SURVIVAL AND PROGNOSIS

Children have benefited from advances in treatment in the same patterns as adults. The Pediatric Spectrum of Disease Cohort has clearly demonstrated this improvement as a function of birth year and correlates with the available antiretroviral treatments. Clinical trials to approve antiretrovirals for children were on a delayed timetable compared to adults. By 1994, most children were on a therapy regimen of one or two antiretrovirals. In 1997, combination antiretroviral therapy of two or three drugs, usually including a protease inhibitor, became standard. The birth cohort of 1997 to 2001 had a significantly higher survival than earlier birth cohorts. The benefits of combination antiretroviral therapy beyond reduced mortality include improved functioning of the immune system and reduced complications from comorbid and opportunistic disease (McConnell et al., 2005).

Because of reductions in new infections and improvements in therapy leading to improved survival for infected infants and children, the median age of surviving perinatally infected children was 14.8 years in 2007 and continues to increase. Additionally, the median age of death has increased from 7.2 years in 1994 to 18.2 years in 2006 (Patel et al., 2008).

Successful antiretroviral therapy in young infants and children is challenged by the limited number of agents available as a liquid or powder formulation. Liquid formulations can also require special storage conditions and are often unpalatable. Children with HIV infection have benefited from legislation aimed at expanding available agents for children. Many new agents are being used in children a little over one year from the date they become available for use in adults.

Despite these successes, perinatally infected children who are aging up into adolescence are challenged by decreasing options for therapy. Many of these children received each new antiretroviral when it became available and had sequential courses of mono or dual therapy, resulting in the presence of multiple resistance mutations, especially to the nucleoside reverse transcriptase inhibitor class of agents. These resistance mutations often necessitate the use of complex regimens that further challenge medication adherence (Rakhmanina et al., 2008).

Complications of Perinatal HIV in Growing Children and Adolescents

Although antiretroviral treatment improves prognosis, complications associated with HIV infection and its treatments may occur. Complications include growth abnormalities, developmental and pubertal delay, abnormal metabolic profiles and fat distribution, decreased bone mineral density, and increased mental health disorders. Furthermore, as these perinatally infected children age into adolescence and young adulthood and become



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