Enhanced U.S. Army HIV diagnostic algorithm used to diagnose acute HIV infection in a deployed soldier.

Antibody screening alone may fail to detect human immunodeficiency virus (HIV) in recently infected individuals. By U.S. Army regulation, HIV-infected soldiers are not permitted to deploy to areas of conflict, including Iraq and Afghanistan. We report here the first case of acute HIV infection (AHI) in a soldier in a combat area of operation detected by an enhanced U.S. Army HIV testing algorithm and discuss features of the tests which aided in clinical diagnosis. We tested the sample from the AHI case with a third generation HIV-1/HIV-2 plus O enzyme immunoassay, HIV-1 Western Blot, and a qualitative HIV-1 ribonucleic acid molecular diagnostic assay. Risk factors for HIV acquisition were elicited in an epidemiologic interview. Evaluation of the blood sample for AHI indicated an inconclusive serologic profile and a reactive HIV-1 ribonucleic acid result. The main risk factor for acquisition reported was unprotected sexual intercourse with casual strangers in the U.S. while on leave during deployment. The clinical diagnosis of AHI in a combat area of operation is important. Diagnosis of HIV is key to preventing adverse effects to the infected soldier from deployment stressors of deployment and further transmission via parenteral or sexual exposures. INTRODUCTION Acute human immunodeficiency virus (HIV) infection (AHI), known as primary HIV infection or acute retroviral syndrome, is the period between HIV acquisition and antibody detection and can be up to 22 days in duration depending on the serologic test used. Intense replication of HIV and the host immune response during this period result in high levels of detectable biomarkers (ribonucleic acid [RNA] and p24 antigen) in blood and semen and in symptoms such as fever, fatigue, rash, headache, and sore throat in up to 89% of patients. Diagnosis of AHI in patients seeking medical care for symptoms can result in improved outcomes for HIVinfected individuals and provide opportunities for public health authorities to prevent further transmission. However, the U.S. Centers for Disease Control and Prevention estimated that at the end of 2006, 21% of the U.S. population was unaware of their infection status. Moreover, approximately 8.6 to 11.4% of new HIV infections in the United States may be acquired from individuals with AHI. Detection and diagnosis are key first steps to HIV care and prevention. U.S. Military personnel on active duty are mandated to undergo biennial HIV antibody screening. In 1986, HIV surveillance policies were instituted by the U.S. Military to ensure the safety of combat blood supply during urgent blood collections within combat casualty resuscitation settings. Currently, Military personnel must screen negative for HIV within 120 days of deployment to U.S. Central Command Areas of Operation (CENTCOM AOR), inclusive of Iraq and Afghanistan. HIV-infected personnel are not permitted to deploy. An estimated 1.64 million Military personnel have deployed to combat operations in Iraq and Afghanistan. The capability to detect and diagnose HIV at a single time point (i.e., from a single sample) is critical for a highly mobile population such as the U.S. Military with unique operational requirements. The standard HIV diagnostic algorithm, repeatedly reactive enzyme immunoassay (EIA) followed by confirmation with HIV-1 Western Blot (WB), used within the United States since 1989, is seriously limited *United States Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720-A Rockledge Drive, Suite 400, Bethesda, MD 20817. †Department of Medicine, Infectious Diseases Service Clinic, Walter Reed National Military Medical Center-Bethesda, 8901 Wisconsin Avenue, Bethesda, MD 20810. ‡75th Battle Command Training Division, Building 5520 Nashville Street, Fort Dix, NJ 08640. §United States Military HIV Research Program, Walter Reed Army Institute of Research, 13 Taft Court, Suite 100, Rockville, MD 20850. kUnited States Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 503 Robert Grant Avenue, Rockville, MD 20910-7500. ¶HQ Army Medical Directorate, FASC, Rm 129, Royal Military Academy at Sandhurst, United Kingdom 09494. **Preventive Medicine Department, Madigan Army Medical Center, Building 9920A, Ramp 3, Tacoma, WA 98431. ††United States Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910. ‡‡United States Military HIV Research Program, Walter Reed Army Institute of Research, 6720-A Rockledge Drive, Suite 400, Bethesda, MD 20817. §§Medical Command, Building 2748, 3151 Scott Road, Suite 1334, Fort Sam Houston, TX 78234. kkUnited States Army Public Health Command Epidemiology & Disease Surveillance, ATTN: MCHB-TS-D, 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5403. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Department of Defense, the U.S. Government, or any of its agencies. MILITARY MEDICINE, Vol. 177, May 2012 609 by the diagnostic window period of the “gold standard” WB which is less sensitive than current third and fourth generation EIAs, and fails to detect AHI and late stage infection. To address these limitations, earlier serological detection methods incorporating p24 antigen have been employed, as well as HIV-1 RNA for AHI diagnosis, a model-based score for targeted screening, and pooled HIV-1 RNA nucleic acid test (NAT) of antibody-negative samples. On December 1, 2009, the U.S. Army HIV Diagnostic Reference Laboratory (HDRL, Rockville, Maryland) implemented an enhanced screening algorithm to address limitations of the standard serological HIV algorithm by incorporating a highly sensitive qualitative HIV-1 RNA diagnostic assay in conjunction with serological testing. Through June 30, 2011, 1,149,773 soldiers in the U.S. Army Active, National Guard, and Reserve components have been tested using this algorithm. We report here the first case of AHI detected in a combat theater of operation and discuss features of the tests introduced in the U.S. Army AHI testing algorithm that aided in clinical diagnosis. The diagnosis of the case was in support of the deployed U.S. Military Command staff in theater and was not considered research by the Walter Reed Army Institute of Research. CASE REPORT In early 2010, a 46-year-old senior enlisted white male soldier presented to a combat support hospital (CSH) in Afghanistan with chief complaints of headache, rectal pain, itching, and discomfort and requested an HIV test. Upon further questioning, he reported that 18 days earlier he had participated in high-risk behavior during a 3-week Rest and Recuperation leave (R&R) in Florida. He reported having fever, sore throat, malaise, and skin rash while returning from R&R, and had been treated en route for presumed streptococcal pharyngitits. His last seronegative HIV test was 7 months before this visit. Physical examination was unremarkable. Initial laboratory work-up at the CSH, which did not include an HIV rapid test, demonstrated a positive rapid plasma reagin for syphilis, which was confirmed by fluorescent treponemal antibody. A serum sample, drawn the same day as the medical visit to the CSH, was shipped to HDRL for HIV testing. Time from acquisition of the specimen to report of results was 27 days. Evaluation of the sample by the Army algorithm (Fig.1) confirmed patient and clinical suspicions of AHI. Index specimen results summary included a repeat reactive EIA (Genetic Systems HIV-1/HIV-2 Plus O EIA, BioRad Laboratories, Redmond, Washington), faint FIGURE 1. Enhanced U.S. Army diagnostic algorithm for diagnosis of HIV. MILITARY MEDICINE, Vol. 177, May 2012 610 Case Report