HIV and Other Sexually Transmitted Infections. Emily J. Erbelding, MD, MPH Johns Hopkins University

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2 HIV and Other Sexually Transmitted Infections Emily J. Erbelding, MD, MPH Johns Hopkins University

3 Objectives 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. 3

4 Section A HIV: The Virus and Its Effects on the Host

5 Anatomy of the AIDS Virus Public Domain 5

6 Replication Cycle of HIV Source: Weiss RA, Gulliver's travels in HIVland. Nature 2001;410: Copyright 2001 Nature Publishing Group. Used with permission. All Rights Reserved. 6

7 Natural History of HIV Infection Source: The Relationship Between the Human Immunodeficiency Virus and the Acquired Immunodeficiency Syndrome. National Institutes of Health,

8 Section B HIV/AIDS Epidemiology

9 U.S. AIDS Statistics, Estimated number of AIDS cases, deaths, and persons living with AIDS in the United States,

10 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 (24% 27%) Estimated new infections annually 40,000 Source: Glynn, M., and Rhodes, P. (2005). HIV Prevention Conference. 10

11 Awareness of Serostatus and Estimates of Transmission Awareness of serostatus among people with HIV and estimates of transmission Data Source: Marks, et al. (2006). AIDS, 20,

12 HIV/AIDS Diagnoses, by Transmission Category HIV/AIDS diagnoses among adults and adolescents, by transmission category (33 states, ) Data Source: Trends in HIV/AIDS Diagnoses States, MMWR 2005, November

13 Twenty-Five Years of AIDS Figure 1.1 from the UNAIDS Report on the Global AIDS Epidemic Available at: 13

14 A Global View of HIV Infection 38.6 million people ( million) living with HIV in 2005 Source: World Health Organization. 14

15 Part C HIV/STI Biologic and Epidemiologic Interactions

16 STDs and HIV: Epidemiologic Synergy 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 16

17 Transmission Risk: Heterosexual Contact 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,

18 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:

19 HIV Heterosexual Transmission 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,

20 Interactions between STDs and HIV 20

21 Effect of Other STDs on Sexual Transmission of HIV Effect of other STDs on sexual transmission of HIV (theoretical) 21

22 Specific Biological Mechanisms: Genital Ulcer Disease 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 infection 1 HSV-2 can stimulate HIV replication in vitro 2 1 Schacker, T. (1998). J Infect Dis, 178, Moriuchi, M. (2000). Virology, 278,

23 Syphilis 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 HIV 1 1 Rompalo, A. M. (2001). STD, 28,

24 HIV Shedding from Genital Ulcer Disease (GUD) 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,

25 Inflammatory STDs: Gonorrhea and Chlamydia Higher rates of HIV shedding in semen of HIV-infected men with GC urethritis 1 Similar findings in cervical-vaginal lavage fluid from HIV-infected women with STDs 1 Cohen, M. (1997). Lancet, 349,

26 More HIV Shedding in HIV-Infected Women with STD 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. 26

27 HIV Acquisition: Factors That Affect Susceptibility Genital ulcers Inflammatory STDs Cervical ectopy Uncircumcised status Traumatic sex Lack of condom use Anal intercourse Sex during menses CCR5 co-receptor status 27

28 HIV Transmission: Factors That Affect Infectiousness Acute HIV infection Advanced clinical stage (AIDS) Genital ulcerations Inflammatory STDs Consistent condom use (reduces) HAART (reduces) 28

29 STDs Alter Natural History of HIV 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 log 10 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,

30 STDs in HIV Infection: Summary Points 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 30

31 Section D STI Control As HIV Prevention

32 Question Does better STD control at the community level decrease HIV transmission? 32

33 STD Treatment Interventions: Tanzania 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 33

34 HIV Incidence in Pair-Matched Villages Mwanza, Tanzania 34

35 HIV Seroconversion Mwanza, Tanzania Data Source: Grosskurth. (1995). Lancet, 346,

36 Mass Treatment, Uganda 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 36

37 The Rakai Intervention 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 High prevalence of HSV as cause of GUD High prevalence of BV (highly recurrent condition that may increase susceptibility) Higher prevalence of HIV at baseline in Uganda (different stage of epidemic than Mwanza) Source: Wawer, M. J., et al. (1999). Lancet, 353, 9152,

38 HSV and HIV Prevention 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 38

39 Conclusions: STD and HIV 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 39

40 Section E Miscellaneous Problems

41 STDs on the Rise among MSM 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 Decreasing rates : 42-->20/100,000 Increasing rates : 21-->38/100,000 Source: (1999). MMWR, 48,

42 Syphilis in Seattle Primary/secondary syphilis virtually eliminated from 1987 to 1996 Resurgence of syphilis in , with 68% of cases among MSM; 66% of MSM known to be HIV+ Source: Williams et al. (1999). Am J Public Health, 89,

43 More on HAART and STDs and Disinhibition HAART use and STDs The use of HAART in San Francisco was associated with greater likelihood of later acquisition of an STD 1 Survey of 350 MSM in Los Angeles 2 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 1 Scheer. (1997). Lancet, 357, Bingham, T. (2001). 8th CROI, Chicago, #

44 HAART and Unsafe Sex: Possible Associations 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 44

45 So How Do We Control Spread of HIV? 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? 45