16 Feb New Test Can Improve Detection of Early, Acute HIV Infections
MedicalResearch.com Interview with:
Philip J. Peters, M.D.
HIV Testing and Biomedical Interventions Activity Lead
CDC’s Division of HIV/AIDS Prevention
Medical Research: What is the background for this study? What are the main findings?
Dr. Peters: Acute HIV infection contributes disproportionately to HIV transmission and identifying individuals with acute HIV infection is critical to prevent further HIV transmission, as diagnosis can lead to several effective HIV prevention interventions. Acute HIV infection can be diagnosed with assays that detect either HIV RNA (the reference standard) or the p24 antigen (an HIV core protein), which are both detectable early after HIV infection and before an antibody response develops. HIV immunoassays that detect both the p24 antigen and anti-HIV antibody (fourth generation antigen/antibody [Ag/Ab] combination immunoassays) are currently being implemented as the initial screening test in the 2014 CDC and American Public Health Laboratories (APHL) recommended HIV diagnostic algorithm. In a prospective study we evaluated the performance of an HIV Ag/Ab combination assay to detect acute HIV infection compared with pooled HIV RNA testing in a high-prevalence population.
All participants were first screened with a rapid HIV test to detect established HIV infection (antibody detectable). All participants with a negative rapid HIV test result were then screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled HIV-1 RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test.
Among 86,836 participants with complete test results (median age, 29 years; 75.0% male; 51.8% men who have sex with men), acute HIV infection was diagnosed in 168 (0.19%). Acute HIV infection was detected in 134 (0.15%) participants with HIV Ag/Ab combination testing (acute HIV infection sensitivity, 79.8%) and in 164 (0.19%) with pooled HIV RNA testing (sensitivity, 97.6%; sensitivity comparison, p<0.001). Overall HIV Ag/Ab combination testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone (which detected established HIV infection), HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both established and acute HIV infections) by 10.4% and pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4%.
Medical Research: What should clinicians and patients take away from your report?
Dr. Peters: In this prospective study evaluating HIV testing in a high HIV prevalence population, the HIV Ag/Ab combination assay in place of rapid HIV testing increased the absolute HIV diagnostic yield by 0.15% (a 10.4% increase in the relative diagnostic yield) and diagnosed 82% of the acute HIV infections detectable by pooled RNA testing. Because rapid HIV testing detected HIV infection in only 87.3% of HIV-infected participants, alternative strategies such as using a lab-based HIV Ag/Ab combination assay that can detect acute infection should be considered in high-prevalence populations in the United States.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Peters: This study highlights three areas for future research:
- Although rapid HIV testing has certain advantages such as the immediate provision of a result and the ability to test in nonclinical outreach settings, our findings indicate that the lower sensitivity for acute HIV infection is a major limitation. Further research is needed to develop improved assays, such as point-of-care HIV-1 RNA tests, that have sufficient sensitivity for acute HIV infection.
- In this testing strategy (rapid HIV testing followed by a screen for acute HIV infection), the HIV Ag/Ab combination assay following a negative rapid test detected 82% of acute HIV infections and had a positive predictive value of 59%. Further research is needed to evaluate this strategy in lower prevalence populations and in persons using pre-exposure prophylaxis (PrEP) for HIV prevention.
- Although diagnosing acute HIV infection has been considered a rare event, in our study almost 12% of HIV infections (n=168) were detected in the acute phase, demonstrating that acute infection can be diagnosed if the testing strategy has adequate acute HIV infection sensitivity. With improved detection of acute HIV infection, strategies to provide immediate antiretroviral treatment to persons in this acute phase of illness are now required. Immediate antiretroviral treatment during the acute phase may have both individual clinical benefit (e.g., decreased HIV reservoir size and protection of long-lived central memory CD4 cells) and public health benefit from viral suppression during this highly infectious phase.
Medical Research: Is there anything else you would like to add?
Dr. Peters: For further information on HIV testing please
Peters PJ, Westheimer E, Cohen S, et al. Screening Yield of HIV Antigen/Antibody Combination and Pooled HIV RNA Testing for Acute HIV Infection in a High-Prevalence Population. JAMA. 2016;315(7):682-690. doi:10.1001/jama.2016.0286.
Dr. Philip J. Peters (2016). New Test Can Improve Detection of Early, Acute HIV Infections