Virologic and Immunologic Characterization of Long-Term Survivors of Human Immunodeficiency Virus Type 1 Infection

N Engl J Med. 1995 Jan 26;332(4):201-8. doi: 10.1056/NEJM199501263320401.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • DNA, Viral / isolation & purification
  • Female
  • HIV Seropositivity / immunology*
  • HIV Seropositivity / virology*
  • HIV-1* / genetics
  • HIV-1* / isolation & purification
  • Humans
  • Immunity, Cellular
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • RNA, Viral / isolation & purification
  • Time Factors

Substances

  • DNA, Viral
  • RNA, Viral