{"id":1867,"date":"2008-04-01T18:21:05","date_gmt":"2008-04-01T17:21:05","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=1867"},"modified":"2014-09-09T09:05:17","modified_gmt":"2014-09-09T09:05:17","slug":"restarting-treatment-after-an-interruption-reduces-the-risk-of-serious-events-but-cd4-recovery-falls-short-of-baseline-levels","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/1867","title":{"rendered":"Restarting treatment after an interruption reduces the risk of serious events but CD4 recovery falls short of baseline levels"},"content":{"rendered":"

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

Wafaa El-Sadr from the INSIGHT research network, presented an analysis of event rates from the large international CD4-guided treatment interruption study (SMART) that occurred in the 18 month period of follow-up since enrolment was stopped and patients were recommended to restart treatment.<\/strong><\/p>\n

The study was halted following a recommendation by the DSMB in January 2006 after only two of the planed seven years, due to significant benefits in terms of mortality and serious AIDS and non-AIDS morbidity, in favour of continuous treatment.<\/p>\n

As well as providing sufficient power to look at the original study question, this trial dataset (5472 patients were randomised) is providing significant insight into other important aspects of HIV management.<\/p>\n

Prior to January 2006, patients randomised to the treatment discontinuation arm (DC=drug conservation) spent 34% of follow-up time on treatment compared to 94% patients in the continuous treatment arm (VS=viral suppression). Post-January 2006 this increased to 71% vs 91% respectively, and when the study closed in July 2007, 83% and 95% of patients in each arm were on treatment,<\/p>\n

It is important that after the recommendation to restart treatment, the rate of opportunistic infection or deaths all declined in the interruption arm (from 3.4 to 2.1\/100 pt yrs) and stayed constant for patients in the continuous therapy group (1.4\/100 throughout). This was a significant change in hazard ratio between the pre- and post January 2006 hazard ratios (p=0.03). Rates reduced in inverse proportion to time since restarting treatment.<\/p>\n

Although similar trends were reported for other endpoints (death, OI, major CVD renal or hepatic disease) the p-value for the change in hazard ratio pre-and post January 2006 was not statistically significant.<\/p>\n

Although the majority of patients in the DC group re-suppressed viral load, mean CD4 count noticeably failed to reach pre-interruption levels. Patients in either arm who had experienced a non-fatal serious event prior to January 2006 (113 in DC and 50 in VS arms) were at 5.8-fold increased risk of death during the follow-up (95%CI 3.2-10.8), p<0.0001).<\/p>\n

These differences were not explained by patients in the DC not following the recommendation to restart treatment; an analysis of a subgroup of patients who all restarted treatment confirmed similar results.<\/p>\n

Clinics where >85% patients followed the recommendation to restart treatment reported a drop from 3.8 to 1.1 in the DC arm (p=0.02, for difference in HR pre- and post- January 2006). The persistence of increased risk in the DC arm was largely explained by lower mean CD4 count and higher proportion of patients with uncontrolled viraemia.<\/p>\n

When looking at the CD4 response to restarting treatment, the researchers found a significant difference between the two groups, even 18 months after restarting treatment: mean 507 vs 648 cells\/mm3 in favour of the continuous treatment arm. Baseline CD4 counts in each group was approximately 600 cells\/mm3.<\/p>\n

This was not explained by patients within the DC group who chose not to restart treatment as an analysis of a sub group of patients who had all followed the recommendation to restart treatment found similar results.<\/p>\n

The investigators concluded that these results further strengthened the earlier recommendation not to use CD4-guided treatment interruptions, as this was associated with long-term impact beyond the period of interruption.<\/p>\n

Comment<\/h3>\n

This provides additional validation for the decision to stop the study early and for the recommendation to restart treatment.<\/strong><\/p>\n

Although the study provides some evidence that long-term clinical outcome may become normalised over time once treatment is restarted, the significantly lower CD4 count, even 18 months after treatment was resumed, was not expected.<\/strong><\/p>\n

Reference:<\/p>\n

    \n
  1. El-Sadr W et al. Re-initiation of ART in the CD4-guided ART Interruption Group in the SMART Study Lowers Risk of Opportunistic Disease or Death. 15th CROI, 3-6 February 2008, Boston. Abstract 36.
    \nhttp:\/\/www.Retroconference.org:8888\/2008\/Abstracts\/32784.htm<\/a><\/li>\n<\/ol>\n

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

    Simon Collins, HIV i-Base Wafaa El-Sadr from the INSIGHT research network, presented an analysis of event rates from the large international CD4-guided treatment interruption study (SMART) that occurred in the 18 month period of follow-up since enrolment was stopped and …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[62],"class_list":["post-1867","post","type-post","status-publish","format-standard","hentry","category-conference-reports","tag-croi-2008"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1867","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=1867"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1867\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=1867"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=1867"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=1867"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}