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[MAY]

PrEP Fails in Gay Man Adhering to Daily Truvada, He Contracts Drug-Resistant HIV

Researchers have for the first time documented a case of an individual contracting HIV, a multi-drug resistant strain, while apparently adhering well to the daily regimen of Truvada (tenofovir/emtricitabine) as pre-exposure prophylaxis (PrEP). The scientists concluded that it is indeed possible for individuals who are adherent to PrEP to contract HIV when they are exposed to a virus that is resistant to both drugs included in Truvada.

While this case is concerning, experts in the PrEP field suggest that such failures of PrEP will likely remain rare.

David Knox, MD, an HIV specialist at the Maple Leaf Medical Clinic and the lead author of the case study, presented findings at the 2016 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.

Evidence suggests that the individual in question, a 43-year-old man who has sex with men, adhered well to PrEP over the long-term. Nevertheless, after 24 months on Truvada he tested positive for HIV. Initial tests indicated that he was acutely (very recently) infected: He tested positive for the p24 antigen, which appears within about three weeks of HIV infection and disappears a few weeks afterward; and at that time he tested negative for HIV antibodies, which typically appear two to eight weeks after infection.

Research suggests that men who have sex with men (MSM) who take Truvada at least four times a week are more than 99 percent protected against HIV. (CDC guidelines advise taking Truvada daily for maximum protection, but the drug apparently has a good amount of dosing ?forgiveness.?) Real-world use of Truvada as HIV prevention has suggested it is indeed highly effective. For example, none of the more than 1,400 generally high-risk individuals taking PrEP through the Kaiser Permanente San Francisco PrEP program have contracted HIV to date, despite their very high rate of other sexually transmitted infections, including hepatitis C virus (HCV) in two of them.

All of PrEP?s power to curb HIV notwithstanding, this new case study underlines the fact that in science there is, unfortunately, no 100 percent guarantee.

?After 32 years of experience with HIV research, I have learned never to say ?never?,? said Robert M. Grant, MD, MPH, a professor at the University of California, San Francisco, who was the head of the iPrEx trial that first proved PrEP?s effectiveness among MSM and transgender women in 2010. ?Yet I also think that gay men benefit from feeling safer during sex, and I am grateful that PrEP affords that feeling.?

Pharmacy records indicated that the man in the case study had consistently filled his Truvada prescription on schedule. Dried blood-spot testing on a sample taken 16 days after he tested positive for HIV indicated that he had adhered well to Truvada during the previous one to two months, a period that overlapped with the estimated time when he contracted the virus.

?This person claims he was taking PrEP every day and I believe him,? said Grant.

Tests for antiretroviral (ARV) resistance that were conducted on a sample taken a week after the man tested positive for HIV indicated that his virus was clade B HIV-1 and CCR5 tropic (meaning it attached to the CCR5 coreceptor on the surface of CD4 cells, as opposed to the CXCR4 coreceptor). Tests also indicated that his drug resistance had been transmitted from another person, rather than acquired post-transmission. And a genetic analysis of his virus conducted on a sample taken a week after he tested positive suggested that he contracted the virus from a single individual.

The man?s virus was resistant to multiple drugs. It had numerous nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations, including those known as 41L, 67G, 69D, 70R, 184V and 215E, which in the resistance tests reduced the response to Ziagen (abacavir) by 1.9 fold, raised the resistance to Epivir (lamivudine) by 61 fold, raised the resistance to Emtriva (emtricitabine, which is one of the two drugs in Truvada) by 38 fold, and reduced the response to Viread (tenofovir, the other drug in Truvada) by 1.3 fold. The virus also had the non-nucleoside reverse transcriptase (NNRTI) resistance mutation 181C, raising the resistance to Viramune (nevirapine) 43 fold. Lastly, the virus had mutations conferring reduced response to all integrase strand-transfer inhibitors (INSTIs), including 51Y and 92Q, which reduced the response to Isentress (raltegravir) 2.7 fold, increased resistance to Vitekta (elvitegravir) by greater than 100 fold, and reduced the response to Tivicay (dolutegravir) 9.6 fold.

Despite all these resistance mutations, the man in the case study is currently taking HIV treatment and has a fully suppressed viral load. He is on Tivicay (dolutegravir), Prezcobix (darunavir/cobicistat), and Edurant (rilpivirine).

Recent research suggested that, among HIV-positive individuals failing treatment regimens, resistance to tenofovir, which is the most commonly prescribed ARV in the world, is increasing. Perhaps as much as 1 percent of all individuals who contract HIV today inherit virus that has mutations conferring resistance to tenofovir. Resistance to emtricitabine is more common, likely because only a single resistance mutation is required to confer resistance to that drug, while for tenofovir more than one mutation is usually required.

What is more rare is a virus that is highly resistant to both tenofovir and emtricitabine, as in this new case report. Indeed, according to Grant, among more than 9,200 participants in the clinical trials of PrEP, such a virus that was highly resistant to both components of Truvada was never seen.

According to Richard Harrigan, PhD, director of the lab program at the British Columbia Center for Excellence in HIV/AIDS in Vancouver, Canada, who was one of the researchers on this case study, ?I think we would assume that the efficacy of PrEP would be lower if there is exposure to virus which is resistant to either drug, and lowered further if there is exposure to virus resistant to both drugs.?

There have been two documented cases of men contracting HIV while taking tenofovir alone for hepatitis B virus (HBV) treatment. One of the individuals did not have a tenofovir-resistant strain of the virus, while researchers could not determine if the other person had such resistance. These cases apparently stress the importance of using two drugs for PrEP rather than one, even in the absence of resistant virus.

Reflecting on the new case study, Harrigan said, ?I certainly don't think that this is a situation which calls for panic. It is an example that demonstrates that PrEP can sometimes be ineffective in the face of drug resistant virus, in the same way that treatment itself can sometimes be ineffective in the face of drug resistant virus.?

Harrigan added, ?This case demonstrates that while PrEP is beneficial, we can?t rely on it to be an infallible magic bullet.?

https://www.poz.com/article/prep-fails-gay-man-adhering-daily-truvada-contracts-drugresistant-hiv

[MAY]

OMG we were just talking about this! 

[tigernathan]

omg the government wants you guys dead!

[∧ ∨ ∩ ∪]

I told y'all. I fucking told it.

[AIDS!]

💅🏾

[Fine Dining]

No science or drug on earth can stop God's plan.

[∧ ∨ ∩ ∪]

and wtf is drug resistant HIV bitch to me it seems like some shit from 12 monkeys lls

[SUPREME]

No science or drug on earth can stop God's plan.

NZNZNXNXN

[Young]

Reading this makes my skin crawl and soul cringe.

Be safe out there girls

[Buy The Stars✨]

lol i mean nothing is 100 percent sure.. even birth control .. hell condoms arent even 100 percent.. abstinence is the only way to full protect  yourself

[AIDS!]

lol i mean nothing is 100 percent sure.. even birth control .. hell condoms arent even 100 percent.. abstinence is the only way to full protect  yourself

Your right
But people were holding on to this thing as though it was a miracle drug

[MAY]

One of my best friends works in HIV research, and he told me that a lot of HIV positive men have raw sex with each other because they figure it's fine since they already have it. However, all they are doing is reinfecting each other and creating stronger, more drug-resistant strains of the virus.

[AIDS!]

I really think this PreP thing is false security, lull the girls into ignorance then release a superstrain 

[MAY]

lol i mean nothing is 100 percent sure.. even birth control .. hell condoms arent even 100 percent.. abstinence is the only way to full protect  yourself

Your right
But people were holding on to this thing as though it was a miracle drug

!!!
The gorls thought it was a free pass

[AIDS!]

One of my best friends works in HIV research, and he told me that a lot of HIV positive men have raw sex with each other because they figure it's fine since they already have it. However, all they are doing is reinfecting each other and creating stronger, more drug-resistant strains of the virus.

This!
They don't get it
What kinda super hot sauce