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Thai residents have a greater risk of heterosexual transmission of human immunodeficiency virus (HIV) than do US residents. To analyze host factors associated with heterosexual transmission, vaginal epithelial biopsies from HIV-seropositive Thai and US women were evaluated for tissue virus load and histologic makeup. In all, 84% of Thai and 14% of US women exhibited a chronic inflammatory T cell infiltrate in the vaginal epithelium. In Thai tissue, the infiltrate was associated with elevated levels of HIV RNA in the epidermis. Uninfected Thai women also had vaginal epithelial inflammation. Inflammation did not correlate with sexually transmitted diseases or HIV disease stage. The higher rates and increased risk of heterosexual transmission in Thailand may be due to chronic inflammation at the site where the virus is transmitted, which leads to the accumulation of activated T cells. Such cells might act as targets for initial viral infection and subsequently as reservoirs that support efficient transmission.

The fundamental clinical, viral, and immunologic features of early-stage human immunodeficiency virus type 1 (HIV-1) disease were examined in a seroprevalent cohort of 28 men and 14 women assessed longitudinally at three equally dispersed time points over a mean of 43 months. There were no gender differences in the relative risk of developing AIDS-defining end points or death. The median serum RNA levels assessed at the three study time points were 3.3-, 4.9-, and 1.5-fold lower, respectively, in women than in men. This suggests that while serum virus load may be as powerful a correlate of disease status in women as it is in men, the absolute values of the virus levels may be different in the 2 populations. These observations may have implications for the interpretation of levels of virus burden in women for the assessment of disease progression, transmission, and treatment.

Human immunodeficiency virus (HIV)-1 DNA and RNA levels and T lymphocyte cell surface markers were measured in blood serum and cell fractions from asymptomatic infected patients to find novel virologic and immunologic features in early disease predictive of subsequent clinical disease course. Thirty-two patients with rapid disease progression (rapid CD4+ cell loss and progression to clinical AIDS) were compared with 25 patients with stable infections (constant or rising CD4+ cell counts, no clinical disease manifestations). All HIV-1 burdens measured by polymerase chain reaction were consistently higher in specimens from rapid progressors than slow progressors. For each patient, virus burden remained relatively constant throughout the study period (mean, 42-44 months). Flow cytometry also disclosed stable lymphocyte immunophenotype patterns that correlated strongly with subsequent rapid progression to clinical disease. Thus, in early HIV-1 infection, a constellation of high virus burden and in vivo costimulatory antigen and lymphocyte activation abnormalities is predictive of rapid disease course.

To better understand the biologic meaning and potential clinical utility of p24 antigen measurements in human immunodeficiency virus (HIV) infection, p24 antigen and antibody and HIV RNA were quantitated in parallel. Specimens (n = 311) were analyzed from 74 participants in a zidovudine treatment study. Parallel antigen and RNA measurements revealed the frequent occurrence of two types of discordant results. First, p24 antigen was often not detected in samples with high antibody levels even when > 10(6) RNA copies/mL were present. Second, in specimens in which p24 antigen was detected, the concentration was greater than expected on the basis of HIV RNA values. These results suggest that optimal use of serum p24 antigen values will require consideration of both specific antibody levels and non-virion associated antigen.

Six procedures for quantifying plasma human immunodeficiency virus type 1 (HIV-1) RNA were evaluated by nine laboratories. The procedures differed in their sample volume and preparation of samples and methods of amplification and detection. Coded samples in a 10-fold dilution series of HIV-1-spiked plasma were correctly ranked by all six procedures. Subsequently, coded duplicate plasma samples from 16 HIV-1-infected patients were tested using a common set of standards. Several HIV-1 RNA procedures were sufficiently reproducible so that an empiric 4-fold change could be viewed as significant. HIV-1 RNA levels in the patients (up to 370,000 RNA copies/mL) correlated with proviral HIV-1 DNA and were inversely correlated with CD4 cell counts; HIV-1 RNA assays were more sensitive than plasma viremia, standard p24 antigen, or immune complex-dissociated p24 antigen assays. This study demonstrated that several HIV-1 RNA quantitative assays are ready for use in clinical trials.