EMEA statement on metabolic and cardiovascular complications of antiretroviral therapy in HIV-infected patients
Two public statements, were published on the EMEA website on Friday, 5 August 2005.
Both statements relate to research initiated by the European regulatory agency in response to safety and toxicity concerns from the long-term use of antiretrovirals in combination therapy. The research has been a unique collaborative response between the companies, independent investigators and the community, and has produced some of the most solid data on this aspect of HIV management.
It has included international cohort collaborations including the D:A:D study and more recently has started to look at implications for patients coinfected with HIV and hepatitis.
These statements were based on the Oral Explanations presented at June meeting of the CHMP and the conclusions reached.
Statement on metabolic and cardiovascular complications of antiretroviral therapy in HIV- infected patients
The issue of metabolic disorders and antiretroviral treatments for HIV-infection was first raised in 1998 following the identification of the lipodystrophy syndrome (fat redistribution) and hyperlipidaemia, which were suspected to be related to combination antiretroviral therapy (CART). The observations of metabolic abnormalities and additional reports of premature cardiovascular and cerebrovascular disease in association with chronic treatment and HIV-infection in itself raised further concerns about adverse effects and the management of patients. Therefore, in 1999, all concerned Marketing Authorisation Holders (MAHs) committed to start a collaboration to address a list of questions from the EMEAs Committee for Proprietary Medicinal Products (CPMP) regarding the prevalence and especially the incidence of long-term complications and short-term effects of body composition and metabolic abnormalities. They set up a Steering Committee and jointly committed to support a number of epidemiological studies (VA Retrospective Study1, D.A.D Study2 and a case definition study for fat redistribution) and an assessment of clinical trials approaching the evaluation of short-term complications including a meta-analysis of large ongoing prospective collaborative trials. The Steering Committee also included representatives of the EMEA/CPMP, the FDA and patient groups in the EU and the USA.
In March 2003, in connection with the assessment of the submitted data, an oral presentation to the CPMP was made by the principal investigators of the studies and by the MAHs. At the time, the CPMP concluded that the studies had to be continued for an extended follow-up time (http://www.emea.eu.int/pdfs/human/press/pus/238303en.pdf). (101 k)
In June 2005, the Steering Committee submitted an updated report presenting new data from the D.A.D. and the VA studies. At an oral explanation at the CHMP (previously CPMP) in June 2005, the MAHs together with the principal investigators presented the results of these studies, their conclusions and proposals for further support to the D.A.D study until January 2008. The Pharmacovigilance Working Party of the CHMP discussed the assessment report in June 2005 and also took part in the oral explanation. The conclusions from this meeting were formally adopted by the CHMP in its July 2005 meeting.
The CHMP endorsed the proposed extended support to the D.A.D study and further they concluded that the studies have provided reassuring data on the risk of cardiovascular and cerebrovascular events associated with exposure to combination antiretroviral treatment in HIV-infected patients. In the D.A.D. study, the risk of myocardial infarction (MI) with this therapy was increased but no increased risk of MI or hospitalisations (for cardiovascular or cerebrovascular disorders) was found in the VA study. Considering the increased risk of MI and of other vascular effects, derived from D.A.D study data, in general both these studies show that the benefit-risk balance of antiretroviral therapy in HIV-infection remains strongly favourable and should not lead to withholding of CART when indicated for these patients. The full final study report from the D.A.D study is expected to be submitted in the beginning of 2009.
European Medicines Agency Post-authorisation Evaluation of Medicines for Human Use. 5 August 2005.
http://www.emea.eu.int/pdfs/human/press/pus/24902205en.pdf (32 k)
- A study entitled A Retrospective Cohort of the Risk of Cardiovascular Events in HIV Patients on HAART utilising the Veterans Administration Database.
- A large multi-cohort prospective study to evaluate cardiovascular risk know as The Data Collection on Adverse Events of Anti-HIV Drugs.