The evaluation of 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 International and Domestic Pediatric and Maternal HIV Clinical Trials Network, International Pediatric Maternal Adolescent AIDS Clinical Trials Network (IMPAACT), and Adolescent Medicine Trials Network for HIV/AIDS Interventions), as well as through investigator-initiated grants. There are unique aspects of HIV infection in children and pregnant women. There are well-documented changes in drug pharmacokinetics during the transition from newborn to adulthood that requires separate evaluation of therapeutic agents in children. Additionally, there are changes in drug pharmacokinetics associated with pregnancy which also make it essential to evaluate therapeutic drugs that will be used for treatment of HIV or associated infections in pregnant women. In addition, 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 toxicities of antiretroviral agents 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.
HIV frequently involves the neurologic system in children, causing developmental delay and encephalopathy, and can severely affect physical growth of children 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.
Given that most HIV-infected children reside in resource-limited settings, 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 to study. There is a dearth of data 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.
Examples of scientific research areas include, but are not limited to:
- Pharmacokinetic and safety studies
- Pharmacokinetics and safety of antiretroviral drugs in HIV-infected infants, children, adolescents, and pregnant and postpartum women
- Treatment of HIV-associated infections (e.g., TB, malaria, and hepatitis) in HIV-infected infants, children, adolescents, and pregnant and postpartum women, including pharmacokinetic and safety studies and studies of interactions between antiretroviral and antimicrobial agents
- Treatment of HIV-associated non-infectious complications in HIV-infected infants, children, adolescents, and pregnant and postpartum women
- Optimizing antiretroviral therapy in HIV-infected infants, children, adolescents, and pregnant and postpartum women with HIV-associated co-infections or co-moribidites such as malnutrition
- Antiretroviral drug resistance
- Studies to evaluate functional “cure” of HIV infection
- Biomedical prevention studies
- Evaluation of vaccines to prevent HIV and other HIV-related infectious diseases in infants, children, adolescents, and pregnant and postpartum women
- Evaluation of microbicides, in collaboration with the Microbicide Trials Network, and other drug-based modalities to prevent HIV and other HIV-related infectious diseases in infants, children, adolescents, and pregnant and postpartum women
- Optimizing malaria prevention in children