LAUSR

BACKGROUND Existing data suggest that certain combination antiretroviral treatment (cART) regimens, especially protease inhibitor (PI)-based, and cART initiation before conception, may be associated with adverse pregnancy outcomes. We examined the risk of having a small for gestational age (SGA) infant among pregnant HIV-infected mothers on 1) PI-based compared to non-PI-based cART, and 2) any cART initiated before compared to after conception. METHODS We searched PubMed, Embase, and Cochrane Library, and did a systematic review of studies published since Dec 1, 1995. We extracted effect estimates with 95% confidence intervals (CIs) and conducted meta-analyses with random-effects models. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. FINDINGS Of 783 identified studies, 28 fulfilled the inclusion criteria. The meta-analysis indicated that PI-based cART was associated with a possible slightly increased risk of SGA compared with non-PI-based cART (pooled odds ratio 1·09, 95% CI 0·76, 1·55). Initiation of cART before conception was also associated with a possible slightly increased risk of SGA compared with after conception (pooled odds ratio 1·08, 95% CI 0·95, 1·22). The overall certainty of evidence was very low and low for the first and second research question, respectively. INTERPRETATION Although the benefits of cART largely outweigh the risks, our findings include the possibility of slightly increased risks of having a SGA infant. This indicates that careful monitoring of fetuses exposed to PI-based cART or cART before pregnancy might be reasonable. Based on the uncertainty of evidence, further research may change this conclusion.