Two reports of HIV infection occurring despite apparent adequate adherence to PrEP, confirmed by drug level testing, are the first reliably-documented cases to be published in peer-reviewed journals since 2018.
Aidsmap reports that the most recent case was reported by Dr Matthew Spinelli at the division of HIV, infectious diseases, and global medicine, department of medicine, University of California-San Francisco (UCSF). It concerns a 44-year old gay man in Texas and appears not to be due to poor adherence, but to infection with an HIV virus with an unusual combination of resistance mutations.
The report says two characteristics of the case make it hard to argue against this being a genuine case of PrEP breakthrough. Firstly, samples of blood and hair confirm that he had had good adherence to PrEP in the two to three months leading up to his infection. Secondly, a pattern of HIV and viral load testing showed this was an acute infection that probably only occurred a few weeks at most before he reported symptoms. Notably, his initial positive HIV test was interpreted as a ‘false positive’ because his adherence appeared to be so good.
Aidsmap reports that the other case was published by Professor Shui-Shan Lee at the Centre for Emerging Infectious Diseases, Prince of Wales Hospital, Hong Kong and concerns a 24-year old gay man from Hong Kong.
The report says it makes an interesting comparison as it is more likely in this case that the failure of PrEP was due to imperfect adherence. However, this is hard to prove because HIV seroconversion – the appearance of the antibodies that are detected by HIV tests – was delayed, occurring two months after a retrospective viral load test showed that he had already been infected, and occurred as long as three to four months after infection.
Both of the 2020 cases suggest that symptoms suggesting acute HIV infection should not be ignored, and tests discounted as false-positives, even in the context of apparent high adherence to PrEP. As the Hong Kong investigators say of their case, “The phenomenon [of delayed seroconversion] argues for the avoidance of infrequent follow-ups of PrEP users, so that the diagnosis of failure and prompt ART will not be inadvertently delayed.”
Cases of seroconversion on PrEP should be carefully investigated given their public health implications and rarity. We report a case of transmitted drug resistance causing seroconversion on PrEP in spite of high adherence, confirmed with dried blood spot and segmental hair drug-level testing and single-genome sequencing.
Matthew A Spinelli, Brentton Lowery, Jennifer A Shuford, Jon Spindle, Mary F Kearney, Jenny R McFarlane, Cheryl McDonald, Hideaki Okochi, Nhi Phung, Karen Kuncze, Kathryn Jee, DeeJay Johannessen, Peter L Anderson, Dawn K Smith, Patricia Defechereux, Robert M Grant, Monica Gandhi
Failure of pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine may occur despite perfect adherence, although this is uncommon. Failure results in breakthrough HIV infection. Delayed seroconversion associated with antiretroviral use may complicate the picture, causing uncertainties in interpreting adherence patterns for establishing the true cause of PrEP failure.
Shui-Shan Lee, Peter L Anderson, Tsz-Ho Kwan, Grace CY Lui, Denise PC Chan, Ngai-Sze Wong, Krystal CK Lee, Teddy TN Lam
Full Aidsmap report
Clinical Infectious Diseases abstract
International Journal of Infectious Diseases abstract