Implementation and outcomes of dolutegravir-based first-line antiretroviral therapy for people with HIV in South Africa: a retrospective cohort study

Background There are few data assessing the uptake of first-line dolutegravir among men and women living with HIV in low-income and middle-income countries, and subsequent clinical outcomes in non-trial settings. We aimed to determine dolutegravir uptake in women, and the effect of dolutegravir on clinical outcomes in routine care in South Africa. Methods In this cohort study, we analysed deidentified data from adults receiving first-line antiretroviral therapy (ART) at 59 South African clinics from Dec 1, 2019, to Feb 28, 2022, using two distinct cohorts. In the initiator cohort, we used Poisson regression models to assess the outcome of initiation with dolutegravir-based ART by gender, and associations between dolutegravir use and the outcomes of 12-month retention in care and viral suppression at less than 50 copies per mL. In the transition cohort, comprising adults who received non-dolutegravir-based first-line ART in December, 2019, we used Cox proportional hazards models to assess the outcome of transition to first-line dolutegravir by gender. We then used time-dependent propensity score matching to compare the outcomes of subsequent 12-month retention in care and viral suppression between people who transitioned to dolutegravir and those who had not yet transitioned at the same timepoint. In both the initiation and transition cohort, the primary viral load analysis was an intention-to-treat analysis, with a secondary as-treated analysis that excluded people who changed their ART regimen after baseline. Findings In the initiator cohort, between Dec 1, 2019, and Feb 28, 2022, 45 392 people were initiated on ART. 23 945 (52 center dot 8%) of 45 392 were non-pregnant women, 4780 (10 center dot 5%) were pregnant women, and 16 667 (36 center dot 7%) were men. The median participant age was 31 center dot 0 years (IQR 26 center dot 0-38 center dot 0) and 2401 (5 center dot 3%) were receiving tuberculosis treatment at time of ART initiation. 31 264 (68 center dot 9%) of 45 392 people were initiated on dolutegravir, 14 102 (31 center dot 1%) on efavirenz, and 26 (0 center dot 1%) on nevirapine. In a univariable Poisson regression model, pregnant women (risk ratio [RR] 0 center dot 57, 95% CI 0 center dot 49 to 0 center dot 66; risk difference -35 center dot 4%, 95% CI -42 center dot 3 to -28 center dot 5) and non-pregnant women (RR 0 center dot 78, 0 center dot 74 to 0 center dot 82; risk difference -18 center dot 4%, -21 center dot 6 to -15 center dot 2) were less likely to be initiated on dolutegravir than were men. In Poisson models adjusted for age, gender (including pregnancy), time, tuberculosis status, and initiation CD4 count, people initiated on dolutegravir were more likely to be retained in care at 12 months (adjusted RR 1 center dot 09, 95% CI 1 center dot 04 to 1 center dot 14; adjusted risk difference 5 center dot 2%, 2 center dot 2 to 8 center dot 4) and virally suppressed (adjusted RR 1 center dot 04, 95% CI 1 center dot 01 to 1 center dot 06; adjusted risk difference 3 center dot 1%, 1 center dot 2 to 5 center dot 1) compared with those initiated on non-dolutegravir-based regimens. For the transition cohort, on Dec 1, 2019, 180 956 people were receiving non-dolutegravir-based first-line ART at the study clinics, of whom 124 168 (68 center dot 6%) were women. The median age was 38 years (IQR 32-45), and the median time on ART was 3 center dot 9 years (2 center dot 0-6 center dot 4) years, with most people receiving efavirenz (178 624 [98 center dot 7%] people) and tenofovir (178 148 [98 center dot 4%]). By Feb 28, 2022, 121 174 (67 center dot 0%) of 180 956 people had transitioned to first-line dolutegravir at a median of 283 days (IQR 203-526). In a univariable Cox regression model the hazard of being transitioned to dolutegravir was lower in women than in men (hazard ratio 0 center dot 56, 95% CI 0 center dot 56 to 0 center dot 57). Among 92 318 propensity score matched people, the likelihood of retention in care was higher among the dolutegravir group compared with matched controls ( adjusted RR 1 center dot 03, 95% CI 1 center dot 02 to 1 center dot 03; risk difference 2 center dot 5%, 95% CI 2 center dot 1 to 2 center dot 9). In the dolutegravir group, 33 423 (90 center dot 5%) of 36 920 people were suppressed at less than 50 copies per mL compared with 31 648 (89 center dot 7%) of 35 299 matched controls (adjusted RR 1 center dot 01, 95% CI 1 center dot 00 to 1 center dot 02; risk difference 0 center dot 8%, 95% CI 0 center dot 3 to 1 center dot 4). Interpretation Women were less likely to receive dolutegravir than men. As dolutegravir was associated with improved outcomes, roll-out should continue, with a particular emphasis on inclusion of women.