Transcript: Twitter Journal Club Ninth Meeting 8pm, Sunday 21st August 2011

Cohen et al. (2011) Prevention of HIV-1 Infection with Early Antiretroviral Therapy, NEJM Available at http://bit.ly/o4oDas Hosted by Natalie Silvey

twitjournalclub Good evening, welcome to week 9 and discussion of Prevention of HIV-1 Infection with Early Antiretroviral Therapy by Cohen et al #twitjc -8:00 PM twitjournalclub Introduction to the paper can be found at http://t.co/gRjJTLF and the discussion points can be found at http://t.co/vNQBoUM #twitjc -8:00 PM twitjournalclub First of all introductions - tonight I will be tweeting from the journal club account and my own as @silv24 #twitjc -8:02 PM PaedsSHO David, (unsurprisingly) a paeds SHO. #twitjc -8:04 PM silv24 Natalie, F2 in acute medicine and trying not to get my tweets messed up tonight #twitJC -8:05 PM mcumcu Michael, med biochem student #twitjc -8:06 PM haomaxie Hao, 3rd year medical student from Cleveland, Ohio #TwitJC -8:07 PM crashmatt Matt, scientist specialising in cancer, p.hd. student. Multitasking, so mostly observing. #twitjc -8:09 PM twitjournalclub 1st point: was the study design robust enough for early treatment of HIV-1 infections as a preventation to be widely adopted? #twitjc -8:12 PM twitjournalclub Of particular note this is the first randomised trial looking at this strategy #twitjc 8:13 PM silv24 @Manjit49 tweet adding the hashtag #twitjc to the end, the discussion points are all avaliable on our website -8:14 PM silv24 First randomised control trial, multicontentb and a good sample size -I think this is an impressive study #twitjc -8:16 PM silv24 Very clear protocol outlined in the paper and a really well thought out study, I was really impressed reading it #twitjc -8:17 PM PaedsSHO The design does look fairly robust. Impressed by the multicentre-ness of it. #twitjc -8:18 PM crashmatt It's very good, early treatment is certainly indicated. Would want to see localised trials as well. #twitjc -8:19 PM haomaxie although it is a multicontinent trial, yet would the behavioral differences dilute or affect the conclusions? #TwitJC -8:19 PM haomaxie @crashmatt subpopulation analysis would be nice to show the difference between Asian and African for example #TwitJC -8:20 PM silv24 A good range of study sites, this makes the results very interesting. Great to see a trial of this sort going ahead #TwitJC -8:20 PM

PaedsSHO @haomaxie May indeed make the conclusions more generalisable. #twitjc -8:20 PM crashmatt @haomaxie Good point, local variations may be lost in large data pool. #TwitJC -8:20 PM haomaxie overall, a great study as the first randomized trial #TwitJC -8:21 PM twitjournalclub Leads nicely to point 2 : How generalisable are these results? Should this strategy be used with all patients with HIV-1 infection? #twitjc -8:23 PM mcumcu It is tempting but perhaps it would be worth looking at individual regions more closely #twitjc -8:24 PM PaedsSHO Subpopulation analysis would be lovely. #twitjc -8:25 PM silv24 The need for research doesn't end here but early treatment does seem to be an effective preventative strategy and can't ignore that #twitjc -8:25 PM silv24 Better testing and treatment programmes are being set up - this paper supports an early intervention that is very effective #twitjc -8:26 PM silv24 However, as amazing as antiretroviral are they do have side effects and cause adverse events, it is a balancing act #twitjc -8:27 PM haomaxie study is usu. controlled, which means good patient compliance, I assume #TwitJC -8:27 PM twitjournalclub @PaedsSHO the supplementary appendix has a huge amount of very interesting information, well worth a look #twitjc -8:27 PM haomaxie for pts without poor compliance, early treatment means early resistance #TwitJC -8:28 PM twitjournalclub @haomaxie they did counsel on compliance at each visit, this highlights the importance of good support as well as ARVs #twitjc -8:28 PM mcumcu Was impressed with the mention of counseling, encouragement to use condoms etc, which may have also helped #twitJC -8:28 PM haomaxie can anyone shine some light on this? #TwitJC -8:28 PM PaedsSHO @twitjournalclub Thanks NS! #twitjc -8:29 PM crashmatt The paper strongly supports the idea of early intervention, but I can foresee objections from some more right wing elements #twitjc -8:29 PM haomaxie @mcumcu exactly!! #TwitJC -8:29 PM twitjournalclub @haomaxie the programme of test and treat I saw in Tanzania included peer support which seemed to really help with compliance #twitjc -8:30 PM twitjournalclub @crashmatt why do you say that? #twitjc -8:30 PM haomaxie @twitjournalclub thanks! this guarantees a high quality study #TwitJC -8:31 PM yazman89 Oo just saw #twitJC's topic for this week. How about the use of CCR5 blockers to prevent HIV infection. #DissertationTitle -8:31 PM silv24 As good as drug therapies are the importance of good support can be underestimated and this paper also supports that #TwitJC -8:32 PM haomaxie @yazman89 not sure about treatment, just a med student here. But is CCR5 a 2nd line therapy? #TwitJC -8:33 PM

silv24 The results of this paper can't be ignored, a 96% reduction in the rate of transmission is just staggering #twitjc -8:33 PM crashmatt @twitjournalclub I think that some sectors may oppose funding the prevention of spread of an HIV-1 as abstinence would also work #twitjc -8:33 PM mcumcu @yazman89 Plug was pulled on Aplaviroc (CCR5) development (liver toxicity) #twitjc 8:34 PM crashmatt @twitjournalclub That's not my view, but it's a possible view from some of the more belligerent sectors #twitjc -8:34 PM twitjournalclub @crashmatt interesting points, I wonder if they would see drug treatment with safe sex advice as better than safe sex advice alone? #twitjc -8:35 PM debmir RT @twitjournalclub: Good evening, welcome to week 9 and discussion of Prevention of HIV-1 Infection with Early Antiretroviral Therapy by Cohen et al #twitjc -8:36 PM twitjournalclub Point 3: immediate treatment lead to a relative reduction of 41% in the number of HIV-1related clinical events #twitjc -8:37 PM twitjournalclub Should the focus be on earlier treatment of HIV-1? #twitjc -8:37 PM silv24 Some very interesting debates around when treated with ARVs should begin - they aren't the nicest of drugs but they are effective #twitjc -8:38 PM mcumcu Transmission reduction is great but I couldn't help but think about an antibody-led vaccine (the hunt for which IAVI have sponsored) #twitJC -8:39 PM silv24 Have been points made that results from this paper are only applicable in areas where TB is common as majority of clinical events #TwitJC -8:40 PM fidouglas @twitjournalclub I guess we have to ask why we wouldn't give treatment sooner. Side effects? Issues with compliance (& resistance)? #twitjc -8:40 PM silv24 @mcumcu still in research but if this strategy could prevent in the meantime I think it must be adopted widely #twitjc -8:41 PM crashmatt @silv24 Well, TB is becoming more common in most places. #TwitJC -8:41 PM haomaxie @silv24 for pts with CD4 between 350 and 550, TB shouldn't be a concern, right? #TwitJC -8:42 PM mcumcu @silv24 absolutely and this paper suggests sooner rather than later #twitjc -8:42 PM debmir Reminder for medical twitters,esp those attending who talk: twitter journal club has just started.See my previous tweet for details. #twitjc -8:44 PM silv24 @haomaxie massive rise in cases even amongst those without HIV, immunosuppression of any cause leads to increased risk #twitjc -8:44 PM silv24 @crashmatt saw three new cases of it last week alone, it is indeed increasingly common #twitjc -8:45 PM fidouglas Another reason to postpone treatment would be cost. How would this be different in e.g. UK (NHS) vs. US vs. developing nations? #TwitJC -8:45 PM silv24 When to start treatment is always going to be a balancing act but increasing evidence about benefits of starting it early #twitjc -8:45 PM fidouglas @silv24 @crashmatt What was the rationale behind stopping BCG vaccinations? Did it lack efficacy or something? #TwitJC -8:45 PM

mcumcu @fidouglas I believe the drug companies made donations in this study- would be willing to do so on a more permnt basis? Wishful? #twitjc -8:47 PM crashmatt @fidouglas I don't know, it didn't make any sense to me, and it doesn't seem to have been a good idea! #TwitJC -8:47 PM silv24 @fidouglas alot of the HIV treatment programmes worldwide are well supported, saw how well it worked in Tanzania #twitjc -8:47 PM Albajuly Physician NOS #twitjc -8:48 PM silv24 @fidouglas @crashmatt now just focuses on high risk groups, wonder if it will change back in future #twitjc -8:49 PM Dr_Stuart @fidouglas @twitjournalclub Yes to those & also the START study recommends that if ARVs are started they shouldn't be stopped #twitJC -8:50 PM twitjournalclub Final discussion point - and I have to admit this is one I have strong feelings about #twitjc -8:51 PM twitjournalclub With the results of this paper should more resources be put into test and treat programmes? Should we be testing everyone for HIV? #twitjc -8:51 PM TWSY Has anyone done the NNT calculation? Or the NNH? #twitjc -8:52 PM crashmatt @silv24 @fidouglas I certainly hope so. We need a committed long term plan to deal with TB. #twitjc -8:52 PM twitjournalclub Have been calls for far more widespread testing programmes than exist at present in most areas, making it a more routine thing #twitjc -8:52 PM haomaxie @fidouglas @silv24 @crashmatt efficacy of BCG varies a lot #TwitJC -8:52 PM fidouglas @haomaxie @silv24 @crashmatt Still required by medical schools in the UK in the form of a positive Mantoux test. #TwitJC -8:53 PM TWSY I make it about 30 needed to treat to stop one linked transmission. #twitjc -8:53 PM haomaxie testing for everyone sounds not practical to me #TwitJC -8:54 PM twitjournalclub That is impressive really...RT @TWSY: I make it about 30 needed to treat to stop one linked transmission. #twitjc -8:54 PM TWSY I'd like to know the the negative outcomes to compare NNT with number needed to harm, and then look at costs #twitjc -8:54 PM crashmatt @fidouglas Yes, for most NHS hospital jobs., variable requirement in private hospitals #TwitJC -8:55 PM fidouglas Rapid HIV testing is remarkably quick and easy. Prick finger to get a drop of blood, then takes about 2 minutes for result. #TwitJC -8:55 PM kevfrost @twitjournalclub currently getting tested for hiv (for any reason) -> higher health insurance premiums #twitjc -8:55 PM silv24 With effective drug treatments and prevention strategies I think testing should be more widespread, need to break down taboos #twitjc -8:55 PM haomaxie @fidouglas @haomaxie @silv24 @crashmatt really? I have to have annual quantiferon test since I had BCG #TwitJC -8:55 PM Dr_Stuart @twitjournalclub Absolutely - HIV testing should be routine, esp in Acute Medical settings & with GP in higher prevalence areas #twitJC -8:56 PM

crashmatt @twitjournalclub In theory I think routine testing for HIV would be a good idea. I do have slight reservations though #twitjc -8:56 PM chocochic +1 RT @Dr_Stuart: HIV testing should be routine, esp in Acute Medical settings & with GP in higher prevalence areas #twitJC -8:56 PM silv24 @kevfrost I have been told that isn't true by a GUM consultant, I have been tested as part of health checks as a doctor #twitjc -8:56 PM fidouglas @haomaxie @silv24 @crashmatt I haven't heard of a quantiferon test before. What is it? #TwitJC -8:57 PM crashmatt @haomaxie I had to demonstrate positive Mantoux or serology when starting in NHS (several years ago), never needed to do it again #TwitJC -8:57 PM silv24 @Dr_Stuart we really need to reduce the stigma around being tested, something that we aren't doing well #TwitJC -8:57 PM Albajuly @twitjournalclub Hi, reading your paper and comments with interest. I'm a physician #twitjc -8:57 PM haomaxie @Dr_Stuart @twitjournalclub agree! higher prevalence means less false postive and less cost on westernblot #TwitJC -8:58 PM crashmatt @silv24 That I wholeheartedly agree with! #TwitJC -8:58 PM silv24 @Dr_Stuart a major issue is the "don't die of ignorance" campaign, the tombstone really still frightens people into not being tested #twitJC -8:58 PM drgandalf52 Sorry in missing #twitjc will try n be there for next time, shame really enjoyed the paper n topic -8:59 PM Albajuly @twitjournalclub Personally, I think the problem is that this is a motivated treatment group. They know their status, #twitjc -8:59 PM mcumcu Agree about removing stigma. Education is key. UNAIDs goal of 'Zero discrimination' very important. #twitjc -8:59 PM silv24 @Albajuly any comments to add? Would love to hear your thoughts #TwitJC -8:59 PM haomaxie @fidouglas @haomaxie @silv24 @crashmatt it is a blood test to confirm TB infection once someone got a postive PPD due to prior BCG #TwitJC -8:59 PM silv24 RT @mcumcu: Agree about removing stigma. Education is key. UNAIDs goal of 'Zero discrimination' very important. #twitjc -9:00 PM Albajuly @twitjournalclub have shared this and are in monogamous relationships and are willing to accept adverse events to reduce the risk #twitjc -9:00 PM crashmatt Very interesting generational attitudes to HIV. I'm mid 30's and grew up with the tombstone adverts, HIV looms as "death sentence" #twitjc -9:01 PM kevfrost @silv24 that was told to my wife by 2 diff midwifes -hiv was part of her ante natal screenings. If out of date/myth thats good news #twitjc -9:01 PM silv24 Saw an amazing test and treat programme in Tanzania at the hospital I worked at - saw first hand how it has transformed lives #twitJC -9:01 PM Albajuly @twitjournalclub their partner. I think others, not willing to engage are more of a risk to their partners? #twitjc -9:02 PM silv24 @kevfrost as far as I know, I have been tested as have all of my year as routine screening, also had hepatitis screening as well #twitjc -9:02 PM

silv24 @crashmatt can't tell you how much I hate those adverts. Worked for a HIV charity and we still haven't got passed that #twitjc -9:04 PM crashmatt @silv24 They were very effective at one of their goals, IME my cohort seems to have a higher rate of condom use than older / younger #twitjc -9:05 PM PenguinGalaxy RT @silv24: Saw an amazing test and treat programme in Tanzania at the hospital I worked at - saw first hand how it has transformed lives #twitJC -9:06 PM TWSY Interesting that my decision whether to take it would be based on benefit to my partner and harm to me. #twitjc -9:06 PM twitjournalclub Thank you all for contributing, I think this paper is fascinating and has the potential to have a real impact - I hope it does #twitjc -9:07 PM twitjournalclub A transcript and summary will be avaliable on our new lovely shiny website at www.twitjc.com #twitjc -9:07 PM haomaxie @twitjournalclub a great discussion! thanks for the efforts! #TwitJC -9:08 PM mcumcu Interesting and informative as usual #twitjc -9:08 PM Albajuly @silv24 @kevfrost As a student in the 90's I had HBV vaccine. As an SHO, I was tested for HCV. HIV test last year before cons post #twitjc -9:09 PM TWSY Though I guess it would also benefit me. Like giving away a kidney #twitjc -9:09 PM BenCosway Disappointed for missing #twitjc today. Had lots to say but circumstances meant I could contribute. Looking forward to next time! -9:09 PM fidouglas Worth watching: A video explaining how patent pools could improve access to HIV drugs in developing countries. http://t.co/AhUF3yc #TwitJC -9:09 PM crashmatt @twitjournalclub Thank you for leading discussion and to both of you for setting this up. #twitjc remains fabulous. -9:09 PM BenCosway Should these big trials be done without a systematic review? Perhaps they should have waited for this http://t.co/u4uEjov #twitjc -9:12 PM Dr_Stuart @silv24 Point of Care testing is helping normalise HIV tests - results in 60 seconds! #twitJC -9:15 PM crashmatt @Dr_Stuart Crikey, that's impressive. How does the false pos / neg rate compare? #twitJC -9:17 PM liquidkermit +1 RT @chocochic: +1 RT @Dr_Stuart: HIV testing should be routine,esp in Acute Medical settings & with GP in higher prevalence areas #twitJC -9:25 PM Dr_Stuart @mgtmccartney @twitjournalclub Indeed. It's an HPA recommendation, but are the frameworks in place? Pre-test counselling etc? #twitJC -9:26 PM docshannon RT @Dr_Stuart: @twitjournalclub Absolutely - HIV testing should be routine, esp in Acute Medical settings & with GP in higher prevalence areas #twitJC -9:30 PM Dr_Stuart @mgtmccartney We're using INSTI which has lower rates now. The real challenge is discussing HIV I think, screening by questions #TwitJC -10:15 PM