Initial supplementary dose of Dolutegravir in second-line antiretroviral therapy: a noncomparative, double-blind, randomized placebo-controlled trial

Zhao, Ying, Griesel, Rulan, Omar, Zaayid, Simmons, Bryony ORCID: 0000-0002-3207-9935, Hill, Andrew, van Zyl, Gert, Keene, Claire, Maartens, Gary and Meintjes, Graeme (2023) Initial supplementary dose of Dolutegravir in second-line antiretroviral therapy: a noncomparative, double-blind, randomized placebo-controlled trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 76 (10). pp. 1832-1840. ISSN 1058-4838

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Abstract

BACKGROUND: Dolutegravir concentrations are reduced by efavirenz induction effect necessitating twice-daily dolutegravir dosing when coadministered. Efavirenz induction persists for several weeks after stopping, which could potentially select for dolutegravir resistance if switching occurred with unsuppressed human immunodeficiency virus type 1 (HIV-1) RNA levels and standard dolutegravir dosing. We evaluated the need for a lead-in supplementary dolutegravir dose in adults failing first-line tenofovir-emtricitabine-efavirenz (TEE). METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2 trial in Khayelitsha, South Africa. Eligible patients had virologic failure (2 consecutive HIV-1 RNA ≥1000 copies/mL) on first-line TEE. Participants were randomly assigned (1:1) to switch to tenofovir-lamivudine-dolutegravir (TLD) with a supplementary 50 mg dolutegravir dose or placebo taken 12 hours later for 14 days. Primary outcome was proportion with HIV-1 RNA <50 copies/mL at week 24. This study was not powered to compare arms. RESULTS: One hundred thirty participants were randomized (65 to each arm). Median baseline HIV-1 RNA was 4.0 log10 copies/mL and 76% had baseline resistance to both tenofovir and lamivudine. One participant died and 2 were lost to follow-up. At week 24, 55 of 64 (86% [95% confidence interval {CI}: 75%-93%]) in the supplementary dolutegravir arm and 53 of 65 (82% [95% CI: 70%-90%]) in the placebo arm had HIV-1 RNA <50 copies/mL. Grade 3 or 4 adverse events were similar in frequency between arms. None of 6 participants (3 in each arm) eligible for resistance testing by 24 weeks developed dolutegravir resistance. CONCLUSIONS: Our findings do not support the need for initial dolutegravir dose adjustment in patients switching to TLD who failed first-line TEE. CLINICAL TRIALS REGISTRATION: NCT03991013.

Item Type:	Article
Additional Information:	© The Author(s) 2023.
Divisions:	LSE Health
Subjects:	R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
Date Deposited:	07 Jun 2023 16:48
Last Modified:	25 Apr 2024 18:36
URI:	http://eprints.lse.ac.uk/id/eprint/119361

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