Published on 17 July 2014
Results of trial to assess second-line therapy in HIV patients in Africa published
The combination of a boosted protease inhibitor (lopinavir) with two nucleoside reverse-transcriptase inhibitors (NRTIs) is a feasible second-line therapy for HIV patients in Africa. These are the results of the EDCTP-funded EARNEST trial, coordinated by Prof. Peter Mugyenyi (Joint Clinical Research Centre, Uganda) and Prof. Nick Paton (UK Medical Research), reported in the New England Journal of Medicine on 16 July 2014.
The Europe-Africa Research Network for Evaluation of Second Line Therapy (EARNEST) trial compared several boosted protease inhibitor-containing second-line regimens in patients in five African countries.. The 3-arm, open label randomised trial, the largest ever study of second-line therapy conducted in sub-Saharan Africa, recruited a total of 1277 HIV-infected adults and adolescents who failed first-line treatment. They received randomised ritonavir-boosted protease inhibitor (lopinavir–ritonavir) plus clinician-selected NRTIs (NRTI group, 426 patients), a protease inhibitor plus raltegravir in a superiority comparison (raltegravir group, 433 patients), or protease-inhibitor monotherapy after 12 weeks of induction therapy with raltegravir in a non-inferiority comparison (monotherapy group, 418 patients). Good HIV disease control was achieved in 60% of the patients (255 patients) in the NRTI group, 64% of the patients (277 patients) in the raltegravir group and 55% of the patients (232 patients) in the monotherapy group. Similar proportions of patients ( ≥ 90%) in the three study groups were alive at week 96.
The EARNEST trial demonstrated that the WHO-recommended regimen of a boosted protease inhibitor (in this case, lopinavir) combined with two NRTIs is effective and has an acceptable safety profile, with a 90% rate of survival free of WHO stage 4 events and an 86% rate of virologic suppression (<400 copies per milliliter) at 96 weeks. Importantly, the trial showed that combining a boosted protease inhibitor with raltegravir, a heat-stable integrase inhibitor, to create a second-line regimen with two completely new drug classes was not superior to NRTIs. This regimen is significantly more expensive and therefore not suitable as a standard second-line regimen for large-scale use in low income settings.
The EARNEST trial involved 14 clinical trials centres in five countries: Kenya (Academic Model for the Prevention and Treatment of HIV/Aids Centre, Eldoret), Malawi (Mzuzu Central Hospital, Mzuzu; University of Malawi, Queen Elizabeth Hospital, Blantyre), Uganda (Infectious Disease Institute (IDI), Kampala; Joint Clinical Research Centre (JCRC) Fort Portal Regional Centre of Excellence, Fort Portal; JCRC Gulu; JCRC Kabale; JCRC Kakira; JCRC Mbale; JCRC Mbarara Regional Centre of Excellence, Mbarara; JCRC Kampala; St Francis Nsambya Hospital, Kampala), Zambia (University Teaching Hospital, Lusaka) and Zimbabwe (University of Zimbabwe Clinical Research Centre, Harare).
EDCTP was the main funder for this clinical trial. It was cofunded by Carlos III Health Institute (Spain); Department for International Development (DfID, United Kingdom); Department of Foreign Affairs, Ireland; Istituto Superiore di Sanità (Italy); Medical Research Council UK; Merck & Co. Inc (United Kingdom); Prince Leopold Institute of Tropical Medicine ( Belgium), and the Swedish International Development Cooperation Agency (Sweden).
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