IMPAACT, RANDOMIZED TRIAL TO EVALUATE VIROLOGIC RESPONSE AND PHARMACOKINETICS OF TWO DIFFERENT REGIMENTS IN HIV INFECTED WOMEN

Westat, Inc., Rockville MD

Investigators

Abstract

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) seeks to support clinical activities for international and domestic pediatric and maternal HIV and other high priority infectious diseases. NICHD provides clinical trial sites to some other clinical trial networks such as the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) The IMPAACT network and its leadership group are in charge of the creation of all their studies, protocols, and clinical trials. These activities are funded through Grants/Cooperative agreements sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The IMPAACT Network is a cooperative group of institutions, investigators, and other collaborators mainly focused on evaluating potential therapies for HIV infection and its related symptoms and co-infections in infants, children, adolescents and pregnant women. This includes clinical trials of HIV/AIDS interventions for the prevention of mother to child transmission. In 1990 the NICHD began collaborating with the Pediatric AIDS Clinical Trials Group, (PACTG) to expand clinical trial availability at NICHD clinical trial centers/sites. This collaboration made possible to conduct clinical trials by the IMPAACT Network to further evaluate antiretroviral therapeutic agents, other therapies targeted at opportunistic infections, and interventions to prevent perinatal HIV transmission. In recent years, the collaboration is expanding to evaluate potential HIV cure approaches and vaccines. The NICHD will continue providing this Coordinating Center Contract support to the IMPAACT Network providing access to sites and the clinical populations of interest. The current prevention of mother to child transmission (PMTCT) strategies based on the use of triple ARV regimens after the first trimester through labor, appropriate management of delivery, and avoidance of breastfeeding have been successful in lowering the rates of HIV perinatal transmission to less than 2%. Results of clinical trials for PMTCT suggest that women receiving triple antiretroviral (ARV) regimens that effectively reduce HIV-1 Ribonucleic Acid (RNA) to<1,000 copies/mL or undetectable levels are associated with significantly lower risk of perinatalHIV-1 transmission. Published data from a study in a cohort of HIV-infected pregnant women from the United Kingdom and Ireland in which the transmission rate was only 0.1% in 2,117 pregnant women on triple ARV regimens who achieved viral suppression. Also, there is evidence that being on a triple ARV regimen at conception and starting a triple ARV regimen earlier in pregnancy are associated with a lower risk of transmission after adjusting for viral load. This strategy is strongly dependent on early access to prenatal care and availability of ARVs for PMTCT with viral suppression and appropriate approach of mode of delivery. A considerable number of pregnant women enter prenatal care after the 20th to 28th week of gestation even in developed countries. Approximately one quarter of HIV-infected persons in the United States (US) are unaware that they are infected. The Mother-Infant Rapid Intervention at Delivery (MIRIAD) study, which was a prospective, multicenter study funded by the Centers for Disease Control and Prevention, offered voluntary, rapid HIV testing to women with undocumented HIV status late in pregnancy. Among 7,753 women with available test results from17 US hospitals, 52 (0.7%) were HIV-infected. Brazilian data published in 2007 from a cohort of HIV-infected pregnant women at a public hospital showed that the mean gestational age of initiation of prenatal care was 24+ or ? 8 weeks of gestation. Also, some pregnant women seroconvert late during pregnancy. A Brazilian study addressing primary HIV-1 infection during pregnancy showed an incidence of HIV-1 seroconversion of 0.8/1,000 (CI 95% 0.4-1.5/1,000). These women are more likely to transmit infection to their newborn, as plasma viral loads directly correlate with the risk of mother-to-child transmission (MTCT) of HIV-1. Decay dynamics of HIV-1 depend on the inhibited stage of the viral life cycle and are used as a measure of the effectiveness of ARV drugs and drug regimens. Therefore, the viral decay dynamics provided by different ARVs combinations could be critical for the effectiveness of the PMTCT effort. A more rapid reduction in viral load may be critical in minimizing both trans placental and intrapartum transmission of HIV-1 to the infant if ARV treatment is initiated late in pregnancy. .