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

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 ritonavirboosted 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.