Perinatal transmission: associated factors and therapeutic approaches.
Int Conf AIDS 1996 Jul 7-12; 11:214 (abstract no. Tu.07) Bryson YJ; Dept. of Pediatrics, UCLA Children's Hospital, Los Angeles, CA, USA. Fax: 310-206-5529/4764. E-mail: trossom@pediatrics.medsch.ucla.edu.
Summary: There have been major advances in the understanding and prevention of maternal fetal HIV-1 transmission and in factors associated with rapid or slow progression in infected infants. Without intervention the majority of pediatric HIV infection is acquired from the mother either in-utero, at the time of birth, or postpartum by breast-feeding; with transmission rates varying from 13% to 40% with an average of 25% in most USA cohorts. ZDV given to the mother during pregnancy and delivery and to the newborn for six weeks reduced transmission by 2/3 or less than 8%. This has changed the standard of care in the US and elsewhere and propagated recommendations for voluntary offering of HIV testing to all pregnant women. The mechanism of protection of ZDV may be reduction of maternal virus load and/or prophylaxis of the infant. Several studies have shown that high maternal virus load as measured by quantitative RNA PCR is a critical risk factor associated with transmission. Although women are more likely to transmit at high virus load, transmission can also occur at low virus load suggesting more than one mechanism. Maximum lowering of maternal virus load could provide goals for targeted intervention as a model of transmission. ZDV can reduce virus load an average of 3-6 fold in drug naive women and has a protective effect at any maternal virus load suggesting that both reduction of virus load prior to delivery and prophylaxis of the fetus/infant are important. There is also data to suggest that neutralizing antibody, virus phenotype, and obstetrical events such as prolonged ruptured membranes (4 hrs) and infant exposure to blood and secretions are also critical factors. Current goals include reduction of HIV transmission to less than 2%. Intervention studies are directed at both further reduction of maternal virus load and providing prophylaxis to the newborn including the use of potent combinations of antiretrovirals, passive antibody, and vaccines given to the mother and/or newborn infant. International studies are addressing the efficacy of shortened courses of ZDV treatment alone and in combination with other antivirals and the individual components. The timing of transmission (in utero and intrapartum), the extent of early virus replication, the transmitted virus phenotype and the infant's immune response all seem to be important in determining the onset and course of disease progression in the HIV-infected infants. The challenge of the future will be to translate the science of prevention of transmission to practical worldwide application.
Keywords: AEGIS, Disease Transmission, Vertical, Viral Load, Zidovudine, HIV-1, HIV Infections, Anti-HIV Agents, Reverse Transcriptase Inhibitors, HIV Protease Inhibitors, Breast Feeding, HIV-1 Reverse Transcriptase, Delivery, Obstetric, Polymerase Chain Reaction, Risk Factors, United States, Human, Female, Infant, Infant, Newborn, Child, Pregnancy, transmission, growth & development, surgery, ICA11
