{"id":15470,"date":"2011-08-01T11:43:43","date_gmt":"2011-08-01T11:43:43","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=15470"},"modified":"2016-11-22T15:39:39","modified_gmt":"2016-11-22T15:39:39","slug":"elvitegravir-vs-raltegravir-48-week-results-in-treatment-experienced-patients","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/15470","title":{"rendered":"Elvitegravir vs raltegravir: 48 week results in treatment-experienced patients"},"content":{"rendered":"

Simon Collins, HIV i-Base<\/strong>
\n\"\"<\/strong><\/p>\n

Elvitegravir is a once-daily integrase inhibitor being developed by Gilead. This was a double-blind, placebo-controlled study that randomised 702 treatment-experienced patients to compare elvitegravir (150 mg once-daily; reduced to 85 mg with atazanavir\/r or lopinavir\/r) to raltegravir (400 mg twice-daily), each with a background regimen of sensitive boosted-PI plus a third sensitive drug selected by phenotype (from NRTI, maraviroc, etravirine or T-20) and including the use of 3TC\/FTC with the M184V mutation. The primary endpoint was proportion of patients with viral load <50 copies\/mL at week 48 (TLOVR analysis, ITT), This was a non-inferiority study with the lower limit of the 95%CI set at \u009610%.<\/p>\n

Baseline characteristics included mean age 45 years; 18% were women; mean CD4 count 260 cells\/mm3 (45% with CD4 <200), median viral load ~ 20,000 copies\/mL (with 26% >100,000 copies\/mL) and approximately 5% and 15% of patients were coinfected with HBV or HCV respectively. Approximately 63% patients had primary resistance to two or more classes (PI 33%, NRTI 72%, and NNRTI 61%), balanced between arms.<\/p>\n

Choice of background PI was largely darunavir (58%), lopinavir\/r (19%) or atazanavir (16%). The third drug was an NRTI in 80% of patients (tenofovir 59%, tenofovir\/FTC 27%, abacavir 4%, 3TC 3%, other 7%) with 13% using etravirine and 6% using maraviroc.<\/p>\n

At week 48 a similar virological response rate was reported in each arm: 59% vs 58% in the elvitegravir vs raltegravir arms respectively which was strongly significant for non-inferiority (difference 1.1%; 95%CI: \u2013 \u00966.0% to +8.2%; p= 0.001). Approximately 20% of patients in each arm were reported as discontinuing due to virological failure: due to viral rebound (11% vs 16%) or never suppressing (8% vs 5%) in the elvitegravir vs raltegravir arms respectively with 1% or patients in each arm failing due to a switch of background drugs. A summary of virological and safety results is included in Table 1.<\/p>\n

However, discontinuations in a following slide were reported at 24% in each arm, mainly due to non-adherence, loss to follow-up or withdrawn consent and are detailed in Table 2, with virological failure reported in only 9 patients in each arm.<\/p>\n\n\n\n\n\n\n\n\n\n
Table 1: Elvitegravir vs raltegravir in experienced patients, 48 week results<\/caption>\n
<\/td>\nEVG n=351<\/th>\nRAL n=351<\/th>\nEVG vs RAL<\/th>\n<\/tr>\n
VL < 50 c\/mL<\/th>\n59%<\/td>\n58%<\/td>\n95% CI, -6.0%\u00968.2%, p= 0.001 for non inferiority<\/td>\n<\/tr>\n
Virological failure<\/th>\n20%<\/td>\n22%<\/td>\n<\/td>\n<\/tr>\n
Discontinuations<\/th>\n24%<\/td>\n24%<\/td>\n<\/td>\n<\/tr>\n
CD4 mean increase (on-treatment analysis)<\/th>\n+138<\/td>\n+147<\/td>\n<\/td>\n<\/tr>\n
D\/c due to AEs<\/th>\n9\/354 (3%)<\/td>\n15\/358 (4%)<\/td>\n<\/td>\n<\/tr>\n
INI resistance<\/th>\n16\/62 (26%)<\/td>\n15\/76 (20%)<\/td>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n\n\n\n\n\n\n\n\n
Table 2: Reasons for discontinuation: elvitegravir vs raltegravir, n (%)<\/caption>\n
<\/td>\nELV n=351<\/th>\nRAL n=351<\/th>\n<\/tr>\n
Discontinuations<\/th>\n85 (24%)<\/td>\n83 (24%)<\/td>\n<\/tr>\n
Non compliance<\/th>\n21<\/td>\n17<\/td>\n<\/tr>\n
Lost to follow-up<\/th>\n22<\/td>\n21<\/td>\n<\/tr>\n
Withdrew consent<\/th>\n15<\/td>\n9<\/td>\n<\/tr>\n
Virological failure<\/th>\n9<\/td>\n9<\/td>\n<\/tr>\n
Side effects<\/th>\n8<\/td>\n12<\/td>\n<\/tr>\n
Death<\/th>\n0<\/td>\n7<\/td>\n<\/tr>\n
Other (pregnancy or investigator decision)<\/th>\n3<\/td>\n2<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

When looking at drug resistance in the patients with virological failure, this included 61 and 75 people in the elvitegravir and raltegravir arms respectively. In this dataset, failure with integrase-associated mutations was reported at a comparable number though with increased frequency (16\/60; 27% vs 15\/72; 21%) in the elvitegravir vs the raltegravir patients. Development of new PI- or NRTI-associated resistance was generally low and similar between the two groups.<\/p>\n

Less than 5% of participants discontinued due to side effects. The only difference between arms in terms of adverse events was a higher rate of diarrhoea with elvitegravir (12% vs 7%), not associated with discontinuation. This was similar for laboratory abnormalities, with a slightly higher percentage of patients reporting grade 3\/4 ALT\/AST elevations with raltegravir (~1-2% vs 5%).<\/p>\n

This study concluded that this demonstrated that once daily elvitegravir was non-inferior to twice-daily raltegravir in treatment-experienced HIV-positive patients.<\/p>\n

comment<\/strong><\/h2>\n

These are impressive results in treatment-experienced patients. The rate of 20% patients failing with integrase-associated mutations was considered low by the investigators given the low barrier to integrase mutations. This was partially explained by the low barrier to virological failure in the study design (<1 log by week 8).<\/strong><\/p>\n

Causes of the seven deaths were not apparently drug related. This included one intestinal perforation in the elvitegravir arm, and one lymphoma and two cardiovascular events in the raltegravir arm.<\/strong><\/p>\n\n

References<\/p>\n

Molina J-F et al. Elvitegravir once-daily is non inferior to raltegravir twice-daily in treatment experienced patients: 48 week results from a phase 3 multicenter, randomized, double blind study. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 17-20 July 2011, Rome. Oral late breaker abstract WELBB05<\/a>. Webcast<\/a>.<\/p>\n


\n<\/strong><\/div>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base Elvitegravir is a once-daily integrase inhibitor being developed by Gilead. This was a double-blind, placebo-controlled study that randomised 702 treatment-experienced patients to compare elvitegravir (150 mg once-daily; reduced to 85 mg with atazanavir\/r or lopinavir\/r) to …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3],"tags":[94],"class_list":["post-15470","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-ias-6th-2011"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/15470","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=15470"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/15470\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=15470"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=15470"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=15470"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}