Come on! Yes, I know that in most cases it is exactly because of the failure to take the medication. If I, a layman, so to speak, can see this, well, it is more than clear, in my modest and limited way of looking at life, it is because it is very visible to the people working on the front lines of these tests. And I wonder if I am mistaken in imagining that they serve Mammon more than any other real or imagined creature! So, I decided to translate this text, whose explanation is this:
PrEP failure Two different cases of despite high adherence
Dtwo reports of HIV infection occurring despite apparent adequate adherence to PrEP, confirmed by drug-level tests, are the first to be reliably documented, to be published in peer-reviewed journals from 2018.
The most recent case was reported by Dr. Matthew Spinelli in Clinical Infectious Diseases. He is a 44-year-old gay man in Texas and appears not to be due to low adherence, but to HIV infection with an unusual combination of resistance mutations.
I, Cláudio, always saw this as more than possible!
Two characteristics of the case make it difficult to argue against this, being a genuine case of PrEP advancement. In the first place, blood and hair samples confirm that he had good adherence to PrEP in two to three months that preceded the infectiono.
Second, a pattern of HIV testing and viral load showed that this was an acute infection that probably occurred only a few weeks at most before he reported the symptoms.
An Imperfect Grip And “Poft”
Notably, his initial HIV test was interpreted as a 'false positive' (…) because his adherence seemed to be very good.
—A revolting hypocrisy! - It sounds like an attempt to deny the PrEP Failure
The other case was published in the May issue of International Journal of Infectious Diseases by Professor Shui-Shan Lee and concerns a 24-year-old gay man from Hong Kong. It is an interesting comparison, as it is likely, in this case, that the failure of PrEP is due to imperfect adhesion. However, this is difficult to prove because HIV seroconversion - the appearance of antibodies that are detected by HIV tests - was delayed, occurring two months after a retrospective viral load test showed that he had already been infected, and it occurred until three to four months after infection.
The case of Texas - a 'false positive'. So not!
O Texan man started PrEP in December 2017. He had anal sex without a condom during PrEP and was mainly the insertive partner, with some experiences of being receptive. His last negative HIV test was in April 2019.
In early June 2019, he attended the clinic complaining of headache, sore throat and chills. The physical examination revealed inflammation of the throat with a characteristic "cobblestone" appearance, which is usually seen in both infections and allergic reactions.
The total lymphocyte count (white blood cells) and the platelet count were quite low. (This is not a very common reference)
An HIV antigen / antibody test The fourth generation test was positive, but a standard antibody test was negative. (Fourth-generation tests can detect an HIV protein (p24) a few days before the body starts producing the antibodies that are detected by standard tests, which usually occurs in two to three weeks after infection.)
In that case, because the patient said he had 100% adherence to PrEP, he was told that he probably had a false-positive result. But the samples were sent to a laboratory for a complete viral load and CD4 count, and when they returned two weeks later, in mid-June, it was clear that it was not a false positive. The patient had a very high viral load of 3,1 million and a low CD4 count of 195.
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These numbers are characteristic of acute HIV infection before the body has assembled the initial antibody response that it moderates, but does not completely contain HIV infection.
Even so, the viral load was greater than the average acute infection, suggesting that the source partner (which was not found) was also in the acute stage, therefore, it was very infectious - given that viral loads in the source partner and the recipient tend to be correlated. A second viral load test done at this point showed that the patient's viral load had already dropped 20 times to 146.000, further evidence of a very recent infection. At that time, the patient was switched to an antiretroviral regimen based on bictegravir.
—The Patient, I say, trusted PrEP and, as my father used to say, took the “rai-fi-óiz” with the failure of PrEP
A resistance test showed that his HIV had a very unusual combination of resistance mutations in his reverse transcriptase gene. He had the common emtricitabine resistance mutation called M184V, and this usually arises in situations where people continue to PrEP while having an acute HIV infection. However, he had a rare mutation that conferred moderate resistance to most other HIV nucleoside drugs (NRTI), including tenofovir, and two even rarer mutations for non-nucleoside drugs (NNRTI), mainly for the drug rilpivirine. . This could not have happened because the patient was taking PrEP, so this must be a case of transmission of a PrEP-resistant virus.
The retrospective drug level test provided further evidence of this. A sample of dried blood obtained in the consultation in early June showed levels consistent with the dosage of seven days a week and more than twice those observed in adherence four days a week.
Levels worse than great
Drug level tests were also done on the patient's hair; these may be earlier than the probable date of infection. The observed levels, of 0,035 nanograms per milligram (ng / mg) in the four weeks prior to the start of ART, and 0,028 ng / mg in the previous four weeks, were compatible with adherence to 5-6 weekly doses. They take us back to mid-April, first of all, except for the most remote probability of HIV infection.
Therefore, it appears to be a case of infection by a virus resistant to NRTI and NNRTI, which may also have crossed the PrEP barrier due to a very high viral load in the source partner. Spinelli and colleagues note that only 1-3% of people with HIV in the U.S. who have unsuppressed viral loads now have resistance to either emtricitabine or tenofovir, and resistance to both is even more rare.
The Hong Kong case - a positive test 3-4 months after infection
O the second contrasting case was published at the beginning of the year, but it is reported here for comparison. The 24-year-old gay man was in a clinical trial of PrEP that compared the effectiveness of daily PrEP versus Event-based PrEP '2-1-1'. He reported receptive anal sex, often involving drugs. He was tested for HIV and started PrEP in September 2018 and now was diagnosed and treated for syphilis, throat gonorrhea and rectal chlamydia.
According to the trial protocol, he switched to event-based PrEP after four months of daily PrEP on January 19, 2019. An HIV antibody test he did on February 2 was negative, but he tested positive six weeks later, on March 16.
In contrast to the Texan patient, he was positive for HIV antibodies, but not for the p24 antigen, suggesting that he had been infected for a longer time - at least a month to six weeks earlier. Also in contrast to the Texan patient, his viral load was quite low at this point in 9500.
His virus also carried the resistance mutation to emtricitabine M184V and it would be tempting to believe that this was an event-based failure of PrEP. However, the retrospective HIV RNA test on stored blood samples showed that he already had HIV on January 19, before starting PrEP '2-1-1'.
A pill count showed that he had taken almost all of his doses during daily PrEP, but had missed eight doses in the five weeks between 13 October and 21 November. This included losing her PrEP on November 1 and 2, which coincided with a single episode of anal sex without a condom on November 2. A sample of dried blood collected on January 19 showed a tenofovir level (685 femtomoles) compatible only with the dosage of four days a week.
So it seems that this is a case where the patient's infection was not due to meeting someone with a resistant virus, but to an infection that happened during a short, less than optimal adherence period. However, what is unusual is the long delay between the likely date of infection and a positive antibody test. If he was infected in early November (and he denied any sex without a condom between November 2 and December 24), there was an interval between 3 and 4,5 months between infection and seroconversion.
People lie about their sex lives
It's normal to be like that!
I say this: when it comes to our sex lives, it is more than common that we tell lies. Some very hairy! (…) See this fantastic reality about heterosexual men with HIV / AIDS
This case appears to be 'attenuated' HIV infection, in which the appearance of antibodies has been delayed by the fact that he continued to take PrEP and thus partially suppressed his HIV - which was also suggested by comparatively low viral load.
A Review2017 finger2011 Partners PrEP study of found that 17% of people who acquired HIV while having suboptimal adherence to PrEP took more than 100 days to produce antibodies against HIV. The 91-133 day period, in this case, would fit that.
The fact, reader, the fact, reader, is that few are those who take pills before they get sick, because it doesn't make sense.
The morning after pill, in your name, explains everything!
If you read mine textosa, daily, you clearly see the reasons why I don't have sponsorship.
I am an uncomfortably resilient person ... And my train of thought ...
New York and Florida Cases in 2017 Illustrate the Facts
Less than optimal adherence is certainly a constant. The person is about to be born who, when he sees himself in the heat of passion, thinks: ih! I forgot to take PrEP the day before yesterday, I'm going to stop this now.
The case is similar to several others reported in the literature, such as a 2016 case from New York e a 2017 case from Florida, where the gap between probable exposure and positive test was two and almost three months, respectively. Delayed seroconversion may also have been a factor No. unusual case of PrEP failure reported in Amsterdam in 2017 and was discussed as one of several difficulties in establishing the frequency of PrEP failures in a Swiss case reported at the 2019 EACS conference.
Both cases in 2020 suggest that symptoms that suggest acute HIV infection should not be ignored and the tests discarded as false positives, even in the context of apparent high adherence to PrEP. As the Hong Kong researchers say about their case, "The phenomenon [of late seroconversion] advocates the prevention of infrequent follow-ups by PrEP users, so that the diagnosis of failure and initiation of ART is not inadvertently delayed."
Translated on April 29, 2021 by Cláudio Souza, from the original in Two different cases of PrEP failure despite high adherence underline that such events are rare, but should not be ignored, written by Gus Cairns on 4th September 2020