A simplified regimen of atazanavir/ritonavir plus lamivudine has similar efficacy and safety as atazanavir/ritonavir plus 2 nucleoside reverse transcriptase inhibitors (NRTIs), according to 48-week results from ATLAS-M published in the Journal of Antimicrobial Chemotherapy.
Combination antiretroviral therapy (cART) significantly improves quality of life and life expectancy in people with human immunodeficiency virus (HIV) infection, but NRTI-related toxicities have raised concerns about long-term NRTI exposure. Data on NRTI-sparing regimens are limited and conflicting, and monotherapy protease inhibitor (PI)/ritonavir regimens are not as effective as standard triple therapy. Emerging data suggest that a simplified dual-therapy regimen with atazanavir/ritonavir plus lamivudine may have similar efficacy as standard regimens that use 2 NRTIs.
In the ATLAS-M trial, researchers evaluated the safety and efficacy of atazanavir/ritonavir plus lamivudine compared with atazanavir/ritonavir plus 2 NRTIs in patients with HIV infection without hepatitis B virus coinfection.
A total of 266 patients with stable disease (HIV-RNA <50 copies/mL and CD4+ count >200 cells/mm3) while taking atazanavir/ritonavir plus 2 NRTIs were enrolled. Participants were randomly assigned to receive atazanavir/ritonavir plus lamivudine (dual therapy) once daily or to continue receiving atazanavir/ritonavir plus 2 NRTIs (triple therapy).
At 48 weeks, 89.5% of patients in the dual-therapy arm and 79.7% in the standard triple-therapy arm achieved the primary outcome, freedom from treatment failure (defined as maintenance of HIV-RNA <50 copies/mL). Compared with triple therapy, dual therapy met noninferiority criteria for efficacy.
Fewer patients in the atazanavir/ritonavir plus lamivudine group had virologic failure compared with patients in the group receiving atazanavir/ritonavir plus 2 NRTIs, although the difference was not statistically significant (1.5% vs 4.5%; P =.282). Virologic failure was not due to resistance mutations in the protease gene or in the reverse transcriptase gene. The incidence of other adverse events was similar in both groups.
A post hoc analysis also demonstrated superiority of atazanavir/ritonavir plus lamivudine over atazanavir/ritonavir plus 2 NRTIs. “This superiority resulted from the combination of several factors: a lower rate of virological failure, a lower discontinuation rate for treatment-related toxicity, and the less frequent withdrawal of consent in patients randomized to atazanavir/ritonavir + lamivudine. All three reasons may be interpreted as signs of an overall better tolerability of this regimen over the comparator,” the investigators wrote.
Several researchers report financial relationships with Gilead, Bristol-Myers Squibb, Abbott, Boehringer Ingelheim, Janssen, GlaxoSmithKline, Merck, ViiV Healthcare, AbbVie, Roche, and Novartis.
Di Giambenedetto S, Fabbiani M, Quiros Roldan E, et al; Atlas-M Study Group. Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M) [published online January 15, 2017]. J Antimicrob Chemother. doi:10.1093/jac/dkw557