HIV-1 infected African populations who use NRTI/NNRTI (two classes of antiretroviral drugs, used for the treatment of AIDS) and suffer from Metabolic Syndrome (MS) have an increased risk of arteriosclerosis or atherosclerotic cardiovascular disease (ASCVD). This is what Dr Titus Francis Msoka described in his dissertation. His supervisors were Prof. dr. A.M. van Tutu-Furth and Prof.dr. M.A. van Agtmael, together with his co-supervisors Prof.dr. Y.M. Smulders and Pr. G. van Guilder.

Dr. Msoka studied HIV, combination antiretroviral therapy (cART) treatment of HIV (with NRTI/NNRTI) and the Metabolic Syndrome in relation to the risk of cardiovascular disease (CVD) in HIV-infected populations. The results of Dr. Msoka and colleagues suggest that the main causality for the increased cardiovascular risk (CVR) is the HIV-infection itself.

Their results suggest that the main culprit for the increased risk of arteriosclerosis or atherosclerotic cardiovascular disease (ASCVD) is the virus itself with cART and Metabolic Syndrome playing an amplifying role. This has also been attested by Rider. Furthermore, previous studies* on ‘elite controllers’ – HIV-infected people who control HIV replication to undetectable levels without antiretroviral therapy – showed increased coronary atherosclerosis and monocyte activation compared to uninfected individuals suggesting that the main cause of this comorbidity is related to HIV infection itself.

Targeting immunological metabolism

Moreover, previous studies* compared transient controllers (patients who lose viral control) with persistent controllers (patients who maintain viral control). They have found differences in the immunometabolism of these groups, suggesting that targeting immunometabolism in therapeutic strategies for HIV-1 infection could reduce atherosclerotic cardiovascular risk in HIV-1-infected populations by enhancing immune response and thus clearing HIV-1 from their reservoirs.

Dr. Msoka and colleagues also showed that those in whom viral control was maintained had a different immunological metabolism than those with transient viral control. This suggests that targeting immunological metabolism could reduce the risk of atherosclerotic cardiovascular disease in HIV-1-infected populations, namely by enhancing the immune response and thereby removing HIV-1 from reservoirs.

The way forward

According to Dr Msoka the best way to proceed would be to decrease HIV-reservoirs and finding a vaccine for HIV-1. However, he states: ‘these are monumental tasks that have not been achieved in decades of research. I think that it would be more achievable to move forward with preventing and treating cardiovascular comorbidities for people suffering from HIV-1 effectively.’

'Given enough funds, I am planning to conduct longitudinal prospective follow-up studies with adequate power to correctly elucidate the differences in cardiovascular risk between HIV-1 infected and uninfected persons and the causative processes of cART and metabolic syndrome in HIV-1-infected individuals.'
Dr. Titus Francis Msoka

Longitudinal prospective studies

Dr Msoka and colleagues have uncovered interesting relationships in this study however more research is needed. Dr. Msoka: 'Specifically, longitudinal prospective studies with adequate power should be conducted to correctly elucidate the differences in cardiovascular disease risk between HIV-1 infected individuals and uninfected individuals and the causative processes of cART treatment (with NRTI/NNRTI) and metabolic syndrome in HIV-1-infected individuals.’ When Dr Msoka has received sufficient funds for this project he will personally be eager to continue this line of research.

Amsterdam Institute for Infection and Immunity (AII) warmly congratulates Dr. Titus Francis Msoka on earning his PhD.

For more information contact Dr. Titus Francis Msoka or read the dissertation.

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    Text: Esmée Vesseur