{"id":407,"date":"2014-06-25T05:12:15","date_gmt":"2014-06-25T05:12:15","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=407"},"modified":"2014-08-31T16:21:24","modified_gmt":"2014-08-31T20:21:24","slug":"should-efavirenz-remain-a-tier-1-art-drug","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2014\/06\/25\/407\/should-efavirenz-remain-a-tier-1-art-drug\/","title":{"rendered":"Should Efavirenz Remain a Tier 1 ART Drug?"},"content":{"rendered":"

\"JAC\"<\/a>In a recent publication Raffi et al. suggest that\u00a0it may be time to drop efavirenz (Sustiva\u00ae) from 1st<\/sup> line HIV treatment recommendations [1]. \u00a0The authors\u00a0make the\u00a0claim that efavirenz was inferior to rilpivirin (Edurant\u00ae) and dolutegravir (Tivicay\u00ae) in a total of 3 recent controlled studies. \u00a0They review\u00a0the CNS side effect profile of efavirenz\u00a0and find the newer drugs superior regarding\u00a0safety and tolerability. With\u00a0similar once-a-day convenience and compliance, they\u00a0feel that\u00a0efavirenz should probably be relegated to 2nd<\/sup> tier status. This article makes a good case against efavirenz at first blush but the argumentation\u00a0does not feel balanced. \u00a0Let me make here the case for efavirenz\u00a0without prejudice.<\/p>\n

Efavirenz is the only representative of the NNRTI class with a long strong track record of clinical testing\u00a0which neither etravirine nor rilpivirine nor dolutegravir\u00a0can\u00a0match. \u00a0 There is little\u00a0evidence that efavirenz has lost efficacy over time as far as VL reduction is concerned. \u00a0The authors present data suggesting superiority of\u00a0rilpivirine over efavirenz in 3 studies but these studies were not designed to test superiority in the first place. \u00a0Not being a statistician, I would still point out that the\u00a095% confidence intervals of difference in efficacy at the primary endpoint includes 0 (zero) indicating\u00a0that superiority cannot be claimed. There is only 1 exception: in the SINGLE study dolutegravir can claim superiority by a slim 2% margin.<\/p>\n

As pointed out by the authors, CNS adverse events have a tendency to disappear over time. Indeed, most\u00a0patients tolerate efavirenz and few need to\u00a0be switched to another drug. \u00a0Not to forget: \u00a0Rilpivirine was not free of CNS issues in its much more limited study program. \u00a0The Warnings and Precautions section in the package insert points mentions\u00a0depressive disorders in 8-9% of study patients [2]. More importantly: Rilpivirine\u2019s efficacy drops off in patients with high VL; it is therefore restricted to \u201cpatients with pre-ART plasma HIV RNA < 100,000 copies\/mL\u201d in the latest Guideline [3].<\/p>\n

My take is that rilpivirine is not the greatest drug for all treatment-naive patients, either.<\/p>\n

The better is always the enemy of the good.\u00a0 Integrase inhibitors are about to take the lead in the ART market, in preference to PIs or NNRTIs. \u00a0Dolutegravir has\u00a0a profile of excellent efficacy, excellent safety, once-a-day dosing, lack of drug-drug interactions and few resistance issues. \u00a0Should everybody now be started on 2 nukes plus dolutegravir?<\/p>\n

Efavirenz remains an excellent alternative, and so are the PIs. \u00a0Efavirenz has some well-known\u00a0safety issues which we have learned to manage. As long as efficacy remains almost identical to\u00a0the newest, latest and most expensive antiretroviral, efavirenz should not be pushed aside too\u00a0quickly.<\/p>\n

Let me know where you come down on the issue. \u00a0And leave a comment if you vehemently agree – or disagree.<\/p>\n

\n

References:<\/strong>
\n[1] Raffi.\u00a0 J Antimicrob Chemother 2014; 69: 1742
\n[2] Edurant Package Insert.\u00a0 http:\/\/www.edurant.com\/sites\/default\/files\/EDURANT-PI.pdf [3] Guidelines for Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents.\u00a0 2014; http:\/\/aidsinfo.nih.gov\/guidelines<\/p>\n","protected":false},"excerpt":{"rendered":"

In a recent publication Raffi et al. suggest that\u00a0it may be time to drop efavirenz (Sustiva\u00ae) from 1st line HIV treatment recommendations [1]. \u00a0The authors\u00a0make the\u00a0claim that efavirenz was inferior to rilpivirin (Edurant\u00ae) and dolutegravir (Tivicay\u00ae) in a total of 3 recent controlled studies. \u00a0They review\u00a0the CNS side effect profile Continue reading Should Efavirenz Remain a Tier 1 ART Drug?<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[227,18],"tags":[403,51,193,188,191,186,194,417,192,419,420,418,190,187,189],"class_list":["post-407","post","type-post","status-publish","format-standard","hentry","category-recent_literature","category-the_viewpoint","tag-antibiotic-blog","tag-art","tag-cns-safety","tag-dolutegravir","tag-edurant","tag-efavirenz","tag-etravirine","tag-first-line","tag-hiv-guidelines","tag-insti","tag-integrase-inhibitor","tag-nnrti","tag-rilpivirin","tag-sustiva","tag-ticivay"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-6z","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":222,"url":"https:\/\/allphasepharma.com\/dir\/2014\/05\/30\/222\/hiv-therapy-guidance-recommendations-diverge-show-us-bias\/","url_meta":{"origin":407,"position":0},"title":"HIV Therapy Guidance Recommendations Diverge, Show US Bias","author":"Harald","date":"May 30, 2014","format":false,"excerpt":"US doctors seem to be very willing to start drugs earlier in disease, while their EU colleagues are slower and more conservative.\u00a0 Recent examples: the ever-wider indication for statins, the disproportionate uptake of drugs for attention-deficit \/ hyperactivity and opioids for pain relief.\u00a0 The new US HIV treatment guidelines are\u2026","rel":"","context":"In "The Viewpoint"","block_context":{"text":"The Viewpoint","link":"https:\/\/allphasepharma.com\/dir\/category\/the_viewpoint\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":1590,"url":"https:\/\/allphasepharma.com\/dir\/2015\/06\/22\/1590\/tenofovir-bmd-and-monitoring-of-renal-function\/","url_meta":{"origin":407,"position":1},"title":"Tenofovir, BMD and Monitoring of Renal Function","author":"Harald","date":"June 22, 2015","format":false,"excerpt":"The approved tenofovir \/ Viread label lists not only standard\u00a0nucleoside-class side effects but also\u00a0\u2013 since an update in 2012 \u2013 makes mention of diminished bone mineral density (BMD) in the Warnings \/ Precautions section. Demonstrating that a particular drug affects BMD in patients who are already at an increased risk\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"BMD TDF","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/06\/BMD-TDF.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":5814,"url":"https:\/\/allphasepharma.com\/dir\/2025\/11\/27\/5814\/obeldesivir-fails-in-yet-another-study\/","url_meta":{"origin":407,"position":2},"title":"Obeldesivir Fails in Yet Another Study","author":"Harald","date":"November 27, 2025","format":false,"excerpt":"There are studies that are bound to succeed, and those that are likely to fail.\u00a0 A failed trial is nothing to be proud of \u2013 and in this case, it was a gamble against overwhelming odds.\u00a0 We feel the Gilead marketing department was pushing their luck big time with this\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/IDSA-Covid-Guideline.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/IDSA-Covid-Guideline.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/IDSA-Covid-Guideline.jpg?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":1859,"url":"https:\/\/allphasepharma.com\/dir\/2015\/08\/12\/1859\/the-beauty-of-science-no-need-to-think-about-costs-when-you-live-in-an-ivory-tower\/","url_meta":{"origin":407,"position":3},"title":"The Beauty of Science: No Need to Think About Costs When You Live in An Ivory Tower","author":"Harald","date":"August 12, 2015","format":false,"excerpt":"The recently published INSIGHT trial showed that starting HIV therapy earlier rather than later has benefit for patients 1. 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