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.
aBotswana–Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education (BHP), Gaborone, Botswana
bHarvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts, USA
cHarvard School of Public Health, Department of Biostatistics, Boston, Massachusetts, USA
dMinistry of Health, Gaborone, Botswana
eVanderbilt University School of Medicine, Vanderbilt Institute of Global Health (VIGH), Nashville, Tennessee, USA.
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