This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License. Your use of this material constitutes acceptance of that license and the conditions of use of materials on this site. Copyright 2007, The Johns Hopkins University and Emily J. Erbelding. All rights reserved. Use of these materials permitted only in accordance with license rights granted. Materials provided “AS IS”; no representations or warranties provided. User assumes all responsibility for use, and all liability related thereto, and must independently review all materials for accuracy and efficacy. May contain materials owned by others. User is responsible for obtaining permissions for use from third parties as needed. HIV and Other Sexually Transmitted Infections Emily J. Erbelding, MD, MPH Johns Hopkins University 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 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 7 Section B HIV/AIDS Epidemiology U.S. AIDS Statistics, 1985–2004 Estimated number of AIDS cases, deaths, and persons living with AIDS in the United States,1985–2004 9 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. 10 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, 1447–1450. 11 HIV/AIDS Diagnoses, by Transmission Category 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. 12 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 13 A Global View of HIV Infection 38.6 million people (33.4–46.0 million) living with HIV in 2005 Source: World Health Organization. 14 Part C HIV/STI—Biologic and Epidemiologic Interactions 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 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, 1097. 17 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. 18 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, 341-346. 19 Interactions between STDs and HIV 20 Effect of Other STDs on Sexual Transmission of HIV Effect of other STDs on sexual transmission of HIV (theoretical) 21 Specific Biological Mechanisms: Genital Ulcer Disease 1 2 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. 22 Syphilis 1 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. 23 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, 277. 24 Inflammatory STDs: Gonorrhea and Chlamydia 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. 25 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 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 HIV Transmission: Factors That Affect Infectiousness Acute HIV infection Advanced clinical stage (AIDS) Genital ulcerations Inflammatory STDs Consistent condom use (reduces) HAART (reduces) 28 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 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. 29 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 Section D STI Control As HIV Prevention Question Does better STD control at the community level decrease HIV transmission? 32 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 HIV Incidence in Pair-Matched Villages Mwanza, Tanzania 34 HIV Seroconversion—Mwanza, Tanzania Data Source: Grosskurth. (1995). Lancet, 346, 530. 35 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 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 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. 37 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 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 Section E Miscellaneous Problems 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 X Decreasing rates 1990–1993: 42-->20/100,000 X Increasing rates 1994–1997: 21-->38/100,000 Source: (1999). MMWR, 48, 45. 41 Syphilis in Seattle 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. 42 More on HAART and STDs and Disinhibition 1 2 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. 43 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 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