Why do epidemiology and clinical trials in international

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

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

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

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

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)

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

Estimated incidence among first 2424 MSM screened = 5. 1% (95% CI = 3. 1 - 9. 4) Findings from “Alaska” Observed incidence = 3. 3% High prevalence of bisexuality • 30% of HIV positive, and 18% of HIV negative reported sex with women in the past 6 months

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

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 CD 4 <200

• 3101 MSM tested in 8 medium cities • Overall HIV prevalence of 7% • Estimated HIV incidence 2. 9%* Year 2000 sentinel surveillance: 8 mediumsized cities • High HIV incidence in 2 jungle cities: Iquitos Pucallpa HIV prevalence Estimated HIV incid. Observed HIV incid. * by LS EIA on reactive sera N=405 13% 7. 1% (2 -15. 1) 2. 2/100 p-yrs N=508 3. 5% 4. 5% (1. 0 -10. 2) 3. 5/100 p-yrs

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

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