56 Dean Street reports M184V common with recent low adherence to PrEP and seven transmissions with good adherence
Although PrEP is highly effective at preventing HIV, a recent report from 56 Dean Street Clinic in central London included seven cases of HIV transmission with self-reported good adherence. Also, that there is a risk of developing drug resistance if adherence to PrEP is low. 
Of 1030 HIV diagnoses between 2016 and 2020, roughly 5% (n=52) reported recent PrEP use. Of these, 98% were gay or bisexual men, with median age 34 (IQR: 28 to 42), 65% white and 65% non-UK-born.
PrEP use was reported by 35% on the day before diagnosis with 46% reporting intermittent adherence. Of these, 11/24 were using daily PrEP and 13/24 were using 2:1:1 dosing. Supply/access difficulties were reported by 9/52 (17%).
Other reasons included: “5/52 (10%) interrupted PrEP after starting a monogamous relationship, 3/52 (6%) did not plan to have sex, 3/52 (6%) chose to interrupt PrEP and 1/52 (2%) was taking an antiretroviral regimen not licensed for PrEP (raltegravir)”.
However, reasons for PrEP failure could not be explained in 7/52 (13%) who reported excellent adherence (though drug levels were not available). Of these 2/7 had the M184V mutation on diagnosis that might indicate infection after exposure to drug-resistant HIV.
Delayed HIV seroconversion and/or unrecognised HIV infection when starting PrEP could be a factor in 5/7 cases who were sourcing PrEP online, and the median time since their last HIV negative test was 124 days. HIV was then detected with the first clinic test.
The M184V mutation was more common in the recent PrEP use group (30% vs 1%, p<0.01). PrEP use also increased over time, reaching 20% by 2020.
The paper reported that all people who intensified from PrEP to ART achieved an undetectable viral load at week 24. ART was tenofovir-based, with the third drug boosted-darunavir (n=28), bictegravir (n=8), dolutegravir (n=7) or raltegravir (n=4). The clinic protocol includes switching from darunavir to integrase inhibitors three months from ART initiation, but this only occurred in 14/28 participants.
Although the short-term response to intensified ART is important, longer follow-up is really needed to show a durable response to ART in case of suboptimal ART due to M184V.
Access to PrEP at 56 Dean Street is impressive: the clinic recently reported prescribing PrEP on the NHS to more than 25,000 people since 2020. 
Also, while the primary analysis focussed on M184V resistance, the otherwise unexplained cases of HIV acquisition in the context good adherence are important enough to deserve a more detailed analysis.
- Girometti N et al. Rising rates of recent PrEP exposure among MSM newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes. AIDS, doi: 10.1097/QAD.0000000000003143.
- Dean Street press release. HIV PrEP awareness week: 29th November – 5th December.