Management of HSV Infection in the HIVInfected Patient

1
Management of HSV Infection in the HIV-Infected
Patient

• Timothy Schacker, M.D.
• University of Minnesota
• USA

2
HSV-2 and HIV

• Most HIV-infected persons are HSV-2 seropositive
• Chronic and incident HSV-2 infection has been
  associated with HIV acquisition
• HSV reactivation is more common in people with
  HIV infection
• Contact with a person who has a genital lesion is
  a reported risk factor for the heterosexual
  transmission of HIV

3
Herpes Simplex and HIV Interactions

• Opportunistic infection
• Transmission and acquisition
• Increased HIV replication

4
HSV/HIV Interactions
5
Frequent multianatomic HSV-2 shedding in
HIV-infected persons
oral
genital
rectal
oral
genital
rectal
oral
genital
rectal
Symptomatic
oral
genital
Subclinical (HSV-2 culture )
rectal
CD4 14 cells/mm
3
6
Rate of Ano-genital HSV-2 Reactivation Amongst
HIV vs HIV- Men

• When measured by PCR the rate is 4x higher than
  culture

7
Detection of HIV-1 RNA in HSV-2 Lesions

• HIV RNA detected in 25/26 episodes
• HIV RNA detected on 112/170 (66) days

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HIV-1 DNA in Genital Ulcers
days
Gadkari, et al. 1998, J AIDS
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Aciclovir and Survival Meta-Analysis
Ionnidis, et al. JID, 1998
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Changes in Plasma HIV-1 RNA With HSV Reactivation
Mole, et al, JID
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Plasma HIV-1 RNA and HSV Shedding
Percentage of study days with positive
HSV culture (no episodic or suppressive HSV
therapy)
NB Adjusted for baseline CD4
12
Valaciclovir for the Suppression of Recurrent
Genital Herpes in HIV Subjects

• Double-blind, randomized trial
• Stable ART for gt 2 months
• 4 genital recurrences in past year
• Valaciclovir 500 mg BID vs placebo(21
  randomization)

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Cohort Characteristics
14
Efficacy of Oral Valaciclovir for Suppression of
Genital Herpes in HIV Persons
15
Time To First Recurrence of Genital Herpes
16
Famciclovir Suppression in HIV Patients
Famciclovir 500 mg BID
Placebo
Randomization
Washout
Placebo
Famciclovir 500 mg BID
8 weeks
7 days
8 weeks
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Intent to Treat Analysis
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Surveillance for Aciclovir Resistance

• CDC conducted study among 22 clinics in early
  1990s
• 2088 isolates, 90.2 HSV-2
• 15 were aciclovir resistant
• 3 (0.18 of HIV-negative)
• 12 (5.3 of HIV-positive)
• Strong association between aciclovir-resistant
  HSV and topical aciclovir use
• Reyes, Arch Intern Med 2003

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Aciclovir Resistance and HIV

• Prevalence of resistant isolates is higher in the
  immunocompromised (5.6) compared with the
  immunocompetent (0.3) population
• No evidence that the prevalence of resistant HSV
  has increased over time in either population
• Most isolates recovered after resolution of
  aciclovir-resistant episodes are
  aciclovir-sensitive
• Resistant isolates not predictive of clinical
  aciclovir failure in healthy persons

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Management Guidelines(proposed)

• As HSV-2 infection may be implicated in the
  transmission of HIV, HIV-positive individuals
  should be offered HSV serologic testing,
  particularly those with advanced immune
  suppression (category 2 recommendation)
• Suppressive antiviral therapy should be routinely
  offered to HIV positive patients with a high
  frequency of clinical HSV-2 reactivation
  (category 2 recommendation)
• Suppressive antiviral therapy is safe and
  effective in people co-infected with HSV-2 and
  HIV. Such therapy should therefore be routinely
  offered to such patients, particularly those with
  advanced immune suppression (category 3
  recommendation)

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Remaining Questions

• What is the rate of HSV reactivation among
  patients with good HIV suppression?
• What is the optimal dose of drug to suppress or
  treat HSV?

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Remaining Questions

• What is the impact of HSV reactivation on HIV
  pathogenesis when HIV is suppressed?
• Would HSV suppression of HSV/HIV co-infected
  persons result in fewer transmissions of HIV?
• Does genital HSV-1 carry the same risk for HIV
  transmission, acquisition, or progression as
  HSV-2 infection?