Future Research Needs

An increasing number of HIV-1-infected women will be receiving antiretroviral therapy for their own health during pregnancy. Preclinical evaluations of antiretroviral drugs for potential pregnancy- and fetal-related toxicities should be completed for all existing and new antiretroviral drugs. More data are needed regarding the safety and pharmacokinetics of antiretroviral drugs in pregnant women and in their neonates, particularly when they are used in combination regimens. Results from several phase I studies will be available in the next year; these results will assist in delineating appropriate dosing and will provide data regarding short-term safety of these drugs inpregnant women and their infants. However, the long-term consequences of in utero antiretroviral exposure for the infant are unknown, and mechanisms must be developed to gather information about the long-term outcome for exposed infants. Innovative methods are needed to enable identification and follow-up of populations of children exposed to antiretroviral drugs in utero. Additional studies are needed to determine the long-term consequences of transient use of ZDV chemoprophylaxis during pregnancy for women who do not choose to receive combination therapy antenatally, including the risk for development of ZDV-resistance.

Although more potent antiretroviral combination regimens that dramatically diminish viral load also may theoretically prevent perinatal transmission, no data are available to support this hypothesis. The efficacy of combination antiretroviral therapy to decrease the risk for perinatal HIV-1 transmission needs to be evaluated in ongoing perinatal clinical trials. Additionally, epidemiologic studies and clinical trials are needed to delineate the relative efficacy of the various components of the three-part ZDV chemoprophylactic regimen. Improved understanding of the factors associated with perinatal HIV transmission despite ZDV chemoprophylaxis is needed to develop alternative effective regimens. Because of the dramatic decline in perinatal HIV-1 transmission with widespread implementation of ZDV chemoprophylaxis, an international, collaborative effort is required in the conduct of such epidemiologic studies and clinical trials.

Regimens that are more feasible for implementation in less developed areas of the world are needed. The three-part ZDV chemoprophylactic regimen is complex and may not be a feasible option in many developing countries for the following reasons: a) most pregnant women seek health care only near the time of delivery, b) wide-spread safe administration of intravenous ZDV infusions during labor may not be possible, and c) the cost of the regimen may be prohibitive and many times greater than the per capita health expenditures for the country. Several studies are ongoing in developing countries that are evaluating the efficacy of more practical, abbreviated modifications of the ZDV regimen. Additionally, several nonantiretroviral interventions also are being studied. Results of these studies will be available in the next few years.

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