Two cases of failure of PrEP with tenofovir monotherapy

tenofovirA report originally submitted to the BHIVA of 2015apresentou details in 2015 year's conference, where two cases at therapeutic levels in PrEP with tenofovir monotherapy failed to prevent unequivocally HIV infection in two homosexual men. In one case, despite the tenofovir apparently show the suppression of viral load man HIV in their blood plasma, failed to prevent HIV from infecting cells of your immune system. Monotherapy tenofovir as PrEP was tested in two large studies,Partner PrEPIt's theBangkok Tenofovir StudyWith moderate to good results and has been taken with ground-based studies with animals that tenofovir may be sufficient to prevent HIV,Although the results have been mixed.

In the case of unambiguous faultTruvada(Tenofovir + emtricitabine) has yet been reported, but a number of cases raise interesting questions: if tenofovir levels needed to prevent infection must be larger than those used for treatment; to co-infection with hepatitis B can be made more likely to HIV infection; if men have been infected if they had been taking tenofovir + emtricitabine Truvada (); and if not, which represent exactly the contributions to the prevention of two drugs. Editor's note (!!!) (...)

The men were not taking tenofovir specifically as pre-exposure prophylaxis (PrEP), but instead were using as a treatment for chronic hepatitis B. One had persistent infection with hepatitis B for six years and had been treated with tenofovir for four years; others had hepatitis B for seven years and had taken tenofovir for three years.

In the case of the first patient (a patient), the date of HIV infection can be identified almost exactly as he tested positive HIV antibody only twelve days after a confirmatory application for western blot HIV antibody testing found negative serology HIV. Although this is an unusually short time to develop anti-HIV antibodies, it is not unknown. It has been estimated that the most likely date for its actual exposure to HIV, based on their receptive intercourse report anal sex with a casual male partner without a condom, was the day after his negative HIV test. Six days later, he reported mild flu symptoms suggestive of HIV seroconversion illness and has been tested again.

The second patient patient (B) not had a recent negative HIV test but was hospitalized with a severe flu-like illness with fatigue and muscle pain, suggestive of HIV seroconversion. Based on their first positive HIV test, where he was HIV-antibody negative but positive p24, and also in their receptive anal sex account without a condom it was estimated that the probable time of infection was about two weeks prior to the test.

human checkBoth men seemed to have excellent adhesion to tenofovir based on pill counts. More to the point, tenofovir drug levels was taken on the day they tested HIV positive. One patient had taken tenofovir 24 hours before his drug level test and was therefore on preventive pattern of Truvada or the lowest level of blood would be expected. The level of tenofovir was about 75 nanograms per milliliter of blood (ng / ml), which means that it had a lower standard than levels of about 80% of patients, but still within the therapeutic range for treating both hepatitis B and HIV. (IC95 tenofovir, which is the amount of drug in the blood sufficiently to reduce HIV replication in 95%It is the 6,8 35 ng / ml.)

Patient B had taken tenofovir seven hours before the result of the HIV test and had a blood level of 230 ng / ml or more than 75% of the average patient, seven hours after a dose. Both results indicate that their absorption tenofovir was normal.

Both patients had CD4 cell counts 550-600 cells / mm3 - namely lower typical CD4 counts observed in HIV-negative patients - and while the patient had a relatively normal CD4: CD8 ratio of 1.16, the patient B had "reversed "the ratio typically observed in people with HIV - 0,49. [HIV-negative people generally have more cells than CD4 CD8 cells: in people with HIV this ratio is normally inverted immediately after acute infection and thus remains untreated. Anyway, these figures show that although there tenofovir, both patients had suffered significant damage to the immune acute phase of HIV infection - as usual.

The biggest difference between the two was that patients in a patient tenofovir, although not prevent HIV infection, do not seem suppressing viral load of HIV in blood. Although HIV positive test, and the integrated HIV in a cell at any point, it produced a viral load over 50 copies / ml. This "dullness" of HIV viral load has been seen before in cases of failure of PrEP, particularly in animal studies that established its effectiveness. This means that your HIV can not be tested to see if it had acquired, or already had resistance to tenofovir. This patient was changed to Eviplera(Rilpivirine / tenofovir / emtricitabine) as soon as he tested HIV positive.

Patient B had a viral load of just over 100.000 copies / ml - not particularly high for acute or recent infection. Despite HIV reproducing actively in the presence of high tenofovir levels, he had no drug resistance mutations, illustrating, as other studies have done, that the resistance to tenofovir rarely develops where people with HIV using Prep. However to prevent resistance, patient B was placed on the intensification of antiretroviral therapy three classTruvada(Tenofovir / emtricitabine), boosted darunavir and raltegravir, which resulted in the successful suppression of viral load.

Both patients had significant intracellular HIV infection and the integrated HIV genetic material of their immune cells - 587 CD4 million copies per cell at the age of the patient A and patient B. 1432 copies This indicates that the virus is very integrated into a continuous infection by HIV production in both patients and effectively transcribed RNA, the test cells were actively producing new virus particles of HIV, was found in both patients, though at one-tenth the level of patients a such as B. patient

These cases may be the first which can be demonstrated is no doubt that a daily dose of tenofovir failed to prevent HIV infection. In one of the largest studies randomgreed PrEP PrEP partners, there were six cases of HIV infection (Donnell) in people who, during the visit were diagnosed with HIV, tenofovir had levels consistent with the daily dosage (two of these were also detected with emtricitabine drug). However in all cases except one, the participants could have caught HIV at any time in the last three months since your last visit, so can not have been taken into PrEP real time that have been infected. In one case the participant had a coherent tenofovir level with the daily dosage for a month before being diagnosed with HIV and the visit was diagnosed: this is the only previous case where the failure of PrEP to protect against infection despite what I should have had the appearance of levels of protection; the more likely it is that you need to interpret the data.

The researchers comment that their cases show that "tenofovir monotherapy PrEP in men who have sex with men has limited effectiveness and data acquisition that HIV can occur in the presence of drug levels of tenofovir within the therapeutic range required to treat HIV." all you have to say it was never really established whether the level of tenofovir (or any other single drug) would be enough to treat HIV is sufficient to avoid. They also consider that the hepatitis B infection might increase susceptibility to HIV, even where it appears largely suppressed and virologically negative. Also cast doubt on the use of monotherapy with tenofovir as PrEP in any patient, and should stimulate further research in further protection schemes and PrEP can add nervousness to recommend some intermittent PrEP regimens.

However, as the researchers note, the overwhelming majority of cases of so-called "failure" PrEP is due to people not really taking PrEP: the fact that these two cases have been reported emphasizes that HIV infection in situations where it seems people on PrEP is consistently extremely rare.

Translated from the original written by Gus Cairns: 14 January 2016 by Claudio Souza in the original English Two cases of PrEP failure on solo tenofovir significant research questions pose in 13 / 03 / 2016

Editor's note: I noticed in this text a big trend, and I do not know if it's a result of my neurological condition known as "desconfiatus Cerebrus" or some pressure made on the author, but Gilead may have noticed that not yet reached the end of rainbow and therefore will not grab quintillion dollars with its produ ... sorry, medicine. What I know is that the natural order of living or semivivas things is the irrepressible desire to continue to exist and therefore it is natural that there is the formation of a completely resistant strain to Truvada and the use of monotherapy with Truvada, after these events, would be a gesture, when little, irresponsible, and its highest expression, would be genocide ... of course this is just a modest chance of a blogger who lives 22 years, which saw the laboratories and its scientists try to amend the Declaration of Helsinki, changing a paragraph that guy who used to be (...) tests receive the best available treatment forthe best treatment available. Put simply, if this change had been achieved, people, human beings used as test tubes in Africa, once infected receive the best available treatment and I have certe absolute that they Terim it stocks and more stocks and DDI and AZT stavudine.

This is the ethic that they themselves attribute, not flinching for a second to recreate the uncontrolled pandemic of AIDS by a handful to more than dollars (or euros would be?).


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