Serological immunity to adenovirus serotype 5 is not associated with risk of HIV infection: a case-control study

Abstract

Background: adenoviruses are among the most promising vectors for the development of an HIV vaccine. The results of the phase IIB study of the adenovirus serotype 5-based Merck Trivalent HIV vaccine have raised the concern that serological immunity to adenovirus serotype 5 (Ad5) could be linked to HIV acquisition risk in high-risk individuals. We examined the association between adenovirus serostatus and the rate of incident HIV infection in populations at elevated risk of HIV acquisition.

Methods: we performed a nested case-control study of Ad5 serostatus among 299 HIV-infected and 590 matched HIV-uninfected persons participating in the Multicenter AIDS Cohort Study (MACS) and in HPTN 039, a study of herpes simplex virus 2 suppression among adults in the United States, South America, and Africa. Appropriate HIV cases and controls were identified in each cohort, and Ad5-neutralizing antibody titers were compared in these two groups.

Results: in MACS and HPTN 039, the relative risks of incident HIV infection among Ad5-seropositive vs. Ad5-seronegative individuals were 1.1 (95% confidence interval 0.8-1.5, P = 0.57) and 1.0 (95% confidence interval 0.4-2.3, P = 0.99), respectively. HIV-1 acquisition rates did not vary significantly by Ad5-neutralizing antibody titer.

Conclusion: the presence of Ad5-neutralizing antibodies is not linked to the risk of HIV acquisition among populations at elevated risk of HIV infection.

2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Figures

Figure 1

Ad5 neutralizing antibody titers and HIV acquisition Normalized case rates by Ad5 titer. Ratio of observed to expected case rate (y-axis) by Ad5 titer (x-axis). Since two controls were selected per case, the expected case rate assuming that Ad5 serostatus has no effect on the risk of HIV acquisition is 33%, and the expected ratio is 1. Ad5 seronegative participants are those with Ad5NAb