tag:blogger.com,1999:blog-2637461283328505191.post8286988440272211061..comments2024-03-28T05:11:22.047-04:00Comments on AIDS Treatment News: HIV PrEP Explained: Critical Prevention OpportunityJohn S. Jameshttp://www.blogger.com/profile/00687027750541840902noreply@blogger.comBlogger10125tag:blogger.com,1999:blog-2637461283328505191.post-76501843126251977662011-10-01T05:02:59.883-04:002011-10-01T05:02:59.883-04:00The drug study was done on a subgroup wich is not ...The drug study was done on a subgroup wich is not representative of the overall trial. It is a matched cohort of less than 200 ppts and it is not appropriate to draw to much form such a small substudy.Pearly Home Remedyhttp://www.pearlyhomeremedy.com/noreply@blogger.comtag:blogger.com,1999:blog-2637461283328505191.post-59367598825710797132011-06-27T21:20:31.050-04:002011-06-27T21:20:31.050-04:00Hi John, I have authored an article that will app...Hi John, I have authored an article that will appear in the next issue of Current HIV Research. You may be interested in reading this article. The abstract is e-published ahead of print. you can email me at the address in the article and I will forward the full text to you. Sincerely, Marc C. E. WagnerAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-2637461283328505191.post-78159799317251540202011-05-02T19:54:06.089-04:002011-05-02T19:54:06.089-04:00Dear John,
Thank you so much for this. I regret t...Dear John,<br /><br />Thank you so much for this. I regret that we did not do more as investigators to help the media and the public understand the results of iPrEx. It was quite apparent to us that the 44% figure far from revealed the high level of effectiveness that Truvada reached in MSM. I find no flaws in any of your reasoning or math here and appreciate your candor. The media, at least initially never really got the study results wrong, I am quite thankful for that, but they rarely got the interpretation quite right either. Many reported 51% and the 72% efficacy numbers too claiming that they represented efficacy when people took their pills as directed. I find these numbers the least informative because they are based on adherence self-reports that we knew were very poor indicators of actual adherence, they simply suggested more pills is more protection. And we simply do not know who, if anybody, actually took the pill daily as directed.<br /><br />We are still working to better understand what happened in iPrEx and doing what we can to help figure out why Truvada failed in FemPrEp, a crushing outcome. For me, in regards to MSM right now the most pressing question is how many men and transgendered women will take how many pills now that they know that Truvada works at least as much as reducing infections by over 90% in people who take it enough to keep drug levels high, and as you have reasonably pointed out quite possibly as much as 100%. Once again I am so pleased that our trial was so international (even though that can be a rough haul some days). We now know that the answer to that question may be profoundly different for individuals in different parts of the world despite being unified by the risk of HIV infection. Our sites are getting ready to start the open label extension (iPrExOLE) where we invite all the men and women of iPrEx back for 18 months and offer everybody the real pill and tell them what we learned with their help from the first trial. We assume that we will get more than 50% adherence under these conditions but we do not know, and if so we do not know how high it might go. <br /><br />John, I trust you will be around to explain our results. I look forward to it.<br /><br />Best regards,<br />Jeff<br />Investigator, Global iPRrExJ. Jeff McConnellhttp://www.globaliprex.com/web/index.donoreply@blogger.comtag:blogger.com,1999:blog-2637461283328505191.post-72820386927341065812011-05-02T13:48:31.710-04:002011-05-02T13:48:31.710-04:00Drug levels are a reflection of adherence. Adhere...Drug levels are a reflection of adherence. Adherence is one aspect of behavior. How do you know that those who adhered to the drug regimen did not also adhere to condom use? Very difficult to isolate a single behavior with any certainty. Intent to treat analysis avoids that trap. Be cautious about claims greater than 44% reduction in risk of infection.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-2637461283328505191.post-26613159884920795742011-04-29T10:30:36.753-04:002011-04-29T10:30:36.753-04:00Let's start with where we agree. To quote Dr. ...Let's start with where we agree. To quote Dr. Grant, the principle investigator of the entire iPrEx study, "No one in iPrEx acquired HIV infection with a drug level that would have been expected with daily dosing" (at the Retroviruses conference, in the video you linked to in a comment above). <br /><br />I believe you DISAGREE with the second sentence in the following, from my article: <br /><br />********** <br /><br />"Of those who actually took one Truvada pill per day throughout the study, not one became HIV-infected during this trial (vs. 64 of those who had been given the placebo). So for those who actually used the drug as directed, throughout the entire study, it was 100% effective in this trial, which had over 1,000 high-risk gay men assigned to take Truvada. <br /><br />"But the blood draws occurred in this study at weeks 4, 8, 12, 16, 24, and then every 12 weeks. So we cannot rule out the possibility that one or more people who had not taken Truvada for about two weeks or more before one of those visits, then got religion after the visit, and starting taking the pills daily -- yet got infected despite having adequate drug levels. This seems unlikely in view of the overall findings. But if it did happen, then it would mean that the protection was less than 100% in those who were using the drug. It was not possible to have everyone wear a device that that could record drug levels continuously -- and also tell exactly when they got HIV. So there is no way to be sure that nobody had enough drug in their body when they were infected. For this reason, 100% effectiveness is not claimed or reported.[5] <br /><br />"Still, the fact remains that Truvada for HIV prevention worked very well in this trial. Truvada when used properly (once a day, throughout the trial) completely prevented HIV infection, in a study of over 1,000 people -- when a comparable, randomly chosen group of 1,000 other people given a placebo had 64 HIV infections during the same time. Almost no drug for anything works this well." <br /><br />********** <br /><br />I think this puts the "100% effective" in an accurate, limited context -- though reasonable people can differ. It's the observed on-treatment result from this trial -- not from the next trial, not from using Truvada PrEP out in the world. Of course the drug will not work perfectly, so the real protection will be somewhat less than 100%. But in this trial, NO ONE who used Truvada at all properly got HIV -- compared to 64 who did not use Truvada at all, in the randomized placebo control group that was designed to be similar to the Truvada group. This looks like 100% to me, as the readout from this particular trial. <br /><br />Notice that the arithmetic steps to get the 100% are exactly the same steps that the iPrEx team used to get the 44%. The difference is that the iPrEx team used intent-to-treat, meaning that it counted 36 people who were assigned to take Truvada as doing so, even though WE KNOW that they used Truvada grossly improperly, if they used it at all, at least part of the time during the study. NONE of them had drug levels expected to be protective (90% of them had no detectable drug at all) -- while 97% of the U.S. participants did have adherence as seen by drug levels, showing that it is possible for a great majority of patients to protect themselves. <br /><br />Here's the math: <br />(64-36)/64 = 43.75%, approximately 44% <br />(64-0)/64 = 100% <br /><br />The reason for the 44% intent-to-treat result is that something went wrong at some of the trial sites. No one yet knows what went wrong. Our guess is that many participants gave or sold their pills to people who had no other HIV treatment access and needed them to stay alive -- and of course concealed this from the researchers, so that their supply would not be cut off. The two U.S. sites were in Boston and San Francisco -- probably the best cities in the U.S. for access to HIV care. Probably none of the U.S. participants knew anybody who wanted their pills.John S. Jameshttps://www.blogger.com/profile/00687027750541840902noreply@blogger.comtag:blogger.com,1999:blog-2637461283328505191.post-51722802495181304342011-04-28T17:04:02.223-04:002011-04-28T17:04:02.223-04:00This comment has been removed by the author.John S. Jameshttps://www.blogger.com/profile/00687027750541840902noreply@blogger.comtag:blogger.com,1999:blog-2637461283328505191.post-70647573898950807002011-04-26T04:47:38.118-04:002011-04-26T04:47:38.118-04:00PS:
Grant's presentation at CROI:
http://bit...PS:<br /><br />Grant's presentation at CROI:<br /><br />http://bit.ly/grjVUg<br /><br />Also whatch Rivet Amico about adherence and what it is possible to say and not to say.<br /><br />In short you can only say that those who became infected did not take their pills regularly.incidence0http://www.incidence0.orgnoreply@blogger.comtag:blogger.com,1999:blog-2637461283328505191.post-12441627937397490632011-04-26T04:34:14.640-04:002011-04-26T04:34:14.640-04:00I agree with the firt part or your comment which d...I agree with the firt part or your comment which does not say the same thing as your main article. <br /><br />However when you say that "But we do know that NOBODY who did use the drugs once a day throughout the whole study, as directed, got HIV." this does not mean that,s because they were protected, as you note yourself, they may have been lucky, or simply they may have not been in contact with the virus. And again we don't know who used the drug everyday in the whole study. You are making an inference here:<br /><br />Your main post suggest that Truvada work 100% when taken as prescribed (daily) but this is an inference as the trial was not comparing daily dosage versus non-daily dosage. This misundertsanding has been repeated many times in the news with the 73% protection figure when the drug was taken 90% of the case, because it is not what the trial was investigating. The subtudy used matched controle whose drug level was detected in 51% of the case (you can check this by watching Bob Grant slides on the CROI website). This clearly suggest that despite drug nit being detected they remained HIV-Neg.<br /><br />Robert Grant never claimed, and would never claimed that it work 100% of the time in this study or in the real world.<br /><br />Please note that it does not mean that it does not work. I am just trying to introduce some cautionary note in your otherwise good article!incidence0http://www.incidence0.orgnoreply@blogger.comtag:blogger.com,1999:blog-2637461283328505191.post-20452120089350679712011-04-25T19:52:19.280-04:002011-04-25T19:52:19.280-04:00We DO know that everyone in the entire study (more...We DO know that everyone in the entire study (more than 1,000 participants in the Truvada arm) who were infected DID NOT take their pills as directed, at least part of the time.<br /><br />Of these 36 people, 33 had no detectable level of either drug in their bodies, when the drugs should have been there. And the other three had very poor levels, just above the limit of detection, consistent with very poor adherence. <br /><br />Everything we know suggests that these 36 could not have been taking one pill a day consistently in the weeks before their blood was tested for the drugs. Whether they took the pills at other times in the trial we don't know.<br /><br />Everyone else in the Truvada arm was not infected during this trial. This compares with 64 who were infected in the placebo arm.<br /><br />True, we don't know how many in the Truvada arm were protected by the drugs, and how many were just lucky.<br /><br />But we do know that NOBODY who did use the drugs once a day throughout the whole study, as directed, got HIV. Unless the researchers could not find the drugs when they looked -- and they were very careful in validating these drug-level tests.<br /><br />While the total number in the drug-level study was under 200, that represents ALL of the Truvada "failures" (36 persons), with two matched controls selected for each. There was no real need to test for drug levels in the people who did not get HIV. So this "small" drug-level study actually represents the whole study, with over 1,000 people in each of the two arms (Truvada and placebo arms).John S. Jameshttps://www.blogger.com/profile/00687027750541840902noreply@blogger.comtag:blogger.com,1999:blog-2637461283328505191.post-45427761899138724002011-04-25T18:40:39.828-04:002011-04-25T18:40:39.828-04:00It is innacurate to say that "Of those who ac...It is innacurate to say that "Of those who actually took one Truvada pill per day throughout the study, not one became HIV-infected during this trial", because the researcher do not know who took their pills everyday and have no means to know that informantion (they were not there to check what each and every participants were doing). This is why the figure of 44% is used and not that of 100% because in the real world that's what the efficacy is.<br />The drug study was done on a subgroup wich is not representative of the overall trial. It is a matched cohort of less than 200 ppts and it is not appropriate to draw to much form such a small substudy.incidence0http://www.incidence0.orgnoreply@blogger.com