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

Journal article

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]=1·14, 95% CI 1·03–1·27; adjusted risk difference [aRD]=10·89%, 95% CI 2·01 to 19·78) but similar with TDF/XTC/DTG (77%, aRR=1·01, 0·94–1·10; aRD=1·04%, –5·03 to 7·12). 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=0·89, 0·78–1·01, p=0·060; aRD=–9·85%, –20·33 to 0·63, p=0·066). 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=1·25, 1·06–1·47; aRD=11·57%, 2·37 to 20·76) and higher with TDF/XTC/DTG (61%; aRR=1·30, 1·14–1·48; aRD=14·16%, 7·14 to 21·18) 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.

Funding Bill & Melinda Gates Foundation.

Translation For the isiZulu translation of the abstract see Supplementary Materials section.

Authors: Asare, K; Sookrajh, Y; van der Molen, J; Khubone, T; Lewis, L

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Lancet Global Health
• Volume: 12
• Issue: 2
• Pages: e282-e291
• Publication date: 2023-12-21
• Acceptance date: 2023-10-30
• DOI: 10.1016/S2214-109X(23)00516-8
• EISSN: 2214-109X
• Language: English