GUEST EDITORIAL

Military Medicine, Mar 2004 by O'Connell, Robert J, Gunzenhauser, Jeffrey D, Michael, Nelson L

The Joint United Nations Programme on HIV/AIDS estimates that more than 42 million people are infected with HIV worldwide, and has uniquely identified this infection as a threat to international security. While United States military forces have historically demonstrated low seroconversion rates (less than 0.2 per 1000 tests over the past 10 years), HIV infection appropriately remains a major force protection concern, and is commonly encountered in military clinical practice. HIV testing is the critical front-line tool in the war against HIV/AIDS as it is the entry point leading to prevention and treatment interventions.

Conventional HIV testing using laboratory-based enzyme immunoassay (EIA) followed by confirmatory Western blot (WB) is the standard DOD diagnostic algorithm. Such tests have been performed on millions of samples DOD-wide since they became available in the 1980s. Although such testing is highly sensitive and specific, it is not suitable for all settings. Limitations arise primarily due to the requirement for shipment of blood samples to sophisticated laboratories and subsequent delays in test execution. Military clinical activities, particularly in deployment settings, may operate without sufficient laboratory capability to support conventional HIV testing. Furthermore, several clinical circumstances demand rapid HIV testing results at the point of contact with a tested individual: 1) post-exposure prophylaxis antiretroviral therapy decision-making following occupational blood and body fluids exposure 2) prior to urgent administration of live vaccines, 3) prior to emergency transfusion of blood products from the "walking blood bank," 4) assessment of HIV status in pregnant women presenting in labor without a history of prenatal HIV testing, and 5) any clinical setting where patients may not appear for follow up visits to learn their HIV testing result.

Until recently, the only PDA-approved rapid test for detection of HIV antibody was the Single Use Diagnostic System HIV-I Test (SUDS, Murex Diagnostics, Inc., Norcross, GA). This test was seldom used by the DOD. The test requires a cold chain, must be executed by a certified medical technologist, and has been unavailable in the past due to manufacturing problems. A recent evaluation of 921 cryopreserved DOD serum samples found SUDS to be 99.4% sensitive but only 81.9% specific posing significant problems for HIV screening in the low prevalent populations such as the Defense Health Program. For example, if SUDS were used as part of the Wilford Hall USAF Medical Center occupational blood and body fluids exposure program where the source patient HIV prevalence is 0.2%, the positive predictive value of a positive SUDS screen would be only 0.011 (negative predictive value of 0.99998).

The FDA approved a new rapid HIV diagnostic device on November 7, 2002, OraQuick� HIVl Rapid HIV-1 Antibody Test, with an indication for finger stick whole blood specimens. Due to its ease of use, OraQuick was granted waived status from the Clinical Laboratory Improvement Amendments on January 31, 2003 enabling its use by health care workers who are not certified laboratorians. OraQuick enables HIV diagnostic capability for many clinical locations or circumstances where conventional testing was unsuitable. OraQuick tests are stored at 2�-27�C, require no additional laboratory equipment, and can be executed in 20 minutes with a sensitivity (95% Cl) and specificity (95% CI) of 99.6% (98.5% to 99.6%) and 100% (99.7% to 100%), respectively(S). The kits are compact and lightweight: a box of 25 individually wrapped test devices is 12" x 9" x 6" and weighs 2 lbs. Each device is expected to cost $8-12 depending on the number of devices purchased.

OraQuick has demonstrated high sensitivity and specificity in a variety of body fluids, using whole blood, serum, plasma, and oral fluids, although FDA approval for indications other than fingerstick whole blood are lacking at this writing. Testing using serial samples from recently HIV infected individuals demonstrates that the seroconversion window period is functionally the same duration for OraQuick as for conventional EIA(5). We recently found a slight decrement in OraQuick sensitivity (96%) using serum or oral fluids from 101 HIV-I infected patients with intense antiretroviral exposure. This may reflect therapy-associated seroreversion at the limited epitopic range represented in the single HIV-I synthetic peptide that OraQuick utilizes.

Implementation of OraQuick into DOD HIV screening algorithms will raise challenges. First, context-sensitive procedures and appropriate risk communication messages are required to maintain privacy and minimize adverse sequelae when disclosing th� provisional nature of a "reactive" screening test result. second, confirmatory testing on individuals who test reactive will still require submission of a second specimen to a reference laboratory for confirmatory Western blot or IFA testing. Obtaining such samples may be delayed in cases where phlebotomy equipment is not readily available (e.g., Level I Combat Health Services). Third, widespread use of OraQuick would both significantly increase testing costs (from about $4 to $10 or more per test) and tax limited personnel resources at testing sites as OraQuick is not optimized for high throughput screening. Fourth, in contrast to services provided under current contract-supported HIV testing, point of care HIV testing is not automatically recorded in information systems which document individual medical readiness. Finally, fmgerstick blood specimens are not suitable for submission to the DOD Serum Repository (http://amsa.army.mil/DoDSR_Items/DoDSR_ Overview.htm).