ABSTRACT
The risk of HIV acquisition is higher during pregnancy and postpartum than other times. Newly acquired maternal HIV infection associated with high primary viraemia, substantially increases the risk of vertical HIV transmission. Pre-exposure prophylaxis (PrEP) reduces the risk of HIV acquisition. Currently available products include oral tenofovir/emtricitabine (TDF/FTC) and tenofovir alafenamide (TAF)/FTC), long-acting cabotegravir (CAB-LA) and the dapivirine ring (DVR). All except oral TDF/FTC have limited safety data available for use in pregnant and breastfeeding women. The safety of new PrEP agents for pregnant women and the fetus, infant and child, either exposed in utero or during breastfeeding is an ongoing concern for health care workers and pregnant and breastfeeding women, particularly as the safety risk appetite for antiretroviral (ARV) agents used as PrEP is lower in pregnant and breastfeeding women who are HIV-uninfected, compared to women living with HIV taking ARVs as treatment. With the widespread rollout of TDF/FTC among pregnant women in South Africa and other low-middle income countries (LMIC) and the potential introduction of new PrEP agents for pregnant women, there is a need for safety surveillance systems to identify potential signals of risk to either the mother or fetus, measure the burden of such a risk, and where appropriate, provide specific reassurance to PrEP users. Safety data needs to be collected across the continuum of the product life cycle from pre-licensure into the post-marketing period, building a safety profile through both passive and active surveillance systems, recognising the strengths and limitations of each, and the potential for bias and confounding. Pharmacovigilance systems that aim to assess the risk of adverse birth outcomes in pregnant women exposed to PrEP and other agents need to consider the special requirements of pregnancy epidemiology to ensure that the data derived from surveillance are sufficiently robust to inform treatment policies. Here we review the known safety profiles of currently available PrEP candidates in women of child-bearing potential, pregnancy and breastfeeding and discuss pragmatic approaches for such surveillance in HIV-endemic LMICs.
ABSTRACT
BACKGROUND: In 2013, a pregnancy exposure registry and birth defects surveillance (PER/BDS) system was initiated in eThekwini District, KwaZulu-Natal (KZN), to assess the impact of antiretroviral treatment (ART) on birth outcomes. OBJECTIVES: At the end of the first year, we assessed the risk of major congenital malformations (CM) and other adverse birth outcomes (ABOs) detected at birth, in children born to women exposed to ART during pregnancy. METHOD: Data were collected from women who delivered at Prince Mshiyeni Memorial Hospital, Durban, from 07 October 2013 to 06 October 2014, using medicine exposure histories and birth outcomes from maternal interviews, clinical records and neonatal surface examination. Singleton births exposed to only one ART regimen were included in bivariable analysis for CM risk and multivariate risk analysis for ABO risk. RESULTS: Data were collected from 10 417 women with 10 517 birth outcomes (4013 [38.5%] HIV-infected). Congenital malformations rates in births exposed to Efavirenz during the first trimester (T1) (RR 0.87 [95% CI 0.12-6.4; p = 0.895]) were similar to births not exposed to ART during T1. However, T1 exposure to Nevirapine was associated with the increased risk of CM (RR 9.28 [95% CI 2.3-37.9; p = 0.002]) when compared to the same group. Other ABOs were more frequent in the combination of HIV/ART-exposed births compared to HIV-unexposed births (29.9% vs. 26.0%, adjusted RR 1.23 [1.14-1.31; p < 0.001]). CONCLUSION: No association between T1 use of EFV-based ART regimens and CM was observed. Associations between T1 NVP-based ART regimen and CM need further investigation. HIV- and ART-exposed infants had more ABOs compared to HIV-unexposed infants.
