Dr. Robert Grant weighs in after the first case of failed PrEP: What does it mean?
BETA is reporting from the 2016 Conference on Retroviruses and Opportunistic Infections (CROI) this week in Boston—bringing you the latest news, updates, and research on HIV treatment and prevention.
At CROI today, researchers and providers heard a detailed case study of a man who was infected with drug-resistant HIV while taking PrEP. No study to date has definitively documented a “breakthrough” HIV infection during PrEP with adherence to Truvada, so the report has garnered a lot of attention and concern from community members.
We spoke with Robert Grant, MD, MPH, to give context to the discussion about what this case means for people currently taking PrEP.
Robert Grant, MD, MPH:
“The person claims he was taking PrEP every day and I believe him.
The prevalence of viruses that are highly resistant to both tenofovir and FTC are rare, and are even less likely to be transmitted. Among 9,222 people taking PREP in trials, this kind of virus was never once seen.
The prevalence of this kind of virus among recently infected persons is less than 1%. Maybe much less. If PrEP is not fully effective against viruses that are HIGHLY resistant to both drugs in FTC/TDF PrEP, the efficacy of PrEP when taken may decrease from 99% to 98%. Or from 99.9% to 98.9%. Or from 100% to 99%. The decimal points are not certain.
My point is that one chooses whether to focus on the glass 99% full or 1% empty.
After 32 years experience with HIV research, I have learned to never say ‘never.’
Yet I also think that gay men benefit from feeling safer during sex and I am grateful that PrEP affords that feeling. People who feel safe feel more power, more confidence in the future, and more desire to discover and pursue their deeply felt personal goals. Believing in the future brings powerful social and personal benefits. There is less trauma. This is all good in my opinion.
PrEP works when taken. Very rarely, PrEP with FTC/TDF may fail to provide full protection against rare multidrug resistant viruses. If that happens, HIV treatment is highly effective and prolongs life to normal levels and makes people less infectious.
His viral load on therapy now is undetectable, meaning extremely low, such that he can expect to stay healthy and live a normal lifespan.”
Case report details:
A 43 year old man in Ontario, Canada seroconverted to multi-class resistant HIV after 24 months of successful PrEP. After starting PrEP, he had seven negative HIV tests before testing positive. He granted his physician permission to investigate his adherence after stating definitively that he had been taking his PrEP doses on a regular basis. Clinical and pharmacokinetic data—including pharmacy data and drug concentrations in dried blood spots—confirmed he had been adherent to PrEP.
The physician who presented the study, Dr. David Knox, an HIV primary care provider at the Maple Leaf Medical Clinic in Toronto, explained that if the patient had only started taking PrEP doses after he was diagnosed with HIV, the expected dried blood spot concentration of drug in his system would have been approximately 722 fmol/punch. The concentrations of drug detected were much higher—2,297 fmol/punch—indicating adherence (and consistent with steady-state levels of tenofovir).
The patient reported having multiple exposures to HIV through anal receptive sex with casual partners in the 42 days preceding his HIV diagnosis. He did not have classic acute seroconversions illness, but was diagnosed after winding up in the emergency room with severe abdominal pain and a high fever. After being diagnosed, the patient was started on darunavir/ritonavir, raltegravir, and was kept on tenofovir/emtricitabine (Truvada).
The patient was tested for drug resistant mutations and the following resistant mutations were found:
- NRTIs: lamivudine, emtricitabine, abacavir (reduced response), tenofovir (reduced response)
- NNRTI: nevirapine
- INSTI: elvitegravir, dolutegravir (reduced responses), raltegravir (reduced response)
After mutations were detected, the patient’s antiretroviral medications were adjusted, and the patient’s viral load now remains undetectable to date.
“The baseline NNRTI and integrase strand transfer inhibitor mutations suggest that this was a case of transmitted, rather than acquired resistance. There were multiple TAMs [thymidine analog mutations] at baseline that are not known to be selected for by FTC or TDF [the components of Truvada]. Importantly, the presence of the 215 E mutation, which is a revertant of the 215 Y/F mutation, is known to evolve in the absence of NRTIs and is a commonly reported transmitted mutation. So its presence also supports the conclusion that this is a case of transmitted resistance. Overall, our patient’s profile suggests that he was exposed to somebody who was failing a regimen of TDF/FTC/elvitegravir/cobicistat, or Stribild,” said Knox.
Knox, D. and others. HIV-1 infection with multiclass resistance despire preexposure prophylaxis (PrEP). CROI, 2016. Abstract 169LB.