Background: National initiatives offering non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy (cART) have expanded in sub-Saharan Africa. The Tshepo study is the first clinical trial evaluating the long-term efficacy and tolerability of efavirenz versus nevirapine-based cART among adults in Botswana.
Methods: A 3-year randomized study (n = 650) using a 3 × 2 × 2 factorial design comparing efficacy and tolerability among: (i) zidovudine/lamivudine versus zidovudine/didanosine versus stavudine/lamivudine; (ii) efavirenz versus nevirapine; and (iii) community-based supervision versus standard adherence strategies. This paper focuses on comparison (ii).
Results: There was no significant difference by assigned NNRTI in time to virological failure with resistance (log-rank P = 0.14), nevirapine versus efavirenz [risk ratio (RR) 1.54, 95% CI 0.86–2.70]. Rates of virological failure with resistance were 9.6% nevirapine-treated (95% CI 6.8–13.5) versus 6.6% efavirenz-treated (95% CI 4.2–10.0) at 3 years. Women receiving nevirapine-based cART trended towards higher virological failure rates when compared with efavirenz-treated women, Holm-corrected (log-rank P = 0.072), nevirapine versus efavirenz (RR 2.22, 95% CI 0.94–5.00). A total of 139 patients had 176 treatment-modifying toxicities, with a shorter time to event in nevirapine-treated versus efavirenz-treated patients (RR 1.85, 1.20–2.86; log-rank P = 0.0002).
Conclusion: Tshepo-treated patients had excellent overall immunological and virological outcomes, and no significant differences were observed by randomized NNRTI comparison. Nevirapine-treated women trended towards higher virological failure with resistance compared with efavirenz-treated women. Nevirapine-treated adults had higher treatment modifying toxicity rates when compared with those receiving efavirenz. Nevirapine-based cART can continue to be offered to women in sub-Saharan Africa if patient education concerning toxicity is emphasized, routine safety monitoring chemistries are performed and the potential risk of efavirenz-related teratogenicity is considered.