Interactions between HSV and HIV

1
Interactions between HSV and HIV

• Dr Simon Barton
• Chelsea Westminster Hospital, London, UK

2
Herpes Simplex Virus Type 2
3
HIV-1
4
Soco-infection is common

• Epidemiological association between HSV and HIV
  established (Wasserheit, JID 1992)
• Sero-prevalence of HSV-1 and HSV-2 infection
  significantly higher in HIV-1 infected persons
  than in uninfected (Heng et al. Lancet 1994)
• But risk of acquisition of HIV and HSV both
  related to sexual behaviour?

5
The link between GUD and HIV transmission

• Rakai study demonstrated that genital ulcer
  disease (not HSV-2 seropositivity) increased the
  risk of HIV transmission

Reference Gray RH et al. Lancet 2001 357
1149-1153
6
Prior infection with HSV-2 is an important risk
factor for HIV acquisition

• Meta-analysis of cohort and case control studies
  showed significant RR of HSV-2 preceding HIV
  infection of 2.1-3.9

Reference Wald A, Link K. J Infect Dis 2002
185 45-52
7
Studies of MSM in USA

• Seroprevalence of HSV-2 is high among MSM. Under
  50 amongst those who are HIV-negative compared
  with over 80 individuals who are HIV positive
• HSV-2 infection is associated with an increased
  risk of HIV seroconversion

Reference Keat IP et al. GENITO URIN MED 1990
66 330-333
8
MSM with HSV and risk of HIV acquisition

• Studied 116 HIV seroconverters and 342 controls
  of MSM. HIV incidence was 2.3 in MSM who
  acquired HSV-2 during follow-up, compared with
  1.5 per 100 patient years in those who remained
  HSV-2 sero-negative

Reference Renzie C et al. J INFECT DIS 2003
18719-25
9
Mechanisms by which HSV-2 may increase risk of
HIV acquisition

• Disruption of the epithelial barrier by HSV
  lesional development
• Recruitment of activated CD4 cells to HSV lesions
  to act as targets for HIV acquisition

10
(No Transcript)
11

• If HSV-2 infection facilitates HIV acquisition,
  then a hypothesis formed that prevention of
  primary HSV-2 infection or suppression of HSV-2
  reactivation may significantly reduce the risk of
  HIV infection

12
HSV Transmission Guidelines, IHMF Seattle
Workshop 2003

• Through serological testing and counselling, and
  by prevention of acquisition (e.g. through
  behavioural interventions), treatment and
  antiviral suppression, HSV-2 should be targeted
  as a modifiable risk factor for HIV acquisition
  (Category 3 recommendation)

13
What does this mean?
14
What does this mean?

• Offering HIV antibody test to all patients with
  genital HSV infection?
• Counselling individuals with genital HSV that
  they have an increased risk of acquiring HIV?
• What more can we do?

15
HSV Transmission Guidelines, IHMF Seattle
Workshop 2003

• Additional biological and epidemiological studies
  are needed to characterize HSV-2 as a risk factor
  for HIV transmission (Research need
  recommendation)

16
HSV Transmission Guidelines, IHMF Seattle
Workshop 2003

• Substantial epidemiological evidence indicates
  HSV-2 increased the risk of acquiring HIV
• A proof of concept intervention trial required to
  establish whether or not HSV-2 suppressive
  therapy in populations with high prevalence of
  HSV-2 and HIV can lower the risk of HIV
  acquisition or transmission (Research need
  recommendation)

17
HSV infection activates HIV replication

• HSV infection activates HIV replication and may
  facilitate transmission of HIV-1 to sexual
  partners

18
HSV Transmission Guidelines, IHMF Seattle
Workshop 2003

• HIV-positive persons should be serologically
  tested for HSV-2 infection (Category 3
  recommendation)

19
Significance of HSV type-specific test results?

• What do we do if HIV-positive patient is
• HSV-2 infected
• HSV-2 negative

20
HSV-2 and HIV Transmission

• HSV-2 reactivation increased at the frequency and
  titre of mucosal HIV shedding
• HSV and HIV co-infect lymphocytes in vitro and in
  vivo
• Several HSV regulatory proteins (e.g. ICP-0 and
  ICP-4) up-regulate HIV replication
• VP-16 which is transactivating protein of HSV
  acts synergistically with HIV tat protein to
  increase HIV transcription
• HSV-2 may increase HIV load locally as infected
  lesions are influxed by activated CD4 cells
• CD4 cell activation up regulates HIV replication

21
HSV Transmission Guidelines, IHMF Seattle
Workshop 2003

• HSV-2 reactivation increases the frequency and
  titre of mucosal HIV shedding (Category 1
  statement)

22
HIV is a risk factor for HSV reactivation

• HIV is a risk factor for HSV reactivation through
  HIV-induced immune suppression

Reference Erlich KS et al. NEW ENGLAND JOURNAL
MEDICINE 1989 320 293-296
23
(No Transcript)
24
Natural history of genital HSV in HIV co-infected
individuals
Natural history of genital HSV in HIV
co-infected individuals is significantly
different from that in uninfected

• Chronic persistent anogenital ulceration was one
  of first recognized manifestations of AIDS
• HSV lesions persistent and progressive in HIV-
  infected individuals
• Reactivation occurs more often clinically and
  sub-clinically

25
Genital Herpes Early AIDS-associated
Opportunistic Infection
26
Summary
HSV
HIV