{"id":2096,"date":"2007-12-02T00:10:27","date_gmt":"2007-12-01T23:10:27","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=2096"},"modified":"2013-09-12T15:56:11","modified_gmt":"2013-09-12T15:56:11","slug":"darunavir-once-daily-is-non-inferior-to-lopinavirr-in-treatment-naive-patients-at-48-weeks-artemis-study","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/2096","title":{"rendered":"Darunavir once-daily is non-inferior to lopinavir\/r in treatment-naive patients at 48 weeks (Artemis study)"},"content":{"rendered":"

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

In an oral late breaker presentation, Nathan Clumeck presented results from a randomised, multinational (26 country) study, comparing darunavir once-daily to lopinavir\/r (once- or twice-daily) in almost 700 treatment-naive patients. Use of lopinavir\/r once-daily by some US patients was a patient\/doctor choice and not subject to randomisation.<\/strong><\/p>\n

Darunavir is approved as a twice-daily protease inhibitor at 600mg\/100mg twice daily, for use in combination with other active drugs as a treatment for PI-experienced patients. In this study, darunavir was dosed at 800mg with 100mg ritonavir once-daily (n=343) and lopinavir\/r was dosed at 400\/100mg twice-daily or 800\/200mg once-daily (n=346). Truvada (tenofovir+FTC) once-daily was included as background nucleosides in both arms. Viral load needed to be >5,000 copies\/mL at screening but there were no CD4 entry restrictions.<\/p>\n

The study was designed as a non-inferiority study based on the primary endpoint of the percentage of patients with viral suppression <50 copies\/mL at week 48. Secondary endpoints include safety, efficacy and tolerability results over 192 weeks.<\/p>\n

All demographics were balanced at baseline: 70% of patients were men and 30% women, mean age 35 (SD+9), and just over 40% of patients were Caucasian. While the group as a whole was not advanced \u0096 with a median CD4 of around 220 cells\/mm3<\/sup> and viral load of 60,000 copies\/mL \u0096 the ranges for these characteristics were broad: CD4 ranged from 2 to 750 cells\/mm3<\/sup> and viral load from 600 \u0096 5.5 million copies\/mL. It is unclear why some of these patients were entered into the study; some patients had CD4 counts far higher than guidelines recommend starting treatment and others had such advanced HIV, that they, arguably, should not be relying on an unproven treatment.<\/p>\n

Approximately 14% patients were coinfected with hepatitis C and 10% were CDC class C.<\/p>\n

Stratification at screening showed 40% patients had CD4 count <200 cells\/mm3<\/sup> and 36% had viral load >100,000 copies\/mL.<\/p>\n

At week 48, by Intent-To-Treat TLOVR (Time to Loss of Virologic Response) analysis, 84% of patients using DRV\/r vs 78% of LPV\/r patients reached <50 copies\/mL. The estimated difference in response compared to LPV\/r for non-inferiority per-protocol analysis was 5.6% (95% CI -0.1;11.3) p<0.001; and for superiority by ITT was 5.5% (95% CI -0.3;11.2) p=0.062. Assessed by primary endpont, darunavir once-daily was found to be non-inferior to lopinavir\/r, and results showed a trend towards superiority.<\/p>\n

71% of the subset of 52 mainly US patients who used lopinavir\/r once daily (who as a group had similar baseline characteristics to the DRV\/r and LPV\/r BID groups) achieved suppression to <50 copies\/mL. This 13% difference showed darunavir\/r to be superior to once-daily lopinavir\/r (95% CI 1; 24; p<0.05). Differences between the LPV\/r once- vs twice daily [9%* (95% CI -3; 21)] and DRV\/r once-daily vs LPV\/r twice daily [(3% (95% CI -3; 9)] were not significant.<\/p>\n

Results in patients with baseline viral load >100,000 copies\/mL saw an even greater difference between DRV\/r and once-daily LPV\/r with 79% vs 56% achieving <50 copies\/mL (P<0.05). The significance remained when comparing DRV\/r to the overall LPV\/r group (67%, p<0.05) but not when comparing to LPV\/r twice-daily (71%).<\/p>\n

Grade 2-4 side effects, summarised in Table 1, showed a higher rate of diarrhoea in the LPV\/r arm overall (4% vs 10%). These rates were 8% in the LPV\/r twice daily and 17% in the LPV\/r once-daily groups. Nausea was similar at 2-3% in both arms and rash was slightly higher in the DRV\/r (3% vs 1% LPV\/r overall).<\/p>\n

The majority of LPV\/r QD use was in the US. The proportion of US patients who used LPV\/r QD was 66% (45 of 68 patients). Only 7 patients outside of the US used LPV\/r QD. 27 (8%) patient used both once- and twice-daily LPV\/r dosing during the study, and were excluded from the QD vs BID LPV\/r analyses.<\/p>\n

Table 1: Grade 2-4 side effects and lipid changes (seen in >2% patients)<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n
<\/td>\nDRV\/r QD n=343<\/td>\nLPV\/r overall n=346<\/td>\nLPV\/r BID n=267<\/td>\nLPV\/r QD n=52<\/td>\n<\/tr>\n
Diarrhoea<\/td>\n14 (4%)<\/td>\n34 (10%)<\/td>\n22 (8%)<\/td>\n9 (17%)<\/td>\n<\/tr>\n
Nausea<\/td>\n6 (2%)<\/td>\n10 (3%)<\/td>\n8 (3%)<\/td>\n0<\/td>\n<\/tr>\n
Rash<\/td>\n9 (3%)<\/td>\n4 (1%)<\/td>\n3 (1%)<\/td>\n1 (2%)<\/td>\n<\/tr>\n
TChol<\/td>\n44 (13%)<\/td>\n78 (23%)<\/td>\n69 (26%)<\/td>\n8 (15%)<\/td>\n<\/tr>\n
LDL<\/td>\n44 (13%)<\/td>\n36 (11%)<\/td>\n31 (12%)<\/td>\n9 (17%)<\/td>\n<\/tr>\n
TG<\/td>\n10 (3%)<\/td>\n38 (11%)<\/td>\n27 (10%)<\/td>\n9 (17%)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Comment<\/h3>\n

This study supports the use of darunavir\/r as a once-daily option in naive patients, especially when viral load is >100,000 copies\/mL, although it would be interesting to know whether twice-daily darunavir\/r would improve on these rates or suppression in this group.<\/strong><\/p>\n

The results of the LPV\/r once-daily analysis should be interpreted cautiously as this is a small non-randomised subset of US patients.<\/strong><\/p>\n

Several studies have previously shown lopinavir\/r once daily to be inferior to twice-daily, with poorer trough concentrations, and although licensed as a once-daily option in the US for naive patients, Abbott no longer appear to be actively pursuing once-daily registration in Europe.<\/strong><\/p>\n

Reference:<\/p>\n

Clumeck N et al. ARTEMIS: Efficacy and safety of lopinavir (BID vs QD) and darunavir (QD) in antiretroviral-naive patients. Late breaker abstract LBPS7\/5. http:\/\/www.multiwebcast.com\/eacs\/2007\/11th<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base In an oral late breaker presentation, Nathan Clumeck presented results from a randomised, multinational (26 country) study, comparing darunavir once-daily to lopinavir\/r (once- or twice-daily) in almost 700 treatment-naive patients. Use of lopinavir\/r once-daily by some …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3],"tags":[71],"class_list":["post-2096","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-eacs-11th-2007"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/2096","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=2096"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/2096\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=2096"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=2096"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=2096"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}