Unlike most infections in past epidemics, AIDS is distinguished by a very long latent period before the development of any visible signs of infection. During this phase, there is little or no viral replication detectable in peripheral blood mononuclear cells and little or no culturable virus in peripheral blood. The CD4 lymphocyte count remains moderately decreased. However, the immune response to HIV is insufficient to prevent continued viral replication within lymphoid tissues. Tests for HIV antibody will remain positive during this time but p24 antigen tests are usually negative. There is no evidence to suggest that seroreversion, or loss of antibody, occurs in HIV infected persons.
The average HIV-infected person may have an initial acute self-limited illness, may take up to several weeks to become seropositive, and then may live up to 8 or 10 years, on average, before development of the clinical signs and symptoms of AIDS. Persons infected with HIV cannot be recognized by appearance alone, are not prompted to seek medical attention, and are often unaware that they may be spreading the infection. There has been no study to date that shows a failure of HIV-infected persons to evolve to clinical AIDS over time, though the speed at which this evolution occurs may vary.
At least 10% of persons infected with HIV-1 are "long survivors" who have not had significant progressive decline in immune function. Findings include: a stable CD4 lymphocyte count, negative plasma cultures for HIV-1, a strong HIV-1 neutralizing antibody response, and a strong virus-inhibitory CD8 lymphocyte response. In addition, the lymph node architecture is maintained without either the hyperplasia or lymphocyte depletion common to progression to AIDS. Though peripheral blood mononuclear cells contain detectable HIV-1 and viral replication continues in long survivors, though their viral burden is low.
The development of signs and symptoms of AIDS typically parallels laboratory testing for CD4 lymphocytes. A decrease in the total CD4 count below 500/microliter presages the development of clinical AIDS, and a drop below 200/microliter not only defines AIDS, but also indicates a high probability for the development of AIDS-related opportunistic infections and/or neoplasms. Plasma HIV-1 RNA increases as plasma viremia becomes more marked. The risk for death from HIV infection above the 200/microliter CD4 level is low.
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