Introduction

This chapter will review our current understanding of the natural history of HIV-1 infection in children and adolescents in an effort to provide the clinician with the background needed to rationally treat HIV disease in children. The advent of highly active antiretroviral therapy (HAART) has radically altered the natural history of pediatric HIV infection, transforming it into a chronic manageable disease requiring complex drug regimens and, for now, lifelong therapy.

Natural history in adults

The natural history of HIV disease was initially described in adults. Knowledge of the natural history of the disease in adults has helped inform pediatric natural history studies and provides a benchmark for the pediatric observations. Infection of adults with HIV-1 is classically followed by three distinct virologic stages: (1) primary or acute infection, (2) clinical latency, and finally (3) progression to AIDS (see Figure 5.1). The time interval between primary infection and the development of AIDS is variable, typically 10 to 11 years [1]. About 20% of individuals will progress in less than 5 years, while a few (< 5%) will remain immunologically normal for over 10 years [2]. The biological basis for this variability is unclear, but undoubtedly reflects differences in viral strains, host immune responses and exposure to other cofactors (microbial or environmental), especially those leading to immune activation.

Several weeks after infection with HIV-1, a variable and non-specific clinical syndrome referred to as primary infection, acute infection syndrome, or acute retroviral syndrome is observed in an unknown proportion of adults (range 10–90%).