{"id":7830,"date":"2010-02-07T00:31:10","date_gmt":"2010-02-07T00:31:10","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=7830"},"modified":"2019-01-10T16:01:17","modified_gmt":"2019-01-10T16:01:17","slug":"us-guideline-update-treat-when-cd4-is-500-cellsmm3","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/7830","title":{"rendered":"US guidelines update (2010): treat when CD4 is less than 500 cells\/mm3"},"content":{"rendered":"<p><strong>On 1 December 2009, the US\u00a0Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents were updated. <\/strong><\/p>\n<p>Changes are highlighted in yellow on the PDF file\u00a0and include:<\/p>\n<p><strong>New section<\/strong><\/p>\n<p>Based on interests and requests from HIV practitioners, a new section entitled \u00a0Considerations in Managing Patients with HIV-2 Infection\u0094 has been added to\u00a0the guidelines. This new section briefly reviews the current knowledge on the epidemiology and diagnosis of HIV-2 infection and the role of antiretroviral\u00a0therapy in the management of patients with HIV-2 mono-infection and HIV-1\/HIV-2 coinfection.<\/p>\n<p><strong>Key updates<\/strong><\/p>\n<p>Drug resistance testing ?In this revision, the Panel provides more specific recommendations on when to use genotypic versus phenotypic testing to guide\u00a0therapy in treatment-experienced patients with viremia while on treatment.<\/p>\n<ul>\n<li>Genotypic testing is recommended as the preferred resistance testing\u00a0to guide therapy in patients with suboptimal virologic responses or virologic failure while on first or second regimens (AIII).<\/li>\n<li>Addition of\u00a0phenotypic testing to genotypic testing is generally preferred for persons with known or suspected complex drug resistance mutation patterns, particularly<br \/>\nto protease inhibitors (BIII).<\/li>\n<\/ul>\n<p><strong>Initiation of antiretroviral therapy <\/strong><\/p>\n<p>In this updated version of the guidelines, the Panel recommends earlier initiation of antiretroviral therapy with the following specific recommendations:<\/p>\n<ul>\n<li>Antiretroviral therapy should be initiated in all patients with a history of an AIDS-defining illness or with CD4 count &lt; 350 cells\/mm<sup>3<\/sup>\u00a0(AI).<\/li>\n<li>Antiretroviral therapy should also be initiated, regardless of CD4 count, in patients with the following conditions: pregnancy (AI),<br \/>\nHIV-associated nephropathy (AII), and hepatitis B virus (HBV) coinfection when treatment of HBV is indicated (AIII).<\/li>\n<li>Antiretroviral therapy is\u00a0recommended for patients with CD4 counts between 350 and 500 cells\/mm<sup>3<\/sup>. The Panel was divided on the strength of this recommendation: 55% of Panel members\u00a0for strong recommendation (A) and 45% for moderate recommendation (B) (A\/B-II).<\/li>\n<li>For patients with CD4 counts &gt;500 cells\/mm<sup>3<\/sup>, 50% of Panel\u00a0members favor starting antiretroviral therapy (B); the other 50% of members view treatment as optional (C) in this setting (B\/C-III).<\/li>\n<li>Patients initiating antiretroviral therapy should be willing and able to commit to lifelong treatment and should understand the benefits and risks of\u00a0therapy and the importance of adherence (AIII). Patients may choose to postpone therapy, and providers may elect to defer therapy, based on clinical\u00a0and\/or psychosocial factors on a case-by-case basis.<\/li>\n<\/ul>\n<p><strong>What to start in antiretroviral-naive patients<\/strong><\/p>\n<p>Increasing clinical trial data in the past few years have allowed for better distinction between the virological efficacy and safety of different\u00a0combination regimens. Instead of providing recommendations for individual antiretroviral components to use to make up a combination, the Panel now defines\u00a0what regimens are recommended in treatment naive patients.<\/p>\n<p>Regimens are classified as \u0093Preferred,\u0094 \u0093Alternative,\u0094 \u0093Acceptable,\u0094 \u0093Regimens that may be acceptable but more definitive data are needed,\u0094 and \u0093Regimens to be\u00a0used with caution.<\/p>\n<p>The following changes were made in the recommendations:<\/p>\n<ul>\n<li>Raltegravir + tenofovir\/emtricitabine\u0094 has been added as a \u0093Preferred\u0094 regimen based on the\u00a0results of a Phase III randomised controlled trial (AI).<\/li>\n<li>Four regimens are now listed as \u0093Preferred\u0094 regimens for treatment-naive patients:<\/li>\n<\/ul>\n<p>i)\u00a0\u00a0 \u00a0efavirenz\/tenofovir\/emtricitabine;<\/p>\n<p>ii)\u00a0\u00a0 \u00a0ritonavir-boosted atazanavir + tenofovir\/emtricitabine;<\/p>\n<p>iii)\u00a0\u00a0 \u00a0ritonavir-boosted darunavir + tenofovir\/emtricitabine; and<\/p>\n<p>iv)\u00a0\u00a0 \u00a0raltegravir + tenofovir\/emtricitabine.<\/p>\n<ul>\n<li>Lopinavir\/ritonavir-based regimens are now listed as \u0093Alternative\u0094 (BI) instead of \u0093Preferred\u0094\u00a0regimens, except in pregnant women, where twice-daily lopinavir\/ritonavir + zidovudine\/lamivudine remains a \u0093Preferred\u0094 regimen (AI).<\/li>\n<\/ul>\n<p><strong>Additional updates <\/strong><\/p>\n<p>The following sections and their relevant tables have been substantially updated:<\/p>\n<ul>\n<li>What not to use<\/li>\n<li>Management of treatment-experienced\u00a0patients<\/li>\n<li>Treatment simplification<\/li>\n<li>Hepatitis C coinfection<\/li>\n<li>Antiretroviral-associated adverse effects<\/li>\n<li>Antiretroviral\u00a0drug interactions<\/li>\n<li>Preventing secondary transmission of HIV<\/li>\n<\/ul>\n<p>These and other DHHS guidelines are available on the NIH aidsinfo website:<br \/>\n<a href=\"http:\/\/www.aidsinfo.nih.gov\">http:\/\/www.aidsinfo.nih.gov<\/a><\/p>\n<p>Direct download (PDF):<br \/>\n<a href=\"http:\/\/aidsinfo.nih.gov\/contentfiles\/AdultandAdolescentGL.pdf\" rel=\"noopener\">http:\/\/aidsinfo.nih.gov\/contentfiles\/AdultandAdolescentGL.pdf<\/a><\/p>\n<p><strong>COMMENT<\/strong><\/p>\n<p><strong>The main concern in these guidelines is the strength of the statement for new recommendations for starting treatment.<\/strong><\/p>\n<p><strong>Currently the document states that the whole panel recommends starting treatment for people with a CD4 count 350-500 <\/strong><strong>cells\/mm<sup>3<\/sup><\/strong>. This leaves no indication of\u00a0support for the view that there is insufficient data to balance the risks against the benefits.<\/p>\n<p><strong>Although this is discussed in the main document in more detail, the summary of the guidelines does not accurately reflect the later discussion.\u00a0The summary is far more widely read than the entire document, and it would therefore be helpful for this wording to be reconsidered.<\/strong><\/p>\n<p><strong>This years recommendations are especially important as they coincide with the enrollment of the NIH-funded START study which may be the only\u00a0opportunity to look at both the risks and benefits from a randomised study.<\/strong><\/p>\n<p><strong>So while there is data supporting short-term safety, there is no data based on long-term risk.<\/strong><\/p>\n<p><strong>An example of risk comes from the trials of the preferred regimens referenced with the latest data (STARTMRK, ARTEMIS etc). Viral suppression to\u00a0&lt;50 copies\/mL (the primary goal of treatment) was not achieved by around 15% patients at 48 weeks and 20% by week 96. In the context of lifelong\u00a0treatment, low levels of resistance currently reported, may become more serious if second-line treatment also fails. Population-based uptake of treatment\u00a0in Western countries is also frequently associated with higher rates of failure.<\/strong><\/p>\n<p><strong>A second example is that no combination has been shown not to cause fat accumulation, itself associated with additional longer-term health\u00a0complications, as well as reduced quality of life. This complication may also be related to race and gender.<\/strong><\/p>\n<p><strong>These potential risks from earlier treatment are not addressed in the main guidelines.<\/strong><\/p>\n<p><strong>In addition, while the summary states that \u0091some people may defer treatment\u0092, this is suggested for \u0091clinical or psychosocial factors\u0092 and is tied to\u00a0an earlier sentence about people who might have difficulty with adherence.<\/strong><\/p>\n<p><strong>While the document is only produced as guidance, the DHHS guidelines are widely interpreted as indicating the minimum recommended standard of\u00a0care, based on the best available evidence. Clinical trials, especially NIH funded trials, become unethical if they recommend less that the current\u00a0standard of care for any participant.<\/strong><\/p>\n<p><strong>While many doctors, researchers and advocates believe that there is still equipoise on the use of treatment by people with counts 350-500, the\u00a0current summary brings them into conflict with what are otherwise, one of the most useful documents for the management of HIV infection.<\/strong><\/p>\n<p><strong>Given the summary has already been widely distributed and publicised, it would help if any subsequent update addresses whether a randomised trial\u00a0in people with CD4 counts lower than 500 cells\/mm<sup>3<\/sup> remains ethical. Currently the guideline summary states that expert opinion believes that further\u00a0research is unnecessary.<\/strong><\/p>\n<p><strong>This is important in the context of the START trial which is just enrolling patients and which will be the most important study to inform on this\u00a0and many other questions.<\/strong><\/p>\n<p><strong>The history of previous recommendations from the DHHS panel on the when treatment should be started shows the importance of collecting evidence\u00a0from a randomised study. Earlier recommendations to start at 500 and 350 have probably resulted in widespread complications from side effects and\u00a0resistance.<\/strong><\/p>\n<p><strong>Other changes in the guidelines are positive, especially the inclusion of a new section on HIV-2.<\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"<p>On 1 December 2009, the US\u00a0Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents were updated. Changes are highlighted in yellow on the PDF file\u00a0and include: New section Based on interests and requests from HIV practitioners, a &hellip;<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[23],"tags":[],"class_list":["post-7830","post","type-post","status-publish","format-standard","hentry","category-guidelines"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7830","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=7830"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7830\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=7830"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=7830"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=7830"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}