Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection: A Randomized Trial.
Adult
Aged
Anti-HIV Agents
/ administration & dosage
Antiretroviral Therapy, Highly Active
/ methods
CD4 Lymphocyte Count
Double-Blind Method
Female
HIV Fusion Inhibitors
/ administration & dosage
HIV Infections
/ drug therapy
HIV-1
/ drug effects
Humans
Male
Maraviroc
/ administration & dosage
Middle Aged
Treatment Outcome
Viral Load
/ drug effects
Young Adult
Journal
Annals of internal medicine
ISSN: 1539-3704
Titre abrégé: Ann Intern Med
Pays: United States
ID NLM: 0372351
Informations de publication
Date de publication:
03 03 2020
03 03 2020
Historique:
pubmed:
11
2
2020
medline:
1
9
2020
entrez:
11
2
2020
Statut:
ppublish
Résumé
Patients diagnosed with advanced HIV infection have a poor prognosis despite initiation of combined antiretroviral therapy (c-ART). 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. Randomized controlled trial. (ClinicalTrials.gov: NCT01348308). Clinical sites in France (n = 25), Italy (n = 5), and Spain (n = 20). 416 HIV-positive, antiretroviral-naive adults with CD4 counts less than 0.200 × 109 cells/L and/or a previous AIDS-defining event (ADE). C-ART plus placebo or maraviroc (300 mg twice daily with dose modification) for 72 weeks. 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. 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]). Sixty-four participants discontinued therapy during follow-up. The study was not designed to evaluate time-dependent outcomes or effect modification. Addition of maraviroc to standard c-ART does not improve clinical outcomes of patients initiating therapy for advanced HIV infection. INSERM-ANRS (French National Agency for Research on AIDS).
Sections du résumé
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).
Identifiants
pubmed: 32040959
pii: 2760879
doi: 10.7326/M19-2133
doi:
Substances chimiques
Anti-HIV Agents
0
HIV Fusion Inhibitors
0
Maraviroc
MD6P741W8A
Banques de données
ClinicalTrials.gov
['NCT01348308']
Types de publication
Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM