Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen. (15th July 2021)

• Record Type: Journal Article
• Authors: Keene, Claire M.; Griesel, Rulan; Zhao, Ying; Gcwabe, Zimasa; Sayed, Kaneez; Hill, Andrew; Cassidy, Tali; Ngwenya, Olina; Jackson, Amanda; van Zyl, Gert; Schutz, Charlotte; Goliath, Rene; Flowers, Tracy; Goemaere, Eric; Wiesner, Lubbe; Simmons, Bryony; Maartens, Gary; Meintjes, Graeme
• Is Part Of: AIDS. Volume 35:Number 9(2021)
• Publication Date: 2021-07-15
• Subjects: antiretroviral therapy -- dolutegravir -- HIV -- second-line; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000002936
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text