Several pregnancy-specific issues will need special consideration when using ART in pregnant women. These include the efficacy of antiretroviral drugs in prevention of mother-to-child HIV transmission, maternal and foetal toxicity, teratogenicity, PK profile, antiretroviral drug resistance testing before and during pregnancy, transplacental transfer of antiretroviral drugs, timing of treatment initiation, hyperemesis and nausea of pregnancy.

If the mother is experiencing severe hyperemesis, ART may need to be ceased temporarily. All antiretroviral drugs will usually need to be stopped simultaneously and re-introduced simultaneously as soon as possible, remembering the potential problem that might arise with drugs that have long half-lives (e.g. nevirapine and efavirenz).

Changes in PK profile of antiretroviral drugs in pregnancy may lead to lower plasma levels of some drugs and necessitate increased dosages, more frequent dosing or boosting e.g. boosted lopinavir (commonly used in pregnancy in the past). PK studies are continuing for the newer antiretroviral drugs. For example, recent studies of once daily ritonavir-boosted darunavir (DRV/r 800/100 mg) indicated that this regimen provided adequate drug exposure to achieve suppression of HIV replication and was safe and well tolerated. ^[35] However, plasma concentrations postpartum were higher than in the second and third trimester, so assessment of adherence is important, as are any concomitant medications that may further decrease DRV levels. DRV/r twice daily has previously been shown to be a treatment option for women with HIV infection with or without DRV resistance-associated mutations. Further PK studies of etravirine 200 mg twice daily indicated higher levels in the second and third trimester than postpartum but this was not considered clinically relevant. ^[36] Further studies are ongoing in this area.

Drug safety in pregnancy

Information regarding the safety of drugs in pregnancy is derived from animal toxicity data, anecdotal experience, registry data, observational cohorts and clinical trials. Preclinical data includes results of in vitro and animal in vivo screening tests for carcinogenicity, reproductive and teratogenic effects. However, the predictive value of such tests in humans is unclear. Ultimately, it could be argued that the choice of ART in pregnancy has often been based on collective experience, accumulated safety data over time and consensus guidelines, rather than on randomised trials.

ARV associated weight gain may be a factor to be considered when initiating, or changing, antiretroviral therapy particularly in women of colour. The exact underlying mechanisms for any ARV associated weight gain, (apart from reported initial weight gain that appears to be associated with the onset of wellness), and its impact on pregnancy related outcomes, are currently unknown.

Long term outcome data for infants who have been exposed at ARVs in utero, especially to the newer agents, is limited but this does not in any way, preclude the use of recommended antiretroviral drugs in pregnancy.

Clinicians who prescribe ARVs in pregnancy, are encouraged to report foetal exposure to all of the drugs to the Antiretroviral Pregnancy Registry at: http://www.APRegistry.com

Teratogenicity of antiretroviral drugs

There is no evidence of an increased risk of congenital abnormalities in infants born to mothers with HIV infection (Table 6). Reports of birth defects in foetuses and infants of women enrolled into observational studies are reassuring with no difference in rates of birth defects for first trimester antiretroviral drug exposure compared with later exposures being observed. The known benefits and potential unknown risks of ART during pregnancy (including limited long-term outcome data for infants with in utero drug exposure) should be discussed with the mother.^[37] The need for strict adherence to prescribed medication throughout the pregnancy should always be reinforced.

Table 6.  Rates of birth defects per live birth associated with first trimester antiretroviral drug exposure, July 2023

Source: The Antiretroviral Pregnancy Registry ^[37] : http://www.APRegistry.com 

Health-care providers caring for women with HIV infection and their infants with prenatal exposure are encouraged to report de-identified, observational, non-experimental pregnancy outcome data to the Antiretroviral Pregnancy Registry (APR) (www.APRegistry.com). The purpose of the APR is to detect any major teratogenic effects of the antiretroviral drugs to which pregnant women are exposed. Although the Registry is international, reports are predominantly from the USA (77.3%). Rates of reported defects are compared with rates from two external comparator populations, the Metropolitan Atlanta Congenital Defects Program (MACDP) and the Texas Birth Defects Registry (TBDR). The APR finds no apparent increases in the frequency of defects with first trimester antiretroviral drug exposures compared to exposures starting later in pregnancy and no pattern to suggest a common cause. However, the potential limitations of such registries should always be recognised.