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An almost certain if PrEP failure due to drug resistance has just been reported in the year 2016

PrEP_failure_1000_707A case report of a man in Toronto who was infected with a strain of HIV multiresistant to drugs despite the seemingly large membership, consistent with PrEP, was presented during theConference on Retroviruses and Opportunistic Infection (CROI 2016)Boston today.

Dr David Knox, a doctor in Toronto Maple Leaf Medical Clinic, said the patient was a gay man of about 43 year-old man who had been subjected to PrEP two years ago. He had an HIV-positive partner who had an undetectable viral load

He was a regular listener in the clinic and tested for HIV on average every three months. It was suggested to him that he startTruvadaPrEP in April 2013 and he seemed to have good adhesion to it depending on the frequency of pharmacy refills.

Two years later in April 2015 he began to have symptoms after a period of exposure to HIV with multiple partners. The symptoms were not symptoms seroconversion to HIV classics, but involved an episode of fever with severe abdominal pain enough for him to go to the hospital for a consultation where a reading revealed an inflammation of the colon.

During this time he took his HIV test and regular showed he had HIV, to help a negative test for HIV antibodies, but a positive test for HIV p24 antigen, which shows earlier. Their HIV viral load three days later was 28.000 copies / ml - very low for acute HIV infection and suggestive your PrEP had "blunted" viral replication without stopping the infection, or that the virus was highly resistant to drugs and it was replicating weakly.

The patient adamantly stated that he maintained excellent adhesion to PrEPde way Dr Knox, calling into question that he may be seeing now a case of real failure in PrEP, ordered more tests. an endurance test was done for all classes of antiretroviral drugs, for your virus patient from a sample taken after a week of their HIV diagnosis.

The other needs explanation. The patient was treated in a public health setting center of limited financial resources and their old blood samples had not been saved. So that there was no direct way to prove that he had drug levels consistent with high adherence around the time of exposure to HIV.

There was an indirect way, however. Dr Knox examined a test called "dried blood" spot (DBS) of 20 days patient after he was diagnosed. The test point of DBS is that the drug levels within measures red blood cells instead of within the white blood cells that HIV infects or blood plasma. The increase much more slowly drug levels in red blood cells, tomando17 days to reach half of its steady-state levels and eight weeks to reach full steady state drug saturated completely. drug levels also rose and regularly are less likely in the short term, with ups and downs. drug levels in the patient were actually DBS 47% higher than the average, suggesting consistent adhesion PrEP during the period covering most of its exposure to HIV. If he had been taking the drug since he presented his diagnosis, drug levels would only 47% of the average steady-state level or 31% of their actual level in this patient.

Laboratory doctor or scientific researcher preparing for the smearThis is an indirect way of measuring drug levels. Since the age of onset of symptoms occurred four weeks before the diagnosis of HIV infection of the patient and the dried blood test was conducted over three weeks and the period of risk according to the patient began two weeks before the onset of symptoms, leaving nine weeks for the drug to accumulate; this test does not completely rule out the possibility that he would have failed in adherence to PrEP when he took a risk and that he had started PreP again. However, the patient insists that is not the case.

There was a small sample of blood from your diagnostic test, taken three days before the patient discover seropositive,

This revealed high levels of tenofovir and emtricitabine levels so high that they were above the assay limit of quantitation. However this was not a long-term test and drug levels and again could not completely rule out the possibility that he had had a lapse in membership around the time he was exposed to HIV.

Resistance tests showed that patients with HIV who had no significant resistance to antiretroviral drug class known as protease inhibitors. It had a resistance mutation for the first generation of drugs NNRTI nevirapine, emtricitabine and complete resistance. He also had extensive resistance to the first generation of NRTIs that drugs such as zidovudine (AZT) and stavudine (d4T), and these mutations also confer some resistance to tenofovir. However it does not have the call to K65R which confers high level resistance to tenofovir and it was estimated that the pattern of change and resistance was only 1,3 fold resistance to tenofovir, which means that the drug levels 30% higher than required for resistant virus should not have been strong enough to prevent infection - and he had drug levels much higher in this test. Resistance, and yet, is a complex process and some combinations of mutations can catalyze higher levels of resistance than they produce themselves.

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

Transmission of HIV with resistance to integrase inhibitor é very rare, especially resistance to all drugs except raltegravir, the first integrase inhibitor. the observed patterns of resistance is compatible with the person unnamed passed the virus is in a failed schemeStribild (Two classes of four to drug pill combination of tenofovir, emtricitabine, cobicistat and elvitegravir).

Since four of the five therapeutic first-line regimens are recommended by the Department of Health and Human Services, are based on integrase inhibitors, and that this class of drugs is being evaluated for use as PrEP, and would be a concern that more viruses resistant integrase inhibitors began to circulate.

The patient himself was placed in a class scheme three powerful drugs like dolutegravir, rilpivirine and boosted darunavir and became undetectable only three weeks after the start.

In conclusion, this is probably not an absolutely thunderous point - would require a level of drug samples collected at the time of infection for this. But on the balance of probabilities, with three different measures all accepted the self patient report, this is probably the first documented case of failure TruvadaPrEP despite high adhesion and more than adequate drug levels although recentlyTwo cases were published in the tenofovir monotherapy.

It is not unexpected that there would be any cases of failure of PrEP; but the fact that this is the first case report of the tens of thousands of people held with PrEP shows that it is very rare.

Translated into 02 March 2016 by Claudio Souza from the text Almost-Certain case of PrEP failure due to drug resistance Reported at CROI 2016 Gus Cairns Published: 25 February 2016 for aidsmap

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