How does antiretroviral therapy (ART) prophylaxis affect pregnancy outcomes in women with HIV infection?

Updated: Apr 02, 2019
  • Author: Ashley T Peterson, MD; Chief Editor: Ronald M Ramus, MD  more...
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The Antiretroviral Pregnancy Registry, where clinicians should report cases of exposure to antiviral therapy in pregnancy, contains approximately 18,000 reported exposures and notes no increase in the congenital malformation rate with exposure to antiretroviral medications, even in the first trimester, with the exception of didanosine and nelfinavir. First trimester exposure to efavirenz was previously reported to be associated with neural tube defects, however further meta-analyses and studies have been reassuring and the WHO continues to recommend efavirenz as an alternative in resource-poor settings.

ART may increase the incidence of adverse pregnancy outcomes. Several studies have shown that zidovudine monotherapy had no negative effect on pregnancy.

Although initial data from cohorts in the United States have not shown an increased risk of preterm birth with combination therapy, a European collaborative study showed an increased risk of preterm labor in women infected with HIV who were taking combination antiretroviral therapy, with an odds ratio for preterm birth of 1.8 for combination therapy without a protease inhibitor and 2.6 for combination therapy that included a protease inhibitor. [8]

The Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, published in 2016, was a well-designed randomized controlled trial of 3,490 mostly African women that reported women who initiated ART in pregnancy were more likely to deliver preterm (< 37 weeks gestation) as well as deliver infants weighing less than 2,500 grams than women receiving non-suppressive monotherapy with zidovudine. [9]

In another US study of pregnant women infected with HIV, the overall rate of adverse pregnancy outcome, including prematurity, low birth weight, stillbirth, and abnormal Apgar scores, was similar in women who received antiretroviral therapy during pregnancy and those who did not. [10] Of the 2123 women in the study, 1590 received monotherapy, 396 received combination therapy without a protease inhibitor, and 137 received combination therapy with a protease inhibitor; 1143 did not receive antiretroviral therapy.

Rates of prematurity and extreme prematurity did not differ significantly according to antiretroviral regimen. Although the risk of low and very low birth weight was greater in the group receiving a protease inhibitor, the results did not reach statistical significance. Furthermore, this may be a reflection of higher viral load or advanced stage of disease rather than exposure to protease inhibitors. [10]

In a more recent retrospective study (2004-2012) that evaluated US infant growth patterns during their first year of life among those born to perinatally HIV-infected (PHIV) (32 infants, 25 mothers) and nonperinatally HIV-infected (NPHIV) mothers (120 infants, 99 mothers) who received care, infants of PHIV mothers had lower mean length-for-age z-scores (LAZ) that were associated with birth length. Other small-for-gestational age anthropometric parameter associations included those of birth weight and weight-for-age z-scores (WAZ) and those of both birth length and weight with weight-for-length z-scores (WLZ). The investigators also reported an association between delivery HIV RNA level below 400 copies/mL with increased WAZ and WLZ. [11]

A large meta-analysis that included articles from several countries between 1998 and 2006 showed that overall, highly active antiretroviral therapy (HAART) did not increase the risk of prematurity; however, the use of regimens with protease inhibitors seemed to increase prematurity slightly. [12]

A possible association exists between HAART and preeclampsia. [13]

The development of glucose intolerance may be more common in pregnant women with HIV. Originally thought to be associated with protease inhibitors, gestational diabetes appears to be somewhat increased regardless of the medication regimen. As such, during pregnancy, women should be screened and monitored for glucose intolerance. [14]

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