Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection: A Randomized Trial.

BACKGROUND

Patients diagnosed with advanced HIV infection have a poor prognosis despite initiation of combined antiretroviral therapy (c-ART).

OBJECTIVE

To assess the benefit of adding maraviroc, an antiretroviral drug with immunologic effects, to standard c-ART for patients with advanced disease at HIV diagnosis.

DESIGN

Randomized controlled trial. (ClinicalTrials.gov: NCT01348308).

SETTING

Clinical sites in France (n = 25), Italy (n = 5), and Spain (n = 20).

PARTICIPANTS

416 HIV-positive, antiretroviral-naive adults with CD4 counts less than 0.200 × 109 cells/L and/or a previous AIDS-defining event (ADE).

INTERVENTION

C-ART plus placebo or maraviroc (300 mg twice daily with dose modification) for 72 weeks.

MEASUREMENTS

The primary end point was first occurrence of severe morbidity (new ADE, selected serious infections, serious non-ADE, immune reconstitution inflammatory syndrome, or death). Prespecified secondary outcomes included primary outcome components, biological and pharmacokinetic measures, and adverse events graded 2 or higher.

RESULTS

409 randomly assigned participants (207 in the placebo group and 202 in the maraviroc group) who received more than 1 dose were included in the analysis. During 72 weeks of follow-up, incidence 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 (hazard ratio, 0.97 [95% CI, 0.57 to 1.67]). Incidence of adverse events graded 2 or higher was 36.1 versus 41.5 per 100 person-years (incidence rate ratio, 0.87 [CI, 0.65 to 1.15]).

LIMITATIONS

Sixty-four participants discontinued therapy during follow-up. The study was not designed to evaluate time-dependent outcomes or effect modification.

CONCLUSION

Addition of maraviroc to standard c-ART does not improve clinical outcomes of patients initiating therapy for advanced HIV infection.

PRIMARY FUNDING SOURCE

INSERM-ANRS (French National Agency for Research on AIDS).