Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial

BACKGROUND: NNRTIs are recommended as part of first-line treatment for HIV-1 in Africa. However, NNRTI-based regimens are more prone to resistance development than protease inhibitors (PIs) in a context in which drug interruptions are frequent. The aim of this study was to compare the efficacy and tolerability of NNRTIs with PIs in HIV-1-infected patients in Guinea-Bissau.

METHODS: This open-label randomised, two-arm superiority trial compared the use of two NRTIs plus either one NNRTI (efavirenz or nevirapine) or one PI (lopinavir/ritonavir) in treatment-naïve HIV-1-infected adults in the Bissau HIV Cohort (ClinicalTrials.gov, NCT0019235). The primary endpoint was HIV-1 RNA <400 copies/ml after 12 months of treatment.

RESULTS: Between May 5, 2011 and April 26, 2013, 400 patients were included in the study. In an intention-to-treat analysis, the proportions of patients with viral suppression were similar in the NNRTI (65/197 (33.0%)) and PI (68/203 (33.5%)) arms (p=0.92). No PI resistance was detected, but high-level NNRTI resistance was seen in 17/30 (56.7%) of NNRTI vs. 3/26 (11.5%) of PI-treated patients, p<0.01. After 1 year of follow-up, 65 patients died (16.3%) and 93 were lost to follow-up (23.3%). There was no difference in mortality (hazard ratio 0.84, 95% CI 0.51-1.36) or frequency of clinical adverse events between treatment arms (NNRTI: 73/197 (37.1%); PI: 69/203 (34.0%); p=0.52).

CONCLUSION: In patients at an HIV clinic in Guinea-Bissau, treatment with PIs led to less development of resistance compared with NNRTIs but was not superior in terms of viral suppression, CD4 cell increment, mortality, or severe adverse events.