Recent Herpes Simplex Virus Type 2 Infection and the Risk of Human Immunodeficiency Virus Type 1 Acquisition in India
Herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease in both developed and developing countries. A clear relationship has been established between genital herpes and HIV acquisition, but almost all studies have evaluated prevalent genital herpes infection. In the current study, researchers assessed the impact of prevalent and incident HSV-2 infection on the acquisition of HIV-1.
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.
Independent predictors of incident HSV-2 infection included the presence of a genital lesion at a previous clinic visit, a current visit, and both visits. When the group of male STD patients was used as a reference in the multivariate model, hijras and female sex workers had significantly higher HSV-2 incidence rates.
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."