final program.qxd - Parallels Plesk Panel

OP 3.2
Interactions between HSV and HIV
Dr Anna Maria Geretti
MD, PhD
Royal Free Hospital, London
HSV-specific T-cell responses are reduced in HIV-1 infected persons compared with
uninfected individuals. Impaired immunological control results in increased frequency of
HSV reactivation and high levels of virus shedding, and can lead to the development of
severe chronic mucocutaneous lesions poorly responsive to antiviral therapy.
The potential impact of poorly controlled HSV replication is significant. In addition to the
effects on HSV disease, frequent HSV reactivations have been shown to promote HIV-1
replication and increase HIV-1 RNA levels in plasma, with implications for HIV-1
transmission and disease progression. This presentation will review the epidemiology and
natural history of HSV infection in HIV-1 positive persons and present data on the impact
of HAART on the clinical expression of genital herpes and HSV-specific immune
reconstitution. Published evidence indicates a high prevalence of HSV-1 and HSV-2
infection among HIV-1 positive persons. In a cohort of 850 adults diagnosed HIV-1
positive in London in 1986-2001, seroprevalence at the time of HIV-1 diagnosis was 88%
(95% CI 86-91%) for HSV-1 and 63% (95% CI 60-66%) for HSV-2. Detection of HSV-2
antibodies was associated with female gender, heterosexual risk group, black ethnicity,
and older age. Over median 3 years of follow-up, HSV-2 seroincidence in the same cohort
was 1.8 per 100 person-years (95% CI 0.8-2.8) and was associated with a diagnosis of
other STDs, including HPV infection and gonorrhea. Underdiagnosis of genital herpes is
common among both HIV-1 positive and HIV-1 negative individuals, in part reflecting the
poor sensitivity of virus culture of mucocutaneous swabs used for HSV detection.
Consistent with this hypothesis, a comparative study showed that the use of real-time
PCR increased HSV detection in genital swabs by 71% relative to virus culture. In
addition, HAART has a significant beneficial effect on the clinical expression of HSV
infection. In a cohort of HIV-1 and HSV-2 seropositive patients, only 21% received a
clinical diagnosis of genital herpes and this was more likely in persons who tested HIV-1
positive before 1997 (adjusted OR 5.11; 95% CI 3.28-7.98) than in those diagnosed in
later years. A prospective study of persons starting first-line HAART found that restoration
of HSV-specific immunity occurred slowly and in parallel with raising CD4 counts. Over
median 40 weeks of therapy, the number of spot forming cells measured in ELISPOT
assays increased by 5.6 (95% CI 1.2-9.9) per month and by 21.3 (95% CI 13.8-28.7) per
100 CD4 cells gained. Thus, persons starting HAART with a CD4 count around 200-250
cells/mm3 require on average 33 months of virologically and immunologically successful
therapy to restore HSV-specific CD4 T-cells responses to the levels observed in healthy
donors. This provides a threshold for HSV-immune reconstitution that may assist with
clinical management.
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