Acquisition of HIV Infections in Youth
In contrast to the success in reducing perinatal HIV infection in the United States and other developed countries, the HIV epidemic among adolescents has remained unchecked. Both domestic and international epidemiologic and clinical information indicate that HIV transmission and acquisition among adolescents and young adults continues to increase.
The Centers for Disease Control and Prevention (CDC) estimates that in the United States, 26% of the approximately 50,000 new HIV infections diagnosed in 2010 were among youth 13 to 24 years of age. Of these, 57% were among young African Americans and 75% among young men who have sex with men (MSM). The CDC estimates that almost 60% of U.S. youth living with HIV infection in 2010 had not yet been diagnosed and were unaware they were infected. Recent trends in HIV/AIDS prevalence in the United States reveal that the burden of AIDS among racial minorities is even greater in youth 13 to 24 years of age (64% to 66% of cases) than in adults over 24 years of age (48% of cases). Furthermore, from 2007 to 2010, HIV diagnoses among adolescents and young adults in 46 states and 5 U.S.-dependent areas decreased or remained stable for all transmission categories except among young MSM, where the rate of infections has increased. Heterosexual transmission is the predominant mode of HIV acquisition in adolescent females. In developing countries, youth, particularly young women, are on the front lines of the HIV epidemic. The World Health Organization estimates that 5 million youth ages 15 to 24 years are living with HIV/AIDS (most without knowing they are infected), and 41% of all new infections occur among young people. Furthermore, WHO estimates that HIV/AIDS is currently the second leading cause of death among adolescents globally. Interventions to prevent HIV transmission to youth are critically needed, including behavioral interventions (both with HIV-infected and -uninfected youth) and studies of HIV vaccines, microbicides, and pre-exposure prophylaxis (PrEP) in uninfected, at-risk youth.
Treatment of HIV-infected adolescents is complicated by unique challenges and management demands. To improve individual outcomes and reduce secondary transmission events, strict adherence to all components of the continuum of care for HIV-infected populations is critical, but even in the best of circumstances, among adults (without the complexity of psychosocial challenges common to adolescents), long-term viral suppression is achieved in only 23% of those entering care. Further complicating care for infected youth are the higher rate of undiagnosed HIV infection, lower rates of linkage to and retention in care, and low antiretroviral adherence rates with resultant poor viral suppression. Trials are urgently needed to study the continuum of care among both domestic and international youth populations to identify strategies that can substantially improve achievement of essential milestones along the care continuum and ultimately help infected youth achieve durable viral suppression. Also needed are trials to study newer drug schedules and formulations that allow simpler regimens, evaluation of programs to promote antiretroviral treatment adherence in youth, and clinical trials to evaluate therapies that may exploit the immunologic resilience of recently infected youth. Development of new sustained-release antiretroviral drug formulations that permit less frequent drug administration—such as administration only once weekly or monthly—is an important area for future research.
The MPIDB has committed significant resources to understanding HIV transmission dynamics, the course of infection, and its management in youth. The MPIDB recognizes that support of research in this group is critical to intervening in the epidemic. Domestically, through the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN), the Branch is supporting interventional research in youth from pre-adolescent age through 24 years that addresses the full scope of prevention activities, including primary prevention through behavioral and preventive vaccine, microbicide, and PrEP research; secondary prevention in clinical management of HIV infection to maintain health and reduce secondary transmission events; and tertiary prevention in restoring HIV-infected youth to optimal functioning and well-being. International research in adolescent HIV infection, disease, and prevention is an expanding area for the Branch in collaboration with other HIV/AIDS research networks supported by NIH.
Perinatally HIV-Infected Youth
With the availability of treatment, increasing numbers of children infected perinatally are now surviving into adolescence and young adulthood in the United States, presenting new treatment and secondary prevention challenges. Internationally, the recent massive scale-up of antiretroviral treatment programs for children in sub-Saharan Africa has resulted in an approximate quadrupling of the number of children receiving therapy globally in recent years. These children, now expected to survive or already surviving into adolescence, young adulthood, and beyond, will face the consequences of prolonged HIV infection and long-term antiretroviral therapy on multiple organs and systems in the body, which may be exacerbated by endemic diseases and co-morbidities, such as malnutrition, not seen in resource-rich countries such as the United States. In addition to the long-term complications of HIV infection and its treatment, many survivors of perinatal HIV infection must face a multitude of transitions, including the usual challenges of adolescence and young adulthood, such as school, career choices, reproductive health, and plans for marriage and families, and the transition to adult medical HIV and non-HIV care. Understanding how HIV and its treatment affect growth and development, sexual maturation, organ function, and socialization of perinatally HIV-infected adolescents and young adults is critical.
The MPIDB is actively conducting research related to the long-term effects of HIV and its therapy in perinatally infected youth both domestically (for example, the Pediatric HIV/AIDS Cohort Study) and internationally (for example, RFA-HD-12-207: Perinatally HIV-Infected Youth in Asia and Africa). Areas of research interest include:
- Prevalence, incidence, management, and outcomes of antiretroviral drug resistance
- Neurodevelopmental, cognitive, academic, vocational, behavioral, and social outcomes; brain imaging correlates and other surrogate markers of these outcomes
- Consequences of HIV-associated long-term immune activation and premature aging for perinatally infected youth
- Substance use and abuse
- Adherence to medication regimens and medical care
- Transition to adult-based care
- Nutrition, growth, and metabolism
- Bone health
- Sexual maturation and health, reproductive capacity and choices, pregnancy outcomes and complications, and behaviors that pose risk for transmission of HIV
- Cardiovascular complications and cardiovascular disease risk; noninvasive imaging to assess risk of premature atherosclerosis and cardiac and vascular dysfunction; evaluation of surrogate markers predictive of cardiovascular disease
- Genetic and epigenetic—including mitochondrial—effects of antiretrovirals and HIV
- Peripheral nervous system complications
- Hepatic complications, including co-infections with hepatitis B and C, and other viral infections associated with malignancies
- Pulmonary complications
- Renal complications