Oral and anogenital shedding of HSV-2 occurs more frequently in HIV-positive men, often without symptoms

Men who are infected with herpes simplex virus-2 (HSV-2) anally or on their genitals, often shed the virus orally without any symptoms, investigators from the University of Washington conclude in an observational study published in the August 15^th edition of The Journal of Infectious Diseases. The investigators found that HSV-2 was frequently shed orally at the same time that it was shed anogenitally, and that HIV-infected men shed HSV-2 more frequently from all sites than HIV-negative men.

Both HSV-1 and HSV-2 can infect the mucosa in the oral-facial and anogenital regions. However, oral shedding of HSV-2 has rarely been observed in previous studies. Therefore, between 1994 and 2002, researchers from the University of Washington recruited 109 men, 91 of whom were gay, with 50 being HIV-positive, to a study to determine the frequency of oral shedding of HSV-2 as detected by HSV DNA polymerase chain reaction (PCR) testing. The investigators wanted to see if any host factors were associated with HSV shedding and if there was any temporal relationship between the shedding of HSV in the oral and anogenital regions.

Just over half of the HIV-positive men were taking potent anti-HIV therapy, but CD4 cell count did not differ between these men and the men who were not taking HIV treatment (approximately 350 cells/mm³). As expected, however, the men who were undergoing HIV therapy had significantly lower HIV viral loads (177 copies/ml) than men not on HIV treatment (32, 000 copies/ml, p < 0.001).

Men recruited to the study were taught how to collect samples from the mouth, penis and anus and had to provide swabs for at least 30 consecutive days to be included in the investigators’ final analysis. The median age of the study participants was 42 years and the median duration of participation was 64 days, meaning that 6505 anogenital and 6422 oral swabs were available for analysis.

A total of 77% of men shed HSV-2 from their genitals on at least one day, and 40% shed HSV-2 orally at least once. HIV-positive men shed HSV-1 and HSV-2 more frequently orally and anogenitally than HIV-negative men.

The investigators noted that oral shedding of HSV-2 was often concurrent with anogenital shedding of the virus: anogenital shedding of HSV-2 being detected on 60% of the days when oral shedding was detected. The proportion of days with concurrent oral and anogenital HSV-2 shedding did not differ between HIV-positive and HIV-negative men.

Oral shedding of HSV-2 never involved lesions. By contrast 27% of all instances of anogential shedding of the virus involved visible lesions.

Very few (5%) men had oral but no anogenital shedding of HSV-2 during the study.

The investigators then looked at the quantity of HSV-2 shed orally and anogenitally. They found that on the days when the days when the virus was being shed concurrently, it was shed in much lower quantities orally (mean 3.6 log₁₀ copies/ml) than anogenitally (mean 6.2 log₁₀ copies/ml, p < 0.001).

The rate of oral shedding of HSV-2 was 170% higher in HIV-positive men than HIV-negative men (p = 0.04). HIV-positive men also had a rate of anogenital shedding of HSV-2 130% higher than that of HIV-uninfected men (p = 0.001). However, the investigators failed to find any significant connection between CD4 cell count, HIV viral load or the use of potent anti-HIV therapy and the rate or site of HSV-2.

“This study defines several new observations about shedding of HSV-2 in the oropharynx”, write the investigators. In particular, they stress that oral shedding of HSV-1 and HSV-2 seems to occur with similar frequency, but that oral shedding of HSV-2 appears to be asymptomatic. They also stress the increased frequency of oral and anogenital shedding of HSV-2 seen in HIV-positive men.

They suggest that oral infection with HSV-2 could happen as a result of touch between the anogenital region and the face, or because of sexual contact.

A possible limitation noted by the investigators was its population – which consisted largely of urban gay men. They suggest that their findings may not be generalised to lower-risk populations.

They are unable to say if the level of HSV-2 viral load shed orally presented a significant risk of infection as the level of HSV-2 shedding required for infection to occur has not been well characterised. Nevertheless, they conclude, “individuals with HSV-2 infection should be informed about the possibility of asymptomatic oral HSV-2 reactivation, particularly if they are coinfected with HIV.”