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ObjectiveRecycling 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.DesignSingle arm, prospective, interventional study.SettingTwo primary care clinics in Khayelitsha, South Africa.ParticipantsSixty adult patients with two viral loads greater than 1000 copies/ml.InterventionParticipants were switched to TLD with additional dolutegravir (50 mg) for 2 weeks to overcome efavirenz induction.Primary outcomeProportion achieving viral load less than 50 copies/ml at week 24 using the FDA snapshot algorithm.ResultsBaseline 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.ConclusionA 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.

Original publication

DOI

10.1097/qad.0000000000002936

Type

Journal

AIDS (London, England)

Publication Date

07/2021

Volume

35

Pages

1423 - 1432

Addresses

Médecins Sans Frontières South Africa.

Keywords

Humans, HIV-1, HIV Infections, Oxazines, Piperazines, Pyridones, Heterocyclic Compounds, 3-Ring, Lamivudine, Anti-HIV Agents, Viral Load, Prospective Studies, Adult, South Africa, Tenofovir