Antiretroviral therapy for pregnant women living with HIV or hepatitis B: a systematic review and meta-analysis

Abstract

Objective: To assess the impact of various antiretroviral/antiviral regimens in pregnant women living with HIV or hepatitis B virus (HBV).

Design: We performed random effects meta-analysis for HIV-related outcomes and network meta-analysis for HBV outcomes, and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess quality separately for each outcome.

Data sources: Embase and Medline to February 2017.

Eligibility criteria: For maternal outcomes, we considered randomised controlled trials (RCTs) comparing tenofovir-based regimens with those with alternative nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). For child outcomes, we included RCTs and comparative observational studies of tenofovir-based regimens versus alternative NRTIs regimens or, for HBV, placebo.

Results: Ten studies (seven RCTs) met the inclusion criteria for maternal and child outcomes, and an additional 33 studies (12 RCTs) met the inclusion criteria for HBV-specific outcomes. The most common comparison was tenofovir and emtricitabine versus zidovudine and lamivudine. There was no apparent difference between tenofovir-based regimens and alternatives in maternal outcomes, including serious laboratory adverse events (low certainty) and serious clinical adverse events (moderate certainty). There was no difference between NRTIs in vertical transmission of HIV: 1 more per 1000, 8 fewer to 10 more, low certainty; or vertical transmission of HBV: 7 fewer per 1000, 10 fewer to 38 more, moderate certainty. We found moderate certainty evidence that tenofovir/emtricitabine increases the risk of stillbirths and early neonatal mortality (51 more per 1000, 11 more to 150 more) and the risk of early premature delivery at <34 weeks (42 more per 1000, 2 more to 127 more).

Conclusions: Tenofovir/emtricitabine is likely to increase stillbirth/early neonatal death and early premature delivery compared with zidovudine/lamivudine, but certainty is low when they are not coprescribed with lopinavir/ritonavir. Other outcomes are likely similar between antiretrovirals.

Trial registration number: PROSPERO CRD42017054392.

Keywords: HIV & AIDS; chronic hepatitis B; mother-to-child transmission; network meta-analysis; pregnancy; tenofovir.

Figure 1

Forest plot of the risk ratio for clinical adverse events (data from randomised trials in non-pregnant adults except Fowler et al12). ART, antiretroviral therapy; M-H, Mantel-Haenszel; NRTI, nucleoside/nucleotide reverse transcriptase inhibitor; TDF, tenofovir disoproxil fumarate.

Figure 2

Forest plot of the risk ratio for laboratory adverse events (data from randomised trials in non-pregnant adults except Fowler et al12). ART, antiretroviral therapy; M-H, Mantel-Haenszel; NRTI, nucleoside/nucleotide reverse transcriptase inhibitor; TDF, tenofovir disoproxil fumarate.

Figure 3

Forest plot of risk ratio for detectable serum viral load 26 weeks after antiretroviral initiation as a proxy for viral load at time of delivery (data from randomised trials of non-pregnant adults). ART, antiretroviral therapy; M-H, Mantel-Haenszel; NRTI, nucleoside/nucleotide reverse transcriptase inhibitor; TDF, tenofovir disoproxil fumarate.

Figure 4

Forest plot of risk ratio for stillbirth and early neonatal mortality from randomised controlled trials. ART, antiretroviral therapy; M-H, Mantel-Haenszel; NRTI, nucleoside/nucleotide reverse transcriptase inhibitor.

Figure 5

Forest plot of maternal antivirals (lamivudine and tenofovir) versus control (no antiviral) for prevention of vertical transmission of hepatitis B, by study type and antiviral. 3TC, lamivudine; ART, antiretroviral therapy; NRTI, nucleoside/nucleotide reverse transcriptase inhibitor; RCT, randomised controlled trial; RR, risk ratio; TDF, tenofovir disoproxil fumarate.