Background: A monoclonal CCR5 antibody, PRO 140 (a humanised form of the PA14 antibody), inhibits CCR5-tropic (R5) HIV-1. This may be an effective new treatment for HIV-infected patients, with the potential to address the limitations of currently available therapies.
Objectives: We aimed to assess the efficacy and safety of PRO 140 for HIV-1-infected patients in randomised controlled trials (RCTs).
Search strategy: Databases including Cochrane's CENTRAL, PubMed, EMBASE and ISI Web of Knowledge, online trials registries and other sources were searched. The reference lists of related literature and presentations from major HIV/AIDS conferences were also screened.
Selection criteria: RCTs and quasi-RCTs comparing PRO 140 with placebo or other antiretroviral drugs, or different doses for individuals infected with HIV.
Data collection and analysis: Two reviewers (L Li and TT Sun) independently screened all retrieved citations and selected relevant citations. Data were extracted independently by two authors (P Zhang and WQ Jia). Any disagreements when selecting studies and extracting data were adjudicated the review mentor (KH Yang). RevMan software was used for statistical analysis based an intention-to-treat analysis. Heterogeneity was examined using the I(2) statistic. I(2) estimates greater than 50% were regarded as moderate or high levels. According to the level of heterogeneity, either fixed or random effects models were used. If significant heterogeneity existed and the reasons could not be found, we reported the results qualitatively.
Main results: We included 2 trials comparing PRO 140 with placebo in adult patients with HIV infection. Our review indicates that PRO 140 may offer significant dose-dependent HIV-1 RNA suppression with tolerable side effects. PRO 140 2mg/Kg, 5 mg/Kg, 162mg weekly, 324 mg biweekly, 324 mg weekly showed statistically significant differences in the changes of HIV RNA level. Both HIV-1 RNA levels of PRO 140 2mg/Kg, 5mg/Kg on day 10 and PRO 140 162mg weekly, 324 mg biweekly, 324 mg weekly on day 22 were significantly reduced. PRO 140 0.5mg/Kg, 2mg/Kg, 5mg/Kg, 162 mg weekly; 324 mg biweekly; 324 mg weekly demonstrated greater antiviral response. Only PRO 140 324 mg weekly showed more patients with ≦400 copies/mL HIV-1 RNA. Only PRO 140 5 mg/Kg showed greater change in CD4(+) cell count on day 8. Headache, lymphadenopathy, diarrhoea, fatigue, and hypertension were reported to be the most frequent adverse events.
Authors' conclusions: Limited evidence from two small trials suggests that PRO 140 might demonstrate potent, dose-dependent, highly significant antiviral activity. The evidence is insufficient, so recommendations cannot yet be made. Larger, longer-term, double-blind RCTs are required to provide conclusive evidence.