HIV treatment and birth defects

During the first 14 weeks of pregnancy, the foetus is most vulnerable to any toxic effects of drugs.

Combination therapy is now more widely used by pregnant women with HIV; however, AZT is the only drug formally cleared for use in pregnancy. Information about the safety of other drugs in pregnancy is limited. There are fewer data on the long-term safety of antiretroviral therapy in women and children generally.

A UK study covering a 17-year period and reported in 2009 showed that no individual anti-HIV drug was associated with an increased risk of birth abnormalities.¹

Moreover, a 2009 analysis found that women who took combination therapy were, in comparison with women who took AZT monotherapy, no more likely to have a baby who was born small for their gestational age. Duration of therapy had no impact on foetal growth either.²

In the light of animal studies, there are concerns about links between efavirenz (Sustiva) and birth defects, specifically neural tube defects. A 2010 meta-analysis found no increased risk of overall birth defects among women who took efavirenz during the first trimester of pregnancy compared with other antiretroviral drugs. The prevalence of overall birth defects was similar to that in the general population, although the sample size (1132 live births to women taking efavirenz) was not large enough to make definitive conclusions about rare outcomes, including neural tube defects.³ The United States Food and Drug Administration classifies efavirenz as being in Pregnancy Category D (may cause harm to the foetus when taken during the first trimester).

The Antiretroviral Pregnancy Register (www.apregistry.com) reports on possible toxicities of all licensed anti-HIV drugs and updates this information twice a year. Currently only two drugs have raised concerns, ddI (didanosine, Videx, Videx EC) and nelfinavir (Viracept).⁴

Current BHIVA/CHIVA guidelines recommend avoiding ddI use in the first three months of pregnancy.⁵

BHIVA guidelines suggest that switching from efavirenz is a possibility, if suitable alternatives are available and viral suppression could be maintained. Clinicians should discuss it with the woman. Stopping all treatment is not recommended as the long half-life of efavirenz means that stopping could effectively expose the woman to efavirenz monotherapy for up to three weeks.

Some experts have argued that the rebound in viral load which occurs when a person stops HIV therapy, may in fact increase the risk of mother-to-child transmission. It is worth noting that any of the toxicities associated with beginning a new treatment regimen may have to be endured all over again, because the body may no longer be adjusted to particular blood levels of the drugs.