ABSTRACT
BACKGROUND: Agents that block the CCR5 coreceptor for human immunodeficiency virus (HIV) have demonstrated potent antiretroviral activity. In early clinical studies, the CCR5 antagonist vicriviroc proved to be a safe and effective component of combination antiretroviral therapy. METHODS: This double-blind, dose-ranging, phase 2 trial randomized subjects to receive 30 mg or 20 mg of vicriviroc or placebo once daily plus re-optimized background therapy containing a protease inhibitor with ritonavir. Subjects were adults infected with CCR5-tropic HIV who were experiencing failure of triple antiretroviral regimens. The primary end point was mean change in baseline log(10) HIV RNA level at 48 weeks, based on an intent-to-treat analysis. RESULTS: One hundred fourteen persons received vicriviroc at 30 mg (n = 39), vicriviroc at 20 mg (n =40), or placebo (n = 35). The mean change in baseline HIV RNA level at week 48 was -1.77 log(10) copies/mL for 30 mg of vicriviroc and -1.75 log(10) copies/mL for 20 mg of vicriviroc, compared with -0.79 log(10) copies/mL for placebo (P =.002 and P=.003, respectively, compared with placebo). Mean CD4 counts increased by 102, 136, and 63 cells/mm(3) for 30 mg vicriviroc, 20 mg vicriviroc, and placebo, respectively (P = .260 and P = .039, respectively, compared with placebo). Rates of adverse events (mostly mild-to-moderate) were 111.4, 112.5, and 147.4 events per 100 subject-years, respectively. CONCLUSIONS: Vicriviroc administered with a protease inhibitor plus ritonavir-containing regimen shows potent antiretroviral and immunologic activity sustained over 48 weeks in treatment-experienced patients. CLINICAL TRIALS REGISTRATION: NCT00243230 .
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Adult , Anti-HIV Agents/adverse effects , CCR5 Receptor Antagonists , CD4 Lymphocyte Count , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Female , HIV Infections/blood , HIV Infections/virology , HIV Protease Inhibitors/therapeutic use , Humans , Male , Middle Aged , Piperazines/adverse effects , Pyrimidines/adverse effects , RNA, Viral/blood , Ritonavir/therapeutic use , Viral LoadABSTRACT
We analyzed mortality among 201 patients with AIDS and tuberculosis in Haiti. Patients who received a diagnosis of tuberculosis during the first 3 months after the initiation of antiretroviral therapy were 3.25 times more likely to die than were other patients with AIDS and tuberculosis. Failure to recognize active tuberculosis at initiation of antiretroviral therapy leads to increased mortality.