Virologic outcomes with tenofovir-lamivudine-dolutegravir in adults failing PI-based second-line ART

Ying Zhao; Jacqueline Voget; Isaac Singini; Zaayid Omar; Vanessa Mudaly; Andrew Boulle; Gary Maartens; Graeme Meintjes

doi:10.4102/sajhivmed.v25i1.1567

Virologic outcomes with tenofovir-lamivudine-dolutegravir in adults failing PI-based second-line ART

South Afr J HIV Med. 2024 Apr 26;25(1):1567. doi: 10.4102/sajhivmed.v25i1.1567. eCollection 2024.

Authors

Ying Zhao^{1

2}, Jacqueline Voget³, Isaac Singini⁴, Zaayid Omar², Vanessa Mudaly³, Andrew Boulle⁵, Gary Maartens^{2

6}, Graeme Meintjes^{1

2}

Affiliations

¹ Department of Medicine, Faculty of Health Science, University of Cape Town, Cape Town, South Africa.
² Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
³ Western Cape Government Department of Health and Wellness, Cape Town, South Africa.
⁴ Biostatistics Research Unit, South African Medical Research Council, Cape Town, South Africa.
⁵ Provincial Health Data Centre, Western Cape Department of Health and CIDER, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
⁶ Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Abstract

Background: In South African antiretroviral guidelines, selected patients failing second-line protease inhibitor (PI)-based therapy qualify for genotypic resistance testing - those with PI resistance receive darunavir-based third-line regimens; those without PI resistance continue current regimen with adherence support. The Western Cape province, from September 2020, implemented a strategy of tenofovir-lamivudine-dolutegravir (TLD) for patients, provided there was no tenofovir resistance, irrespective of PI resistance.

Objectives: To evaluate virologic outcomes with TLD among adults failing second-line PI regimens with no tenofovir resistance.

Method: An observational cohort study comparing outcomes in patients switched to TLD with those continuing the same PI or switched to darunavir-based regimens. Follow-up was until virologic suppression (HIV-1 RNA < 400 copies/mL), or at the point of censoring.

Results: One hundred and thirty-three patients switched to TLD, 101 to darunavir-based regimens, and 121 continued with the same PI. By 12 months, among patients with PI resistance, 42/47 (89%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 91/99 (92%) in the darunavir group (hazard ratio, 1.11; 95% confidence interval, 0.77-1.60). In patients without PI resistance, 66/86 (77%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 42/120 (35%) in those continuing with the same PI (hazard ratio, 4.03; 95% confidence interval, 2.71-5.98). Two patients receiving TLD developed virologic failure with high-level dolutegravir resistance.

Conclusion: Amongst patients failing second-line PI with no PI resistance, switching to TLD was associated with higher virologic suppression, likely due to improved adherence. Virologic outcomes were similar in patients with PI resistance switched to darunavir-based regimens or TLD.

Keywords: HIV; antiretroviral therapy; dolutegravir; third-line; virologic failure.

Grants and funding

Funding information This work was supported by the Wellcome Trust (212265/Z/18/Z). The corresponding author, G. Meintjes, was supported by the Wellcome Trust (214321/B/18/Z) and the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Grant no. 64787). The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The opinions, findings and conclusions expressed in this manuscript reflect those of the authors alone. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. For the purpose of open access, the author has applied a Creative Commons by public copyright licence to any Author Accepted Manuscript version arising from this submission.