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STD-HIV Interactions

STD-HIV Interactions. Peter R. Kerndt, MD, MPH. Fundamental questions. Do other STDs facilitate sexual transmission of HIV infection? What is role of STD treatment in prevention & control of an HIV epidemic?. Sexual Transmission of HIV Depends on:. The infectiousness of the index case:

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STD-HIV Interactions

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  1. STD-HIV Interactions Peter R. Kerndt, MD, MPH

  2. Fundamental questions • Do other STDs facilitate sexual transmission of HIV infection? • What is role of STD treatment in prevention & control of an HIV epidemic?

  3. Sexual Transmission of HIV Depends on: • The infectiousness of the index case: • Plasma viral load • Genital viral load • The susceptibility of the uninfected partner: • Presence of STDs, genital inflammation • Innate host factors (i.e., CCR5 receptors)

  4. Resistance to HIV Infection • Chemokine receptor CCR5 important for infection • Mutation in CCR5 found to be protective • homozygosity = resistance to infection • heterozygosity = slowed progression of disease • Frequency of mutation varies among different populations

  5. STD-HIV Interactions: Where do we look? • Seroconversion studies • Susceptibility & infectiousness data • Intervention trials • Shifting HIV epidemic • STD services data

  6. Genital Ulcer Disease Syphilis Herpes Simplex Chancroid

  7. Genital Ulcers and HIV Seroconversion *Univariate analysis, **H. ducreyi seropositivity, ***Predominantly herpes

  8. Genital Ulcers and HIV Seroconversion *Remained signif. In multivariate analysis; ** Adjusted OR.

  9. Non-Ulcerative STDs Chlamydia Gonorrhea BV Trichomonas

  10. Nonulcerative STDs and HIV Seroconversion *Univariate analysis

  11. Population Attributable Risk (PAR) of Selected STDs for HIV Seroconversion Site/Population

  12. Genital Ulcers Mucosal disruption Target cell recruitment & activation Enhanced viral replication Alteration of chemokine receptors Non-ulcerative STDs Target cell recruitment Enhanced viral replication? Mechanisms by Which STDs Increase HIV Susceptibility

  13. Frequency of HIV Shedding* with Non-ulcerative STDs Males Females *By PCR **p < 0.05 for pre-post STD treatment

  14. Frequency of HIV Shedding* with Genital Ulcers (GUD) Males Female CSWs *By PCR except in Kreiss study which used HIV culture **Univariate risk estimate

  15. Median Concentration of HIV-1 RNA in Semen Among 104 Men With and Without Urethritis in Malawi X 104 copies/ml

  16. Hypothetical Model of Impact of STD on HIV Genital Shedding in Men Antibiotic therapy STD Seroconversion Asymptomatic HIV progression AIDS

  17. Impact of Improved STD Control on HIV Infection in Mwanza,Tanzania • 12,537 individuals in rural Tanzania followed for 2 years (1000 people from 6 control and 6 intervention communities) • Interventions: • Established a STD reference clinic and lab • Trained staff at health centers on Rx of STDs • Regular supply of medications to Rx STDs • STD education and free condoms for clients • Periodic visits to village by health education team

  18. HIV Incidence Over 2 Years in 6 Intervention and 6 Control Communities, Mwanza Trial(continuous clinics) Overall reduction of HIV 42%

  19. Impact of Improved STD Control on HIV Infection, Mwanza,Tanzania • Results: • Lower prevalence of all STDs in intervention villages • 42% lower incidence of HIV infection in intervention villages (1.2% vs. 1.9%) • No significant change in sexual practices (number of partners or use of condoms) Grosskurth et al, Lancet 1995, 346:530-6

  20. Impact of Intermittent Mass Treatment of STDs in Raki, Uganda • Community-based, randomized, controlled trial of mass STD treatment and referral for symptoms or positive syphilis test • People seen at home every 10 months, specimens were collected and directly observed therapy was given (intervention = azithro 1g + cipro 250 + metro 2g, placebo = mebendazole + iron-folate + MVI) • No change in local STD services

  21. HIV Incidence Over 20 Months in Intervention & Control Communities in the Rakai Trial(intermittent clinics) Source: Wawer et al. Lancet 1999; 353:525-35

  22. Impact of Intermittent Mass Treatment of STDs in Uganda • Over 10,000 people followed for 1-2 rounds • Initial prevalence of diseases: HIV 16%, GC 1-2%, CT 2-4%, trich 24%, BV 50% syphilis 10% and HSV-2 30-60% • Results: All curable STDs decreased in intervention groups, but no difference in HIV seroincidence between the groups Wawer, Lancet 1999; 353:525-35

  23. STD Intervention TrialsReasons for Different Outcomes • Baseline HIV prevalence much higher in Ugandan than in Tanzanian trial (16% vs 4%) • High prevalence of difficult to treat STDs (BV, HSV-2) in Ugandan trial • Effect of asymptomatic STDs on HIV transmission unclear • Conclusion: treatment of symptomatic STDs in areas with early HIV epidemics appears to be effective, but more research needed to establish efficacy in other situations

  24. STD Treatment for HIV Prevention Implications • Continuous access to improved STD services is likely to have greater impact than an intermittent mass treatment approach to STD control • Untreated symptomatic STDs probably more important than asymptomatic for HIV transmission (asymptomatic key to STD spread & other STD complications) • In later stage HIV epidemics, contribution of curable STDs may decline • Population impact will be greatest where curable STD rates are substantial

  25. Role of STDs in HIV Transmission Summary • At least 2 to 5-fold increased risk of HIV seroconversion confirmed by data from 4 continents • Attributable risk of STDs for HIV transmission substantial in some populations • HIV susceptibility likely increased through endocervical CD4 recruitment by nonulcerative STDs, as well as through “portal of entry” created by ulcers

  26. United States vs. international settings STD epidemiology is different HIV/AIDS epidemiology is different STD clinical services are stronger

  27. STDs in the USA • U.S. has highest rates of STDs in the industrialized nations • Heterosexual transmission of HIV increasing • STD control in U.S. likely to be beneficial because of early HIV epidemic and substantial rates of STDs

  28. Syphilis and Gonorrhea Rates in the U.S. Are the Highest in the Industrialized World

  29. Prevention Implications of Advances in HIV Treatment • Potential substantial decrease in average infectiousness • Longer duration of life • Increased well-being and diminished fear of HIV leading to increased sex • Potential increase in proportional role of intermittent factors that increase infectiousness (e.g., STDs)

  30. Syphilis Outbreaks in MSM • Since 1997 STD rates have risen dramatically among MSM • Seattle, San Francisco, Los Angeles and Miami have all reported increasing syphilis rates, especially among MSM • Up to 70% have been co-infected with HIV in some cities • Complacency secondary to new HIV therapies and treatments is thought to be the cause of increased unsafe sex practices

  31. STD Trends Among MSM • Doubling in proportion of MSM with GC in STD clinics in 8 large cities (12% to 23.5%, 1993-96) - MMWR • Increases in male rectal GC in San Francisco (21 to 38 per 100,000, 1994-97) after declines (42 to 20 per 100,000, 1990-93) - MMWR • Increases in syphilis, GC (125%) & chlamydia (50%) rates among MSM in Seattle/King Co. (1997-98) - AJPH • 60% of MSM with syphilis HIV-infected • 25% of MSM with GC or chlamydia HIV-infected

  32. Percentage of MSM Reporting Selected Sexual Behaviors & Male Rectal Gonorrhea Rates - San Francisco, 1990-1997 *Per 100,000 men aged > 15 years +Condoms always used during anal sex during the previous 6 months **Unprotected anal sex with two or more partners during the previous 6 months

  33. Early Syphilis by HIV StatusLos Angeles County, 2000-2005 6 in 10 MSM Early Syphilis Cases Report Being HIV Infected

  34. HIV Seroconversion Among Early Syphilis Using Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS), Los Angeles, Jan 2002 – April 2004* * JAID, Taylor, M, Volume 38, Number 5, April 15 2005

  35. New HIV Infection Among Men with Early Syphilis Los Angeles County, Jan 2002- April 2004 , N=212 Estimated Recent HIV Infection Among Early Syphilis Cases Per Year % 95% CI Males 17 12 - 22% 26 19 - 33% MSM Source: Taylor, M.M. et al., JAIDS: 38(5), 2005

  36. STD Co-infection Among Acute HIV Patients in Los Angeles County

  37. Objective To examine the prevalence of STDs among a cohort of acutely infected HIV patients in Los Angeles County

  38. HIV Viremia and Antibody Response HIV RNA (plasma) HIV Antibody 11 22 0 10 20 30 40 50 60 70 80 90 100 Days Acute HIV Infection (Window Period)

  39. Detection of HIV Symptoms p24 Antigen HIV RNA HIV EIA* Western blot 0 1 2 3 4 5 6 7 8 9 10 Weeks Since Infection *3rd generation, IgG & IgM *2nd generation EIA IgG *1st generation EIA IgG After Fiebig et al, AIDS 2003; 17(13):1871-9

  40. Pooled NAAT Screening for Early HIV Infection A B C D E F G H I J 100 Individual specimens (HIV antibody negative) 10 Pools of 10 A B C D E F G H I J 1 Screening Pool

  41. Multistage pooling Quinn et al [AIDS 2000] 2-Stage Pooling A B C D E F G H I J A B C D E F G H I J Individual specimens N=100 10 Intermediate Pools A B C D E F G H I J A B C D E F G H I J 1 Master Pool

  42. HIV Testing EIA non-reactive Vironostika® HIV1 antibody test Pooled NAAT Roche Amplicor® Monitor HIV-1 or GenProbe Aptima assay Neg. Pos. Presumptive AHI HIV Negative

  43. AIDS Acute Infection 3 wks STD Episode STD Episode Background • STDs in HIV-positive individuals increases the risk of HIV transmission HIV RNA in Semen (Log10 copies/ml) Cohen, Pilcher, UNC Center for AIDS Research

  44. Background • In acute HIV infection, individuals are highly infectious • Studies have suggested over 40% of new infections may be caused by persons with primary HIV infection • Treatment of STD in HIV co-infected may reduce HIV transmission • After people become aware they are HIV-positive, the prevalence of high-risk sexual behavior is reduced substantially – reduced number of partners and sero-sorting

  45. Study Population 13 Public Health Department STD clinics Mobile Testing Unit (MTU) 2 community STD clinics, majority of clients are MSM (sites A&B) Jail Unit for MSM and transgenders

  46. Results

  47. Pooled Testing - Acute HIV Detection Studies Los Angeles, 02/06 – 03/08

  48. Pooled Testing - Acute HIV Detection Studies Los Angeles, 02/06– 01/08 HIV NAAT testing led to: • 6% increase in HIV detection • 20% increase (Site A) • 7% increase (Site B) • 1 in 1000 • 1 in 275 (Site A) • 1 in 433 (Site B)

  49. Patients with Acute HIV Infection (AHI) VL (cp/ml) at time of initial HIV-1 Ab negative test: 6 <100,000 (lowest 1,502;1,827 to >500,000 in 9 days) 10 >100,000 19 >500,000 6 w/ invalid quantitative assay 1 <75 (false positive) 25/41 (61%) patients presented with symptoms 10 AHI symptoms only (flu-like &/or rash &/or fever) 4 AHI and STD symptoms 10 STD symptoms 1 cervical lymphadenopathy N=41

  50. Number of Sex Partners 3 months prior to diagnosis N=41, range=1 to 72 partners *6 with no information on gender of sex partner

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