Investigating Comorbidity in relation to HIV/AIDS with the COBRA Study
The COBRA Study, which is an abbreviation of COmorBidity in Relation to HIV/AIDS, is a project funded through the European Union 7th Framework Program and coordinated by Prof. Peter Reiss, that started in March this year. A team from 12 institutions in 6 countries collaborate in this study from a diverse range of fields, including Stichting HIV Monitoring. We discussed COBRA further with Dr. Ferdinand Wit, an HIV physician and epidemiologist at the AMC and the Amsterdam Institute for Global Health and Development, who is co-responsible for the COBRA study’s scientific coordination and data analysis.
Research focused on link
As a result of combination antiretroviral therapy (cART), individuals infected with HIV are now living longer. As a consequence of ageing, those living with HIV are experiencing an increasing number of age-associated non-communicable comorbidities such as cardiovascular disease, diabetes mellitus, chronic kidney and liver disease, osteoporosis, non-AIDS associated malignancies, chronic obstructive pulmonary disease and neurocognitive decline. These comorbidities may occur more frequently and at an earlier age when compared to HIV-negative individuals. As HIV-infected patients age their care is becoming increasingly complex and challenging because of the need to prevent and manage multiple comorbidities.
COBRA aims to clearly establish the link between HIV infection and ageing-associated comorbidities. The study aims to explain and clarify this link by identifying whether there is a causal relationship between HIV infection and ageing-associated comorbidities, and by understanding this in terms of underlying pathogenic mechanisms. The study also aims to provide new insights into the potential role of cART on comorbidity development and to develop biomarkers that can be used for better prevention, treatment and management of comorbidities.
“The big question is what risk factors are contributing to these comorbidities?” comments Dr. Wit. “There appear to be many links and multiple causes, both traditional risk factors and HIV-related risk factors. Thought processes about the reason why comorbidities occur has changed over time but it is now thought low grade immune activation and inflammation, possibly triggered by various mechanisms including residual replication of HIV production and increased gut microbial translocation, may be involved. Linked to this, HIV may accelerate or amplify the regular ageing processes, leading to a greater risk of diseases such as heart disease, for instance, to become apparent earlier than if that person was HIV-negative. It is important to establish links between these causative factors.”
Two clinical sites
Recruitment of participants has started with the aim of enrolling 150 HIV-infected and 100 comparable HIV-uninfected middle-aged individuals. These participants are being recruited from two ongoing studies - the POPPY or Pharmacokinetic and Clinical Observations in People over Fifty study in London, and the AGEhIV cohort study in Amsterdam (see elsewhere in this newsletter). These studies are both linked to national HIV databases, which are the CHIC cohort in the UK and the Athena/Stichting HIV Monitoring cohort in the Netherlands.
“Participants will undergo comprehensive testing at study entry and again after 2 years,” says Dr. Wit. “A range of samples will be taken and stored for biomarker analysis. All subjects will undergo neurocognitive function assessments including a lumbar puncture (spinal tap), extensive brain imaging and standardized neuropsychological assessments.”
Collaborative effort
COBRA brings together researchers with experience in diverse areas of clinical and basic science from fields including HIV, age-associated non-communicable comorbidities and ageing. Close involvement of a number of partners with existing large collaborations, including the EuroCoord Network of Excellence and the MARK-AGE project, to establish biomarkers of human ageing, will significantly contribute to the dissemination of results to a wide range of diverse stakeholders.
Making an impact
It is anticipated that COBRA will increase understanding of the clinical burden, the degree of premature onset, risk factors, and biomarkers predictive of a range of ageing-associated comorbidities. Knowledge gained from the project may have a significant impact on future best practices regarding the management of comorbidities in HIV-positive patients.
“COBRA is really the first step,” explains Dr. Wit. “Once evidence on causal links is collected this will lead to spin-off projects to validate these findings in larger cohorts. I expect this study will contribute to the development and validation of new diagnostic tests and therapeutic strategies. It will also be important in improving prevention, treatment and management of comorbidities in HIV-infected patients.”
Organisations participating in the COBRA study include the Academic Medical Center and the Amsterdam Institute for Global Health and Development, Erasmus University Medical Center, Municipal Health Services of Amsterdam (GGD), Stichting Katholieke Universiteit Nijmegen and Stichting HIV Monitoring from the Netherlands; Imperial College London and University College London from the United Kingdom; VIB Life Sciences Research Institute from Belgium; Goeteborgs Universitet from Sweden; Universita di Bologna and Universita degli Studi de Modena from Italy; and Universitat Konstanz from Germany.