Why do epidemiology and clinical trials in international settings?

1. Why do epidemiology and clinical trials in international settings? -Or- “Tales of my circuitous career path” Connie Celum, MD, MPH Associate Professor of Medicine University of Washington

2. Why do epidemiology and clinical trials in international settings? • Problems of public health importance are most concentrated in resource-poor countries • Thus, opportunities are greater for addressing issues with potential impact • Allows for potentially lasting contributions in research, training, services, and infrastructure

3. Tales of a circuitous career path • Started undergraduate major in International Relations  Human Biology • Medical school & internal medicine residency, UCSF • MPH (Robert Wood Johnson) & ID fellowship at UW • UW faculty since 1991 • Harborview STD clinic director: 1991-98 • HIV & STD epidemiologic research: 1995–now • HIV prevention & clinical trials: 1997-now

4. Evolution of our research program in Peru • UW - Fogarty training in epidemiology in 1991 • Past decade, >30 Peruvians trained at UW • Very high “return rate” • Critical mass of internists, pediatricians, Ob-Gyns trained in epidemiology; most interested in clinical research • Initially observational, descriptive epidemiology • Steep growth in clinical trials over past 5 years

5. HIV and STD research in Peru • 1998-2000: Development of cohort of men who have sex with men (MSM) to determine HIV seroincidence, STD prevalence & risk behaviors (Dr. Jorge Sanchez) • 2000: NIH funding to develop HIV Prevention Trials Unit (HPTU) & Vaccine Unit (HVTU) • 2002: NIH funding to develop Int’l AIDS Clinical Trials Unit • 2003: Submission of Andean Comprehensive AIDS Research Program (CIPRA)

6. Findings from “Alaska” • More than 8000 MSM were screened in Lima between 1998and 2000

7. Estimated incidence among first 2424 MSM screened = 5.1% (95% CI = 3.1 - 9.4) Observed incidence = 3.3% Findings from “Alaska” High prevalence of bisexuality • 30% of HIV positive, and 18% of HIV negative reported sex with women in the past 6 months

8. Lessons from “Alaska” cohort • Large capacity for recruiting MSM in Lima • High HIV prevalence (13%) & incidence (3.3%) • High STD prevalence • 15% syphilis seropositive; 18% with early syphilis • 5% rectal GC/CT & 3% urethritis • 50% of HIV- MSM and 92% of HIV+ MSM have HSV-2 • Mixture of delivery of prevention & clinical services; limited resources and focus on retention • Need to identify effective retention strategies

9. Current HIV clinical trials in Peru • Phase I HIV vaccine trials: • Canarypox & gp 120: 28 enrolled in 5 mos • Merck adenovirus-gag vector: to begin March 2003 • Vaccine preparedness work: • MSM cohort in Iquitos, city of 300,000 in Amazon • HIV prevention: • Intervention to test whether HSV-2 suppression reduces HIV acquistion • Cross-over study of HSV-2 suppression on HIV shedding • HIV treatment: Randomized trial of 3 regimens of HAART for CD4 <200

10. Year 2000 sentinel surveillance:8 medium-sized cities • 3101 MSM tested in 8 medium cities • Overall HIV prevalence of 7% • Estimated HIV incidence 2.9%* • High HIV incidence in 2 jungle cities: IquitosPucallpa N=405 N=508 HIV prevalence 13% 3.5% Estimated HIV incid. 7.1% (2-15.1) 4.5% (1.0-10.2) Observed HIV incid. 2.2/100 p-yrs 3.5/100 p-yrs * by LS EIA on reactive sera

11. Lessons learned from my research collaborations in Peru • Feasible & rewarding • Requires patience & persistence in start-up phase • Need to train in Good Clinical Practices, protocol adherence • Clinical trials are more demanding than epid studies • Need to have the “long view” • Collaboration is essential • Requires sensitivity to working relationships, institutional history, & barriers

12. My advice • Find the questions that “grab” you • Find mentors to guide (& hopefully inspire) you • Be patient; even circuitous paths get you there • Keep your sense of humor and purpose • Find good collaborators • Stay the course