The purpose of this current study was to gain further understanding of the long-term safety and tolerability of alternatives to efavirenz-based combinations for the first-line treatment of HIV. The regimens evaluated all consisted of a NRTI backbone of tenofovir and emtricitabine, plus either ritonavir-boosted atazanavir (protease inhibitor), ritonavir-boosted darunavir (protease inhibitor), or raltegravir (HIV integrase inhibitor).
All regimens were equivalent in terms of virological failure (HIV-1 RNA >1000 copies/mL at or after 16 weeks and before 24 weeks or >200 copies/mL at or after 24 weeks). The cumulative probability of virological failure by 96 weeks was 12.6% in the ritonavir-boosted atazanavir group, 9.0% in the raltegravir group, and 14.9% in the ritonavir-boosted darunavir group (the 97.5% confidence intervals for all comparisons were within the prespecified equivalence bound of ±10%, meeting the definition of equivalence).
Differences in tolerability were however apparent. Ritonavir-boosted atazanavir resulted in a 12.7% and 9.2% higher incidence of tolerability discontinuation than raltegravir and ritonavir-boosted darunavir, respectively, primarily because of hyperbilirubinaemia. When tolerability and virological response are considered together, raltegravir-based therapy was superior overall to both protease inhibitor-based therapies and ritonavir-boosted darunavir was superior to ritonavir-boosted atazanavir. An advantage of the ritonavir-boosted protease inhibitors over the raltegravir-based regimen is the reduced likelihood of drug resistance if virological failure occurs.
Guidelines from the British HIV Association (BHIVA) recommend initial therapy with two NRTIs plus either a ritonavir-boosted protease inhibitor, an NNRTI, or an integrase inhibitor. The three regimens evaluated in this study are all considered as first-line choices in these guidelines; drug choice for individual patients should consider the presence or future risk of co-morbidities and potential adverse effects.