A case report of a man in Toronto who was infected with a strain of HIV multiresistant to drugs despite the apparent large membership, consistent with PrEP, was presented during theConference on Retroviruses and Opportunistic Infection (CROI 2016)in Boston today.
Dr David Knox, a doctor in Toronto Maple Leaf Medical Clinic, said the patient was a gay man of about 43 years, the 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 startTruvada PrEPin April 2013 and he seemed to have good adhesion to it depending on the pharmacy trip frequency for the provision of antiretroviral drugs for PrEP.
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 of 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 it went through their regular HIV test which showed that it had HIV infection, with the aid of a test negative for HIV antibodies but tested positive for the HIV antigen p24, showing earlier. His 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 was replicating weakly.
The patient adamantly stated that he maintained excellent adherence to PrEP so that Dr Knox, put in question 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 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 compatible with high adhesion around the time of exposure to HIV.
There was an indirect way, however to assess the issue. 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 drug levels are measured inside the red blood cells instead of within the white blood cells that HIV infects or blood plasma. Increased levels of drug is much slower in red blood cells, 17 taking 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 taken the drug since he met his diagnosis, drug levels would only 47% of the steady-state level of the average or 31% of their actual level in this patient.
This 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 performed over three weeks and the period of risk according to the patient started 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 be disconnected from PrEP when he took a risk and that it had asked to start again. However, the patient emphasizes this is not the case.
Before the patient being diagnosed with HIV + blood dry test was collected during the following three weeks, and the period of risk according to the patient began two weeks before diagnosis.
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 can 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 mutation and resistance did have only gives 1,3 times resistance to tenofovir, which means that the drug levels 30% higher than required for resistant viruses it should not have been sufficient to prevent infection - and he had much higher levels of drug present in the tests. Resistance, however, is a complex process and some combinations of mutations can catalyze higher levels of resistance they produce alone.
There are no material facts 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 integrase inhibitor resistance isVery rareAnd particularly resistance to all drugs except raltegravir, the first integrase inhibitor. The resistance pattern observed is consistent with the person who has no name on the virus is in a failed schemaStribild (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, would be the concern that more resistant viruses resistant integrase inhibitors was circulated.
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 in samples taken at the time of infection for this. But on the balance of probabilities, with three different measures all accepted Dauto 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 29 February 2016 by Claudio Souza from the text In the transmission of HIV integrase inhibitor-resistant seen in California PatientsGus Cairns Published: 25 2016 in February aidsmap.com
Note: This photo date 2014, an event that my blog was voted the best health blog.
I felt very honest