Clinical outcomes with second-line dolutegravir in people with virological failure on first-line non-nucleoside reverse transcriptase inhibitor-based regimens in South Africa: a retrospective cohort study

Background Dolutegravir (DTG) is recommended for second-line antiretroviral therapy (ART) after virological failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in people living with HIV in low-income and middle-income countries. We compared the effectiveness of DTG versus the previously recommended ritonavir-boosted lopinavir (LPV/r) regimen for second-line treatment in South Africa. Methods In this retrospective observational cohort study, we used routinely collected, de-identified data from 59 primary health-care facilities in eThekwini Municipality, KwaZulu-Natal, South Africa. We included people living with HIV aged 15 years or older with virological failure (defined as two consecutive viral loads of >= 1000 copies per mL at least 56 days apart) on first-line NNRTI-based ART containing tenofovir disoproxil fumarate (TDF) and who switched to second-line ART. Our primary outcomes were retention in care and viral suppression (<50 copies per mL) at 12 months after starting second-line treatment. We used modified Poisson regression models to compare these outcomes between second-line regimens (zidovudine [AZT]/emtricitabine or lamivudine [XTC]/DTG; TDF/XTC/DTG; and AZT/XTC/LPV/r). Findings We included 1214 participants in our study, of whom 729 (60%) were female and 485 (40%) were male, and whose median age was 36 years (IQR 30-42). 689 (57%) were switched to AZT/XTC/LPV/r, 217 (18%) to AZT/XTC/DTG, and 308 (25%) to TDF/XTC/DTG. Compared with AZT/XTC/LPV/r (75%), retention in care was higher with AZT/XTC/DTG (86%, adjusted risk ratio [aRR]=114, 95% CI 103-127; adjusted risk difference [aRD]=1089%, 95% CI 201 to 1978) but similar with TDF/XTC/DTG (77%, aRR=101, 094-110; aRD=104%, -503 to 712). Observed retention in care was lower with TDF/XTC/DTG than with AZT/XTC/DTG, although in multivariable analysis evidence for a difference was weak (aRR=089, 078-101, p=0060; aRD=-985%, -2033 to 063, p=0066). Of 799 participants who were retained in care with a 12-month viral load test done, viral suppression was higher with AZT/XTC/DTG (59%; aRR=125, 106-147; aRD=1157%, 237 to 2076) and higher with TDF/XTC/DTG (61%; aRR=130, 114-148; aRD=1416%, 714 to 2118) than with AZT/XTC/LPV/r (47%). Interpretation These findings from routine care support further implementation of WHO's recommendation to use DTG instead of LPV/r in people living with HIV who experience virological failure while receiving first-line NNRTI-based ART. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.