{"id":1590,"date":"2015-06-22T15:19:23","date_gmt":"2015-06-22T19:19:23","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=1590"},"modified":"2015-06-22T15:34:57","modified_gmt":"2015-06-22T19:34:57","slug":"tenofovir-bmd-and-monitoring-of-renal-function","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2015\/06\/22\/1590\/tenofovir-bmd-and-monitoring-of-renal-function\/","title":{"rendered":"Tenofovir, BMD and Monitoring of Renal Function"},"content":{"rendered":"

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.<\/p>\n

Demonstrating that a particular drug affects BMD in patients who are already at an increased risk of bone fractures due to HIV-related osteoporosis is not easy.<\/p>\n

This is what Mulligan and colleagues did in a large (N=498) pre-exposure prophylaxis (PrEP) trial of Truvada (TDF\/FTC) [1]<\/span>.\u00a0 The groups were well matched by demographics, initial BMD and HIV risk factors.\u00a0 The study was double-blinded, with a placebo comparison arm.\u00a0 Results showed a clear and statistically significant decrease in BMD in the TDF group by ITT analysis.\u00a0 Even more pronounced differences were noted in the group of study participants (approx. 50% of the entire cohort) that had detectable drug levels at the time of BMD measurements. In contrast, placebo patients had a slight increase in BMD at both spine and hip\u00a0at 24, 48 and 72 weeks (see graph).\"BMD<\/a><\/p>\n

Since the original launch of tenofovir, the drug\u2019s use\u00a0has expanded significantly and now\u00a0includes an earlier treatment start for HIV-positive patients as well as\u00a0pre-exposure prophylaxis (PrEP) for high-risk individuals.\u00a0\u00a0 As a result, the duration of tenofovir exposure is now many years,\u00a0f not decades longer compared to its original labeling.<\/p>\n

What may have been considered an acceptable\u00a0side effect with more limited exposure and the more limited population of HIV patients with advanced disease (CD<350 cells\/mL) \u00a0now should\u00a0be reevaluated.<\/p>\n

The time has come\u00a0to monitor kidney function more regularly for tenofovir recipients. Reduced glomerular filtration and proximal tubular damage caused by adefovir, cidofovir, and tenofovir is well described. Commonly referred to as partial or complete Fanconi syndrome, it results in glucosuria, aminoaciduria, phosphate and bicarb wasting\u00a0[2]<\/a>. Urinary phosphate loss can certainly contribute to osteopenia and a decreased BMD.<\/p>\n

This has short- and long-term consequences.\u00a0 Short-term, reduction in creatinine clearance is\u00a0a concern.\u00a0 Even if progression to overt renal failure seems to be a rare event\u00a0in prospective clinical trials, substantial elevations in serum creatinine are not rare in clinical practice. Long-term, the effect of tenofovir\u00a0on BMD is indisputable but underreported and inadequately studied.\u00a0 Publications addressing renal impairment, Fanconi syndrome and how tenofovir impacts BMD have increased in recent years but Gilead is probably sitting on tons of additional data not yet shared with the public.<\/p>\n

A search on the FDA web site for Post-Market Drug Safety Evaluations comes back empty for tenofovir\u00a0[3]<\/a>. Surprisingly, the FDA label for Viread is quite benign.\u00a0 It specifies that creatinine clearance should be assessed prior to\u00a0treatment.\u00a0 There is\u00a0no recommendation for\u00a0monitoring kidney function unless a patient is considered \u2018at risk\u2019 for renal dysfunction.\u00a0\u00a0 Which amounts to no f\/u monitoring for 95% of tenofovir\u00a0recipients.<\/p>\n

Maybe a renewed risk\/benefit assessment is in order. Interestingly, the recommendations from the Spanish AIDS and ID societies, updated in 2014,\u00a0[4]<\/a>\u00a0 have done just that. \u00a0They advocate yearly monitoring of renal function for all HIV-infected in general, and more frequent checks for those receiving tenofovir\u00a0specifically.<\/p>\n

Solid and timely advice. \u00a0An FDA or Cochrane\u00a0safety review\u00a0should be encouraged.<\/p>\n

References:
\n<\/strong><\/p>\n

[1]<\/span> Mulligan CID May 2015
\n[2]<\/a> A Hall Q J Med 2014; 107:261
\n[3]<\/a> http:\/\/www.fda.gov\/Drugs\/GuidanceComplianceRegulatoryInformation\/Surveillance\/ucm204091.htm#postmarket_summaries
\n[4]<\/a> Enferm Infecc Microbiol Clin.<\/a>\u00a02014;32:583<\/p>\n","protected":false},"excerpt":{"rendered":"

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 Continue reading Tenofovir, BMD and Monitoring of Renal Function<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":1598,"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":[227,3,18],"tags":[360,1084,403,1075,1078,1076,1069,1073,5,1079,1081,126,1083,1072,1082,1077,1074,1071,1070,843,1080,1067,1068,1066],"class_list":["post-1590","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_news","category-the_viewpoint","tag-adverse-events","tag-aminoaciduria","tag-antibiotic-blog","tag-bmd","tag-bone-fracture","tag-bone-mineral-density","tag-emtricitabine","tag-fanconi-syndrome","tag-fda","tag-fda-post-market-assessment","tag-ftc","tag-gilead","tag-glucosuria","tag-hiv-treatment","tag-kidney-function-testing","tag-osteoporosis","tag-phosphaturia","tag-pre-exposure-prophylaxis","tag-prep","tag-renal-toxicity","tag-tdf","tag-tenofovir","tag-truvada","tag-viread"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/06\/Fanconi-slider.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-pE","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":1741,"url":"https:\/\/allphasepharma.com\/dir\/2015\/07\/17\/1741\/does-the-taxpayer-get-rewarded-for-funding-studies\/","url_meta":{"origin":1590,"position":0},"title":"Does The Taxpayer Get Rewarded For Funding Such Studies?","author":"Harald","date":"July 17, 2015","format":false,"excerpt":"Cabotegravir (S-1265744) is an integrase inhibitor similar to dolutegravir. \u00a0When formulated as a long-acting drug using crystalline nanoparticle technology it is called GSK'744 LAP.\u00a0 When injected intramuscularly, '744 LAP it has a half-life of >1 month which makes it ideally suited for PrEP\u00a0of HIV for high-risk patients who nowadays are\u2026","rel":"","context":"In "Did you know...?"","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"LAP HIV Drugs - slider copy","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/LAP-HIV-Drugs-slider-copy.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/LAP-HIV-Drugs-slider-copy.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/LAP-HIV-Drugs-slider-copy.jpg?resize=525%2C300 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":1590,"position":1},"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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