Inhibition of HIV-1 disease progression by contemporaneous HIV-2 infection

N Engl J Med. 2012 Jul 19;367(3):224-32. doi: 10.1056/NEJMoa1113244.

Abstract

Background: Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood.

Methods: We analyzed data from 223 participants who were infected with HIV-1 after enrollment (with either HIV-1 infection alone or HIV-1 and HIV-2 infection) in a cohort with a long follow-up duration (approximately 20 years), according to whether HIV-2 infection occurred first, the time to the development of AIDS (time to AIDS), CD4+ and CD8+ T-cell counts, and measures of viral evolution.

Results: The median time to AIDS was 104 months (95% confidence interval [CI], 75 to 133) in participants with dual infection and 68 months (95% CI, 60 to 76) in participants infected with HIV-1 only (P=0.003). CD4+ T-cell levels were higher and CD8+ T-cell levels increased at a lower rate among participants with dual infection, reflecting slower disease progression. Participants with dual infection with HIV-2 infection preceding HIV-1 infection had the longest time to AIDS and highest levels of CD4+ T-cell counts. HIV-1 genetic diversity was significantly lower in participants with dual infections than in those with HIV-1 infection alone at similar time points after infection.

Conclusions: Our results suggest that HIV-1 disease progression is inhibited by concomitant HIV-2 infection and that dual infection is associated with slower disease progression. The slower rate of disease progression was most evident in participants with dual infection in whom HIV-2 infection preceded HIV-1 infection. These findings could have implications for the development of HIV-1 vaccines and therapeutics. (Funded by the Swedish International Development Cooperation Agency-Swedish Agency for Research Cooperation with Developing Countries and others.).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome
  • Adult
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes
  • Cohort Studies
  • Coinfection*
  • Disease Progression*
  • Evolution, Molecular
  • Female
  • Genetic Variation
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV Seropositivity
  • HIV-1* / genetics
  • HIV-1* / isolation & purification
  • HIV-2*
  • Humans
  • Kaplan-Meier Estimate
  • Likelihood Functions
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Viral Load