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

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

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Department of Experimental Immunology, Landsteiner Laboratory Sanquin Research, and Center for Infection and Immunity (CINIMA), Academic Medical Center at the University of Amsterdam, Amsterdam, The Netherlands.



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.


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.


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.


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.

[Indexed for MEDLINE]

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