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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.
Asare, Kwabena; Sookrajh, Yukteshwar; van der Molen, Johan; Khubone, Thokozani; Lewis, Lara; Lessells, Richard J; Naidoo, Kogieleum; Sosibo, Phelelani; van Heerden, Rosemary; Garrett, Nigel; Dorward, Jienchi.
Afiliación
  • Asare K; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; Discipline of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa. Electronic address: kwabena.asare@caprisa.org.
  • Sookrajh Y; eThekwini Municipality Health Unit, eThekwini Municipality, Durban, South Africa.
  • van der Molen J; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
  • Khubone T; eThekwini Municipality Health Unit, eThekwini Municipality, Durban, South Africa.
  • Lewis L; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
  • Lessells RJ; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; KwaZulu-Natal Research and Innovation Sequencing Platform (KRISP), University of KwaZulu-Natal, Durban, South Africa.
  • Naidoo K; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; South African Medical Research Council (SAMRC)-CAPRISA-TB-HIV Pathogenesis and Treatment Research Unit, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
  • Sosibo P; eThekwini Municipality Health Unit, eThekwini Municipality, Durban, South Africa.
  • van Heerden R; eThekwini Municipality Health Unit, eThekwini Municipality, Durban, South Africa.
  • Garrett N; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; Discipline of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.
  • Dorward J; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Lancet Glob Health ; 12(2): e282-e291, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38142692
ABSTRACT

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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxazinas / Piperazinas / Piridonas / Infecciones por VIH / Fármacos Anti-VIH / Compuestos Heterocíclicos con 3 Anillos Límite: Adult / Female / Humans / Male País/Región como asunto: Africa Idioma: En Revista: Lancet Glob Health Año: 2024 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxazinas / Piperazinas / Piridonas / Infecciones por VIH / Fármacos Anti-VIH / Compuestos Heterocíclicos con 3 Anillos Límite: Adult / Female / Humans / Male País/Región como asunto: Africa Idioma: En Revista: Lancet Glob Health Año: 2024 Tipo del documento: Article