{"id":1871,"date":"2008-04-01T18:24:28","date_gmt":"2008-04-01T17:24:28","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=1871"},"modified":"2013-08-30T10:26:15","modified_gmt":"2013-08-30T10:26:15","slug":"atazanavirr-vs-lopinavirr-in-treatment-naive-patients-48-week-results","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/1871","title":{"rendered":"Atazanavir\/r vs lopinavir\/r in treatment-naive patients: 48 week results"},"content":{"rendered":"

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

Although widely used off-label, atazanavir\/r is not currently approved in Europe for use in first-line combinations, nor recommended in European guidelines, due to limited data in naive patients. Results from a large randomised international head-to-head study against lopinavir\/r, sponsored by BMS, are therefore important to report.<\/strong><\/p>\n

Jean-Michel Molina from St Louis Hospital, Paris, presented the 48-week analysis from this 96-week CASTLE study. This was a non-inferiority study (10% margin) and the primary endpoint was the proportion of patients with HIV RNA <50 copies\/mL at week 48.<\/p>\n

The trial randomised 883 treatment-naive patients to either atazanavir 300 mg \/ ritonavir 100 mg once-daily or lopinavir\/ritonavir 400 mg\/100 mg twice-daily, both in combination with fixed-dose tenofovir\/FTC once-daily.<\/p>\n

Baseline demographics and characteristics included median CD4 count 205 cells\/mm3 (range 2-810) with 12% less than 50 cells\/mm3; and viral load around 5 log copies\/mL (range 2.6-5.9), with 50% patients starting above 100,000 copies\/mL. Only around 5% had CDC class C diagnosis, and 12% were coinfected with hepatitis B or C.<\/p>\n

Only around 10% of patients discontinued prior to week 48, with a balance between each arm, detailed in Table 1.<\/p>\n

Table 1: Patient disposition at week 48<\/strong><\/p>\n\n\n\n\n\n\n\n\n
<\/th>\nATV\/r n=121<\/th>\nLPR\/r n=127<\/th>\n<\/tr>\n
BL<\/th>\nMo12<\/th>\nChange<\/th>\nBL<\/th>\nMo12<\/th>\nChange<\/th>\n<\/tr>\n
TG > 500mg\/dL<\/td>\n3%<\/td>\n4%<\/td>\n+1%<\/td>\n10%<\/td>\n17%<\/td>\n+7%<\/td>\n<\/tr>\n
TC > 240mg\/dL<\/td>\n23%<\/td>\n20%<\/td>\n-3%<\/td>\n20%<\/td>\n26%<\/td>\n+6%<\/td>\n<\/tr>\n
LDL-c > 130mg\/dL<\/td>\n20%<\/td>\n25%<\/td>\n+5%<\/td>\n20%<\/td>\n30%<\/td>\n+10%<\/td>\n<\/tr>\n
HDH-c < 40mg\/dL<\/td>\n16%<\/td>\n32%<\/td>\n+16%<\/td>\n21%<\/td>\n29%<\/td>\n+8%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The percentage of patients with viral load <50 copies\/mL at week 48 in the atazanavir\/r and lopinavir\/r arms was 78% vs 76% (estimated difference 1.9, 95% CI \u00963.6 to 7.4), by intent-to-treat analysis.<\/p>\n

Stratified by baseline viral load, the results were 82% vs 81% (<100,000 copies\/mL) and 74% vs 72% (>100,000 copies\/mL), in the ATZ\/r and LPV\/r groups respectively, with no statistical difference between arms.<\/p>\n

A post-hoc analysis of results by baseline CD4 counts showed no impact for ATZ\/r, but a statistically significant poorer response for the LPV\/r arm, ranging from 80% <50 copies\/mL in patients with >200 CD4 cells\/mm3 to 63% for those starting with <50 cells\/mm3, p = 0.0085.<\/p>\n

CD4 response was similar in each arm (+203 vs + 219 cells\/mm3).<\/p>\n

Side effects generally reflected the known profile of each drug, with ATZ\/r having higher incidence of jaundice, and LPV\/r reporting greater GI-related ae\u0092s, that are detailed in Table 2.<\/p>\n

Table 2: Adverse events in CASTLE study<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
<\/th>\nATZ\/r\n

n=441 (%)<\/p><\/th>\n

LPV\/r\n

n=437 (%<\/p><\/th>\n<\/tr>\n

Serious AE\u0092s<\/td>\n54 (12%)<\/td>\n42 (10%)<\/td>\n<\/tr>\n
All grade 2-4<\/td>\n115 (26%)<\/td>\n129 (30%)<\/td>\n<\/tr>\n
– Jaundice*<\/td>\n16 (4%)<\/td>\n0<\/td>\n<\/tr>\n
– Nausea*<\/td>\n17 (4%)<\/td>\n33 (8%)<\/td>\n<\/tr>\n
– Diarrhoea*<\/td>\n10 (2%)<\/td>\n50 (11%)<\/td>\n<\/tr>\n
– Rash*<\/td>\n14 (3%)<\/td>\n9 (2%)<\/td>\n<\/tr>\n
Renal (all grades)<\/td>\n14 (3%)<\/td>\n9 (2%)<\/td>\n<\/tr>\n
Total bilirubin >2.5xULN<\/td>\n146 (34%)<\/td>\n1 (<1%)<\/td>\n<\/tr>\n
Total cholesterol (>240 mg\/dL)<\/td>\n30 (7%)<\/td>\n77 (18%)<\/td>\n<\/tr>\n
Triglycerides (>750 mg\/dL)<\/td>\n2 (<1%)<\/td>\n15 (4%)<\/td>\n<\/tr>\n
Hyperglycemia (>251 mg\/DL)<\/td>\n1 (<1%)<\/td>\n1 (<1%)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

* Grade 2-4 in >3% of patients<\/p>\n

With laboratory AE\u0092s, grade 3-4 ALT\/AST elevations were low (>2%) in both arms.<\/p>\n

Lipid profile favoured ATZ\/r with fewer patients at week 48 having total cholesterol >240 mg\/dL (7% vs 18%), and significantly lower changes from baseline for TC, non HDL and TG (all p<0.0001). Lipid lowering drugs were used by 2% and 7% of the ATZ\/r and LPV\/r arms respectively.<\/p>\n

Comment<\/h3>\n

The study concluded that atazanavir\/r is an appropriate treatment for first line therapy. Regulatory and guidelines committees will hopefully review these data carefully and promptly.<\/strong><\/p>\n

Reference:<\/p>\n

Molina JF et al. Efficacy and safety of once-daily atazanavir\/ritonavir compared to twice-daily lopinavir\/ritonavir, each in combination with tenofovir and emtricitabine in ARV-naive HIV-1-infected subjects: the CASTLE study, 48-week results. Abstract 37.
\nhttp:\/\/www.retroconference.org\/2008\/Abstracts\/31137.htm<\/a><\/p>\n

This oral presentation is available to view online from the conference website (Monday 4 February).<\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base Although widely used off-label, atazanavir\/r is not currently approved in Europe for use in first-line combinations, nor recommended in European guidelines, due to limited data in naive patients. Results from a large randomised international head-to-head study …<\/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":[62],"class_list":["post-1871","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-croi-2008"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1871","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=1871"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1871\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=1871"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=1871"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=1871"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}