{"id":24895,"date":"2014-03-24T12:00:32","date_gmt":"2014-03-24T12:00:32","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=24895"},"modified":"2014-03-28T16:24:47","modified_gmt":"2014-03-28T16:24:47","slug":"dual-therapy-less-effective-at-high-viral-load-neat-001-study-with-raltegravirdarunavirr","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/24895","title":{"rendered":"Dual therapy less effective at high viral load: NEAT 001 study with raltegravir\/darunavir\/r"},"content":{"rendered":"

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

\"CROIAn experimental dual therapy combination of an integrase inhibitor plus a boosted-PI was non-inferior at week 96 compared to PI-based triple therapy, but was less effective in patients starting with a high viral load. <\/strong><\/p>\n

Francois Raffi, from University Hospital, Nantes, presented results from a European independent investigator collaboration comparing twice-daily raltegravir (n=401) to once-daily tenofovir\/FTC (n=404) in combination with once-daily darunavir\/ritonavir (800 mg\/100 mg) in treatment-naive patients.<\/p>\n

This was the NEAT001 study (ANRS143 in France), and the first from a EU network of independent investigators, with 78 sites in 15 countries. NEAT001 is a randomised, phase 3, open-label, 96 week study with a composite primary endpoint of time to virological or clinical failure. It is a non-inferiority study with an absolute difference of 9% defined for failure of raltegravir by ITT analysis. Entry criteria included CD4 count <500 cells\/mm3<\/sup>, hepatitis B negative and having no major drug resistance mutations.<\/p>\n

Virological failure was defined as <1 log reduction by week 18 or viral load >400 copies\/mL at week 24, or if viral load was >50 copies\/mL at or after week 32. Clinical endpoints included any new or recurrent serious event.<\/p>\n

Participants were largely male (88%) and white (82%) with median age 37 years. At baseline, median viral load was 4.8 (IQR 4.2, 5.1) log copies\/mL with 36% vs 32% having >100.000 in the raltegravir vs tenofovir\/FTC arms respectively (and 6% vs 5% with >500,000). Median CD4 count was 340 (IQR 260, 394) vs 325 (IQR 248, 401) respectively with approximately 15% having a count <200 cells\/mm3.<\/p>\n

There were more discontinuations prior to week 96 in the raltegravir arm (n=38 vs 22), mainly driven by greater loss to follow-up (n=24 vs 15), although there were also more deaths (n=4 vs 0) compared to the tenofovir\/FTC arm. Although numerically the raltegravir arm had a greater probability of reaching the primary endpoint at week 96, with 17.4% vs 13.7% having treatment failure, this supported a non-inferiority result with an adjusted between-arm difference of 3.7% (95% CI: -1.1 to 8.6%), p=0.12).<\/p>\n

This difference was driven by more patients having viral load >50 copies\/mL after week 32 (n=32 vs 22). At week 96, 89% vs 93% patients had viral load <50 copies\/mL in the raltegravir and darunavir\/r arms respectively. Serious AIDS-related events occurred in 5 vs 3 people and serious non-AIDS event occurred in 7 people in each arm.<\/p>\n

In a planned stratified analysis, raltegravir was inferior in more advanced patients. Primary endpoint results at week 96 when baseline CD4 count was <200 cells\/mm3 were 39.0% vs 21.3%, p=0.02 with a trend to non-inferiority when baseline viral load was >100,000 copies\/mL (36% vs 27%; p=0.09).<\/p>\n

No resistance was detected in 13\/15 patients with virological failure and genotypic results in the tenofovir\/FTC arm compared to five major mutations in 28\/36 patient with results with raltegravir. This included one case of K65R and five patients with N155H. In questions after the presentation, 4\/5 of these patients were said to have had baseline viral load \u201cconsiderably higher than 500,000 copies\/mL\u201d.<\/p>\n

The differences in serious side effects were numerically higher in the raltegravir arm, but differences were not statistically significant. There were 89 vs 75 events (in 73 vs 61 patients; incidence rate 10.2 vs 8.3\/100 PY, p=0.17).<\/p>\n

The four deaths in the raltegravir arm were from Burkitt\u2019s lymphoma, DRESS syndrome, \u00a0melanoma and \u00a0suicide, with the single death in the tenofovir\/FTC arm from morphine \u00a0overdose. Life threatening events occurred in 8 vs 4 patients (CK increase (n = 5), hepatitis, Hodgkin lymphoma, pancreatitis vs CK increase (n = 2), myocardial infarction and gGT increase).<\/p>\n

Changes in fasting lipids were more significant in the raltegravir group (TC p<0.001, LDL-c p=0.02, HDL-c p<0.001 and TG p=0.49) but there were no significant different in TC:HDL-c ratio (p=0.7). Grade 3\/4 creatinine kinase elevation occurred in 6.2% vs 5.0% and grade 3\/4 ALT increase in 3.0 vs 1.0% of the raltegravir vs tenofovir\/FTC arms respectively.<\/p>\n

Creatinine clearance measured by eGFR at week 96 increased by 0.9 in the raltegravir group compared to dropping by -3.8 in the tenofovir\/FTC arm (p=0.02) with the drop occurring in the first four weeks of treatment.<\/p>\n

Reference<\/p>\n

Raffi F et al. First-line raltegravir (RAL) + darunavir\/ritonavir (DRV\/r) is non-inferior to tenofovir\/emtricitabine (TDF\/FTC) + DRV\/r: the NEAT 001\/ANRS 143 randomised trial. \u00a021st CROI, 3\u20136 March 2014, Boston. Late breaker oral abstract 84 LB.
\nhttp:\/\/www.croiwebcasts.org\/console\/player\/22164<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base An experimental dual therapy combination of an integrase inhibitor plus a boosted-PI was non-inferior at week 96 compared to PI-based triple therapy, but was less effective in patients starting with a high viral load. Francois Raffi, …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3,41],"tags":[187],"class_list":["post-24895","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","category-treatment-strategies","tag-croi-2014"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/24895","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=24895"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/24895\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=24895"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=24895"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=24895"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}