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Reported 2ª PrEP Failure Due to HIV Drug Resistance

 

.More a PrEP Failure Due to a Truvada Resistant Viral Strain!

A user of the PrEP in New York City has become HIV positive with a virus that is resistant to Truvada and other antiretroviral drugs, according to a report presented at the HIV Research for Prevention (HIVR4P 2016) conference in Chicago.

It is the second reported case, highlighting the rarity of HIV infection among people adhering to PrEP.

The man appears to have acquired HIV from a casual male partner who had multiple resistance mutations.

These resistance included some resistant to tenofovir and emtricitabine, components of Truvada.

The man who acquired HIV reported not using condoms when taking on the insertive role.

And so it was with 2 casual partners while wearing PrEP.

He also had unprotected sex with his main partner, who is HIV positive and has an undetectable viral load.

Tests phylogenetic showed that there was no relationship between his virus and that of his main partner, then he must have acquired HIV from outside the couple.

PrEP is not silver bullet

Howard Grossman presenting at HIVR4P. Photo by Roger Pebody / aidsmap.com

Howard Grossman, now at the Cleveland Clinic in Florida, said the case involved a twenty-something gay man who tested HIV negative many times before starting PrEP on 1 on January 2016. While the man had already used condoms with the HIV-positive partner, he did not do so after starting PrEP. In mid-February and the end of March, the couple had trio with 2 different casual partners.

The user of PrEP reports that only had anal insertive sexual intercourse without a condom with casual partners.

He did not have receptive sex.

The man missed a scheduled follow-up visit, but made an appointment in early May.

At that time, the diagnostic test of 4th generation (antigen and p24 antigen) was reagent.

Also in the nucleic acid amplification test (NAAT).

What is a viral load type test that directly detects the genetic material of HIV.

However, the standard HIV RNA test used for viral load was not reactive.

In other words, he did not detect any signs of infection.

When the tests were repeated two and five weeks later they were reactive, but indicated an undetectable viral load !!!

This is unusual during early HIV infection and made the situation more difficult to interpret!
Both the man and his partner insisted that he had been 100% adherent to PrEP.

There was good adherence to PrEP as tested in dry blood

Testing for dry bloodstains and hair samples showed drug levels indicative of good adhesion!

There was enough adherence to Truvada in the previous 30-60 days.

However, this occurs after the period during which the man reported sex with casual partners.

There are no objective biological data to assess man's adherence during February and March.


Instead of being a case of PrEP failure due to poor adherence, the transmitted virus has multiple mutations!
Including those that give resistance to Truvada components.

Resistance testing has shown that man's virus is resistant to most nucleoside / nucleotide reverse transcriptase inhibitors (NRTIs, the backbone of HIV treatment).
And also as several non-nucleoside reverse transcriptase inhibitors (NNRTIs).
This is due to the mutations K65R and M184V, which offer high level resistance to tenofovir fumarate.
As well as emtricitabine (Emtriva), lamivudine (Epivir), abacavir (Ziagen) and didanosine (Videx).

K103S, E138Q and Y188L mutations confer high-level resistance to efavirenz (Sustiva), rilpivirine (Edurant) and nevirapine (Viramune); Other 13 mutations have been identified.

As a result, the man received an intensive drug regimen by adding the following medications:

  • integrase inhibitor dolutegravir (Tivicay)
  • the darunavir protease inhibitor (Prezista),
  • and the "booster cobicistat, which impels the existing Truvada.

Viral Load Detectable - Not One Viral blipe

Grossman said maintaining tenofovir and emtricitabine would probably be better than not having an NRTI element. The man is well on this treatment and he kept an undetectable viral load.

A phylogenetic analysis showed that the viral strains of the newly infected man and those of his HIV-positive primary partner were unrelated. It is likely that the man has acquired HIV from one of the casual partners; it is plausible that this man was in the acute stage of infection with a high viral load himself.

"The patient became infected with a variant of multi-drug resistant HIV-1 despite adherence to PrEP," concluded Grossman.
The case bears some resemblance to the first case report of PrEP failure, reported earlier this year. This also involved the acquisition of HIV that was resistant to multiple medications.

Grossman told a press conference that there is no reason to think that Truvada PrEP protects against viruses that are already resistant to their medications. However, he said such cases of resistance are extremely rare. Very few people with newly acquired HIV have reported resistance to tenofovir and emtricitabine; Resistance to other antiretroviral drugs that are not used as PrEP is more common.

A very low failure rate says the author ... - And yet, it is a failure and this in a universe where failures in one way or another compromise human lives. And I, the editor of this blog I think things, before they have become great, start small. How many have you infected with this sturdy strain before being diagnosed? Is he going to stop now? !!! ... (...) ... Or will you participate in "bareback parties"? It is a pertinent question, given the case, for the person seemed to act as if he were invulnerable, the superman himself! He had no concern for his own health! Does he have any regard for that of other people? I do not know ... But these questions are pregnant with other questions ...

He also said that 2 infection reports in the context of perhaps 100.000 people who took PrEP accounted for a very low failure rate.
What else can we learn from the case? Grossman noted that the man only reported taking the role of insertion with his occasional partners. There is a "myth in the community" that "the summits do not contract HIV," he said, which this case defies.

He also noted the difficulty of interpreting the lab results in the case. Both the conventional viral load tests and the Multispot HIV 1 / 2 test (used to distinguish between HIV-1 and HIV-2) were unable to remove the new infection.

Grossman requested the experience and lab capabilities of Martin Markowitz from the Aaron Diamond AIDS Research Center and Robert Grant of the University of California, San Francisco to help manage the case. There needs to be forms for PREP frontline providers who are dealing with unusual cases to access such features, he said.

Monitoring of Soroconverts.

Another presentation at the conference addressed the issue of the immune response and viral set-point of people who get HIV, despite the provision of PrEP. They can still take some PrEP medications during the early stages of infection.

Perhaps lower levels of antiretrovirals prescribed as PrEP may affect the course of infection ...

On the one hand, intensive antiretroviral therapy early in HIV infection decreases the viral set point and reduces the size of the latent viral reservoir.

And this has the apparent gift of delaying the progression of the disease.

It is plausible that the presence of lower levels of antiretrovirals prescribed as PrEP may affect the course of infection.

Deborah Donnell analyzed data from the randomized study of PrEP Partners from serodiscordant heterosexual couples in East Africa, in which 138 participants acquired HIV. About half were in the placebo arm, while many others had poor or inconsistent adherence to PrEP. Cases of HIV acquisition in PrEP are assumed to be due to poor adherence, rather than a failure in PrEP.

Truvada levels in seroconverted individuals in PrEP!

By comparing seroconverts with detectable blood drug levels to detectable drug-free seroconverts, Donnell found that the development of antibody responses (as indicated by the Fiebig stage, which measures the 6 stages of HIV seroconversion and the time it takes to pass through each stage) was somewhat slower, but the antibody response characteristics were unchanged.

Laboratory latency in the detection of PrEP!

In addition, it took a little longer for some people who took PrEP to have their infection diagnosed using rapid tests. A minority of cases took more than 90 days. Rapid tests may lose cases of acute infection, especially after PREP.

The initial viral load of people with detectable levels of drugs in their blood was slightly lower!

Finally, the initial viral load of people with detectable levels of drugs in their blood was on average slightly lower - probably due to viral suppression while taking PrEP. The viral set point (the mean viral load in the months after the primary infection period) was lower in people who took some PrEP around the time of HIV acquisition; This persisted after stopping PrEP.

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Translated by Claudio Souza's originalSecond case report of PrEP failure due to drug-resistant virus

Reviewed by Mara Macedo

Sources

H Grossman, P Anderson, R Grant, et al. Newly acquired HIV-1 infection with multidrug-resistant HIV-1 (MDR) in a TDF / FTC-based PrEP patient. HIV Research for Prevention (HIVR4P 2016). Chicago, 17 to 21 October 2016. OA03.06LB Summary.
DJ Donnell, EM Ramos, JM Baeten, et al. The effect of pre-exposure oral prophylaxis on the progression of HIV-1 seroconversion. HIV Research for Prevention (HIVR4P 2016). Chicago, 17 to 21 October 2016. OA03.01 Summary.
KT Thomas, DJ Donnel, JM Baeten, et al. Level of HIV RNA setpoint after infection during PrEP: a placebo-controlled comparison. HIV Research for Prevention (HIVR4P 2016). Chicago, 17 to 21 October 2016. PD04.05 Summary.

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Yes, this is the photo of me! My niece asked me to put this picture on my profile! .... I had here a description of me that one person described as "irreverent". This is really a euphemistic way of classifying what was here. All I know is that an "NGO" which occupies a building of 10 floors has established a partnership with me, and I have the logs of the partnership time, which was more a vampirism because for each 150 people leaving my site, clicking on them, there was, on average, one that came in. WHEN I ENTERED AND ENTERED

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