Natural history of HIV-1 cell-free viremia

Abstract

Objective: To characterize the natural history of viremia with human immunodeficiency virus type 1 (HIV-1) and its association with disease progression from infection to acquired immunodeficiency syndrome (AIDS).

Design: Prospective cohort study. Annual specimens were tested for quantitative virion-associated HIV-1 RNA, p24 antigen, and CD4+ lymphocyte levels.

Participants: A total of 42 homosexual men who seroconverted to HIV-1 between 1982 and 1985.

Main outcome measures: Trends over time in serum HIV-1 RNA level, correlations between serum HIV-1 RNA and other markers, and prediction of AIDS using these markers.

Results: HIV-1 RNA levels were stable over time, increasing by 10-fold or more in only six (14%) of the 42 subjects during 3 to 11 years of follow-up. Mean HIV-1 RNA levels were 10(3.8) copies/mL if AIDS occurred in less than 4 years, 10(3.07) copies/mL if AIDS developed within 4 through 9 years, and 10(2.27) copies/mL if AIDS did not develop within 6 through 11 years. In both univariate and multivariate models, initial and subsequent HIV-1 RNA levels, p24 antigenemia, and percentage of CD4+ lymphocytes were independently predictive of AIDS.

Conclusions: The stability of virion-associated HIV-1 RNA levels suggests that an equilibrium between HIV-1 replication rate and efficacy of immunologic response is established shortly after infection and persists throughout the asymptomatic period of the disease. Thus, defective immunologic control of HIV-1 infection may be as important as the viral replication rate for determining AIDS-free survival. Because individual steady-state levels of viremia were established soon after infection, HIV-1 RNA levels may be useful markers for predicting clinical outcome.