Prevalence of cross-reactive HIV-1-neutralizing activity in HIV-1-infected patients with rapid or slow disease progression

AIDS. 2009 Nov 27;23(18):2405-14. doi: 10.1097/QAD.0b013e32833243e7.


Objective: The native envelope gp160 trimer of HIV-1 is thought to shield vulnerable epitopes that could otherwise elicit effectively neutralizing antibodies. However, little is known about the prevalence of naturally occurring broadly neutralizing activity in serum of HIV-1-infected individuals.

Methods: Here, we studied 35 participants of the Amsterdam Cohort Studies on HIV-1 infection (20 long-term nonprogressors and 15 progressors) for the presence of cross-reactive neutralizing activity in their sera at 2 and 4 years after seroconversion. Neutralizing activity was tested in a pseudovirus assay, against a panel of HIV-1 envelope variants from subtypes A, B, C, and D.

Results: Already at year 2 after seroconversion, seven out of 35 individuals (20%) had cross-reactive neutralizing activity, which increased to 11 individuals (31%) at 4 years after seroconversion. There was no difference in the prevalence of cross-reactive neutralizing serum activity between long-term nonprogressors and progressors.Interestingly, high plasma viral RNA load and low CD4(+) cell count at set-point were associated with early development of cross-reactive neutralizing activity. Neutralization titers in serum increased during the course of infection for 91% of individuals studied here, although less rapidly for those who did not develop cross-reactive neutralizing activity.

Conclusion: Overall, we here demonstrate a relatively high prevalence of cross-reactive neutralizing serum activity in HIV-1-infected patients, which increased with duration of infection. These data may imply that immunogenicity of the native envelope spike of HIV-1 for eliciting cross-reactive humoral immune responses may be better than previously anticipated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • CD4 Lymphocyte Count
  • Cross Reactions / immunology
  • Disease Progression*
  • HIV Antibodies / immunology
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Humans
  • Male
  • Neutralization Tests
  • RNA, Viral / blood*
  • Viral Load


  • Antibodies, Neutralizing
  • HIV Antibodies
  • RNA, Viral