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

The HIV viral burden and RNA expression in a selected group of infecte d, clinically non-progressor patients were investigated. Five fast-pro gressor patients and 10 AIDS cases were included as controls. The HIV viral load was investigated by semiquantitative polymerase chain react ion (PCR) in adherent macrophages and in genomic and extragenomic frac tions of lymphocytes. HIV DNA was not found in macrophages in the non- progressor subjects, was weakly positive in 2 of 5 fast-progressors an d strongly positive in most of the AIDS patients. The number of HIV pr oviruses found in lymphocytes of the non-progressor subjects varied fr om 5 to 160 copies/mu g DNA, values ten times lower than those recorde d in fast-progressors and AIDS patients. The extragenomic HIV DNA (2 L TR 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 late nt state of HIV provirus exists in the lymphocytes of these subjects. To investigate this point, cultivation and stimulation with PHA (phyto hemoagglutinin) and PMA (phorbol 12-myristate 13-acetate) of lymphocyt es from these subjects were attempted but after 6 days HIV RNA (RT-PCR for gag region) was still absent or barely detectable in these patien ts. There are no other reports of the absence of HIV provirus inductio n in lymphocytes from infected individuals. If confirmed in a larger n umber of patients, such non-inducibility might serve as a predictor ma rker of progression of the disease. (C) 1995 Wiley-Liss, Inc.