Clinical outcomes after the introduction of dolutegravir for second-line antiretroviral therapy in South Africa: a retrospective cohort study

Kwabena Asare; Yukteshwar Sookrajh; Johan van der Molen; Thokozani Khubone; Lara Lewis; Richard J Lessells; Kogieleum Naidoo; Phelelani Sosibo; Rosemary van Heerden; Nigel Garrett; Jienchi Dorward

doi:10.1101/2023.07.07.23292347

Clinical outcomes after the introduction of dolutegravir for second-line antiretroviral therapy in South Africa: a retrospective cohort study

medRxiv [Preprint]. 2023 Jul 8:2023.07.07.23292347. doi: 10.1101/2023.07.07.23292347.

Authors

Kwabena Asare^{1

2}, Yukteshwar Sookrajh³, Johan van der Molen¹, Thokozani Khubone³, Lara Lewis¹, Richard J Lessells^{1

4}, Kogieleum Naidoo^{1

5}, Phelelani Sosibo³, Rosemary van Heerden³, Nigel Garrett^{1

2}, Jienchi Dorward^{1

6}

Affiliations

¹ Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
² Discipline of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa.
³ eThekwini Municipality Health Unit, eThekwini Municipality, Durban KwaZulu-Natal, South Africa.
⁴ KwaZulu-Natal Research and Innovation Sequencing Platform (KRISP), University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa.
⁵ South African Medical Research Council (SAMRC)-CAPRISA-TB-HIV Pathogenesis and Treatment Research Unit, University of KwaZulu-Natal Nelson R Mandela School of Medicine, Durban, South Africa.
⁶ Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxfordshire, United Kingdom.

Abstract

Background: Dolutegravir is now recommended for second-line anti-retroviral therapy (ART) in low- and middle-income countries. We compared outcomes with dolutegravir (DTG) versus the previous lopinavir/ritonavir (LPV/r) regimen in South Africa.

Methods: We used routinely collected, de-identified data from 59 South African clinics. We included people living with HIV aged ≥ 15 years with virologic failure (two consecutive viral loads ≥1000 copies/mL) on first-line tenofovir disoproxil fumarate (TDF)-based ART and switched to second-line ART. We used modified Poisson regression models to compare outcomes of 12-month retention-in-care and viral suppression (<50 copies/ml) after switching to second-line regimens of zidovudine (AZT), emtricitabine/lamivudine (XTC), DTG and TDF/XTC/DTG and AZT/XTC/LPV/r.

Findings: Of 1214 participants, 729 (60.0%) were female, median age was 36 years (interquartile range 30 to 42), 689 (56.8%) were switched to AZT/XTC/LPV/r, 217 (17.9%) to AZT/XTC/DTG and 308 (25.4%) to TDF/XTC/DTG. Retention-in-care was higher with AZT/XTC/DTG (85.7%, adjusted risk ratio (aRR) 1.14, 95% confidence interval (CI) 1.03 to 1.27; adjusted risk difference (aRD) 10.89%, 95%CI 2.01 to 19.78) but not different with TDF/XTC/DTG (76.9%, aRR 1.01, 95%CI 0.94 to 1.10; aRD 1.04%, 95%CI -5.03 to 7.12) compared to AZT/XTC/LPV/r (75.2%). Retention-in-care with TDF/XTC/DTG was not statistically significantly different from AZT/XTC/DTG (aRR 0.89, 95%CI 0.78 to 1.01; aRD -9.85%, 95%CI -20.33 to 0.63). Of 799 participants who were retained-in-care with a 12-month viral load, viral suppression was higher with AZT/XTC/DTG (59.3%, aRR 1.25, 95%CI 1.06 to 1.47; aRD 11.57%, 95%CI 2.37 to 20.76) and TDF/XTC/DTG (60.7%, aRR 1.30, 95%CI 1.14 to 1.48; aRD 14.16%, 95%CI 7.14 to 21.18) than with the AZT/XTC/LPV/r regimen (46.7%).

Interpretation: DTG-based second-line regimens were associated with similar or better retention-in-care and better viral suppression than the LPV/r-based regimen. TDF/XTC/DTG had similar viral suppression compared to AZT/XTC/DTG.

Funding: Bill & Melinda Gates Foundation, Africa Oxford Initiative.

Keywords: HIV; anti-retroviral therapy; dolutegravir; lopinavir-ritonavir; retention-in-care; second-line treatment; viral suppression.

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