Julian Langton-Lockton

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

Pathogenesis of HIV complications - HIV related morbidity

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 Greetings from CROI 2015

This is a big conference with a substantial focus on topics such PrEP programmes and Hepatitis C treatments. However I would like to write on the data looking at HIV pathogenesis and long term persistent systemic inflammation which contribute to increasing age related morbidity such as cancer and cardiovascular risks.

In current HIV care, age related HIV morbidities such as cardiovascular disease; cancers, neurocognitive and frailty not only have a huge impact on the patient but also on what the service can offer. It may impact the HIV drugs prescribed and the drug to drug interactions must be considered.  General practice and specialist HIV monitoring may need to be increased and multidisciplinary support for lifestyle modifications such as smoking cessation, diet, exercise etc.

Peter W Hunt of University of California convened and presented a workshop – Pathogenesis of HIV complications, which was an overview of HIV complications many of which present as HIV age related morbidities, immune modulated pathogenesis factors and the use of inflammatory bio markers.

What this session highlighted is the pathogenesis of HIV is complex with chronic inflammatory processes playing a significant role in the end organ disease. It also questioned if traditional HIV markers such as CD4 and VL have any predictive value for morbidity and illness such as cancer or cardiovascular events.

It is well documented that both primary HIV infection and chronic HIV infections have a direct and significant impact on the in the lymphatic system, especially when looking at the Gut Associated Lymphoid Tissue GALT. In this workshop it highlighted two pathways, firstly that persistent HIV infection and inflammation causes lymphoid tissue fibrosis, which changes the structure of lymphoid tissue and this in turn reduces lymphoid tissue availability for HIV naïve T cells and IL7 responses. A second suggested pathway is the HIV associated “leaky gut” which involves the lamina propria of the gut wall. This is a process effects the integrity of the gut immunity with specific depletion of T and B cells and disruption of the epithelial tight junctions, with impaired function and cytokine regulation.

In this overview workshop it presented a series of data looking at plasma inflammatory biomarkers (IL6 and D Dimer) in HIV positive individuals who were not on treatment, a second group who commenced treatment after longstanding HIV infection and a third group who started treatment early after primary HIV infection, these were compared to HIV negative control group. The IL6 and D dimer were markers were measured at baseline of treatment and subsequent follow up time intervals.

At baseline all HIV positive groups showed raised levels of IL6 and D dimer compared to controls. In the follow up of the second group (delayed HIV treatment), the levels improved but still remained elevated compared to the control group.  Interestingly for those individuals who commenced treatment soon after HIV diagnosis or during sero- conversion the D-Dimer and IL6 levels returned to a similar level as found in the HIV negative control group.

The take home message from this workshop is that the pathogenesis of HIV morbidity is complex and that a chronic persistent HIV with a chronic inflammatory immune response may contribute to the risk of developing HIV age related morbidity. Early HIV treatment is likely to have a positive impact on the process. Complex inflammatory markers have a role to play, but will not yet replace CD4, VL as the traditional markers for HIV management.

I would like to further blog on current research looking at persistent inflammation after initiation of HAART in acute HIV infection and HIV disease in the gut during acute HIV infection...


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