Confocal microscopic detection of human immunodeficiency virus RNA-producing cells

A central anomaly in the pathogenesis of AIDS is that few actively infected CD4⁺ cells (1 in 10⁴-10⁵) have been detected in the peripheral blood, even though dramatic depletion (often >90%) of CD4⁺ cells is the hallmark of disease progression. A sensitive, ³⁵S-based human immunodeficiency virus (HIV) RNA in situ hybridization technique was coupled with a new detection method, confocal laser scanning microscopy, to examine transcriptionally active HTV-infected cells from individuals at different disease stages. In 35 symptomatic HIV-infected individuals (AIDS and AIDS related complex), an average of 1 in 350 mononuclear cells produced HIV RNA. In contrast, in an asymptomatic group of 30 individuals, an average of 1 in 2000 mononuclear cells produced HIV RNA. These data, obtained using this improved detection method, suggest there are more HIV RNA-producing cells in HIV-infected individuals than previously reported. In addition, increased numbers of HIV transcribing cells were found to correlate with declining clinical condition as assessed by Karnofsky performance score. These data suggest that viremia per se may account for the pathologic consequences in HIV infection.