What is the difference between Deoxyribonucleic Acid (DNA) Human Immunodeficiency Virus (HIV) test and Ribonucleic Acid (RNA) HIV test, and when to perform these tests?

From the Guidelines

DNA HIV tests detect the virus's genetic material integrated into human cells, while RNA HIV tests identify viral RNA in the bloodstream, with RNA tests being more commonly used for early detection and monitoring viral load in people living with HIV, as recommended by the 2018 guidelines 1. The primary difference between DNA and RNA HIV tests lies in their application and the stage of infection they are used to diagnose or monitor. DNA tests are primarily used for confirming HIV infection in infants born to HIV-positive mothers and for research purposes. In contrast, RNA tests are used for early detection of HIV infection, as early as 10-33 days after exposure, and for monitoring viral load in people living with HIV. For initial HIV screening, antibody or combination antibody/antigen tests are typically performed first. If these screening tests are positive, RNA tests are used for confirmation and to determine if the infection is acute.

• RNA tests are essential for monitoring treatment effectiveness in HIV-positive individuals, as they measure the amount of virus in the blood, with the goal of achieving viral suppression, defined as an HIV RNA level below 50 copies/mL, as recommended by the 2018 guidelines 1.
• The timing of RNA tests is crucial, as they can detect HIV earlier during the "window period" before antibodies develop, making them valuable for diagnosing acute infections when viral loads are high but antibodies haven't yet formed.
• According to the 2018 guidelines 1, HIV RNA testing should be performed within 6 weeks of starting antiretroviral therapy (ART), and then every 3 months until viral suppression is achieved, and every 6 months thereafter if the patient maintains consistent medication adherence.
• The 1998 guidelines 2 also recommend measuring plasma HIV RNA levels at the time of diagnosis and every 3-4 months thereafter in untreated patients, and immediately prior to and again at 4-8 weeks after initiation of antiretroviral therapy. Both tests have specific clinical applications based on the stage of infection and the clinical question being addressed, with RNA tests being more commonly used for early detection and monitoring viral load, as supported by the 2018 guidelines 1.

From the Research

Difference between DNA and RNA HIV tests

• DNA HIV tests detect the genetic material of the virus, which is integrated into the host cell's DNA [ 3 ].
• RNA HIV tests detect the genetic material of the virus in the blood, which is present in the form of RNA [ 4 ].

When to perform these tests

• RNA HIV tests are recommended for early detection of HIV infection, as they can detect the virus sooner than DNA tests [ 5 ].
• DNA HIV tests are recommended for confirming the diagnosis of HIV infection, as they can detect the integrated virus in the host cell's DNA [ 3 ].

Window period for HIV tests

• The window period for HIV tests refers to the time between exposure to the virus and when the test can reliably detect the presence of the infection [ 6 ].
• The window period for RNA HIV tests is generally shorter than that for DNA HIV tests, ranging from 5.9 to 24.8 days [ 6 ].
• The 99th percentiles of the window period probability distribution range from 44 days for laboratory screening tests to 65 days for the Western blot test [ 6 ].

Clinical implications

• Early detection of HIV infection using RNA HIV tests can allow for earlier treatment initiation and potentially reduce the risk of resistance to antiretroviral therapy [ 3 ].
• The choice of HIV test depends on the clinical context and the individual's risk factors, and healthcare providers should consider the window period and the sensitivity of the test when interpreting results [ 5 ].