STI/HIV Interactions
H. Hunter Handsfield, M.D.
Battelle Seattle Center for Public Health Research and
Evaluation
University of Washington Center for AIDS and STD
STI-HIV Interactions
 Enhanced HIV transmission
- Behavioral
- Biological: Inflammatory STDs, bacterial vaginosis, ?HPV
• Susceptibility: CD4+ cells recruited to sites of
inflammation
• Transmission: HIV replication turns on when
inflammatory cells replicate
high viral loads at
infected sites
• BV and HIV mechanism(s) not well understood
 Clinical interactions
- HIV on STD (HSV, HPV [warts, cervical neoplasia] syphilis,
-
others)
STD on HIV (HSV, ?others)
Influence of STI on HIV Incidence
STI
Strength of Association
Pop Attrib Fraction
Chancroid
Syphilis
HSV-2
4+
3+
4+
Trivial
Low
High (up to 50%)
Gonorrhea
Chlamydia
Trichomoniasis
Bacterial vaginosis
HPV
4+
2+
3+
3+
1+
Moderate
Low
Moderate
High (20-40%?)
Low (?)
Probability of HIV Transmission in 174 HIV Discordant
Monogamous Couples: Rakai, Uganda
HIV Transmission Risk per 1000 Exposures
Viral Load in HIVInfected Ptr
• <1700
• 1700-12,499
• 12,500-38,499
• >38,500
HSV-2 Antibody in HIV Neg Partner
Negative
Positive
0. 04
1.0
0.5
2.3
0.2
1.8
0.7
3.6
Relative Risk of HIV Acquisition in HSV-2 Positive
Versus HSV-2 Negative Persons
Freeman EE et al, AIDS 2006;20:73-83
Females
Males
Risk of HIV Acquisition According to HSV2 Infection Status: STD/FP Clients, Pune,
India (N = 2732)
Adjusted Hazard Ratio
4.5
HR 3.8
4.0
3.5
22.6*
* Incidence per 100 person-yr
3.0
2.5
2.0
1.5
1.0
0.5
HR 1.9
HR 1.7
HR 1.0
(Referent)
7.5*
7.5*
3.6*
0.0
None
Reynolds SJ et al
JID 2003;187:1513
Prevalent
Remote
Incident
HSV-2 Status
Recent
Incident
Bacterial STI Treatment Trials to Prevent HIV
Barnabas RV, Wasserheit JN Sex Transm Dis 2009;36:365-7
Trial
HIV Inc
Mwanza 1991-95
HIV Prev I:P Ratio
STI Rx Efficacy
1.9
4.4
0.43
Yes
1.5
15.5
0.10
No
0.8
10
0.08
No
1.5
21
0.07
No
4.1
39
0.11
No
1.5
17
0.09
No
Grosskurth et al
Rakai 1994-98
Wawer et al
Masaka 1995-2001
Kamali et al
Manicaland 98-2003
Gregson et al
Harare 1999-2004
van de Wijgert et al
Kampala 1999-2004
van de Weijgert et al
Bacterial STI Treatment Trials to Prevent HIV
Trial
Bact STI
and TV
Mwanza 1991-95
HSV-2
Yes No
BV
No
STI Rx Efficacy
Yes
Grosskurth et al
Rakai 1994-98
Yes
No
No
No
Yes
No
No
No
Yes
No
No
No
Yes
No
Yes
No
Yes
No
Yes
No
Wawer et al
Masaka 1995-2001
Kamali et al
Manicaland 98-2003
Gregson et al
Harare 1999-2004
van de Wijgert et al
Kampala 1999-2004
van de Weijgert et al
What About Herpes?


Two RCTs have tested the hypothesis that acyclovir suppressive
therapy in HSV-2 infected persons would reduce HIV incidence
- Celum et al, Lancet 2009 (women, MSM in Africa, USA, Peru)
- Watson-Jones et al, NEJM 2009 (women in Tanzania)
No difference in HIV acquisition with ACV versus placebo. Why??
- Association of HSV-2 with incident HIV is wrong?
No
- Inadequate HSV-2 suppression with acyclovir?
No
- Continued subclinical reactivation of HSV-2?
No (?)
- Best bet: Continued inflammatory response and/or recruitment
of HIV-susceptible cells at HSV-2 infected mucocutaneous sites
• CD4+ macrophages and T lymphocytes reacting to HSV-2
abound despite antiherpetic therapy (without ulceration)
University of Washington, Johns Hopkins University
Where Do We Go from Here?





Despite disappointing results of most trials, epidemic phaseappropriate management of bacterial STIs, trichomoniasis, and BV
still has potential to reduce HIV incidence
Preventing HSV-2 has high promise
- Suppressive treatment? Immunization?
In view of the apparently high PAF of HIV infections from BV,
investigation of BV therapy to prevent HIV is warranted
- Selective mass treatment? Repeated?
- Also would bring likely benefits against trichomoniasis
- Continued research on etiology and pathogensis of BV
At the individual level, it remains likely that diagnosis and treatment
of bacterial STD and symptomatic genital herpes helps prevent
HIV acquisition and perhaps transmission in treated patients
STDs themselves warrant effective prevention, diagnosis and
treatment