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: nclumeck@stpierre-bru.be

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Received September 13, 2013

Accepted January 15, 2014

© 2014 Lippincott Williams & Wilkins, Inc.