Vol. 25 No. 11 Page 41
Wider use of fourth-generation HIV tests may help improve outcomes.
From detection and diagnosis to treatment and ongoing health and wellness maintenance, laboratory testing plays a central role in the management of patients infected with the human immunodeficiency virus (HIV), the cause of AIDS. It is critical that people infected with HIV are diagnosed as early as possible following initial infection to ensure the best possible outcome for treatment and quality of life, reduce the risk of transmission to others and minimize the cost burden on the healthcare system.
Yet, facilitating early diagnosis of HIV is a long-standing healthcare challenge. In 2014, the CDC updated its guidelines to include a recommendation that laboratories adopt p24 antigen or “fourth-generation” HIV tests in order to improve diagnosis of acute infection. The HIV testing algorithm, known as “third-generation” testing, begins with an HIV-1/HIV-2 antibody immunoassay, followed by supplemental testing to confirm repeatedly reactive results. While this type of test is effective at detecting antibodies, it cannot detect an acute infection.
Fourth-generation tests identify both HIV antibodies and p24 antigen. They may also be called combined antigen/antibody tests. Testing for p24 detects some cases of HIV infection before antibodies are produced, shortening the window period in which people may test negative by antibody testing. Fourth-generation assays have >99.7% sensitivity and >99.3% specificity for HIV infection and can identify most (>80%) acute infections that would otherwise require nucleic acid testing for detection (of note, the testing algorithm does include an HIV qualitative test for patients who test positive with fourth-generation testing).1,2 In general, they can detect infection in an average of five to seven days before third-generation immunoassays.3-5
Though the distinction in detection times between third and fourth-generation HIV assays may seem negligible, it can mean the difference between an accurate and false negative test result.
First, the importance of detecting HIV before seroconversion is increasingly acknowledged as important to reducing the likelihood of transmission. This is because this time period is associated with higher viral load, which can contribute disproportionately to transmission. An infected person who is tested with a third-generation assay before seroconversion may receive a negative test result, but be highly contagious. This danger may be compounded in higher risk individuals such as those who practice unsafe sex and injection drug users, who may be infected at the time of their screening, but not detected on a third-generation assay. Early detection and diagnosis may prompt behavior changes that reduce the risk of spreading HIV to others during the most transmittable period of the infection.
Second, earlier detection can increase the odds a patient will begin potentially life-saving treatment sooner. Life expectancy for many people living with HIV who start antiretroviral therapy (ART) early, remain adherent and are under the care of a healthcare practitioner may have lifespans similar to that of HIV-negative individuals. Determining the appropriate therapy typically requires baseline viral resistance testing as well as other tests required to access general health and well-being of the patient and may require other testing. Earlier HIV detection through a fourth-generation assay gives a patient quicker access to these tests and ultimately quicker access to the most appropriate treatment, which increases the likelihood of a favorable outcome for that patient.
Third, the ultimate goal of HIV care is to help people living with the virus live as long and healthy as possible, and earlier diagnosis through fourth-generation testing can help achieve this by identifying those individuals who are HIV positive, and subsequently direct them to healthcare providers putting patients under the care of a physician earlier to manage their holistic health and well-being. People living with HIV may present with cardiovascular, kidney, liver, cognitive function and metabolic issues more so than people who are not infected. Healthcare providers caring for people living with HIV must be knowledgeable not only about HIV treatment but also about the management of the patient’s general health and wellness. Both HIV infection and the drugs used to treat it may have adverse effects on various organ systems. Healthcare providers who manage a patient’s general health and wellness earlier in the disease progression help patients achieve better outcomes.
Additionally, because patients with HIV infection now tend to live normal lifespans, more emphasis is being given to routine testing for managing general health and wellness and co-morbid conditions. Periodic monitoring of patient health after entry into care for HIV/AIDS typically includes complete blood count, basic chemistry tests, markers of liver and kidney function and bone health, and evaluation of fasting glucose and lipid profile. Additionally, co-infections such as hepatitis C (HCV) affect the overall prognosis of people with HIV as well. Earlier disease detection through a fourth-generation assay allows a patient to seek the care of a physician sooner to better manage their general health and wellness as well as address any potential co-infections or co-morbidities that may negatively impact disease progression.
Finally, patients who are diagnosed earlier may expedite access to treatment options, which may improve quality of life, reducing hospitalizations and ultimately lessening the burden on the healthcare system and improving the economy by keeping more patients out of the hospital and able to work.6
Laboratories that direct physicians to fourth-generation HIV testing are serving the best interests of patients and the healthcare system. For this reason, Quest Diagnostics has eliminated third-generation testing from its HIV test menu, choosing to focus on fourth-generation testing because of its proven benefits. Fourth-generation testing benefits more than patients; it involves minimal technician time to process specimens and reduces turnaround time relative to third-generation screening, providing advantages for laboratories and physicians health care providers. Elimination of third-generation testing from large laboratories and the wide adoption of fourth-generation testing will help improve the quality of HIV detection and encourages more timely access to treatment and long-term care.
- Nasrullah M, Wesolowski LG, Meyer WA, III, et al. Performance of a fourth-generation HIV screening assay and an alternative HIV diagnostic testing algorithm. AIDS. 2013;27:731-737.
- Chavez P, Wesolowski L, Patel P, et al. Evaluation of the performance of the Abbott ARCHITECT HIV Ag/Ab Combo Assay. J Clin Virol. 2011;52 (suppl 1):S51-S55.
- Criteria for Laboratory Testing and Diagnosis of Human Immunodeficiency Virus Infection; Approved Guideline. M53-A ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2011.
- Fiebig EW, Wright DJ, Rawal BD, et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS. 2003;17:1871-1879.
- ARCHITECT HIV Ag/Ab Combo [package insert]. Wiesbaden, Germany: Abbott Laboratories; 2009.