Safety of HAART for HIV-Positive Pregnant Women and Their Infants

When highly active antiretroviral therapy (HAART) is used in conjunction with appropriate labor management, the rate of vertical HIV transmission can be as low as <1%. While these strategies have been proven effective, the question of the safety of the pharmacologic interventions is now raised. The objective of the article is to summarize and contextualize the latest data on the safety of antiretroviral therapy in pregnancy.
Little evidence suggests that HAART increases teratogen risk. Efavirenz is a class D medication on the basis of case reports of spina bifida and Dandy-Walker syndrome. Concern has also been raised about didanosine but no specific associated abnormality has been identified. Furthermore because of the concern surrounding maternal lactic acidosis and even death in those taking didanosine and stavudine, the combination is no longer recommended in the context of pregnancy. Data addressing the newer drug classes continues to be collected but overall mothers in need of HAART can be reassured the most commonly used antiretrovirals in pregnancy are not associated with increased risk of teratogenicity.
There has been concern surrounding mitochondrial toxicity in infants exposed antenatally to zidovudine. This stems from a single study that has not been replicated. The reported toxicity may have been a result of HIV exposure in conjunction with monotherapy, as therapy that fully suppresses HIV replication reduces this effect.
Through studies conducted throughout the world in both developed and underdeveloped countries, authors have found a correlation with the use of HAART and the risk of preterm delivery (PTD) and small for gestational age (SGA) infants. These studies have compared HAART with monotherapy (zidovudine) or with no therapy at all. Similar studies conducted in both the local and international arena have not consistently reproduced these finding. There are multiple confounding variables such as drug use, socioeconomic status, preexisting illness, degree of immunocompetence/deficiency, obstetrical history, etc, that may contribute to this association that need to be carefully examined warranting further investigation.
The benefits of antiretroviral therapy in the context of pregnancy are unquestionable. The risks incurred by women taking these medications and to her fetus overall are low. The concern surrounding the increased risk of PTD and SGA infants deserves further investigation and should be weighed against the benefits gained with HAART. It is also critical to understand the risks incurred in both resource rich and poor settings as the impact could have different consequences and implications for these diverse populations.
--Summarized by Whitney You, MD
Whitney You is a Maternal-Fetal Medicine Fellow at Northwestern Memorial Hospital, where she participates in the ongoing care of one of Illinois’ largest clinics exclusively servicing HIV-positive pregnant patients.
Martin, F and Taylor, GP. The safety of highly active antiretroviral therapy for the HIV-positive pregnant mother and her baby: is 'the more the merrier'? J Antimicrob Chemother 2009;64:895-900.

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