Determining how HHV-8 is transmitted and acquired

Corey Casper, MD, MPH, Anna Wald, MD, MPH, and Lawrence Corey, MD

1) The Discordant Couple Study

Infection with Human Herpesvirus 8 (HHV-8) is common worldwide, but is found most often among men who have sex with men (MSM) in the United States (US). Despite over a decade of behavioral and biologic studies, the mode of transmission and risk factors for infection with HHV-8 among MSM remains unknown, largely because almost all studies are cross-sectional in nature. Previous work has shown that HHV-8 shedding is most frequent in the oropharynx, oral epithelial cells are competent sites for HHV-8 replication, and the behavior of "deep kissing" is associated with HHV-8 infection. Genital shedding of the virus occurs less frequently, yet sexual behaviors with exposure to genital secretions have been correlated with HHV-8 infection.

This project focuses on defining the mode(s) of transmission of HHV-8 among MSM. We hypothesize that: HHV-8 is primarily transmitted through saliva, albeit the efficiency of transmission from oral genital contact may be less than genital contact. We are exploring these hypotheses using two approaches. First, are using a prospective cohort study of MSM couples who are discordant in their HHV-8 serostatus (one HHV-8 seropositive, one HHV-8 seronegative). The seropositive partner is evaluated for HHV-8 oral and genital shedding, and details of sexual behavior will be collected. The seronegative partner is followed with regular serologic assays and virologic assessment of shedding to determine the time of infection with HHV-8. Second, we are longitudinally following a cohort of MSM for new cases of HHV-8 seroconversion (see below). A contact investigation will recruit recent sexual partners of incident cases to assess their oropharyngeal and genital HHV-8 shedding patterns, in addition to collecting details of sexual behavior. The relationship between HHV-8 oropharyngeal shedding and HHV-8 transmission will be analyzed using a novel combination of molecular epidemiology and a case-control study that has recently been validated with herpes simplex virus type 2. The importance of genital shedding in the transmission of HHV-8 will be determined by comparing the partners of all cases of HHV-8 infection identified in both cohorts to the partners of persistently persons from the discordant couple cohort.   Using logistic regression, we will estimate the odds of an incident case having a partner who sheds HHV-8 from the genital tract. These two studies will provide data on the association between the anatomic site and quantity of HHV-8 shedding and transmission.

2) The EXSEDE Study

We are currently conducting a large prospective cohort study of nearly 800 MSM at high-risk for HIV infection, monitored with a sensitive and specific serologic assay for HHV-8 infection, with behavioral data collected via the use of automated computer-assisted interview technology (ACASI), and extensive queries regarding the practice of behaviors resulting in oral exposure.

A cohort of HIV-negative MSM are being recruited from the Seattle and Denver area as part of the HIV Prevention Trials Network (HPTN), a multi-site network that conducts HIV prevention clinical trials (Dr. Connie Celum, Principal Investigator). Men are recruited to participate in a randomized, controlled trial of a 10 session behavioral intervention delivered in the first 4 months, or the community standard of brief counseling and testing. HIV seroincidence is the primary endpoint of this study, which was conducted from 1999-2003. Men who have sex with men, are at least 18 years of age, test HIV-negative, and have engaged in anal sex in the prior 12 months were eligible for study entry.   Information was obtained regarding sexual behavior, drug use, STIs and clinical symptoms (including constitutional, oropharyngeal, gastrointestinal, rheumatic, and neurologic) in the prior 6 months.   Participants were given the option to enroll in an HHV-8 ancillary study. After obtaining written informed consent, upon enrolling in the HHV-8 ancillary study participants complete a detailed questionnaire. This questionnaire, with specific queries about behaviors that may lead to exposure to saliva, is self-administered and supervised by trained counselors. A blood draw for HHV-8 serologic testing is also done. Information from questionnaires, diaries, and laboratory studies will be entered into an electronic database and statistical analysis will seek correlations between demographic, laboratory and behavioral characteristics and incident HHV-8 infection.