PERIPHERAL LYMPHOCYTES OF CLINICALLY NONPROGRESSOR PATIENTS HARBOR INACTIVE AND UNINDUCIBLE HIV PROVIRUSES

The HIV viral burden and RNA expression in a selected group of infected, clinically non-progressor patients were investigated. Five fast-progressor patients and 10 AIDS cases were included as controls. The HIV viral load was investigated by semiquantitative polymerase chain reaction (PCR) in adherent macrophages and in genomic and extragenomic fractions of lymphocytes. HIV DNA was not found in macrophages in the non-progressor subjects, was weakly positive in 2 of 5 fast-progressors and strongly positive in most of the AIDS patients. The number of HIV proviruses found in lymphocytes of the non-progressor subjects varied from 5 to 160 copies/mu g DNA, values ten times lower than those recorded in fast-progressors and AIDS patients. The extragenomic HIV DNA (2 LTR forms) was absent or barely detectable in the lymphocytes from non-progressors and abundant in the other groups. HIV RNA was not found in the lymphocytes of all non-progressors. This may indicate that a latent state of HIV provirus exists in the lymphocytes of these subjects. To investigate this point, cultivation and stimulation with PHA (phytohemoagglutinin) and PMA (phorbol 12-myristate 13-acetate) of lymphocytes from these subjects were attempted but after 6 days HIV RNA (RT-PCR for gag region) was still absent or barely detectable in these patients. There are no other reports of the absence of HIV provirus induction in lymphocytes from infected individuals. If confirmed in a larger number of patients, such non-inducibility might serve as a predictor marker of progression of the disease. (C) 1995 Wiley-Liss, Inc.