June 10, 2003
HIV-1-seronegative patients attending three referral STD clinics and a reproductive tract infection clinic were enrolled in a prospective study of HIV infection in Pune, India, from May 1993 through April 2000. The study population represented a mix of male patients with STDs, female partners of male STD patients, female commercial sex workers, and women with reproductive tract infections.
Of 2,732 persons enrolled, 2,260 were male, 9 were hijra (eunuchs), and 463 were female; 1,175 participants (43 percent) had HSV-2 antibodies. Median duration of follow-up was 10.7 months, and the median number of follow-up visits was three.
During the study, 217 participants seroconverted to HSV-2 positive, resulting in a crude HSV-2 incidence rate of 11.4 cases/100 person-years. Risk factors for HSV-2 in the unadjusted analysis included earlier calendar period of follow-up (1993-1996), younger age, female sex worker, lower education level, living away from family, lack of condom use, genital lesion at the current or a previous visit, and coincident HIV-1 infection.
The unadjusted rate ratio of HIV acquisition among participants exposed to prevalent HSV-2 infection was 2.07. Of the 224 participants with incident HIV-1 infection, 28 were found to have both incident HSV-2 infection and incident HIV-1 infection during the follow-up period. For the majority (n=22), serologic evidence of these two infections was detected simultaneously. The unadjusted rate ratio of HIV-1 acquisition among participants exposed to remote incident HSV-2 infection was found to be 2.08; among participants exposed to recent incident HSV-2 infection, the rate ratio was 6.26. The adjusted HR of HIV-1 acquisition increased with relative timing of HSV-2 infection, from 1.67 among those exposed to prevalent HSV-2 infection to 1.92 among those exposed to remote incident HSV-1. Exposure to recent incident HSV-2 infection conferred a 3.81-fold increased hazard of HIV-1 acquisition.
Of the 217 incident HSV-2-infected participants, 51 (23.5 percent) had a genital lesion documented at the same visit at which seroconversion was demonstrated. A presence of asymptomatic HSV-2 infection (no clinically apparent or self-reported genital ulcer) conferred an adjusted HR for HIV-1 infection of 2.14. Symptomatic prevalent HSV-2 infection conferred an adjusted HR of 5.06.
"Individuals with serologic evidence of recent incident HSV-2 infection in our study had the highest HIV-1 incidence (adjusted HR, 3.55) when the analysis was controlled for other sexual risk behaviors, which illustrates that incident infection with this common sexually transmitted virus is independently associated with HIV-1 acquisition," the authors concluded. "... The elevated risk of HIV-1 acquisition ... provides a strong argument for the prioritization of HSV-2 vaccine development and other HSV-2 prevention strategies as key components of the current global HIV prevention research agenda."
Journal of Infectious Diseases
05.15.03; Vol. 187; No. 10: P. 1513-1521; Steven J. Reynolds; Arun R. Risbud; Mary E. Shepherd; Jonathan M. Zenilman, Ronald S. Brookmeyer, Ramesh S. Paranjape, Anand D. Divekar; Raman R. Gangakhedkar; Manisha V. Ghate; Robert C. Bollinger; Sanjay M. Mehendale
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