[LINK] On PrEP in Canada

[rfmcdonald]

Daily Xtra and The Homo Culture were among the first news sources in my Facebook timeline to announce the approval of Truvada for PrEP. Toronto's Metro was among the many mainstream news sources to carry the news.

A drug that can stop the transmission of HIV is getting within reach of Torontonians who can’t afford its steep price.

Health Canada approved the use of Truvada on Monday as a prevention tool commonly called PrEP, giving people who can’t afford its $830 a month cost hope that they might be able to take it someday soon.

Until now, people using the drug for prevention have mostly been part of a “lucky minority” with “good, private drug insurance coverage,” said Dr. Darrell Tan, an infectious diseases specialist at St. Michael’s Hospital.

“That leaves people with the option of going without or purchasing it out of pocket —which is exorbitantly, prohibitively expensive for the vast majority of individuals,” he said.

Truvada was approved in Canada a decade ago as a management tool for people who already have HIV. Monday’s decision takes that approval further, extending it to include use by HIV negative people who are looking to stay negative.

At roughly the same time, there was also a news report noting the first verifiable report of PrEP failing to protect a user. Aidsmap described how a user in Toronto had the bad luck to get infected with a Truvada-resistant virus in a sexual partner whose HIV was suppressed.

During this time he came in for his regular HIV test and this showed he had acute HIV infection, with a negative test for HIV antibodies but a positive test for the HIV p24 antigen, which shows up sooner. His HIV viral load three days later was 28,000 copies/ml – rather low for acute HIV infection and suggestive that either his PrEP had ‘blunted’ viral replication without stopping infection, or that the highly drug-resistant virus was replicating weakly.

[. . .]

The resistance test showed that the patient had HIV that had no significant resistance to the protease inhibitor class of antiretrovirals. He had one resistance mutation to the first generation NNRTI drug nevirapine, and complete resistance to emtricitabine. He also had extensive resistance to the first-generation NRTI drugs like zidovudine (AZT) and stavudine (d4T), and these mutations also confer some resistance to tenofovir. However he did not have the so-called K65R mutation that confers high-level resistance to tenofovir, and it was estimated that the resistance pattern he did have only confers 1.3-fold resistance to tenofovir, meaning that drug levels 30% higher than those needed for non-resistant virus should have been enough to prevent infection – and he had much higher drug levels than this in the tests. Resistance, however is a complex process and some combinations of mutations can catalyse higher levels of resistance than they would produce alone.

Not relevant to the apparent PrEP failure, but to the spread of drug resistance, was the fact that this patient also had two resistance mutations to the integrase inhibitor drugs and complete resistance to the drug elvitegravir.

Transmission of HIV with integrase inhibitor resistance is very rare, and especially resistance to drugs other than raltegravir, the first integrase inhibitor. The pattern of resistance observed is compatible with the unnamed person who passed on the virus being on a failing regimen of Stribild (the two-class, four-drug combination pill of tenofovir, emtricitabine, elvitegravir and cobicistat). Given that four out of the five first-line HIV drug regimens recommended by the US Department of Health and Human Services are integrase inhibitor-based, and that this drug class is being investigated for use as PrEP, it would be of concern if more integrase inhibitor-resistant virus started to circulate.

The patient himself was put on a potent three-class regimen of dolutegravir, rilpivirine and boosted darunavir and became virally undetectable only three weeks after starting it.

This sort of failure is the sort of failure to be expected in an instance of PrEP failing. It does not undermine the utility of this technique.