Adverse effects of ARV use in pregnancy: prematurity continues to raise concerns.
Article Type: Report
Subject: Pregnant women (Health aspects)
Protease inhibitors (Complications and side effects)
Protease inhibitors (Research)
Premature labor (Risk factors)
Premature labor (Research)
Pub Date: 05/01/2011
Publication: Name: Reproductive Health Matters Publisher: Elsevier Science Publishers Audience: General Format: Magazine/Journal Subject: Family and marriage; Health; Women's issues/gender studies Copyright: COPYRIGHT 2011 Reproductive Health Matters ISSN: 0968-8080
Issue: Date: May, 2011 Source Volume: 19 Source Issue: 37
Topic: Event Code: 310 Science & research Canadian Subject Form: Premature labour; Premature labour
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 259077152
Full Text: Premature births in HIV-positive women continue to be a concern, and need to be anticipated and managed actively in developing countries, researchers said at the 18th Conference on Retroviruses and Opportunistic Infections in Boston. Conflicting findings persist over the use of antiretroviral therapy, especially protease inhibitors, during pregnancy due to adverse effects on infants, including premature birth and low birthweight, which increase the risks for death and disease in both low-resource and high-resource settings. (1)

Some studies have shown an elevated risk of premamre delivery among women who receive ritonavir-boosted protease inhibitors during pregnancy. An ANRS French Perinatal Cohort French study presented at the conference showed that women who received these specific drugs were almost twice as likely to deliver prematurely compared to women getting non-boosted protease inhibitors during pregnancy, which could be explained by more toxicity in the third trimester. (2) However, a prospective cohort study in 2000-2008 among 803 children born to HIV-positive women in seven Spanish hospitals found that while the rate of pre-term birth and low birthweight was high, it was not linked to any ARV combination regimen and that HIV-positive women not on ARVs were at the greatest risk for pre-term delivery and low birthweight (RR 2.064, 95% CI: 1.262-3.376; p=0.006). (3)

Pre-term delivery is incompletely understood. Populations selected and methods used are critical to interpretation of the diverse and often conflicting findings because large inequalities exist in survival chances of a premature infant between developed and developing countries and possible adverse effects of ARV use in pregnancy may be more difficult to manage in resource-poor settings. Older age, intravenous drug use, tobacco use, no antenatal care or late access to care increased the risks for pre-term delivery and low birthweight. In the Spanish study, hepatitis C co-infection, low CD4 count and high viral load at delivery also increased the risks. (3)

The risk factors, including the use of ARVs for very premature and very small-for-age infants born to HIV-positive mothers in six hospitals across Botswana. Among 16,203 live births from October 2007 to March 2010, 28% (4,343) were born to HIV-positive women, of which 4.3% were very pre-term deliveries (<32 weeks) and 3.7% were very small for gestational age. The associated rates of neonatal deaths were 26% and 8%, respectively. High maternal blood pressure, HIV infection and a history of poor obstetric outcomes, including stillbirth, pre-term delivery or low birthweight were linked to both very preterm delivery and very small for gestational age. Continued use of antiretrovirals starting before conception was associated with very small for gestational age and high blood pressure during pregnancy but not with very pre-term delivery. It was suggested that control of hypertension in pregnancy may improve outcomes. (4)

A randomised trial comparing antiretroviral regimens among pregnant HIV-positive women with CD4 cell counts [less than or equal to] 200 was also conducted in Botswana. Pregnant HIV-positive women were randomised between 26 and 34 weeks of gestation to two ARV regimens, one with a protease inhibitor (PI) and one with NRTI, in a clinical trial designed to prevent mother-to-child transmission. Women in the PI group were almost twice as likely to deliver pre-term. Those in the PI group gained less weight than those in the NRTI group. However, weight change was not a significant risk for pre-term delivery. Infant hospitalisations and infant deaths were highest in the first six months of life but did not differ significantly according to maternal ARV regimen. These two studies highlight the importance of prioritising high-risk antenatal and neonatal services in countries like Botswana with generalised HIV epidemics where ART regimens are used for PMTCT. (5)

Didier Ekouevi, co-discussant, of the University of Bordeaux, France, and of the ANRS Abidjan, Cote d'Ivoire, concluded that while ARVs can reduce mother-to-child transmission rates to as low as 1%, they can also induce premature delivery (11%-20%), as a result of which 6% of infants will die within the first six months. He proposed a pregnancy register in low-income countries to study frequency of pre-term delivery, relation to type of ARV started, long-term follow-up data (death/growth), and haematological and neuro-development disorders. (1)

(1.) Leach-Lemens C. AIDSmap News, 10 Match 2011. At: .

(2.) Sibiude J, et al. Large increase in prematurity between 1990 and 2009 in HIV-infected women in the national French perinatal cohort: does ritonavir boost play a role. 18th Conference on Retroviruses and Opportunistic Infections, Boston, 2011. Abstract 743, 2011.

(3.) Gonzalez-Tome MI, et al. Risk factors of preterm delivery and low birth weight in a multicentre cohort of HIV + pregnant women. 18th Conference on Retroviruses and Opportunistic Infections, Boston, 2011. Abstract 744.

(4.) Parekh N, et al. Risk factors for very premature and very small for gestational age infants in Botswana. 18th Conference on Retroviruses and Opportunistic Infections, Boston, 2011. Abstract 745.

(5.) Powis K, et al. Protease inhibitor-based ART was associated with pre-term delivery, bur not adverse infant outcomes, in a randomized MTCT prevention study in Botswana. 18th Conference on Retroviruses and Opportunistic infections, Boston, 2011. Abstract 746.
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