Adverse perinatal outcomes associated with antiretroviral therapy regimens: systematic review and network meta-analysis

Journal article

Objective: Assess adverse perinatal outcomes associated with antenatal antiretroviral therapy (ART) regimens.

Design: Systematic review and network meta-analysis of randomized controlled trials (RCTS).

Methods: We conducted a systematic literature review by searching PubMed, CINAHL, Global Health, EMBASE, and the Cochrane Central Register of Controlled Trials and four clinical trial databases from 1 January 1980 to 28 April 2018. We included RCTs of antenatal ART regimens in HIV-positive pregnant women, which assessed preterm birth (PTB), spontaneous preterm birth (sPTB), very preterm birth (VPTB), low birthweight (LBW), very low birthweight (VLBW), small-for-gestational-age (SGA), neonatal death (NND), and mother-to-child-transmission. We used random-effects network meta-analysis models to calculate relative risks for treatment comparisons and the hierarchy of treatments.

Results: Of 83 260 citations identified, 10 manuscripts were included, assessing 6285 women. Compared with zidovudine (ZDV) monotherapy, we found a higher risk of LBW after exposure to zidovudine/lamivudine/efavirenz (ZDV/3TC/EFV; relative risk 1.61; 95% CI 1.03–2.51), tenofovir disoproxil fumarate/emtricitabine/ritonavir-boosted lopinavir (TDF/FTC/LPV/r; 1.64; 1.18–2.29), or zidovudine/lamivudine/ritonavir-boosted lopinavir (ZDV/3TC/LPV/r; 1.87; 1.58–2.20). TDF/FTC/LPV/r carried an increased risk of VLBW, compared with ZDV monotherapy (5.40; 1.08–27.08). ZDV/3TC/LPV/r posed a higher risk of PTB than ZDV monotherapy (1.43; 1.08–1.91) and a higher risk of sPTB than zidovudine/lamivudine/abacavir (ZDV/3TC/ABC) (1.81; 1.21–2.71). LPV/r-containing regimens also carried the highest risks of VPTB, SGA and NND, although the limited data showed no significant differences.

Conclusion: Of the ART regimens assessed in RCTs in pregnancy, LPV/r-containing regimens were associated with the highest risks of adverse perinatal outcomes.

Authors: Tshivuila-Matala, C; Honeyman, S; Nesbitt, C; Kirtley, S; Kennedy, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wolters Kluwer
• Journal: AIDS
• Volume: 34
• Issue: 11
• Pages: 1643-1656
• Publication date: 2020-07-21
• Acceptance date: 2020-05-21
• DOI: 10.1097/QAD.0000000000002593
• EISSN: 1473-5571
• ISSN: 0269-9370
• Language: English
• Keywords: neonatal death; preterm birth; low birthweight; FFR; systematic review; HIV; small-for-gestational-age; perinatal outcome; antiretroviral therapy; network meta-analysis