To evaluate the comparative safety and effectiveness of antiretroviral drugs in
To evaluate the comparative safety and effectiveness of antiretroviral drugs in HIV-infected pregnant women and their infants who were exposed to HIV in-utero, during delivery or while breastfeeding, through performance of a systematic review and network meta-analysis.Methods/DesignProtocolA protocol was compiled for our systematic review and circulated for feedback from the policy-makers who posed the query within Health Canada, systematic review methodologists, clinicians, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29069523 and pharmacologists. After completion, the protocol was registered with the PROSPERO database (CRD42014009071). The Preferred Reporting Items for Systematic reviews and Meta-analyses Protocols (or PRISMAP) was used to guide the reporting of this protocol [18].Eligibility criteriaOnly studies fulfilling our eligibility criteria will be included [19], as outlined in Additional file 1: 1. Patients: Pregnant women infected with HIV-1 and/ or the fetuses and infants of mothers who are HIVpositive. Studies of women infected with HIV-2 will be excluded. Women at any stage of pregnancy will be eligible for inclusion. Infants and Pleconaril site children exposed in-utero, during delivery or breastfeeding are eligible for inclusion until 18 months of age or until breastfeeding is discontinued. All countries and settings are eligible for inclusion. 2. Interventions: Any of the 24 antiretroviral medications approved for use in Canada from the aforementioned classes, as presented in Additional file 2 [20]. We will include studies of all combinations and PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/25645579 doses of these medications. In order to be included, the antiretroviral medication must be administered to HIV-infected pregnant women; we will not include studies examining antiretroviral treatment directly administered to infants or children. 3. Comparators: Antiretroviral medications against each other, against placebo/no treatment, or combinations of two or more antiretroviral drugs. 4. Outcomes: The primary effectiveness outcome is mother-to-child transmission of HIV, which is defined as infant HIV-infection from 2 weeks of age to 18 months or until breastfeeding is discontinued. The primary safety outcome is major congenital malformations (overall and by specific type), which is defined as a malformation present from birth that requires substantial medical intervention, includingTricco et al. Systematic Reviews 2014, 3:51 http://www.systematicreviewsjournal.com/content/3/1/Page 3 ofsurgery. The secondary safety outcomes include stillbirths, infant/child death (up to 18 months of age), minor congenital malformations (overall and by specific types), small for gestational age infants (defined as weight below the 10th percentile for gestational age), and preterm delivery, 5. Study designs: Experimental (randomized clinical trials (RCTs), quasi-RCTs, and non-RCTs), quasiexperimental (controlled before and after studies and interrupted time series) and observational (cohort, case control, and registry studies) studies. 6. Other limitations: No limitations will be imposed on publication status, language of dissemination, duration of study follow-up or period of study conduct.Information sources and literature searchThe primary source of literature will be a structured search of major electronic databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The secondary source of potentially relevant material will be a search of the gray literature [21], including dissertation databases (ProQuest Dissertations and.