OBJECTIVE To quantify spontaneous and activation-induced apoptosis in peripheral blood mononuclear cells (PBMC) of HIV-infected patients and to look for correlations between PBMC apoptosis levels, stages of HIV disease, CD4 count, and plasma viral load. METHODS 75 consecutive inpatients and outpatients infected with HIV (mean CD4 count, 202 +/- 182 x 10(6)/L; mean plasma viral load, 4 +/- 1.29 log10 RNA copies/ml) and a control group composed of 18 healthy, HIV-negative adults. METHODS Spontaneous apoptosis was detected at the single-cell level by direct incorporation of fluorescein-deoxyuridine triphosphate (dUTP) in PBMC DNA strand breaks. Activation-induced apoptosis was determined after in vitro stimulation with anti-CD3 antibodies and interleukin-2 (IL-2). RESULTS Spontaneous apoptosis was low in patients and controls, whereas activation-induced apoptosis was significantly higher in HIV-infected patients (5.22 +/- 4.32% versus 2.46 +/- 1.77%, respectively; p = .009). The degree of activation-induced apoptosis was positively correlated with the plasma viral load (r = 0.29; p = .029) and negatively correlated with the CD4 count (r = -0.37; p = .0009). Although activation-induced apoptosis was significantly higher in patients fulfilling AIDS criteria, it did not differ significantly between patients with an acute AIDS-defining event and those with stable disease. CONCLUSIONS Susceptibility of PBMC to apoptosis in HIV-1-infected patients is correlated to the plasma viral load and the stage of the disease.