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HIV and Other Sexually Transmitted Infections
Emily J. Erbelding, MD, MPH
Johns Hopkins University
Objectives
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Describe HIV as a pathogen
Review epidemiology of HIV/AIDS
Discuss STIs as cofactors in the spread of HIV
Review evidence that improved STD control prevents new HIV
Discussion: Opt Out HIV testing as prevention policy in the U.S.
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Section A
HIV: The Virus and Its Effects on the Host
Anatomy of the AIDS Virus
Public Domain
5
Replication Cycle of HIV
Source: Weiss RA, Gulliver's travels in HIVland. Nature 2001;410:963–967. Copyright © 2001
Nature Publishing Group. Used with permission. All Rights Reserved.
6
Natural History of HIV Infection
Source: The Relationship Between the Human Immunodeficiency Virus and the Acquired
Immunodeficiency Syndrome. National Institutes of Health, 1995
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Section B
HIV/AIDS Epidemiology
U.S. AIDS Statistics, 1985–2004
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Estimated number of AIDS cases, deaths, and persons living with
AIDS in the United States,1985–2004
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Awareness of HIV Status among HIV+, United States
Number infected with HIV
1,039,000–1,185,000
Number unaware of HIV infection
252,000–312,000 (24%–27%)
Estimated new infections annually
40,000
Source: Glynn, M., and Rhodes, P. (2005). HIV Prevention Conference.
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Awareness of Serostatus and Estimates of Transmission
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Awareness of serostatus among people with HIV and estimates of
transmission
Data Source: Marks, et al. (2006). AIDS, 20, 1447–1450.
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HIV/AIDS Diagnoses, by Transmission Category
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HIV/AIDS diagnoses among adults and adolescents, by transmission
category (33 states, 2001–2004)
Data Source: Trends in HIV/AIDS Diagnoses --- 33 States, 2001--2004 MMWR 2005, November 18.
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Twenty-Five Years of AIDS
Figure 1.1 from the UNAIDS Report on the Global AIDS Epidemic 2006.
Available at: http://www.unaids.org/en/HIV_data/2006GlobalReport/default.asp
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A Global View of HIV Infection
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38.6 million people (33.4–46.0 million) living with HIV in 2005
Source: World Health Organization.
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Part C
HIV/STI—Biologic and Epidemiologic Interactions
STDs and HIV: Epidemiologic Synergy
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STDs (both ulcerative and non-ulcerative) enhance HIV transmission
− Untreated STDs make those uninfected more susceptible
− STDs in those with HIV infection enhance HIV shedding and
make them more infectious
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Transmission Risk: Heterosexual Contact
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Male to female: 5/10,000 encounters
Female to male: 3/10,000 encounters
Anal receptive: 8/1,000 encounters
Source: Downs. (1996). JAIDS, 11, 388; Royce. (1997). N Engl J Med, 336, 1097.
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HIV Transmission if STD Present (Non-index Partner)
Data Source: de Vincenzi I. A longitudinal study of human immunodeficiency virus transmission by heterosexual partners.
European Study Group on Heterosexual Transmission of HIV. N Engl J Med 1994;331:341-346.
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HIV Heterosexual Transmission
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Elevated transmission risk, M to F
− CD4 ≤ 200, index case (OR 2.7)
− Anal sex ever (OR 5.1)
− Advanced age of female partner (OR 3.9 for age > 45 years)
Elevated transmission risk, F to M
− CD4 ≤ 200, index case (OR 17.6)
− Sexual contact during menses (OR 3.4)
Source: DeVincenzi. (1994). N Engl J Med, 331, 341-346.
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Interactions between STDs and HIV
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Effect of Other STDs on Sexual Transmission of HIV
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Effect of other STDs on sexual transmission of HIV (theoretical)
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Specific Biological Mechanisms: Genital Ulcer Disease
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HSV-2
− Ulcerations more persistent with HIV infected
− Those co-infected with with HSV-2/HIV have more HSV-2
shedding than those without HIV infection1
− HSV-2 can stimulate HIV replication in vitro2
Schacker, T. (1998). J Infect Dis, 178, 1616.
Moriuchi, M. (2000). Virology, 278, 534.
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Syphilis
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Chronic systemic infection that is sexually acquired, natural history
and response to therapy my be altered by HIV
STD patients with primary syphilis and HIV more likely to have
multiple chancres than those without HIV1
Rompalo, A. M. (2001). STD, 28, 448.
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HIV Shedding from Genital Ulcer Disease (GUD)
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HIV DNA present in 34% of GUD specimens (24/75 from HIV+
persons)
All four HIV seroconverters with GUD were HIV-PCR positive (vs.
20/67 HIV+ non-seroconverters, p = 0.01)
Presence of chancroid (OR 4.9), long duration of symptoms
(OR 4.3) and concurrent dx of cervicitis/urethritis (OR 4.9) were
significantly associated with HIV shedding
Source: Gadkari, D. A. (1998). JAIDS, 18, 277.
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Inflammatory STDs: Gonorrhea and Chlamydia
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1
Higher rates of HIV shedding in semen of HIV-infected men with GC
urethritis1
Similar findings in cervical-vaginal lavage fluid from HIV-infected
women with STDs
Cohen, M. (1997). Lancet, 349, 1868.
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More HIV Shedding in HIV-Infected Women with STD
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Detection of HIV-RNA in cervical-vaginal lavage specimens
− +GC
OR 2.1
− +CT
3.0
− STS
NS
− GUD
4.6
− Mucopus
2.3
− Candida
2.6
Source: Ghys. (1997). AIDS, 11, F85.
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HIV Acquisition: Factors That Affect Susceptibility
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Genital ulcers
Inflammatory STDs
Cervical ectopy
Uncircumcised status
Traumatic sex
Lack of condom use
Anal intercourse
Sex during menses
CCR5 co-receptor status
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HIV Transmission: Factors That Affect Infectiousness
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Acute HIV infection
Advanced clinical stage (AIDS)
Genital ulcerations
Inflammatory STDs
Consistent condom use (reduces)
HAART (reduces)
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STDs Alter Natural History of HIV
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Compare HIV-RNA and CD4 levels before/after syphilis treatment
Chart review of 52 HIV+ men with primary/secondary syphilis
Syphilis associated with indicators of immune loss
− Higher HIV during syphilis infection (0.22 log10 RNA; p = 0.02)
than levels before syphilis
− Lower CD4 count during syphilis infection (-62 cells; p = 0.04)
than before syphilis
− Changes most substantial in secondary syphilis and in those not
on HAART
Source: Buchacz. (2006). AIDS, 20, 305.
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STDs in HIV Infection: Summary Points
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Epidemiologic and biologic data support concept of “epi synergy”
Early detection/prevention benefits individual AND the community
Identification also important from a public health standpoint: new
STDs identify persons who are likely to be transmitting HIV to others
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Section D
STI Control As HIV Prevention
Question
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Does better STD control at the community level decrease HIV
transmission?
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STD Treatment Interventions: Tanzania
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If STDs biologically enhance HIV transmission, does STD treatment in
a community decrease STD incidence?
Randomize matched villages to receive enhanced syndromic
management over “baseline” care, compare HIV incidence in
comparison villages
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HIV Incidence in Pair-Matched Villages
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Mwanza, Tanzania
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HIV Seroconversion—Mwanza, Tanzania
Data Source: Grosskurth. (1995). Lancet, 346, 530.
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Mass Treatment, Uganda
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Study design: periodic mass treatment of intervention villages for all
adults of reproductive age
− Azithromycin 1 gm
− Ciprofloxacin 250 mg
− Metronidazole 2 gm
− Benzathine Pen G 2.4 mu if report of ulcer, or if reactive
serology
Control arm
− nutritional treatments, antihelminthics and syndromic
management for STDs
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The Rakai Intervention
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Does mass STD treatment decrease HIV incidence?
Primary outcome measure: HIV incidence in intervention villages
compared to control villages
− No change between mass treatment and syndromic treatment
conditions
− Difference in results (as compared to Mwanza) attributable to
several factors
X High prevalence of HSV as cause of GUD
X High prevalence of BV (highly recurrent condition that may
increase susceptibility)
X Higher prevalence of HIV at baseline in Uganda (different
stage of epidemic than Mwanza)
Source: Wawer, M. J., et al. (1999). Lancet, 353, 9152, 525.
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HSV and HIV Prevention
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HSV accounts for 20–80% of GUD in Africa
HSV increases HIV viral shedding in HIV+
HSV makes HIV- persons more susceptible to HIV acquisition
Current multi-site HIV prevention trials
− RCT enrolling discordant couples, at least one
person HIV+/HSV-2+
− Compare ACV vs. placebo on outcome of HIV
seroconversion
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Conclusions: STD and HIV
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Epidemiologic synergy exists
STD control important to population health for many reasons
Depending upon characteristics of STI/HIV epidemics, improved STI
control may avert HIV transmission
BUT, mass treatment at community level not best HIV prevention
strategy
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Section E
Miscellaneous Problems
STDs on the Rise among MSM
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In San Francisco, increases in unprotected anal intercourse (UAI)
and rectal gonorrhea among MSM
− Proportion of MSM reporting UAI: 23.6% in 1994, 33.3% in 1997
(largest increases among men under 25)
− Male rectal gonorrhea
X Decreasing rates 1990–1993: 42-->20/100,000
X Increasing rates 1994–1997: 21-->38/100,000
Source: (1999). MMWR, 48, 45.
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Syphilis in Seattle
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Primary/secondary syphilis virtually eliminated from 1987 to 1996
Resurgence of syphilis in 1997–1998, with 68% of cases among MSM;
66% of MSM known to be HIV+
Source: Williams et al. (1999). Am J Public Health, 89, 1093.
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More on HAART and STDs and Disinhibition
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HAART use and STDs
− The use of HAART in San Francisco was associated with greater
likelihood of later acquisition of an STD1
Survey of 350 MSM in Los Angeles2
− 63% aware of HAART
− 18–22% of those aware were “confident in its ability to reduce
HIV transmission”
− Those “confident” in HAART were three times more likely to
report recent unprotected anal intercourse
Scheer. (1997). Lancet, 357, 432.
Bingham, T. (2001). 8th CROI, Chicago, #213.
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HAART and Unsafe Sex: Possible Associations
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Health restored to previously sick people through HAART, so that
normal activities (including risky or safe sex) could be resumed
Knowledge of “undetectable” viral load in HIV+ may make them feel
confident that they are not infectious to others
HAART may have changed public perception: HIV is no longer a killer
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So How Do We Control Spread of HIV?
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Effective prevention needs many components
− Modify cofactors (STD)
− Circumcision
− Promote knowledge of serostatus
− Link to treatment
− HAART to prevent AIDS
− HAART early?
− Detect seroconverters and intervene?
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