ART and PrEP May Present Challenges in Detecting HIV Infection in Blood Donations

While antiretroviral (ARV) drugs and pre-exposure prophylaxis (PrEP) are effective tools to help reduce the burden of HIV, a new study published in Blood cites their use by blood donors as a potential cause for concern, as it may hinder the detection of HIV in donated blood. According to the study, approximately 15% of HIV-positive individuals who donated blood took ARVs within days of donation, and nearly 5% of men who have sex with men (MSM) who donated blood reported taking PrEP within the same period as blood donation.

“Use of antiretroviral therapy (ART) causes HIV-infected persons to exhibit modified biomarkers of infection such as undetectable RNA by nucleic acid test/viral load assays and may result in undetectable antibodies by third- and fourth- generation serological screening assays,” the authors, led by Brian Custer, PhD, MPH, from the University of California San Francisco, explained. “In addition to suppression of viremia, ART is known to alter biomarkers of HIV infection progression and may result in antibody ‘seroreversion,’ [which may affect] the ability to detect HIV infection through current blood donation screening.”

In this study, Dr. Custer and colleagues analyzed blood samples of 299 HIV-positive individuals and a comparison group of 300 infection-nonreactive donors obtained from U.S. blood collection organizations. The HIV-positive samples were tested with liquid chromatography-tandem mass spectrometry for the presence of ARVs. The testing facility was blinded to the HIV infection status of each blood sample.

Simultaneously, the investigators screened the blood donor samples from male infection-nonreactive first-time blood donors for the presence of ARV drug analytes, focusing on emtricitabine and tenofovir. De-identified blood donations from MSM with self-reported PrEP use during a close timeframe to donation also were assessed.

According to an analysis of the 2017 National HIV Behavioral Surveillance (NHBS) MSM survey, 27 of 565 HIV-negative individuals (4.8%) reported that they had donated blood in 2016 or 2017 while taking a PrEP medication close to the time of donation.

All blood sample specimens from the infection-nonreactive donors were below the lower limit of quantification for 13 ARV drugs analyzed. A total of 46 samples from the HIV-confirmed donors – or 15.4% – showed evidence of ARVs.

Most of the ARV-positive samples (93.5%) were from first-time donors, with 74% of these samples coming from men. Compared with repeat or younger donors, first-time donors with HIV and donors with HIV between the ages of 45 and 54 were more likely to have evidence of ARVs in their samples. Superior virologic control was found in the plasma from donors on ART compared with those not on ART, as demonstrated by lower HIV viral load values in the plasma of the former.

In the 1,494 samples from the first-time male donors who were infection-nonreactive, 9 had detectable levels of tenofovir and emtricitabine. The investigators estimated that 5 of the 9 donors with detectable tenofovir and emtricitabine had taken a PrEP medication within a 2-day period of donating blood.

Dr. Custer stressed that the risk of transfusion transmission of HIV in the U.S. is currently lower than 1 in 1 million transfusions. “From a public health perspective, the concept of ‘undetectable equals untransmittable’ for sexual contact is very important, but does not directly apply to donated blood because a transfused unit of blood is a much larger volume than would occur from body fluid exposure during sex,” said Dr. Custer. “Testing of donations contributes the most to the safety of the blood supply because not all donors disclose risks or may not even know they have risks for infections that could be transmitted by transfusion.”

The authors report no relevant conflicts of interest.


Custer B, Quiner CA, Haaland R, et al. HIV antiretroviral therapy and prevention use in US blood donors: A new blood safety concern. Blood. 2020 July 9. [Epub ahead of print]