{"id":2349,"date":"2006-08-03T18:13:00","date_gmt":"2006-08-03T17:13:00","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=2349"},"modified":"2013-12-06T17:23:45","modified_gmt":"2013-12-06T17:23:45","slug":"ritonavir-reduces-virological-failure-and-resistance-in-treatment-naive-patients-treated-with-atazanavir","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/2349","title":{"rendered":"Ritonavir reduces virological failure and resistance in treatment naive patients treated with atazanavir"},"content":{"rendered":"

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

Atazanavir was licensed in the US in June 2003 as a treatment for naive or experienced patients, and in Europe it was licensed in March 2004 for use in treatment-experienced patients only. In practice, especially when once-daily combinations are important, and when there is a caution against using efavirenz, atazanavir is becoming used off-label in the UK as first line treatment. It\u0092s lack of effect on lipids and good tolerability, also contributes to this use.<\/strong><\/p>\n

The licensing indication is further complicated by recommendations for ritonavir boosting. Although the US product specifications specify that a daily dose of 300mg ritonavir, boosted with 100mg ritonavir is the preferred dose, unboosted atazanavir (400mg once-daily) is still included in recommendations. In Europe atazanavir was approved as a boosted PI.<\/p>\n

At the Resistance Workshop, Donna McGrath and colleagues from Bristol-Myers Squibb presented an evaluation of resistance in treatment naive patients randomised to either boosted (ATV300\/RTV100mg; n=95) or unboosted (ATV400; n=105) atazanavir, as part of first line therapy. Background nucleosides for both regimens were 3TC plus d4T extended release (once-daily).<\/p>\n

Virological failure occurred in approximately 10% of patients using unboosted atazanavir compared to 3% in patients using ritonavir boosting, and is detailed in Table 1.<\/p>\n

Table 1: Virological response and resistance in patients receiving atanazavir +\/- ritonavir<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n
<\/th>\nATV 400mg<\/th>\nATV 300mg\/RTV 100mg<\/th>\n<\/tr>\n
N<\/td>\n105<\/td>\n95<\/td>\n<\/tr>\n
Virological failure<\/td>\n10 (10%)<\/td>\n3 (3%)<\/td>\n<\/tr>\n
Never supressed & on-study wk 48<\/td>\n2\/10<\/td>\n0\/3<\/td>\n<\/tr>\n
Viral rebound<\/td>\n6\/10<\/td>\n3\/3<\/td>\n<\/tr>\n
D\/c due to poor VL response<\/td>\n2\/10<\/td>\n0\/3<\/td>\n<\/tr>\n
No. of isolates for Rx testing<\/td>\n8\/10<\/td>\n2\/3<\/td>\n<\/tr>\n
New emergent mutations<\/td>\n4\/8<\/td>\n0\/2<\/td>\n<\/tr>\n
PI: I50L, I50I\/L<\/td>\n3\/8<\/td>\n0\/2<\/td>\n<\/tr>\n
PI: 63A\/P\/S, 63P, 63P\/S<\/td>\n1\/8<\/td>\n0\/2<\/td>\n<\/tr>\n
RT: M184V at failure<\/td>\n7\/8<\/td>\n1\/2<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

New PI resistance was seen in 4\/8 patients (3 with I50L or mixed I50I\/L, with emergent E34E\/Q, and one with G73G\/S plus T74T\/A substitutions, respectively) vs 0\/2 patients in the unboosted vs boosted groups respectively. Baseline genotype showed 1 to 3 protease substitutions at L10, K20, M36, L63 and A71 in all patients who subsequently failed treatment. No data was provided for patients who successfully responded to treatment.<\/p>\n

Only one of the failing patients (on unboosted atazanavir) showed phenotypic resistance (28-fold change) but retained phenotypic sensitivity to other PIs. The other 7 patients not using ritonavir, also retained phenotypic sensitivity to other PIs. The M184V substitution and phenotypic resistance to 3TC developed in 1\/2 and 7\/8 patients whose treatment failed in the ATV300mg\/RTV100mg and ATV400mg groups respectively.<\/p>\n

The study concluded that these data suggested a protective benefit from ritonavir boosting for naive patients in both reduced risk of virological failure and that, if failure occurs, a reduced risk of resistant mutations.<\/p>\n

Reference:<\/p>\n

McGrath D et al. Evaluation of resistance patterns in treatment-naive subjects with virological failure on atazanavir- or atazanavir\/ritonavir containing regimens. XV International Drug Resistance Workshop, 13-17 June 2006, Sitges, Spain Abstract 87.<\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base Atazanavir was licensed in the US in June 2003 as a treatment for naive or experienced patients, and in Europe it was licensed in March 2004 for use in treatment-experienced patients only. In practice, especially when …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,36],"tags":[112],"class_list":["post-2349","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-drug-resistance","tag-idrw-15th-2006"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/2349","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=2349"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/2349\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=2349"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=2349"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=2349"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}