Y Cao1, L Qin, L Zhang, J Safrit, D D Ho. 1. Aaron Diamond AIDS Research Center, New York University School of Medicine, NY 10016.
Abstract
BACKGROUND: In most subjects infected with human immunodeficiency virus type 1 (HIV-1), clinical or laboratory evidence of immunodeficiency develops within 10 years of seroconversion, but a few infected people remain healthy and immunologically normal for more than a decade. Studies of these subjects, termed long-term survivors, may yield important clues for the development of prophylactic and therapeutic interventions against the acquired immunodeficiency syndrome. 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, long-term survivors had a vigorous, virus-inhibitory CD8+ lymphocyte response and a strong neutralizing-antibody response. In two subjects the kinetics of viral replication were 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.
BACKGROUND: In most subjects infected with human immunodeficiency virus type 1 (HIV-1), clinical or laboratory evidence of immunodeficiency develops within 10 years of seroconversion, but a few infected people remain healthy and immunologically normal for more than a decade. Studies of these subjects, termed long-term survivors, may yield important clues for the development of prophylactic and therapeutic interventions against the acquired immunodeficiency syndrome. 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, long-term survivors had a vigorous, virus-inhibitory CD8+ lymphocyte response and a strong neutralizing-antibody response. In two subjects the kinetics of viral replication were 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.
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Authors: A Ciurea; P Klenerman; L Hunziker; E Horvath; B M Senn; A F Ochsenbein; H Hengartner; R M Zinkernagel Journal: Proc Natl Acad Sci U S A Date: 2000-03-14 Impact factor: 11.205
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