First-line antiretroviral therapy with nevirapine versus lopinavir-ritonavir based regimens in a resource-limited setting

Clumeck, Nathana; Mwamba, Claudeb; Kabeya, Kabambaa; Matanda, Sergeb; Vaira, Dolorèsc; Necsoi, Cocaa; Kadiebwe, Davidb; Delforge, Marca; Kasamba, Ericb; Milolo, Chantalb; Ilunga, Joeb; Kapend, Liévinb

doi: 10.1097/QAD.0000000000000214
Clinical Science

Objective: To compare WHO first-line antiretroviral therapy (ART) with nonnucleoside reverse transcriptase inhibitors (NNRTI)-based regimen with a boosted protease inhibitor (bPI) regimen in a resource-limited setting regarding treatment outcome and emergence of drug resistance mutations (DRMs).

Methods: Treatment-naive adults were randomized to nevirapine (NVP) or ritonavir-boosted lopinavir (LPV/r) regimens each in combination with tenofovir (TDF)/emtricitabine (FTC) or zidovudine (ZDV)/lamivudine (3TC). Primary endpoint was the incidence of therapeutical (clinical and/or virologic) failure at week 48 with follow-up till week 96.

Results: Four hundred and twenty-five patients (120 men; 305 women) received at least one dose of the study drug. mITT analysis showed no difference in proportion of therapeutical failure between treatment arms [67/209 (32%) in NVP vs. 63/216 (29%) LPV/r at week 48 (P = 0.53); 88/209 (42%) in NVP vs. 83/216 (38%) in LPV/r at week 96 (P = 0.49)]. Per-protocol analysis demonstrated significantly more virologic failure with NVP than with LPV/r regimens [at week 48: 19/167 (11%) vs. 7/166 (4%), P = 0.014; at week 96: 27/158 (17%) vs. 13/159 (8%), P =  0.019)]. Drug resistance mutations to NNRTI were detected in 19 out of 22 (86.3%) and dual-class resistance to nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI in 15 out of 27 (68.2%) of NVP failing patients. K65R mutation was present in seven out of 14 patients failing NVP-TDF/FTC regimen. No major protease inhibitor-DRM was detected among LPV/r failing patients. Discontinuation for adverse events was similar between treatment groups.

Conclusion: In resource-limited settings, first-line NNRTI-NRTI regimen as compared with bPI-based regimen provides similar outcome but is associated with a significantly higher number of virologic failure and resistance mutations in both classes that jeopardize future options for second-line therapy.

aSaint-Pierre University Hospital, 1000 Brussels, Belgium

bLubumbashi Network & PNMLS, Bureau de Coordination PNMLS/Katanga, Avenue Likasi, Lubumbashi, Congo RDC

cCHU Liège, 1 Avenue de l’Hôpital, Domaine Universitaire du Sart Tilman, Liège 1, Belgium.

Correspondence to Nathan Clumeck, MD, PhD, Division of Infectious Diseases, Saint-Pierre University Hospital, 1000 Brussels, Belgium. Tel: +32 2 535 41 20; e-mail:

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Received September 13, 2013

Accepted January 15, 2014

© 2014 Lippincott Williams & Wilkins, Inc.