In patients initiating therapy for advanced HIV infection, the addition of maraviroc to the standard combined antiretroviral therapy (c-ART) for 18 months does not provide any clinical benefit, according to study results published in the Annals of Internal Medicine.
Late HIV diagnosis, defined as a CD4 T-cell count <0.200 Í109 cells/L or the presence of AIDS, occurs in roughly one-third of people with HIV and is associated with a significant risk for mortality and AIDS-defining events that can persist for years despite initiation of c-ART. Maraviroc is a C-C chemokine receptor type 5 (CCR5) antagonist that has antiviral efficacy and could provide other immunologic effects. Therefore, this randomized, placebo-controlled, parallel, double-blind, multicenter, phase 3 trial was conducted to assess the benefit of adding maraviroc to standard c-ART in patients with advanced disease at HIV diagnosis (ClinicalTrials.gov identifier: NCT01348308).
In total, 409 patients with HIV from 50 clinical sites in France, Spain, and Italy were included in the study. Participants were adults who had no history of receiving ART and had CD4 counts <0.200 Í109 cells/L and/or a previous AIDS-defining event. The participants were randomly assigned to receive either c-ART plus placebo (n=207) or c-ART plus maraviroc (n=202) 300 mg twice daily for 72 weeks. The primary endpoint was the first occurrence of severe morbidity, including new AIDS-defining events, selected serious infections, serious non-AIDS-defining events, immune reconstitution inflammatory syndrome, or death. Secondary outcomes included biologic and pharmacokinetic measures and grade ³2 adverse events.
The results suggested that the addition of maraviroc provided no clinical improvement. The incidence of the first occurrence of severe morbidity was 11.1 per 100 person-years in the maraviroc group and 11.2 per 100 person-years in the placebo group (adjusted hazard ratio [HR], 0.97; 95% CI, 0.57-1.67; P =.91). Subgroup analyses demonstrated a significant difference in treatment effect only for age (P =.04): patients aged <40 years had an HR of 0.50 ((5% CI, 0.21-1.19) compared with those aged ³40 years who had an HR of 1.60 (95% CI, 0.77-3.32).
Grade ³2 adverse events occurred at an incidence of 36.1 per 100 person-years in the maraviroc group and 41.5 per 100 person-years in the placebo group; more study drug-related serious adverse events occurred in the maraviroc group compared with the placebo group. At weeks 48 and 72, the virologic success rates (plasma viral load <50 copies/mL) were 67.3% and 72.8% in the maraviroc group and 76.3% and 78.3% in the placebo group, respectively (P =.048 and P =.21, respectively).
Limitations of this study included that it was not designed to evaluate time-dependent outcomes and that 64 participants were lost to follow-up.
Overall, the study authors concluded, “Moreover, although new drug regimens are associated with better immuno-virologic outcomes and may be associated with better clinical outcomes in HIV-1-infected persons presenting with advanced HIV infection, new strategies, such as host-directed therapies or improved prophylaxis, are clearly needed to decrease the higher morbidity and mortality observed in this population.”
Lévy Y, Lelièvre JD, Assoumou L, et al. Addition of maraviroc versus placebo to standard antiretroviral therapy for initial treatment of advanced HIV infection [published online February 11, 2020]. Ann Intern Med. doi:10.7326/M19-2133