Results
350–700, bowel obstruction, rash, virological suppression, insomnia, treatment-resistant oesophageal candidiasis, deaths, acute renal impairment, community-acquired pneumonia
ADVERSE EVENTS, EVENT, BOWEL OBSTRUCTION, CARDIAC ARREST, NOSOCOMIAL PNEUMONIA, SECONDARY, EVENTS, COMMUNITY-ACQUIRED PNEUMONIA, ATROPHIC GASTRITIS
Between Nov 28, 2019, and July 23, 2021, we screened 140 patients for the study (Trial profileTLD=tenofovir disoproxil fumarate, lamivudine, and dolutegravir. mITT=modified intention to treat. *As per the US Food and Drug Administration snapshot approach, patients lost to follow-up were included in the mITT analysis and were considered to have virological failure.Baseline characteristics were similarly distributed between arms (Baseline characteristics of participants by study armData are median (IQR) or n (%). Baseline was date of screening. ART=antiretroviral therapy.The primary outcome, virological suppression at week 24 by modified intention to treat, was acceptable, with the lower bound of the 95% CI equal to our predefined margin of 70% in both arms (Proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL)Data are n/N (%, 95% CI).Primary endpoint.Secondary endpoint.Virological suppression (HIV-1 RNA <50 copies per mL) over timeModified intention-to-treat (A) and per-protocol (B) analysis. The points and error bars show the proportion (95% CI). TLD=tenofovir disoproxil fumarate, lamivudine, and dolutegravir.The proportion of participants with virological suppression at week 48 decreased in both arms from week 24 (Participants with study-defined virological failure were similarly distributed between groups (Adherence as assessed by tenofovir diphosphate concentrations in dried blood spots was similar between the study arms at weeks 12, 24, and 48, but decreased from week 24 to week 48 (Participant adherence at weeks 12, 24, and 48Data are median (IQR). Adherence measured as tenofovir diphosphate concentrations in dried blood spots and presented as categories of presumed doses of medication taken per week. Adherence categories, <350 fmol/punch (equivalent in men: <1·2 doses per week and women: <0·6 doses per week), 350–700 fmol/punch (men: 1·2–3·2 doses per week and women: 0·6–2·0 doses per week), 701–1250 fmol/punch (men: 3·2–6·0 doses per week and women: 2·0–5·3 doses per week), and >1250 fmol/punch (men: >6·0 doses per week and women: >5·3 doses per week).18 participants still on antituberculosis therapy (12 in the supplemental dolutegravir arm and six in the placebo arm) at week 24 were excluded from analysis of dolutegravir trough concentrations at weeks 4, 24, and 48 (Median CD4 count increase from baseline was 111 cells per μL in the supplemental dolutegravir arm and 101 cells per μL in the placebo arm at week 24, and 149 cells per μL in the supplemental dolutegravir arm and 163 cells per μL in the placebo arm at week 48.Self-reported grade 3 or 4 insomnia events occurred more frequently in the supplemental dolutegravir arm than in the placebo arm (three [6%] of 53 patients Clinical and laboratory grade 3 or 4 adverse events, serious adverse events, and deaths that occurred until week 48Data are n (%) or n. Data capture adverse events that took place at any point from the first dose of study drug until the end of week 48.Total number of adverse events.Drug-related clinical adverse events defined as at least possibly related to treatment.One participant was admitted to hospital with treatment-resistant oesophageal candidiasis, atrophic gastritis, and acute renal impairment and died secondary to presumed cardiac arrest; one participant died secondary to a trauma-related event; one participant was admitted to hospital with severe community-acquired pneumonia and had a subsequent readmission for nosocomial pneumonia, one participant was admitted to hospital with a lichenoid rash possibly related to antituberculosis therapy, and one participant was admitted to hospital with bowel obstruction and died shortly after corrective surgery.