{"id":7556,"date":"2015-07-26T08:52:46","date_gmt":"2015-07-26T12:52:46","guid":{"rendered":"http:\/\/blogs.nejm.org\/hiv-id-observations\/?p=7556"},"modified":"2015-07-27T16:04:24","modified_gmt":"2015-07-27T20:04:24","slug":"really-rapid-review-ias-2015-vancouver","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/really-rapid-review-ias-2015-vancouver\/2015\/07\/26\/","title":{"rendered":"Really Rapid Review &#8212; IAS 2015, Vancouver"},"content":{"rendered":"<div>\n<p><a href=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/07\/IAS-2015.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignright size-full wp-image-7565\" src=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/07\/IAS-2015.jpg\" alt=\"IAS 2015\" width=\"306\" height=\"95\" srcset=\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/07\/IAS-2015.jpg 306w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/07\/IAS-2015-300x93.jpg 300w\" sizes=\"auto, (max-width: 306px) 100vw, 306px\" \/><\/a>Vancouver will always have a special place in HIV treatment history. It\u00a0was here, in 1996, that many of us\u00a0first\u00a0saw the potential of combination antiretroviral therapy to control this disease.<\/p>\n<p>Specifically,\u00a0<a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJM199709113371102#t=articleTop\" target=\"_blank\">Study 035 of AZT, 3TC, and indinavir<\/a>\u00a0(presented by Trip Gulick) demonstrated the\u00a0astounding finding that triple therapy induced\u00a0sustained virologic\u00a0suppression and dramatic immunologic improvement.<\/p>\n<p>Could it be that not everyone would eventually die of AIDS?\u00a0<a href=\"http:\/\/www.nytimes.com\/1996\/11\/10\/magazine\/when-plagues-end.html\" target=\"_blank\">Optimists certainly felt so<\/a>\u00a0&#8212;\u00a0and indeed they turned out to be right.<\/p>\n<p>It was only natural, then, that Trip would be given the chance to give\u00a0<a href=\"https:\/\/youtu.be\/1Rx3BODt0o0\" target=\"_blank\">an overview of\u00a0HIV therapy<\/a>\u00a0at the conference\u00a0&#8212; he did a terrific job of reviewing &#8220;What to Start,&#8221; with a summary\u00a0of where we&#8217;ve been, where we are today, and where we might be going.<\/p>\n<p>(And no,\u00a0<a href=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/a-slightly-less-painful-way-to-learn-the-3-letter-abbreviations-for-hiv-meds\/2015\/06\/04\/\" target=\"_blank\">he didn&#8217;t sing.<\/a>)<\/p>\n<p>But what about new research? Without having the density of new material presented at CROI &#8212; something of a relief, really, during these summer months &#8212;\u00a0the IAS 2015 conference still featured many interesting papers, some of which I&#8217;ve summarized in this Really Rapid Review\u2122. I refer you to the (kind of clunky)\u00a0<a href=\"http:\/\/www.ias2015.org\/\" target=\"_blank\">conference website<\/a>\u00a0for the full abstracts and slide sessions; below I&#8217;ve listed the abstract numbers, because I can&#8217;t figure out how to link the abstracts.<\/p>\n<ul>\n<li><strong>Long-term &#8220;remission&#8221; in an infected adolescent without ART.<\/strong>\u00a0Got to start\u00a0with the story that (inexplicably) <a href=\"https:\/\/news.google.com\/news\/story?ncl=dU6j1YpKFl_mjNMiWpM1OhTk4q-5M&amp;q=hiv+remission+vancouver&amp;lr=English&amp;hl=en&amp;sa=X&amp;ved=0CCoQqgIwAGoVChMImIXXkuj4xgIVSHI-Ch3X0war\" target=\"_blank\">got the most press<\/a>: A perinatally infected child stopped HIV therapy (or more accurately,\u00a0<em>family<\/em>\u00a0stopped therapy) at\u00a0age 6. Patient\u00a0is now 18 years old and has had a detectable HIV\u00a0viral load\u00a0only once since stopping treatment. Remission? Or just an HIV controller? You decide, but I&#8217;m going with the latter, and no, the investigators did not use the word &#8220;cure&#8221; &#8212; which hasn&#8217;t <a href=\"http:\/\/www.bloomberg.com\/news\/articles\/2015-07-20\/trial-for-aids-treatment-planned-after-french-teen-s-cure\" target=\"_blank\">stopped the media from tossing it around freely<\/a>. [MOAA0105LB]<\/li>\n<li><strong>HPTN 052 final results.<\/strong>\u00a0In the landmark study that proved HIV treatment prevented transmission, we now have evidence of eight linked transmissions from people on HIV therapy to their partners &#8212; and\u00a0all occurred either early in HIV therapy (before suppression) or during treatment failure. In other words,\u00a0<em>zero<\/em>\u00a0transmissions from participants with stable virologic suppression. Excellent news! [MOAC0101LB]<\/li>\n<li>And while we&#8217;re on the topic of landmark trials, Jens Lundgren presented<strong>\u00a0the results of the START study<\/strong>\u00a0on the very same day it was published in a\u00a0<strong><a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa1506816\" target=\"_blank\">highly\u00a0prestigious medical journal<\/a>.\u00a0<\/strong>Key takeaways: HIV therapy is beneficial for patients with CD4 &gt; 500 in preventing\u00a0<em>both<\/em>\u00a0AIDS complications and, in developed countries in particular, non-AIDS complications (mostly cancers). And note that most of the clinical events happened when the CD4 was &gt; 500. [MOSY0302 &#8212; but read the paper!]<\/li>\n<li>In a large, randomized, double-blind trial done exclusively in women,\u00a0<strong>elvitegravir\/cobicistat\/FTC\/TDF is superior to TDF\/FTC, ATV\/r<\/strong>. Amazingly, the study (called WAVES) was given\u00a0a poster and not an oral presentation &#8212; a completely\u00a0inexplicable oversight given 1) it was a well-done study with an important result, 2) there were no other large randomized treatment trials at the conference, and 3) women have been terribly underrepresented in many recent clinical trials. Plus, the late-breaker posters were placed in the poster hall equivalent of Siberia, way over at the far edge of the room. Bizarre. [MOLBPE08]<\/li>\n<li>This presentation included a series of remarkable figures on\u00a0<strong>proportion of people with HIV who are diagnosed, on treatment, and virologically suppressed<\/strong>. For the record, the USA is third in percentage diagnosed (86%), ninth in successfully treated (30%) &#8212; one whole percentage point above Sub-Saharan Africa. [MOAD0102]<\/li>\n<li><strong>Three switch studies demonstrate the potential benefits of switching to\u00a0elvitegravir\/cobicistat\/FTC\/TAF (tenofovir alafenamide).<\/strong>\u00a01) A large randomized trial compared staying on current regimen (TDF\/FTC plus EFV or ATV\/r or EVG\/COBI) to switching, and the switch was overall superior [TUAB0102]; 2) Patients with chronic hepatitis B coinfection maintained or improved hepatitis B control [WELBPE13]; 3) Patients with stable chronic renal insufficiency\u00a0(eGFR as low as\u00a030) had stable renal function after the switch [TUAB0103]. In all three studies, switching from TDF-based treatment led to\u00a0improvements in renal and bone parameters, with\u00a0small increases in lipids. This &#8220;ECF-TAF&#8221; regimen is currently in the late stages of FDA review.<\/li>\n<li>In this large Spanish cohort study,\u00a0<strong>TDF\/FTC\/EFV given as a single tablet was better virologically\u00a0<em>and<\/em>\u00a0economically than 1) other multi-pill regimens, 2) the same regimen given as multiple pills<\/strong>. Not a controlled study, but strongly suggestive of the benefits of coformulation nonetheless. [TUPEB264]<\/li>\n<li>In the aggregate ACTG clinical trials data that demonstrated\u00a0<a href=\"http:\/\/annals.org\/article.aspx?articleid=1884528\" target=\"_blank\">an excess of suicidality for those randomized to EFV-containing regimens<\/a>, 75% of participants participated in a genetic substudy. When these subjects were analyzed based on genetic predictors of of\u00a0EFV metabolism, those with the\u00a0<strong>slowest clearance of the drug had the highest relative risk of suicidality<\/strong>. These data do strengthen the findings from the original paper.\u00a0(Disclosure: I&#8217;m a co-investigator.) [TUPEB273]<\/li>\n<li>In virologically suppressed patients receiving a boosted PI plus 2 NRTIs, switching to\u00a0<strong>the two-drug regimen of DRV\/r + RPV maintained virologic suppression<\/strong>\u00a0as well as staying on the baseline regimen. Small sample size alert (n=60), so consider this a pilot study only. [TUPEB270]<\/li>\n<li>Another\u00a0<strong>case report of resistance to dolutegravir in a treatment-experienced patient, with emergence of the R263K mutation.<\/strong> Additional integrase mutations emerged with ongoing failure, leading to a 5-fold loss of DTG susceptibility. Note that at baseline, the patient (a 12-year-old perinatally infected child) had no detected NRTI mutations (though extensive prior ART), and though treated with TDF\/FTC + DTG, oddly did not select for RT mutations. This case (and those from the SAILING study) notwithstanding, resistance to DTG remains rare event &#8212; though it does happen. [TUPEA068]<\/li>\n<li>At\u00a024 weeks in a phase II randomized double-blind study,\u00a0<strong>the investigational NNRTI doravirine is comparable to EFV with a lower incidence of CNS side effects.\u00a0\u00a0<\/strong>Though the 24 week results for the &lt; 40 cop\/mL result seem unimpressive for both arms (around 70%), this is due to the patients with high baseline viral loads still having low-level viremia &#8212; no resistance detected in either arm, HIV RNA still declining. Two phase III studies of doravirine are underway.\u00a0[TUAB0104]<\/li>\n<li>BMS-955176 is a<b>\u00a0<\/b>second-generation maturation inhibitor that has activity even against viruses &#8220;resistant&#8221; to the first-generation drug in this class,\u00a0<a href=\"http:\/\/www.aidsmap.com\/Bevirimat-PA-457-or-MPC-4326\/page\/1731273\/\" target=\"_blank\">bevirimat<\/a>. In a small randomized trial,\u00a0<strong>reductions in HIV RNA were comparable with BMS-955176 plus atazanavir to a standard-of-care regimen of TDF\/FTC, ATV\/r.<\/strong>\u00a0 A larger study of this two-drug combination is planned. [TUAB0106LB]<\/li>\n<li>In a large claims\u00a0analysis of newly-diagnosed patients\u00a0in the USA,\u00a0<strong>the rate of comorbid conditions (hypertension, diabetes, CV, renal disease) was higher in 2013 than 2003.\u00a0<\/strong>Not surprisingly, rates of these conditions were particularly high in the Medicare group. We HIV specialists really need to buff up our\u00a0management skills as our population of patients ages! Maybe get to use the <a href=\"http:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm455883.htm\">shiny new lipid lowering tool!<\/a>\u00a0Can you say &#8220;proprotein convertase subtilisin kexin type 9&#8221;? [MOPEB157]<\/li>\n<li><strong>Neither DRV\/r or EVG\/COBI\/FTC\/TDF induced insulin resistance<\/strong>\u00a0over 14 days in this normal volunteer study. LPV\/r did. [TUPEB105]<\/li>\n<li>Remember the regimen of simeprevir and sofosbuvir for HCV? That was briefly the preferred interferon-free regimen for HCV genotype 1 &#8212;\u00a0<em>way<\/em>\u00a0back when in early 2014, ancient history &#8212; based largely on results of the small COSMOS trial. Here the<strong>\u00a0OPTIMIST-1 and 2 studies give a more precise estimate of efficacy of &#8220;SIM-SOF&#8221; in HCV monoinfected patients<\/strong>, with 12 weeks of treatment looking better than 8, and a higher rates of response in non-cirrhotic, treatment naive patients. Regardless, the regimen is probably not going to be used much in the post SOF\/LDV era, or the one\u00a0<em>about<\/em>\u00a0to start (see next study), unless there is a big reduction in cost. [TULBPE10 and\u00a0TULBPE11]<\/li>\n<li>In the C-EDGE study,<strong>\u00a0HIV\/HCV (genotypes 1, 4, and 6) co-infected patients were treated with the one-tablet regimen of grazoprevir (protease inhibitor)\/elbasvir (NS5A inhibitor), with 96% cured.\u00a0<\/strong>Five virologic\u00a0failures (all relapses) out of 218 enrolled. Based on drug-drug interactions, HIV regimens were limited to TDF\/FTC or ABC\/3TC plus raltegravir, dolutegravir, or rilpivirine. FDA approval likely this year. [TUAB0206LB]<\/li>\n<li>In a compassionate use program in France, <strong>daclatasvir and sofosbuvir was highly effective in HIV\/HCV coinfected patients with no other HCV treatment options and advanced liver disease.<\/strong> Treatment was 12 or 24 weeks, and RBV could be added at the discretion of the clinician. Overall cure rate 90-96% (tricky to get exact numbers given heterogeneity of treatments), with\u00a0no apparent benefit of extending to 24 weeks or using ribavirin. Note that over 70% had cirrhosis. Note also that daclatasvir was\u00a0<a href=\"http:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm455888.htm\" target=\"_blank\">just approved by the FDA<\/a> for treatment of genotype 3 (along with sofosbuvir). [TUAB0207LB]<\/li>\n<li><strong>Two studies about optimizing HIV therapy\u00a0during stem cell transplants cite strategies to maintain virologic suppression.\u00a0<\/strong>This is particularly important given the\u00a0<a href=\"http:\/\/annals.org\/article.aspx?articleid=1889547\" target=\"_blank\">risk of severe viral\u00a0rebound<\/a>\u00a0in these patients who have both\u00a0uninfected target cells and no HIV-related immune response. Both papers cite the occasional need to use enfuvirtide &#8212; talk about a niche indication! [WEPEB337 and\u00a0TUPEB298]<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright size-medium wp-image-7568\" src=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/07\/Stanley_Park_Vancouver_7889964786-300x170.jpg\" alt=\"Stanley_Park,_Vancouver_(7889964786)\" width=\"300\" height=\"170\" srcset=\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/07\/Stanley_Park_Vancouver_7889964786-300x170.jpg 300w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/07\/Stanley_Park_Vancouver_7889964786-1024x579.jpg 1024w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/07\/Stanley_Park_Vancouver_7889964786-900x509.jpg 900w, https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2015\/07\/Stanley_Park_Vancouver_7889964786.jpg 1600w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/>Finally, a little bit about the setting &#8212; Vancouver is, of course, a spectacularly beautiful city. It is much changed since 1996, with high-rise luxury\u00a0office and residential buildings pretty much everywhere, and an even stronger international presence. But it&#8217;s still far from overly crowded, has those\u00a0extraordinary waterfront vistas, wonderfully cool summer weather, gorgeous urban parks, great food, and the\u00a0<a href=\"http:\/\/vancouver.ca\/parks-recreation-culture\/seawall.aspx\" target=\"_blank\">longest uninterrupted walkway in the world, the incredible Seawall.<\/a><\/p>\n<p>A city biker&#8217;s dream.<\/p>\n<p>Now, for a tune with a Canadian theme &#8230;<\/p>\n<\/div>\n<div>\n<p>[youtube http:\/\/www.youtube.com\/watch?v=mL7n5mEmXJo&amp;w=560&amp;h=315]<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Vancouver will always have a special place in HIV treatment history. It\u00a0was here, in 1996, that many of us\u00a0first\u00a0saw the potential of combination antiretroviral therapy to control this disease. Specifically,\u00a0Study 035 of AZT, 3TC, and indinavir\u00a0(presented by Trip Gulick) demonstrated the\u00a0astounding finding that triple therapy induced\u00a0sustained virologic\u00a0suppression and dramatic immunologic improvement. Could it be that [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,4,10],"tags":[783,1055],"class_list":["post-7556","post","type-post","status-publish","format-standard","hentry","category-health-care","category-hiv","category-research","tag-really-rapid-review","tag-vancouver-ias-2015"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/7556","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/comments?post=7556"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/7556\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=7556"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=7556"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=7556"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}