Background

The clinical effects of infection with human immunodeficiency virus (HIV) are diverse, ranging from an acute syndrome associated with primary infection to a prolonged asymptomatic state to advanced disease. Experts regard HIV disease as beginning at the time of primary infection and progressing through numerous stages. For most patients, active virus replication and progressive immunologic impairment occur throughout the course of HIV infection, even during the clinically latent stage. HIV disease can be divided empirically based on the degree of immunodeficiency into early stage (ie, CD4 T-cell count >500/µL), intermediate stage (ie, CD4 cell count 200-500/µL), and advanced stage (ie, CD4 cell count <200/µl).

The stage of HIV infection when CD4 cell counts are greater than 200/µL has been given a variety of names, including pre–acquired immune deficiency syndrome (AIDS) and AIDS-related complex. Note that these 2 terms are being used less frequently.

The time from initial infection to clinical disease is highly variable, with a median time of approximately 10 years. HIV disease with active virus replication usually progresses during this asymptomatic period, and the rate of disease progression correlates directly with HIV RNA levels. Patients with high levels of HIV RNA progress to symptomatic disease faster than patients with low levels of HIV RNA.

In many patients, opportunistic diseases may be the first manifestations of HIV infection. Some patients who are otherwise asymptomatic develop persistent generalized lymphadenopathy (PGL) during this time. With few exceptions, CD4 cell counts decline progressively during this asymptomatic period at an average rate of approximately 50/µL/y. Patients with early symptomatic HIV infection have CD4 cell counts greater than 200/µL. When the CD4 cell count falls to less than approximately 200/µL, the resulting state of immunodeficiency places patients at high risk for opportunistic infections and neoplasms, thus, clinically apparent disease.

Many of the initial problems encountered while CD4 cell counts remain greater than 200/µL are not sufficiently indicative of a defect in cell-mediated immunity to be considered AIDS-defining illnesses. Some of these problems appear to be direct effects of long-standing HIV infection. Equally important is the fact that the clinical findings at the stage of disease encompassed by early symptomatic HIV infection, while indicative of a decline in immune function, are generally less predictive of overall patient status than the data obtained from serial measurements of CD4 cell counts.