Herpes Simplex Virus Type 2 infection among U.S. military service members: Public Health Implications and Opportunities for HIV Prevention Christian T. Bautista, MSc Dept. Epidemiology and Threat Assessment U.S. Military HIV Research Program Walter Reed Army Institute of Research Rockville, Maryland, USA Poster: MOAC101 July 23, 2007

U.S. Military HIV Research Program Mission Statement Prevention of HIV infection in U.S. Military through: –Development of GLOBALLY effective HIV-1 vaccine(s) –Epidemiologic surveillance of HIV-1 GENOTYPE to guide vaccine development –Evaluation and implementation of disease PREVENTION and treatment modalities

Background HSV-2 is the most prevalent STD, and it has been recognized as a significant risk factor for HIV acquisition In the U.S. military population a marked decline in HIV diagnosis has occurred after 1998 (~0.2 cases/1,000 person-years) The HSV-2 incidence rate (per 1,000 person-years) has increased in the U.S. military population from 1.25 in 1998 to 1.94 in 2004

Matched Case-control Study Population All U.S. Army and Air Force service members with incident HIV infection between June 2000 and February 2004 were considered as “cases” Two HIV-uninfected service member “controls” were randomly matched by gender and date of case HIV screening test (± 30 days) HIV serum samples were collected from the DoD Serum Repository or from the U.S. Air Force Central HIV Testing Service. HIV diagnosis is determined by ELISA and Western blot HSV-2 infection was determined by type-specific ELISA. A cut-off optical density value > 3.5 was used to improve assay specificity 492 cases and 984 controls would allow detection of an OR = 2.0 (power = 80%, significance level = 95%, and exposure rate > 5%)

Results – Study Population A total of 456 (87%, 525) cases and 912 controls with demographic data and serum available were included in this analysis FeatureCases (N=456)Controls (N=912) no.% % Male * > White * Black > High school < High school Married * Single * p-value < 0.05

Results - HSV-2 prevalences FeatureCasesControls HSV-2 %(n/N) HSV-2 % (n/N) Overall30.3(138/456)9.7(88/912) Female48.1(13/27)1.9(1/54) Male29.1(125/429)10.1(87/858) (15/66)12.8(32/251) (30/113)9.3(21/227) (41/125)9.3(19/204) > (52/152)7.0(16/230) White25.0(39/156)9.3(61/657) Black34.5(92/267)11.4(20/176) > High school30.7(38/124)9.6(26/272) < High school29.8(96/322)9.4(58/620) Married32.3(50/155)6.8(34/498) Single29.0(76/262)13.6(50/369)

Results – HSV-2 prevalences FeatureCasesControls HSV-2 %*(n/N) HSV-2 % (n/N) West30.6(11/36)8.6(10/116) Midwest30.0(18/60)12.7(17/134) Northeast24.3(9/37)10.1(11/109) South33.9(72/221)9.0(26/288) Guard/Reserve32.5(63/194)11.1(38/342) Active Duty28.6(75/262)8.8(50/570) Air Force25.3(25/99)8.8(28/317) Army31.7(113/357)10.2(60/589) * For all demographic data, the prevalence of HSV-2 was significantly higher among cases than among their controls (P < 0.05).

Results – Association with HIV HSV-2 was significantly associated with HIV infection OR = 4.2 (95% CI = ) This strong association remained after adjusting for age, race / ethnicity, and marital status AOR = 3.9 (95% CI = ) The population attributable risk percentage of HIV infection due to HSV-2 was 23% (95% CI = 18-28%)

Results – Adjusted Odds Ratios

Conclusions We found a high HSV-2 prevalence and a strong association between HSV-2 and HIV in the U.S. military population The overall risk of HIV infection in HSV-2 seropositive individuals was similar to a summary estimate from 22 case-control and cross-sectional studies (meta-analysis report, OR = 3.9)* Our results indicated that the risk of HIV acquisition due to HSV-2 infection was increased approximately three- fold. However, in some sub-populations, this effect size (association) was higher. * Wald A, Link K. Risk of human immunodeficiency virus (HIV) infection in herpes simplex virus type 2 (HSV-2) seropositive persons: a meta-analysis. J Infect Dis 2002; 185:45-52.

Public Health Implications and Opportunities for HIV Prevention * Corey L, Wald A, Patel R, et al. Valacyclovir HSV Transmission Study Group. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med 2004; 350: Based on our study findings, potential public health approaches to reduce the silent epidemic of HSV-2 and to prevent HIV infections among U.S. military personnel are suggested: - First, at military STD clinics, HSV-2 testing should be performed among service members who report high-risk sexual behaviors - Second, all U.S. military service members, who are routinely tested throughout their careers for HIV infection (~2 yrs), and are found to be HIV-positive, should also be tested for HSV-2 infection, and - Third, patients diagnosed with HSV-2 infection should be treated with valacyclovir, an antiviral drug that can suppress genital herpes, and therefore reduce the risk of sexual transmission of genital herpes, with potential benefits in reducing the acquisition and transmission of HIV infection*

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