More than one million people in the United States and in excess of 14 million people worldwide are infected with the human immunodeficiency virus type 1 (HIV-1). Many of those infected are in an asymptomatic phase of the illness; this latent period has a median duration of 10 years. However, with rare exceptions, all individuals who are infected will ultimately develop a severe immunodeficiency which predisposes them to both opportunistic infections and certain types of neoplasms.

Recent studies have shown that there is an intimate relationship between viral burden and disease progression. The initial infection is usually associated with a high level of viral replication; this occurs in both the blood and lymphoid tissues. One consequence of this initial viremic state is the development of a mononucleosis-like syndrome two-to-four weeks after initial infection. This viremic state is generally of short duration. Specific cellular and humoral immune responses are elicited which cause a dramatic reduction in the levels of free virus in the plasma. Unfortunately, these immune responses are insufficient to completely control viral replication. Recent studies suggest that there is continuous proliferation of virus, particularly in lymph nodes. The continuous viral replication results in gradual damage to the host's immune system as manifested by the progressive depletion of peripheral blood CD4⁺ T cells. Once a critical threshold of immune system damage is reached, usually a CD4⁺ cell count of less than 200/mm³, the individual becomes highly vulnerable to opportunistic infections or development of neoplasms such as Kaposi's sarcoma or non-Hodgkin's lymphoma.

Three drugs aimed at arresting HIV-1 replication, Zidovudine (AZT), Didanosine (DDI), and Zalcitabine (DDC) have been approved for the treatment of HIV infection. All three are inhibitors of the viral enzyme reverse transcriptase. This enzyme serves to copy the viral RNA into DNA which is subsequently integrated into the cells own DNA. Unfortunately, all three drugs are virostatic, not viricidal. A serious but common problem associated with reverse transcriptase inhibitor therapies is the emergence of drug-resistant isolates. Many other antiviral agents are currently under investigation including other reverse transcriptase inhibitors, protease inhibitors, and inhibitors of regulatory proteins such as TAT. Their long-term effectiveness is now being assessed.

As a means of monitoring therapy, the p24 antigen assay has been of limited value because of its lack of sensitivity. The enzyme immunoassay detects antigen early in infection when the viral load is high. Shortly after seroconversion though, the p24 antigen level falls below detectable levels and remains undetectable until the late stages of the disease. In the pre-terminal stages, high levels are again detected in the plasma.

An important distinction must be made between identifying HIV proviral DNA and HIV RNA. PCR testing for HIV proviral DNA is a very sensitive test for recognizing early infection and for identifying infected neonates born to seropositive mothers. It is of limited use as a therapy monitoring tool. The HIV DNA assay detects integrated, often latent virus rather than replicating virus. All infected individuals will have a positive test. By contrast, HIV RNA quantitation by either polymerase chain reaction (PCR) or branched-DNA assay provides a direct assessment of replicating virus and thus is more likely to reflect prognosis and response to therapy. For example, high titers after seroconversion have been found to predict more rapid disease progression. Recent studies have also shown that high plasma viral levels are associated with transmission from a pregnant mother to her newborn child. HIV viral RNA may be an important criteria in selecting patients who would benefit most from early treatment and in guiding therapeutic regimens for patients on treatment. Decreasing titers are indicative of a successful response to therapy and are usually followed by a gradual improvement in immune status including increases in CD4+ cell counts. By contrast, increasing viral titers in a treated patient are suggestive of emergence of drug-resistant stains. The increase in viral titers are often followed weeks later by clinical deterioration.

Central Blood Bank's Molecular Diagnostics Laboratories will be offering a panel of three tests, Quantitative HIV-RNA, immune complex dissociated p24 antigen levels, and CD4⁺ counts to clinicians as a means of following HIV-infected patients.