Portal de Periódicos da CAPES

Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen

2021; Lippincott Williams & Wilkins; Volume: 35; Issue: 9 Linguagem: Inglês

10.1097/qad.0000000000002936

1473-5571

Claire Keene, Rulan Griesel, Ying Zhao, Zimasa Gcwabe, Kaneez Sayed, Andrew Hill, Tali Cassidy, Olina Ngwenya, Amanda Jackson, Gert U. van Zyl, Charlotte Schutz, René Goliath, Tracy Flowers, Eric Goemaere, Lubbe Wiesner, Bryony Simmons, Gary Maartens, Graeme Meintjes,

HIV/AIDS Research and Interventions

Objective: Recycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir would provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized nucleoside reverse transcriptase inhibitor (NRTI) backbone. We evaluated efficacy of tenofovir/lamivudine/dolutegravir (TLD) in patients failing first-line tenofovir/XTC/efavirenz or nevirapine. Design: Single arm, prospective, interventional study. Setting: Two primary care clinics in Khayelitsha, South Africa. Participants: Sixty adult patients with two viral loads greater than 1000 copies/ml. Intervention: Participants were switched to TLD with additional dolutegravir (50 mg) for 2 weeks to overcome efavirenz induction. Primary outcome: Proportion achieving viral load less than 50 copies/ml at week 24 using the FDA snapshot algorithm. Results: Baseline median CD4 + cell count was 248 cells/μl, viral load 10 580 copies/ml and 48 of 54 (89%) had resistance (Stanford score ≥15) to one or both of tenofovir and XTC. No participants were lost to follow-up. At week 24, 51 of 60 [85%, 95% confidence interval (CI) 73–93%] were virologically suppressed, six had viral load 50–100 copies/ml, one had viral load 100–1000 copies/ml, one no viral load in window, and one switched because of tenofovir-related adverse event. No integrase mutations were detected in the one participant meeting criteria for resistance testing. Virological suppression was achieved by 29 of 35 (83%, 95% CI 66–93%) with resistance to tenofovir and XTC, 11 of 13 (85%, 95% CI 55–98%) with resistance to XTC, and six of six (100%, 95% CI 54–100%) with resistance to neither. Conclusion: A high proportion of adults switching to second-line TLD achieved virologic suppression despite substantial baseline NRTI resistance and most not suppressed had low-level viraemia (≤100 copies/ml). This suggests recycling tenofovir and XTC with dolutegravir could provide an effective second-line option.