N Engl J Med 2021 07;385(4):330-341
From the Infectious Diseases Translational Research Programme and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (N.I.P.); the London School of Hygiene and Tropical Medicine, London (N.I.P.); the Infectious Diseases Institute, Makerere University (J.M., S.W., A.H., A.B., A. Kaimal, J.A., B.C., A. Kiragga, A. Kambugu), the Joint Clinical Research Centre (JCRC) (C.K., H.M.), and the Makerere University Walter Reed Project (G.M.), Kampala, JCRC, Mbarara (P.T.), and JCRC, Fort Portal (G.A.) - all in Uganda; the University of Zimbabwe Clinical Research Centre, Harare (J.H.); and the Moi University School of Medicine, Eldoret, Kenya (A.S.).
Background: The World Health Organization recommends dolutegravir with two nucleoside reverse-transcriptase inhibitors (NRTIs) for second-line treatment of human immunodeficiency virus type 1 (HIV-1) infection. Evidence is limited for the efficacy of this regimen when NRTIs are predicted to lack activity because of drug resistance, as well as for the recommended switch of an NRTI from tenofovir to zidovudine.
Methods: In a two-by-two factorial, open-label, noninferiority trial, we randomly assigned patients for whom first-line therapy was failing (HIV-1 viral load, ≥1000 copies per milliliter) to receive dolutegravir or ritonavir-boosted darunavir and to receive tenofovir or zidovudine; all patients received lamivudine. Read More