of the DTG + FTC regimen was defined as keeping the patient’s HIV viral load below 100 copies/ml through 48 weeks of study duration. The combination of DTG with FTC had a similar efficacy in maintaining viral suppression through 48 weeks of treatment as standard combined antiretroviral therapy, without jeopardizing safety, and it improved patient quality of life. What do these findings mean? These results provide further evidence on the efficacy of 2-drug DTG-based regimens as a simplified switch option for patients whose viral load is well controlled on standard treatment, including those with a low CD4 nadir, and expands the currently existing options for dual maintenance therapy. Our efficacy definition allowed us to observe the occurrence of HIV viral load blips, irrespective of the treatment arm, without any consequences for HIV management. The quality of life of the participants was already very satisfactory at the start of the study and further increased over time with the simplified DTG + FTC treatment.

Background: Dolutegravir-containing maintenance therapy is a promising simplification strategy for virologically suppressed HIV-infected individuals. However, most of the available data to inform this strategy come from small, uncontrolled studies. We estimated the proportion of HIV-infected patients experiencing virological failure (VF) and developing drug resistance on dolutegravir (DTG)-based maintenance therapy. Methods: We searched Medline, Embase, Cochrane Central, Web of Science, and conference abstracts for studies assessing VF on DTG-based maintenance therapy. Studies including ≥5 adults with an undetectable viral load on antiretroviral therapy (ART) who switched to a DTG-based mono- or dual therapy were included. Pooled proportions of VF were estimated using random-intercept logistic meta-regression and acquired drug resistance mutations described for each strategy. Results: Of 1719 studies considered, 21 met our selection criteria, including seven interventional and 14 observational studies. Eight studies including 251 patients assessed VF on DTG monotherapy and fourteen studies including 1670 participants VF on dual therapy. The participant’s median age ranged from 43 to 63 years, their median nadir CD4 count from 90 to 399 cells/µl, and 27.6% were female. The proportion of participants experiencing VF on DTG-monotherapy was 3.6% (95% confidence interval [CI] 1.9-6.7) at 24 weeks and 8.9% (95% CI 4.7-16.2) at 48 weeks. Resistance mutations developed in seven (3.6%) participants on DTG-monotherapy. Among patients on dual therapy, ten (0.7%, 95% CI 0.4-1.3) experienced VF by 48 weeks and none developed resistance to DTG. In adjusted analyses, VF at 24 weeks was less likely on dual therapy than on monotherapy (adjusted odds ratio: 0.10, 95% CI 0.03-0.30). Conclusions: Whereas VF is relatively common on DTG maintenance monotherapy, DTG-based dual therapy appears to be a promising simplification strategy for individuals with a suppressed HIV viral load on triple-ART.

Background Rilpivirine is safe and effective in HIV-naïve patients with low baseline HIV-RNA or in switch strategy. It offers the advantages of few drug-drug interactions and a favourable toxicity profile. We aimed to determine the reasons for prescribing the rilpivirine (RPV)/tenofovir disoproxil (TDF)/emtricitabine (FTC) co-formulation within the Swiss HIV Cohort Study and to assess its effectiveness and safety over a 24 months period. Methods All individuals enrolled in the Swiss HIV Cohort Study who initiated a RPV/TDF/FTC co-formulation between April 2013 and March 2014 were included. Primary outcomes were the HIV-RNA viral load (copies/mL) and CD4 cell count (cells/mm3) at 6, 12 and 24 months. Reasons for a switch to RPV/TDF/FTC were evaluated through a standardized questionnaire. We also assessed discontinuation and reasons for discontinuation of RPV/TDF/FTC until October 30, 2015. Results Of 644 individuals who started the RPV/TDF/FTC co-formulation, only 7.5% were treatment-naïve. At 24 months, viral suppression (HIV-RNA