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
Brown JA., Lewis L., Sookrajh Y., Hobe L., Ngwenya T., van der Molen J., Asare K., Tlhaku K., Khanyile M., Khubone T., Bottomley C., Garrett N., Dorward J.
Abstract 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.