Primary HIV Infection: the CDC study Pragna Patel, MD MPH Medical Epidemiologist Behavioral and Clinical Surveillance Branch DHAP, CDC February 28, 2005

Background Primary HIV infection (PHI) –HIV viral replication and shedding occurs before detectable antibody appears –Viremia peaks in blood and genital fluid –Contributes to the spread of HIV because individuals are: unaware of infection highly infectious Important opportunity for HIV prevention Studies have used nucleic acid amplification testing (NAAT) to diagnose PHI

Background Quinn et al. [AIDS 2000] - multistage pooling cost-saving method for HIV RNA detection Pilcher et al. [JAMA 2002] – pooled NAAT for PHI diagnosis feasible in a routine testing population and increased sensitivity of HIV detection Pilcher et al. – pooled NAAT detects PHI in high-risk populations even relative to more sensitive antibody assays Liska et al. – pooled NAAT feasible for PHI diagnosis in high risk populations Busch et al. – cost-effectiveness of pooled NAAT in donor screening is low Fiscus et al. – pooled NAAT feasible in Africa, however, parallel rapid and p24 antigen testing may detect 80% of PHI cases

Unanswered questions Cost-effectiveness analysis of pooled NAAT relative to 2 nd and 3 rd generation HIV antibody testing Type of specimen: serum vs. plasma Size of pools: effect on sensitivity Evaluation of pooled NAAT relative to rapid tests in United States

CDC study: Objectives Primary objectives: To assess the feasibility and cost-effectiveness of pooled NAAT relative to 2 nd and 3 rd generation HIV antibody assays, rapid tests, and p24 antigen To identify PHI and other HIV infections that would otherwise be missed by current testing To evaluate the effect of pool size and HIV prevalence on sensitivity of pooled NAAT

CDC study: Objectives Secondary objectives: To describe the epidemiology of PHI To study PHI using epidemiological and molecular approaches to assess transmission correlates and clusters To describe the outcomes of partner notification of persons with PHI To describe antiretroviral resistance in persons with PHI

Study Collaborators Florida Department of Health: Marlene LaLota, Tony Falvo, Joanna Bentley Florida Bureau of Laboratories: Berry Bennett Los Angeles Department of Health Services: Peter Kerndt, Lisa Smith, Apurva Uniyal New York State Department of Health Wadsworth Center, Diagnostic HIV Laboratory: Judith Wethers, Joe Schwendemann, Tim Sullivan

Methods Health Department: Los Angeles Laboratory: New York State Collect specimens from: –14 STD clinics –STD mobile testing unit – LA Gay and Lesbian Center Routine HIV screening performed at LA Public Health Laboratory 28,000 specimens for pooled NAAT Further testing at the NYS lab 50 persons with PHI

Methods Health Department: Florida Laboratory: Florida 4 counties: Hillsborough, Duval, Orange, & Pinellas Specimens from public health clinics All testing at the Florida Public Health Laboratory in Jacksonville 39,000 specimens for pooled NAAT 35 persons with PHI

Methods All specimens will be tested with 2 nd and 3 rd generation antibody assays Sero-negative specimens will be pooled for NAAT NAAT positive specimens will be tested with rapid tests and p24 antigen Outcomes: Number of persons with PHI identified Cost-effectiveness of testing strategy: incremental cost of adding NAAT to antibody screening with either 2 nd or 3 rd generation EIAs Effectiveness of NAAT relative to rapid tests and p24 antigen

Methods Sub-study of seroconverters Persons with PHI followed through seroconversion –Laboratory documentation of seroconversion –Antiretroviral resistance testing –Phylogenetic analysis –Interview to assess recent risk behaviors, factors that may affect seroconversion, and HIV testing history

Timeline Study design, IRB approval –Present to June 2005 Study enrollment, data collection & analysis –June 2005 to June 2006 Longitudinal follow-up, data analysis, project close-out –June 2006 to December 2006

Discussion Points How can we simultaneously promote rapid testing and screening for PHI? To which type of EIA should public laboratories switch? Which is the best HIV RNA test for NAAT screening? How do we identify which populations should be screened with NAAT? Can laboratories easily incorporate pooled NAAT to standard testing algorithms?

Contact information Pragna Patel