Rapidly cleared episodes of oral and anogenital herpes simplex virus shedding in HIV-infected adults

Abstract

Objective: To determine whether rapidly cleared episodes of herpes simplex virus (HSV) reactivation occur in HIV-infected adults.

Methods: Twenty HSV-2-seropositive, HIV-seropositive adults, including 9 (45%) who were also HSV-1 seropositive, collected oral and anogenital swabs for HSV DNA polymerase chain reaction 4 times a day for 60 days. Samples were positive for HSV if we detected > or =150 copies of HSV DNA/mL of specimen.

Results: Median HSV shedding episode duration was 7.5 (range 4-253) hours for oral and 11 (range 4-328) hours for anogenital reactivation. Thirty-five percent of oral and 29% of anogenital reactivations lasted < or =6 hours, and 59% of oral and 53% of anogenital reactivations lasted < or =12 hours. Seven of 9 participants who shed orally and 10 of 15 who shed anogenitally had > or =1 reactivation lasting < or =6 hours. The median maximum level of HSV DNA detected in an episode increased with episode duration for both oral and anogenital episodes. Concurrent oral and anogenital shedding occurred more frequently than expected: oral HSV shedding was detected on 17% of time points with anogenital but 1% of time points without anogenital, shedding (P < 0.001).

Conclusions: Rapidly cleared episodes of oral and anogenital HSV shedding occur in HIV-infected persons, supporting the hypothesis that frequent anogenital mucosal immune activation caused by HSV-2 is present in HIV coinfected persons, potentially contributing to HIV infectiousness.

Figure 1

Herpes simplex virus (HSV) shedding episode duration and viral copy number, of 29 oral and 66 anogenital shedding episodes of known duration. (A) Oral and (B) anogenital episode duration and (C) oral and (D) anogenital HSV copy number by episode duration.

Figure 2

Concurrent oral and anogenital herpes simplex virus shedding in two HSV-1/HSV-2 seropositive participants. Participant 1, a 37 year old man diagnosed with genital herpes 17 years earlier, had been off antiretrovirals for ∼4 months prior to study entry and had a CD4 of 160 cells/mm3 and an HIV viral load of 148,000 copies/mL. Participant 2, a 49 year old man diagnosed with asymptomatic HSV-2 infection at least 4 years earlier but subsequently noted to have typical genital, perianal, and perineal recurrences of which he was previously unaware, was on antiretrovirals with a CD4 of 706 cells/mm3 and an undetectable HIV viral load. The asterisk in Figure 2B shows the one day that genital symptoms and lesions were present; all other shedding was asymptomatic.

Figure 2

Concurrent oral and anogenital herpes simplex virus shedding in two HSV-1/HSV-2 seropositive participants. Participant 1, a 37 year old man diagnosed with genital herpes 17 years earlier, had been off antiretrovirals for ∼4 months prior to study entry and had a CD4 of 160 cells/mm3 and an HIV viral load of 148,000 copies/mL. Participant 2, a 49 year old man diagnosed with asymptomatic HSV-2 infection at least 4 years earlier but subsequently noted to have typical genital, perianal, and perineal recurrences of which he was previously unaware, was on antiretrovirals with a CD4 of 706 cells/mm3 and an undetectable HIV viral load. The asterisk in Figure 2B shows the one day that genital symptoms and lesions were present; all other shedding was asymptomatic.