Cytotoxic-T-cell Responses, Viral Load, and Disease Progression in Early Human Immunodeficiency Virus Type 1 Infection

N Engl J Med. 1997 Oct 30;337(18):1267-74. doi: 10.1056/NEJM199710303371803.

Abstract

Background: Early in human immunodeficiency virus type 1 (HIV-1) infection there is a decline in viral replication that has been attributed to host immunity, but the components of this response, particularly the ability of cytotoxic T lymphocytes to control viral burden and influence the outcome of disease, are poorly understood.

Methods: We prospectively studied 33 patients with primary HIV-1 infection for HIV-specific activated cytotoxic T lymphocytes and memory cytotoxic T lymphocytes and compared these lymphocyte responses with changes in viral load and clinical status over the subsequent 18 to 24 months.

Results: Soon after infection, activated HIV-specific cytotoxic T lymphocytes, mediated primarily by CD8+ cells, were detected in 17 of 23 patients (74 percent). Memory cytotoxic T lymphocytes were found in 6 of 6 patients tested (100 percent) during the first three months of infection and in 17 of 21 patients (81 percent) tested during the first six months. The frequencies of memory cytotoxic T lymphocytes varied markedly over time, but overall they declined over the first 6 to 8 months and then stabilized over the next 12 to 18 months. The patients with higher frequencies of Env-specific memory cytotoxic T lymphocytes had a median level of plasma HIV-1 RNA about one third that of the patients with lower frequencies, (median number of RNA copies per milliliter, 22,000 vs. 62,000; P=0.006). Patients with low frequencies of Env-specific memory cytotoxic T lymphocytes (or none) in early infection had a more rapid decline to less than 300 CD4+ cells per cubic millimeter (P = 0.05).

Conclusions: In early HIV-1 infection, the induction of memory cytotoxic T lymphocytes, particularly those specific for Env, helps control viral replication and is associated with slower declines in CD4+ cell counts. Host cytolytic effector responses appear to delay the progression of HIV-1 disease.

Publication types

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

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • Disease Progression
  • Female
  • Gene Products, env / immunology
  • Gene Products, gag / immunology
  • Gene Products, pol / immunology
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1* / immunology
  • HIV-1* / physiology
  • Humans
  • Lymphocyte Count
  • Male
  • Prospective Studies
  • RNA, Viral / blood
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / physiology*
  • Viral Load*
  • Virus Replication

Substances

  • Gene Products, env
  • Gene Products, gag
  • Gene Products, pol
  • RNA, Viral