Meanwhile, we can make indirect comparisons  using studies that compare CCR5 inhibitors and other new drugs with placebo. We performed a systematic review
and meta-analysis of RCTs that compared new antiretroviral drugs with placebo among treatment-experienced patients on optimized background therapy (OBT). We evaluated the overall virological and immunological efficacy of new antiretroviral drugs compared with placebo, as well as the factors associated with efficacy. We also performed an indirect comparison between CCR5 inhibitors and other new drugs using immunological efficacy data at week 48 (W48). We included RCTs that were published or presented at conferences between January 2003 and March 2010. Eligible studies were those that enrolled treatment-experienced HIV-infected patients with a plasma HIV-1 RNA level of at least 1000 copies/mL at the selleck chemicals screening visit on stable antiretroviral therapy. Studies compared, at W48, the immunological Fostamatinib ic50 and virological responses in patients on OBT plus new antiretroviral drugs with responses in patients on OBT plus placebo. New drugs included maraviroc and vicriviroc (CCR5 inhibitors), enfuvirtide (a fusion inhibitor), raltegravir (an integrase inhibitor), etravirine [a nonnucleoside reverse transcriptase inhibitor (NNRTI)], tipranavir and darunavir [protease inhibitors (PIs)]. When
studies evaluated multiple doses of a new drug, we only included the group assigned to the recommended dose. Although vicriviroc was not licensed at the time of data collection, it was in advanced clinical development. We included studies that administered a 30 mg/day dose, in accordance with Phase III clinical trials. Patients were defined as treatment-experienced based on their treatment histories and/or
current genotypic sensitivity score (GSS) or phenotypic sensitivity score (PSS). Although definitions differed among studies, all patients had previously taken at least one NRTI, one NNRTI, and one PI for at least 3–6 months or they had documented genotypic or phenotypic resistance to drugs in at least two or three of these classes. We included studies in any language in which HIV-1-infected patients aged ≥16 years were enrolled and that reported CD4 cell counts and HIV RNA levels at W48. Orotidine 5′-phosphate decarboxylase In accordance with the Cochrane collaboration guidelines , we conducted our search in the Medline database, the Cochrane controlled clinical register, clinicaltrials.gov, and the websites of major international conferences. We used the following keywords: HIV, adult, treatment-experienced, maraviroc, vicriviroc, enfuvirtide, raltegravir, etravirine, tipranavir, and darunavir. Two reviewers (M.P. and L.C.) independently screened titles and abstracts and obtained the full text of potentially eligible articles. Two reviewers (M.P. and L.C.) used a structured questionnaire, in accordance with the PRISMA method , to independently extract data. A third reviewer (Y.Y.) resolved any discrepancies.