Monitoring and modelling prognosis in the era of HAART (Extension to Strategic Grant G0100221)
Lead Research Organisation:
University of Bristol
Department Name: Social Medicine
Abstract
Highly effective treatments, consisting of a combination of different drugs, are now available for people infected with HIV. These treatments have dramatically reduced the risk of acquired immune deficiency syndrome (AIDS) and the risk of death. Since 1996, when these treatments became available, causes of death among adults dying with or due to HIV-infection have changed. The aim of the ART Cohort Collaboration (ART-CC) is to study rates of serious diseases and death in HIV-infected patients who have started combination therapy. The collaboration is coordinated by a small team at Bristol University, and admininistered by a steering committee of cohort representatives. Our most recent dataset contains data on 45,000 HIV-infected individuals combined from 16 cohort studies (studies in which HIV-infected individuals have been followed over time). The present grant covers the period February 2008 to January 2011. Our objectives are (1) To describe the risk of AIDS, AIDS-defining illnesses and deaths from all causes and specific causes in patients starting combination therapy; (2) To define groups of illnesses that have similar implications for the subsequent risk of death, and to propose a classification of these illnesses that is relevant now that effective treatments are available; (3) To examine causes of death in the era of effective treatment, and death rates compare with the general population; (4) To use data from both cohort studies and clinical trials to compare different drug regiments; (5) To examine how outcomes differ between regions, studies, and settings and to conduct comparisons with a sister collaboration in low-income countries. We will derive updated datasets twice during the period covered by the present application. An expert committee will classify causes of death. We will compare mortality rates in HIV-infected individuals with those in the general population. The results of this research will be of direct relevance to the care of HIV-infected patients.
Technical Summary
Highly active antiretroviral therapy (HAART) has substantially improved the prognosis of HIV-infected patients, but has to be continued indefinitely once initiated. 90% of HIV-infected people live in resource-poor settings. HAART has resulted in a shift in the causes of death among adults dying with or due to HIV-infection. Randomized controlled trials (RCTs) of antiretroviral drugs typically examine differences or equivalence in short-term surrogate markers: the extent to which such effects can be extrapolated to clinical outcomes is unclear.
The aim of the ART Cohort Collaboration (ART-CC) is to examine the prognosis of HIV-infected, antiretroviral-na?ve patients starting HAART, with a focus on clinical events (AIDS-defining conditions, death and cause-specific mortality). The collaboration is coordinated by a small team at Bristol University, and admininistered by a steering committee of cohort representatives. Our most recent dataset contains data on 45,000 HIV-infected individuals combined from 16 cohort studies. In the present proposal, we request funding from February 2008 to January 2011.
Our objectives are (1) To describe the risk of progression to AIDS, AIDS-defining events (ADEs), and deaths from all causes and specific causes in treatment na?ve patients starting HAART; (2) To define groups of ADEs with comparable prognostic significance, and to propose a classification for the HAART era; (3) To examine causes of death in the era of HAART, and how cause-specific and all-cause mortality compare with the general population; (4) To examine the relationship between the effects of different HAART regimens on short-term, surrogate outcomes and those on longer term clinical outpoints; (5) To examine how outcomes differ between regions, cohorts, and settings and to conduct comparisons with a sister collaboration in low-income countries.
We will derive updated datasets twice during the period covered by the present application. The development of prognostic models will use our previously published methods. We will examine the prognostic importance of different AIDS-defining events for subsequent mortality. An expert committee will classify causes of death. We will use actuarial methods to compare mortality rates in HIV-infected individuals with those in the general population. We will compare the estimated effects of different initial HAART regimens using data from both RCTs and ART-CC. We will use meta-analytic approaches to examine heterogeneity between regions, cohorts and settings. The results of this research will be of direct relevance to the care of HIV-infected patients.
The aim of the ART Cohort Collaboration (ART-CC) is to examine the prognosis of HIV-infected, antiretroviral-na?ve patients starting HAART, with a focus on clinical events (AIDS-defining conditions, death and cause-specific mortality). The collaboration is coordinated by a small team at Bristol University, and admininistered by a steering committee of cohort representatives. Our most recent dataset contains data on 45,000 HIV-infected individuals combined from 16 cohort studies. In the present proposal, we request funding from February 2008 to January 2011.
Our objectives are (1) To describe the risk of progression to AIDS, AIDS-defining events (ADEs), and deaths from all causes and specific causes in treatment na?ve patients starting HAART; (2) To define groups of ADEs with comparable prognostic significance, and to propose a classification for the HAART era; (3) To examine causes of death in the era of HAART, and how cause-specific and all-cause mortality compare with the general population; (4) To examine the relationship between the effects of different HAART regimens on short-term, surrogate outcomes and those on longer term clinical outpoints; (5) To examine how outcomes differ between regions, cohorts, and settings and to conduct comparisons with a sister collaboration in low-income countries.
We will derive updated datasets twice during the period covered by the present application. The development of prognostic models will use our previously published methods. We will examine the prognostic importance of different AIDS-defining events for subsequent mortality. An expert committee will classify causes of death. We will use actuarial methods to compare mortality rates in HIV-infected individuals with those in the general population. We will compare the estimated effects of different initial HAART regimens using data from both RCTs and ART-CC. We will use meta-analytic approaches to examine heterogeneity between regions, cohorts and settings. The results of this research will be of direct relevance to the care of HIV-infected patients.
