4.8 Article

Inhibition of HIV-1 Disease Progression by Contemporaneous HIV-2 Infection

Journal

NEW ENGLAND JOURNAL OF MEDICINE
Volume 367, Issue 3, Pages 224-232

Publisher

MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJMoa1113244

Keywords

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Funding

  1. Swedish International Development Cooperation Agency-Swedish Agency for Research Cooperation with Developing Countries
  2. Swedish Research Council
  3. Crafoord Foundation
  4. Royal Physiographic Society
  5. Lars Hierta Memorial Foundation
  6. Konsul Thure Carlsson Fund for Medical Research
  7. Tegger Foundation
  8. Medical Faculty of Lund University
  9. Region Skane

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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.)

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