Evaluating new and improved therapies for treatment of HIV infection and its associated complications is a high priority for the Branch, and research is conducted through a variety of mechanisms, including clinical trials networks (such as the NICHD Domestic and International Pediatric and Maternal HIV Clinical Studies Network, International Maternal, Pediatric, Adolescent AIDS Clinical Trials [IMPAACT] Network, and Adolescent Medicine Trials Network for HIV/AIDS Interventions) and investigator-initiated grants. HIV infection in children and pregnant women has unique aspects. Therapeutic agents must be evaluated separately in children because of well-documented changes in drug pharmacokinetics and pharmacodynamics during the transition from newborn to adulthood. Additionally, because of changes in drug pharmacokinetics and pharmacodynamics associated with pregnancy, it is essential to evaluate therapeutic drugs that will be used for treatment of HIV or associated infections in pregnant women. Drugs may have increased risks of toxicity during pregnancy and may have negative effects on pregnancy and infant outcomes, such as increased risk of preterm birth.
There are also many important differences between the manifestations of HIV in infected children and infected adults that may require specific characteristics of therapeutic agents for use in pediatrics (e.g., central nervous system penetration). Children may have increased susceptibility to antiretroviral agent toxicities because of their continuing growth and development (e.g., toxic effects of drugs on bone development). Additionally, perinatal transmission is a mode of transmission unique to pediatrics. HIV disease in children with perinatal HIV infection progresses more rapidly (both clinically and immunologically), probably because HIV infection is superimposed upon a naive and immature immune system and the still-developing organ systems of the infant. Finally, comorbid serious non-AIDS sequelae and other HIV-associated complications resulting from chronic immune dysregulation are surfacing in aging adults with HIV infection. Similarly, it is largely unknown what impact such immune activation may have on the long-term end-organ (cardiovascular, kidney, neurocognitive, liver, etc.) outcomes of children with lifelong exposure to HIV and its therapy.
HIV frequently involves the neurologic system in children, causing developmental delay and encephalopathy, and it can severely affect children's physical growth early in the course of infection. Evaluation of the effect of therapeutics on these unique pediatric manifestations of HIV is crucial. Additionally, the range of opportunistic infections that complicate the immunologic dysfunction secondary to HIV infection in children differs from that in adults.
Because most HIV-infected children reside in resource-limited settings, studying optimal management of HIV infection in children and pregnant women co-infected with tuberculosis (TB), hepatitis, malaria, and other diseases endemic to such settings is critical. Data are lacking on the pharmacokinetics of drugs to treat these diseases even in children and pregnant women who are not infected with HIV, and studies of the interactions of anti-HIV drugs with drugs to treat these infections are crucial.
Research to find a cure for HIV infection among children has been jump-started by the recent report of a 4-year-old child born with HIV infection who was treated with antiretroviral drugs and did not have detectable levels of virus (using conventional testing methods) despite not taking HIV medication for over 2 years. More information is needed to identify where HIV hides—sometimes called the HIV reservoir—how this reservoir is established and maintained in children, and to identify ways to control and eliminate this viral reservoir. To stimulate research in this area, the NICHD issued RFA-HD-14-026: Evaluation of the Latent Reservoir in HIV-Infected Infants and Children with Early Antiretroviral Treatment and Virologic Control (R01), in collaboration with NIAID and NIMH. The IMPAACT Network has designed a proof-of-concept clinical trial to test the hypothesis that very early treatment can control the HIV reservoir in infants with perinatal HIV infection.
Examples of scientific research areas include:
All related topics
All related news
All related FOAs