Primary outcomes were change in CD4 cell count from baseline, and proportion of patients reaching undetectable HIV RNA levels, defined as <50 copies/mL. We collected information on study characteristics and the demographic and clinical characteristics of patients at inclusion. We contacted the authors or sponsors of eligible studies to request additional information when necessary. We used data from intention-to-treat analyses, which assessed HTS assay patients according to their assigned treatment group, regardless of their actual adherence or follow-up. We estimated treatment effects in two ways: (1)
we compared the proportion of patients with undetectable HIV RNA at W48 in the treatment and placebo groups using odds ratios (ORs) and 95% confidence intervals (CIs); (2) we compared CD4 cell count increases at W48 using standardized and nonstandardized mean differences and 95% CIs. The standardized mean differences, used for the analysis, are calculated as the ratio of the observed mean differences to an estimate selleckchem of the standard deviation obtained from pooling the standard deviations from both treatment
groups [18,19]. The nonstandardized mean differences are just the observed mean differences and were used for the interpretation. Positive mean differences in CD4 cell counts indicated superior treatment responses. Missing values were imputed as virological failure and no increase in CD4 cell count from baseline. We used a random effects model and the DerSimonian and Laird method [20] to combine virological suppression Tenoxicam proportions. We used the same random effects model and the Hedges method [18,19] to combine changes in CD4 cell count. We used a random effects meta-regression model to estimate the extent to which covariates explained heterogeneity in treatment effects. We entered the following baseline population characteristics into the model: mean age; percentage of men; percentage of individuals with AIDS-defining events; median CD4 cell count; median HIV RNA level; percentage of individuals
on OBT regimens with GSS of 0, ≤1, or ≤2; and use of CCR5 inhibitors. Missing GSS values were considered to be 0. All analyses were performed using stata 9.0 (StataCorp LP, College Station, TX, USA). Our process for identifying eligible studies is summarized in Figure 1. By combining keywords, we identified 1121 titles and abstracts, of which 961 were not eligible. Of the remaining 160 potentially relevant studies, we examined in detail 80 clinical trials and excluded 70 of them because the design of the study was ineligible (n=50), because of lack of randomization (n=2) or data at W48 (n=17). Moreover, we excluded one clinical trial that evaluated vicriviroc and met all inclusion criteria [21], because the doses used [10 or 15 mg once a day (qd)] differed from those used in Phase III clinical trials. We finally retained 10 trials that met our inclusion criteria [12,13, 22–29]. Four of these used CCR5 inhibitors and six used other new antiretroviral drugs.