A case report of a man in Toronto who was infected with a multidrug-resistant strain of HIV despite apparent large adherence, consistent with PrEP, was Conference on Retroviruses and Opportunistic Infection (CROI 2016) in Boston today.
Dr. David Knox, a physician at the Toronto Maple Leaf Clinic, said the patient was a gay man of approximately 43 years old, a man who had been undergoing PrEP two years ago. He had an HIV positive partner who had undetectable viral load
He was a regular listener at the outpatient clinic and tested for HIV on average every three months. It was suggested to him to initiate PrEP with Truvada in April 2013 and he seemed to have good adherence to it depending on the frequency of going to the pharmacy to get the supply of antiretroviral drugs to PrEP.
Two years later in April of 2015 he began to have symptoms after a period of exposure to HIV with multiple partners. The symptoms were not classic HIV seroconversion symptoms, but involved an episode of fever with abdominal pain intense enough for him to go to the hospital for a consultation, where a reading revealed an inflammation of the colon.
During that time he went through his regular HIV test that showed he had HIV infection, with the help of a negative HIV antibody test, but a positive test for the HIV p24 antigen, which shows earlier. Its viral load three days later was 28.000 copies / ml - quite low for acute HIV infection and suggestive that its PrEP had "blunted" viral replication without stopping the infection, or that the virus was highly resistant to the drugs and was replicating weakly.
The patient stated peremptorily that he maintained excellent adherence to PrEP so that Dr. Knox has questioned that he may now be seeing a case of true failure in PrEP, ordered further tests. A resistance test was performed for all classes of antiretroviral drugs for the virus patient from a specimen collected one week after their HIV diagnosis.
The patient was treated within a public health setting of low financial resources and his former blood samples had not been stored. So there was no direct way to prove that it had levels of compatible drugs with high adherence around the time of exposure to HIV.
There was an indirect way, however, to assess the issue. Dr Knox analyzed a test called the "dry blood" site (DBS) of the 20 patient days after he was diagnosed. The test point of a DBS is that drug levels are measured inside the red blood cells, rather than inside the white blood cells that HIV infects, or in the blood plasma. The increase in drug levels is much slower within red blood cells, taking 17 days to reach half of their steady state levels and a full eight weeks to reach the stationary drug saturated completely. Drug levels also rose steadily and are less susceptible, in the short term, to ups and downs. Drug levels in the DBS patient were effectively 47% higher than the mean value, suggesting consistent PrEP adherence during most of the period covering their HIV exposure. If he had taken the drug since he knew his diagnosis, drug levels would be only 47% of the mean steady-state level or 31% of his actual level in this patient.
This is an indirect way of measuring drug levels. Since the age of onset of symptoms occurred four weeks prior to the patient's HIV infection diagnosis and the dry blood test was performed over three weeks thereafter and the patient-period of risk started two weeks earlier of the onset of symptoms, thus leaving nine weeks for the drug to accumulate; this test does not entirely rule out the possibility that he would have disengaged himself from PrEP at the time he took a risk and that PrEP had asked him to start again. However, the patient insists this is not the case.
Before the patient was diagnosed with HIV + the dry blood test was collected over three subsequent weeks, and the period of risk according to the patient started two weeks prior to diagnosis.
This revealed high levels of tenofovir and emtricitabine levels so high that they were above the limit of quantification of the test. However this was not a long-term test and drug levels and again can not totally rule out the possibility that he had had a lapse in adherence around the time he was exposed to HIV.
Resistance testing showed that the HIV patient did not have a significant resistance to the class of antiretroviral drugs known as protease inhibitors. He had a mutation of resistance to the first generation of NNRTI nevirapine drugs, and complete resistance to emtricitabine. 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 present the call to K65R which confers high level of resistance to tenofovir and it was estimated that the pattern of mutation and resistance did have only conferred 1,3 times resistance to tenofovir, which means that 30 drug levels% higher than required for resistant viruses should not have been enough to prevent infection - and it had much higher levels of drug present in the tests. Resistance, however, is a complex process and some combinations of mutations can catalyze the higher levels of resistance they will produce alone.
There are no relevant facts for the apparent failure of PrEP, but for the spread of drug resistance, it was the fact that this patient also had two mutations of resistance to drug integrase inhibitor and drug resistance elvitegravir.
HIV transmission with integrase inhibitor resistance is very rare, and in particular resistance to all drugs except raltegravir, the first integrase inhibitor. The observed resistance pattern is compatible with the unnamed person who has passed on the virus being in a fault scheme Stribild (two classes of four the combination drug pill of tenofovir, emtricitabine, cobicistat and elvitegravir).
Since four of the five 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, it would be the concern that more resistant viruses to resistant integrase inhibitors began to circulate.
The patient himself was placed on a class three regimen potent medications such as dolutegravir, rilpivirine and darunavir boosted and became undetectable only three weeks after onset.
In conclusion, this is probably not an absolutely booming point - it would take a level of drugs in samples collected at the time of infection for this. But on the balance of probabilities, with three different measures all accepted the patient report dauto, this is probably the first documented case of failure of Truvada PrEP despite high adherence and more than adequate drug levels although recently Two cases were reported on monotherapy with tenofovir.
It is not unexpected that there would be cases of PrEP failure; but the fact that this is the first case report among 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 Patients by Gus Cairns Published in: 25 of February of 2016 in aidsmap.com
Note: This photo date 2014, an event that my blog was voted the best health blog.
I felt very honest