Uptake and 24-month outcomes of dolutegravir- versus lopinavir-based second-line antiretroviral therapy for people with HIV in South Africa: a retrospective cohort study and emulated target trial

Background Aligning with the WHO, South Africa has replaced LPV/r with DTG in second-line ART after treatment failure with TDF/XTC/EFV. Initial guidance included special considerations for DTG use among women. Methods We analysed routine de-identified data of adults switched from TDF/XTC/EFV to second-line AZT/XTC/LPV/r, AZT/XTC/DTG, or TDF/XTC/DTG between December 2019 and December 2023 at 108 healthcare facilities in KwaZulu-Natal, South Africa. Among people switched before July 2021, we emulated a target trial comparing 24-month death or loss to follow-up (LTFU), and viraemia (>50 copies/mL). We conducted intention-to-treat and per-protocol analyses using weighted logistic regression with bootstrapped CIs. Results Overall, women were less likely than men to switch to DTG (RR: 0.92 [95% CI: 0.88, 0.96]; N=3649). Of 2321 people switched before July 2021, 915 (39%) switched to AZT/XTC/LPV/r, 415 (18%) to AZT/XTC/DTG, and 991 (43%) to TDF/XTC/DTG. Median age was 36 years (IQR: 30, 43) and 1364 (59%) were women. In intention-to-treat analyses, the standardised 24-month risk of death or LTFU was similar with AZT/XTC/LPV/r (31%), AZT/XTC/DTG (30%), and TDF/XTC/DTG (34%). The standardised risk of 24-month viraemia among those retained in care with a viral load result (N=1270) was higher with AZT/XTC/LPV/r (50%) than with AZT/XTC/DTG (40%; aRD: -10% [95% CI -19%, -2%]) or TDF/XTC/DTG (39%; aRD: -11% [95% CI -18%, -5%]). Per-protocol analyses gave similar results. Conclusions While retention was similar across regimens, viraemia was less common on DTG-based ART, supporting current guidelines.