BACKGROUNDTwo drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeiciency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF). There are limited data on their use in low-and middle-income countries. METHODSWe conducted a 96-week, phase 3, investigator-led, open-label, randomized trial in South Africa, in which we compared a triple-therapy combination of emtricitabine (FTC) and DTG plus either of two tenofovir prodrugs -TAF (TAF-based group) or tenofovir disoproxil fumarate (TDF) (TDF-based group) -against the local standard-of-care regimen of TDF-FTC-efavirenz (standard-care group). Inclusion criteria included an age of 12 years or older, no receipt of ART in the previous 6 months, a creatinine clearance of more than 60 ml per minute (>80 ml per minute in patients younger than 19 years of age), and an HIV type 1 (HIV-1) RNA level of 500 copies or more per milliliter. The primary end point was the percentage of patients with a 48week HIV-1 RNA level of less than 50 copies per milliliter (as determined with the Snapshot algorithm from the Food and Drug Administration; noninferiority margin, −10 percentage points). We report the primary (48-week) efficacy and safety data. RESULTSA total of 1053 patients underwent randomization from February 2017 through May 2018. More than 99% of the patients were black, and 59% were female. The mean age was 32 years, and the mean CD4 count was 337 cells per cubic millimeter. At week 48, the percentage of patients with an HIV-1 RNA level of less than 50 copies per milliliter was 84% in the TAF-based group, 85% in the TDF-based group, and 79% in the standard-care group, findings that indicate that the DTG-containing regimens were noninferior to the standard-care regimen. The number of patients who discontinued the trial regimen was higher in the standard-care group than in the other two groups. In the per-protocol population, the standard-care regimen had equivalent potency to the other two regimens. The TAF-based regimen had less effect on bone density and renal function than the other regimens. Weight increase (both lean and fat mass) was greatest in the TAF-based group and among female patients (mean increase, 6.4 kg in the TAF-based group, 3.2 kg in the TDF-based group, and 1.7 kg in the standard-care group). No resistance to integrase inhibitors was identified in patients receiving the DTG-containing regimens. CONCLUSIONSTreatment with DTG combined with either of two tenofovir prodrugs (TAF and TDF) showed noninferior efficacy to treatment with the standard-care regimen. There was significantly more weight gain with the DTG-containing regimens, especially in combination with TAF, than with the standard-care regimen. (ADVANCE ClinicalTrials.gov number, NCT03122262.

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Obesity develops in a substantial number of people initiating and maintaining modern antiretroviral therapy. The comorbidities associated with obesity make significant weight gain and metabolic changes a major consideration in clinical trials studying different regimens’ potency and safety. It is as yet unclear what role individual antiretrovirals or classes play in weight gain but the issue is a complex one for clinical trial design, especially when deciding when “too much” weight has been gained, in a context where we do not yet know if switching to alternative regimens will slow, halt or reverse weight gain or metabolic changes. In addition, clinician and trial participant opinion on acceptable weight gain may differ. We offer preliminary guidance for discussion for future antiretroviral clinical trial design.

Background: HIV programmes world-wide currently make decisions regarding new antiretroviral therapy (ART) regimens with less side-effects and higher resistance barriers, which may improve adherence and viral suppression. Economic evaluation helps inform these decisions. Methods:We conducted an economic evaluation of three ART regimens included in the ADVANCE trial from the provider's perspective: tenofovir alafenamide (TAF)/ emtricitabine (FTC)þdolutegravir (DTG) and tenofovir disoproxil fumarate (TDF)/ FTCþDTG, compared with TDF/FTC/efavirenz (EFV). We used top-down and bottom-up cost analysis with resource utilization based on trial data and adjusted to emulate routine care. We estimated the cost-effectiveness of each regimen as cost per person virally suppressed or retained and per life-year saved, at 48 and 96 weeks.Results: Though the DTG-based trial arms were 2% more costly than TDF/FTC/EFV, both had slightly lower cost-per-outcome

Background South Africa has the largest HIV treatment program worldwide. Retention in care and medication adherence remain problematic necessitating innovative solutions for improving HIV care. The increasing availability and use of mobile technology can support positive clinical outcomes for persons living with HIV. iThemba Life is a mobile health app designed with input from South African health professionals and patients, promoting engagement with HIV care through access to medical results. Objective This study aimed to test the feasibility and acceptability of receiving HIV viral load (VL) results through the app and compare the time to HIV VL result return for study participants before and after app use. Methods Using convenience sampling, adults having routine VL phlebotomy were recruited from 2 Johannesburg health facilities. After signed consent, the app was downloaded on their Android smartphones, phlebotomy was performed, and the sample barcode was scanned through their phone to link the sample and app. Participants received a notification of the result availability and logged into the app to view results, their explanation and recommended action. Results Overall, 750 people were screened to enroll 500 participants. Of 750, 113 (15.1%) failed eligibility screening. 21.5% (137/637) had smartphone technical limitations preventing enrollment. Results were released to 92.2% (461/500) of participants’ phones. App technical issues and laboratory operational issues limited the number of released results. Approximately 78.1% (360/461) results were viewed in the app. Median time from notification of availability to result viewed being 15.5 hours (0.6; range 0-150 days). Turnaround time from phlebotomy to the result being received was 6 (range 1-167) days for users versus 56 days (range 10-430 days; P<.001) before app use. Overall, 4% (20/500) of participants received unsuppressed results (VL>1000 copies/mL). Turnaround time for unsuppressed results was 7 days for participants versus 37.5 days before app use (P<.001). The difference before and after app use in the suppressed and unsuppressed users for time from sample collection to result delivery was statistically significant. Of 20 participants, 12 (60%) returned for a confirmatory VL during the study period. The time from an unsuppressed VL to a confirmatory VL was 106 days for app users versus 203 days before app use (P<.001). Overall, 52.4% (262/500) of participants completed an exit survey; 23.2% (58/250) reported challenges in viewing their VL results. Moreover, 58% (35/60) reported that they overcame challenges with technical assistance from others, and 97.3% (255/262) wanted to continue using the app for VL results. Conclusions Using iThemba Life for VL results was well-received despite limited smartphone access for some participants. App users received results 10 times sooner than before the app and 5 times sooner if their VL >1000 copies/mL. This increased notification speed led to participants wanting to continue using iThemba Life.