Methods and Results. We studied 10 seropositive subjects who remained asymptomatic with normal and stable CD4+ lymphocyte counts despite 12 to 15 years of HIV-1 infection. Plasma cultures were uniformly negative for infectious virus. However, particle-associated HIV-1 RNA was detected in four subjects with a sensitive branched-DNA signal-amplification assay, whereas in five others the levels of HIV-1 RNA were too low to detect. Infectious HIV-1 was detected in peripheral-blood mononuclear cells (PBMC) of three subjects by standard limiting-dilution cultures, and infectious virus was recovered from another subject with use of a CD8-depleted culture. The other six subjects had no detectable infectious virus in their PBMC. A quantitative polymerase-chain-reaction assay revealed that all subjects had detectable but low titers of viral DNA in PBMC. Overall, the viral burden in the plasma and PBMC of long-term survivors was orders of magnitude lower than that typically found in subjects with progressive disease.

There was no in vitro evidence of resistance by host CD4+ lymphocytes to HIV-1 infection. However, longterm survivors had a vigorous, virus-inhibitory CD8+ lymphocyte response and a strong neutralizing-antibody response. In two subjects the kinetics of viral replication was consistent with the presence of a substantially attenuated strain of HIV-1.

Conclusions. Subjects who remain asymptomatic for many years despite HIV-1 infection have low levels of HIV-1 and a combination of strong virus-specific immune responses with some degree of attenuation of the virus.