Adding maraviroc to standard treatment for advanced HIV does not improve outcomes
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Adding maraviroc to a standard three-drug antiretroviral therapy regimen in patients with advanced HIV did not improve outcomes, according to research published in the Annals of Internal Medicine.
Yves Lévy, MD, PhD, director of the department of clinical immunology and infectious diseases at Henri Mondor Hospital in Créteil, France, and colleagues explained that a third of patients with HIV are diagnosed late in the disease course, and that “follow-up of these patients has shown excess risk for AIDS-defining events and mortality that persists for years.”
“The excess mortality, which is due to opportunistic infections, seems to be related to immune restoration that is too long or weak despite control of viral replication,” they continued.
In addition to its efficacy as an antiretroviral, previous research has indicated that the C-C chemokine receptor type 5 antagonist maraviroc (Selzentry, Pfizer) could have immunologic effects, according to the study authors.
Lévy and colleagues conducted a randomized controlled trial of ART-naive adults with HIV-1 who had a CD4 count less than 0.2 × 109 cells/L or a previous AIDS-defining event. More than 400 participants at 50 clinical sites in France, Italy and Spain were randomly assigned to initiate standard combined-ART with placebo (n = 207) or 300 mg of maraviroc (n = 202) twice daily for 72 weeks.
Researchers evaluated the occurrence of severe morbidity, including a new AIDS-defining event, certain serious infections, a serious non-AIDS-defining event, immune reconstruction inflammatory syndrome and mortality among participants. They also examined the incidence of biological and pharmacokinetic measures and other adverse events.
During follow-up, Lévy and colleagues found that the incidence of severe morbidity in those assigned to maraviroc was 11.1 per 100 person-years compared with 11.2 per 100-person years among those who received placebo (HR = 0.97; 95% CI, 0.57-1.67). The incidence of serious adverse events was 36.1 in the maraviroc group compared with 41.5 per 100 person-years in the placebo group (IRR = 0.87; 95% CI, 0.65-1.15).
Maraviroc was associated with an increased risk for virologic failure at week 48 compared with placebo (21.3% vs. 15%), but not at 72 weeks, according to the researchers. There was a similar gain in CD4 T-cells between the groups, but the increase in CD4-CD8 ratio was lower among participants who received maraviroc.
In a post-hoc Poisson regression analysis, researchers found that the maraviroc group had a slightly lower incidence of severe morbidity in the first 24 weeks of treatment (IRR = 0.61; 95% CI, 0.33-1.08), which increased from 24 through 72 weeks (IRR = 2.9; 95% CI, 0.86-12.49).
This finding suggests that maraviroc may initially provide beneficial effects that are no longer present after the infection is controlled, and more studies are needed to evaluate maraviroc plus combined-ART during the initial 6 months of treatment, Lévy and colleagues reported
“Although new drug regimens are associated with better immunovirologic 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,” they wrote. – by Erin Michael
Disclosures: Lévy reports no relevant financial disclosures. Please see study for all other authors’ relevant financial disclosures.