HIV virus, Credit: C. Goldsmith Content Providers: CDC/ C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus
Is there a strain of HIV that is resistant to PrEP? That’s the question being asked following a presentation by Dr. David C. Knox, of the Maple Leaf Medical Clinic in Toronto, Ontario.
Knox told an audience at the Conference on Retroviruses and Opportunistic Infections about his clinic’s study of one gay man who seroconverted to become HIV-positive while adhering to a prescription drug regimen designed to prevent HIV, known as pre-exposure prophylaxis,or PrEP.
In his presentation, Knox detailed the story of what he believes is a rare incidence of “multi-class resistance” leading to HIV infection, calling attention to a 43-year-old man who had sex with men and seroconverted to HIV-1 after two years of being on PrEP. Blood tests indicated he had levels of PrEP in his blood suggesting he had been regularly adherent. Knox also noted that no other case of “breakthrough HIV infection” had been documented in a study to date.
The patient had reportedly been taking medications for “depression, anxiety and herpes labialis [cold sores]” but presented “no evidence of STIs” and “had no history of substance abuse.” He first tested negative for HIV in Feb. 2013, and two months later began taking PrEP. Over the course of two years, the patient had seven more HIV tests that all came back negative. However, a screening in May of 2015 showed positive signs of HIV.
Chart by Knox showing timeline of patient’s HIV test results while on PrEP.
Knox also presented information about the man’s sexual history and symptoms before the final positive tests. Prior to his diagnosis, the man reported that he had engaged in multiple acts of receptive, condomless sex with different partners.
“At this point, as the treating provider, I became concerned that this could be a true breakthrough HIV infection, in the context of PrEP, because my patient was adamant that he was adhering to his PrEP over the preceding 24 months,” Knox said.
Knox said the clinic investigated the patient’s claim, including the examination of his pharmacy dispensing records, collection of dried blood spots, and testing of TDF & FTC concentrations in his plasma. He stated that “phylogenetic analysis indicated infection from a single source,” and that the drug resistance appeared to have been “transmitted rather than acquired.” Evidence indicated that the patient “was exposed to somebody who was failing a regimen of…Stribild [an antiretroviral treatment consisting of FTC, TDF, elvitegravir (ELF) and cobicstat (COBI)].”
The patient has since been put on a combination of Prezcobix, Tivicay and Edurant and achieved viral suppression within 21 days, remaining undetectable to date.
“The clinical history, pharmacy records, the mass spec results consistent with recent dosing, the dried blood spots consistent with long-term dosing of FTC/TDV suggest that HIV infections is possible despite adherence to daily oral PrEP,” Knox said during his presentation. “To our knowledge, this is the first reported case of breakthrough HIV infection with evidence of long-term adherence to PrEP. Failure of PrEP in this case was likely due to the transmission of a PrEP-resistant, multi-class resistant strain of HIV-1.”
Megan Coleman, a family nurse practitioner and director of community research at Whitman-Walker Health, says that while this case appears to be the first of its kind, this particular form of resistant virus is quite uncommon.
“In medicine, we’ve learned never to say anything is 100 percent,” Coleman says. “This particular virus, which is very, very rare, had a lot of mutations and a very complicated interplay of mutations that seemed to make it resistant to Truvada.”
Coleman cautions against widespread panic — particularly since the patient was infected with an already drug-resistant strain, as opposed to developing resistance to PrEP internally — and says medical providers will continue to make scientific-based recommendations to their patients, including prescribing PrEP as one of several HIV prevention strategies.
“When I counsel patients about Truvada for PrEP, my message won’t change,” Coleman says. “It’s to continue to encourage people to take it daily…. We can say, with authority, that PrEP is over 90 percent effective. And the other information, which is based on modeling data, ranges anywhere from 92 to 99 percent effective. So one out of tens of thousands of individuals still translates to 99 percent effective.”
The original presentation by David Knox was posted on CROI’s website on Thursday, Feb. 25, and can be viewed here.
Senior Editor John Riley also contributed to this report.