Surprisingly Iniparib male gender was associated with larger treatment effects, but this association may be a consequence of the presence of confounding variables. Most HIV infected men in high ome settings are men who have sex with men, have longer histories of exposure to antiretroviral drugs, and thus have fewer active drugs in their OBT regimens. The association between male gender and treatment outcome is probably confounded by GSS. In fact, when we adjusted our results for GSS, this association was no longer significant . Our study used indirect comparison to demonstrate that the use of CCR5 inhibitors was not associated with higher reases in CD4 cell counts. This result contradicts the meta analysis of Wilkin which showed greater CD4 cell count reases among CCR5 inhibitor users at week 24, even when controlling for degree of virological suppression .
Wilkin used a multivariate linear regression model to evaluate predictors of CD4 IGF-1R Signaling Pathway cell count gains. In their analysis, each clinical trial arm was assigned a single data point. Our analysis also used a meta regression model, but we luded both clinical trial arms as a single data point and considered the difference in CD4 gains between arms. Our analysis probably accounted for potential confounding variables more accurately. Nevertheless, we acknowledge that our findings are observational, and therefore vulnerable to bias. Baseline patient characteristics were heterogeneous in both treatment and placebo groups, with large variations in the proportion of patients with AIDS, the median CD4 cell count, the median HIV RNA level and the OBT regimen GSS.
We could not adjust ion milling our results for these differences. Even if we had done so, we would only have been able to adjust for information aggregated at the trial level. Moreover, our results cannot be extrapolated to immunological nonresponders, who have weak immunological responses despite virological suppression , or to treatment naı¨ve patients initiating cART at very low CD4 cell counts. However, two recent studies that assessed immunological responses to adding maraviroc to existing cART regimens among patients with undetectable HIV RNA and CD4 counts 250 cells/mL did not find significant CD4 count improvements at week 24 . Our systematic review demonstrates that luding new antiretroviral drugs in cART regimens improves outcomes among treatment experienced patients.
This review also demonstrates that the most important predictive factor for achieving undetectable HIV RNA or higher CD4 cell count reases is the number of fully active drugs luded in the regimen. Future RCTs should evaluate whether patients with multidrug resistant HIV should receive two or three fully active drugs. Finally, we show that CCR5 inhibitors are not associated with higher reases in CD4 cell count. A large RCT directly comparing CCR5 inhibitors with other new drugs should be conducted to confirm or refute these findings. Acknowledgments We acknowledge the STOP SIDA Association for their support. Funding: None. Conflicts of interest: MP does not report any association that might pose a conflict of interest. SDB has received grants from Roche and Janssen Cilag. LC has received travel grants, honoraria for presentations at workshops and consultancy fees from Bristol Myers.