QUANTIFYING HIV-1 PROVIRAL DNA USING THE POLYMERASE CHAIN-REACTION ONCEREBROSPINAL-FLUID AND BLOOD OF SEROPOSITIVE INDIVIDUALS WITH AND WITHOUT NEUROLOGIC ABNORMALITIES

To quantify the number of human immunodeficiency virus type 1 (HIV-1) proviral copies per 1,000 CD4(+) cells in cerebrospinal fluid (CSF) an d blood in relationship to stage of infection and HIV-1 neurologic dis ease (HND), 87 HIV-1 seropositive men without CNS opportunistic infect ions, tumors, or neurosyphilis, 9 high-risk, and 14 not-at-risk serone gative controls underwent a structured interview, and physical and neu rologic examination followed by blood and CSF collection. A custom-des igned, fully automated polymerase chain reaction (PCR) system performe d amplification with use of two HIV-1 gag primer pairs, Southern blott ing, and hybridization with product-specific probes. Image analysis wa s used to quantify band intensities relative to a dilution series. Eig hty-one of 87 (93%) seropositive patients, 1 of 9 high-risk patients, (11%) and none of 14 seronegative controls had PCR-detectable HIV-1 in their blood. Fifty-seven of 63 (90%) seropositive patients, 2 of 5 (4 0%) high-risk seronegative patients, and none of 14 controls had HIV-1 in their CSF. The proviral load in seropositive patients, all stages, was significantly greater in CSF than blood [median 25 vs. 0.6 copies /1,000 CD4(+) cells (p = 0.0001)]. The median proviral load in blood w as 0.09 copies/1,000 CD4(+) cells in seropositive, asymptomatic subjec ts, 10.7 in patients with AIDS, and 1.4 in patients with AIDS-related complex (p = 0.0281). CSF proviral load was greater in seropositive pa tients with HND than those without HND, median 43.5 vs. 17.6 copies/1, 000 CD4(+) cells (p = 0.0614). Proviral load was greater in the blood and CSF of subjects with more advanced systemic disease and HND. There was a substantial penetration of HIV-1 into the CNS/CSF in both syste mically and neurologically asymptomatic HIV-1 disease.