Is protease inhibitors based antiretroviral therapy during pregnancy associated with an increased risk of preterm birth? Systematic review and a meta-analysis

Background: Antiretroviral therapy is recommended during pregnancy to decrease the risk of perinatal transmission of HIV-1 infection and to improve maternal health. However, some studies have reported that antiretroviral treatment (ART) containing protease inhibitors (PI) is associated with an increased risk of preterm birth. In contrast, other studies have reported no increased risk. This meta-analysis was conducted to derive a more reliable estimate of the association between the prenatal use of PI based ART regimen and preterm birth. Methods: A systemic review and meta-analysis was conducted using published studies which were identified through a computerized search using the Medline/PubMed database, Google Scholar and Health Inter Network Access to Research Initiative (HINARI). The analysis was undertaken using STATA version 11.0 software and studies were described by forest plot. Heterogeneity across studies was checked using Cochran Q test and I2 test. An adjusted odd ratio with 95 % confidence intervals [95 % CI] was pooled using a random effects model. Results: The Cochrane Q test (Q test p = 0.051) showed a good homogeneity among studies. However, medium heterogeneity was observed in up to 46 % of the sample using the I2 test (I2 = 46.5 %). The Egger weighted regression method (p = 0.04) showed evidence of publication bias, but Begg rank correlation statistics (p = 0.47) did not show evidence of publication bias. The pooled analysis of 10 studies showed that protease based ART exposure during pregnancy was associated with an increased risk of preterm birth (pooled odds ratio 1.32 (95 % CI, 1.04 to 1.59). Conclusions: This meta-analysis revealed that the PI based ART exposure during pregnancy is significantly associated with an increased risk of preterm birth. There should be strong cautions against initiating ART during pregnancy and PI based ARV should be replaced by others drug regime. Protease inhibitor ART drugs should not be included as part of therapy during pregnancy.