Real-time, Universal Screening for Acute HIV Infection in a Routine HIV Counseling and Testing Population

Pilcher, Christopher D. MD
McPherson, J. Todd MS
Leone, Peter A. MD
Smurzynski, Marlene MSPH
Owen-O'Dowd, Judy BS
Peace-Brewer, Amy L. PhD
Harris, Juanita BS
Hicks, Charles B. MD
Eron, Joseph J. Jr MD
Fiscus, Susan A. PhD

Contributing Editor.
Departments of Medicine (Drs Pilcher, Leone, and Eron), Epidemiology (Ms Smurzynski), and Microbiology and Immunology (Drs Peace-Brewer and Fiscus), University of North Carolina at Chapel Hill; North Carolina State Laboratory of Public Health, Serology/Virology Laboratory, Raleigh (Mr McPherson and Ms Harris); HIV/STD Prevention and Care Branch, North Carolina Department of Health and Human Services, Raleigh (Dr Leone and Ms Owen-O'Dowd); and Department of Medicine, Duke University, Durham, NC (Dr Hicks).

Corresponding Author and Reprints: Christopher D. Pilcher, MD, CB No. 7030, 547 Burnett-Womack Bldg, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599–7030 (e-mail: [email protected]).

Financial Disclosures: Dr Pilcher has received research grants or funding, honoraria including for continuing medical education (CME) programs, lecture sponsorships, assay kits or reagents, or government grants or research funding from or is a consultant to Beckman-Coulter, Biomerieux, GlaxoSmithKline, Immunex, and Roche; Dr Hicks has research grants or funding, honoraria including for CME, or government grants or research funding from or is a consultant to Abbott, Agouron, Bristol-Myers Squibb, Boehringer Ingelheim, DuPont, Merck, Roche, Triangle, and ViroLogic; Dr Eron is a principal investigator for University of North Carolina research contracts from Abbott, Merck, Roche/Trimeris, and Pharmasett; consultant to, receives research grant funding or honoraria for ad hoc consulting, sponsored talks, or CME programs from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Merck, NIH-NIAID, Substance Abuse and Mental Health Services Administration, Triangle Pharmaceuticals, Trimeris, ViroLogic, and Tibotec-Virco; Dr Fiscus has received research grants or funding, assay kits or reagents, or government grants or research funding from or is a consultant for BioMerieux, Centers for Disease Control and Prevention, CONRAD, GlaxoSmithKline, National Institutes of Health, PerkinElmer LifeSciences, Roche Molecular Systems, and Visible Genetics.

Author Contributions: Dr Pilcher had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Pilcher, Leone, Hicks, Eron, Fiscus.

Acquisition of data: Pilcher, McPherson, Leone, Owen-O'Dowd, Peace-Brewer, Harris, Eron, Fiscus.

Analysis and interpretation of data: Pilcher, Leone, Smurzynski, Hicks, Eron

Drafting of the manuscript: Pilcher, Leone, Owen-O'Dowd, Harris, Eron.

Critical revision of the manuscript for important intellectual content: McPherson, Leone, Smurzynski, Peace-Brewer, Hicks, Eron, Fiscus

Statistical expertise: Smurzynski.

Obtained funding: Pilcher, Hicks, Eron.

Administrative, technical, or material support: Pilcher, McPherson, Leone, Owen-O'Dowd, Peace-Brewer, Harris, Hicks, Eron, Fiscus.

Study supervision: Pilcher, Leone, Eron, Fiscus.

Funding/Support: This work was funded in part by UNC Center for AIDS Research grants NICHD/NIAID 9-P30-AI50410-04 from the National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases, grants NIDDK-R0149381, AI-07001, K23AI01781-01, and K24 AI01608-01 from the National Institutes of Health. Boehringer Ingelheim supported a poster presentation but had no input into its content.

Previous Presentation: This work was presented in part at the 9th Conference on Retroviruses and Opportunistic Infections, Seattle, Wash, February 2002. Abstract 359-M.

Acknowledgment: We thank Lou Turner, PhD, and the staff of the Laboratory of Public Health Serology/Virology who did the antibody testing and pooling. Regina Lee, BS, provided assistance with data collection and management. Ada Cachafeiro, BS, Mark Turner, BS, Amy James, BS, Paul Alabanza, BS, and Priya Joshi, BS, of the UNC Center for AIDS Research Retrovirology Core Laboratory pooled specimens for the pilot phase; Melissa Kerkau, BS, performed the virologic testing throughout. Confirmatory antibody testing was done by the staff of the McLendon Clinical Laboratories at UNC-Chapel Hill. We especially thank the Disease Intervention Specialists of the HIV/STD Prevention and Care Branch of the NC Department of Health and Human Services for contacting and interviewing patients, and Del Williams, PhD, for assistance with the HIV Prevention and Care Database. Sonia Napravnik, MPH, and William Miller, MD, PhD, and Myron Cohen, MD, MPH, provided critical review of the manuscript.

JAMA: The Journal of the American Medical Association 288(2):p 216-221, July 10, 2002.

Context

Acute human immunodeficiency virus (HIV) infection cannot be diagnosed by routine antibody tests and is rarely diagnosed in clinical practice. However, HIV nucleic acid–based testing is widely used to screen for antibody-negative acute infection among low-risk blood donors.

Objective

To assess the feasibility of screening in high-volume laboratories for acute and long-term HIV infection in a routine HIV testing population, in which HIV infection prevalence is low, using specimen pooling and HIV RNA reverse transcriptase-polymerase chain reaction (RT-PCR) tests.

Design and Setting

Clinical diagnostic performance evaluation at a state-funded public health virology and serology laboratory.

Participants

A total of 8505 consecutive individuals presenting for routine HIV counseling and testing during a total of 20 business days to simulate a month of testing in August and December 2001 at 110 publicly funded testing sites in North Carolina.

Main Outcome Measures

Prevalence of acute and long-term HIV infection. Serum specimens negative by HIV enzyme immunoassay (EIA) were screened in pools by an ultrasensitive HIV RNA RT-PCR test. Results for individual HIV RNA–positive specimens were reclassified as true or false according to results of confirmatory testing.

Results

Of the 8505 individuals screened, 8194 had not previously tested HIV positive and had sufficient serum to complete the testing protocol. Of those, 39 had long-term HIV infection (prevalence, 47.6 per 10 000 at-risk persons [95% confidence interval, 33.8–65.0 per 10 000]). Of the 8155 at-risk individuals whose antibody tests were negative, 5 were HIV RNA positive. Four of those had true-positive acute infection (prevalence, 4.9 per 10 000 [95% confidence interval, 1.3–12.5 per 10 000]). All 4 were women; 2 developed symptoms consistent with an acute retroviral syndrome in the week after testing. Screening all specimens required 147 HIV RNA tests. Overall specificity of the strategy was 0.9999.

Conclusions

These findings suggest the widespread diagnosis of acute HIV infections in a routine testing population is not only possible but feasible using specimen pooling and nucleic acid testing. These additional procedures may increase diagnostic yield by approximately 10% compared with conventional HIV antibody testing.