by Gus Cairns

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.

The most recent case was reported by Dr Matthew Spinelli in Clinical Infectious Diseases. 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. 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.

The other case was published in the May issue of the International Journal of Infectious Diseases by Professor Shui-Shan Lee and concerns a 24-year-old gay man from Hong Kong. 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. Read more via AIDSmap

Spinelli MA et al. Use of drug-level testing and single-genome sequencing to unravel a case of HIV seroconversion on PrEP. Clinical Infectious Diseases, early online edition, July 2020.

Abstract: 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.

Lee S-S et al. Failure of pre-exposure prophylaxis with daily tenofovir/emtricitabine and the scenario of delayed HIV seroconversion. International Journal of Infectious Diseases 94:41-43. 2020.

Abstract | Full Text: 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.