Two members of the amfAR Institute for HIV Cure Research, Drs. Priscilla Hsue and Steven Deeks of the University of California, San Francisco, have long been interested in clinical, non-AIDS defining complications linked to chronic HIV infection. Such disorders of the heart, kidneys, bone, and metabolism are known to be associated with diseases characterized by persistent inflammation in patients without HIV. In prior publications, these researchers have documented that heart attacks, sudden death due to heart failure, and stroke are more frequent among HIV-infected individuals, despite complete viral suppression by antiretroviral therapy (ART). These conditions are particularly worrisome as people with HIV are aging.
Now, writing in the February issue of JAMA Cardiology, Hsue, Deeks, and colleagues at Harvard Medical School, the Academic Medical Center in Amsterdam, Leidos Biomedical Research in Frederick, MD, the National Institutes of Health (NIH), and the University of Montreal dissect some of the obstacles to preventing or treating these complications.
Seventy-four men, including 45 who are HIV-positive and 29 uninfected controls, with a median age about 52, were recruited from an ongoing observational study. There were three types of HIV-positive participants: those with undetectable viral loads on ART; “elite controllers,” with undetectable viral loads despite not taking ART; and “noncontrollers,” characterized by detectable virus despite ART. All of them underwent PET scanning to examine the extent of inflammation in the lymph node and large artery. Inflammation in lymph nodes is of interest as it may permit HIV replication and spread. It may also lead to fibrosis (the thickening and scarring of connective tissue), impairing the necessary communication between immune cells in these organs that could help fight the virus. Inflammation revealed by these scans was compared with HIV activity, T cell counts, and monocyte (a type of white blood cell) activity in their blood.
As expected, arterial inflammation was higher in the HIV-positive individuals and it directly correlated with blood markers for inflammation, including levels of activated monocytes. However, these levels were not associated with the amount of HIV activity. Conversely, there was a closer association between HIV disease and inflammation in the lymph nodes. Thus, HIV is strongly associated with inflammation in the lymph nodes but not in the arterial walls, suggesting that the root causes of inflammation in each of these tissues may differ.
The reasons for this lack of coordination between tissues are unclear. The authors theorize that these differences “may have an important impact on treatment strategies."
They summarize: "(The) therapeutic interventions that reduce viral disease activity may not predictably reduce arterial inflammation in HIV or its downstream consequence (i.e., cardiovascular disease).”
Dr. Laurence is amfAR’s senior scientific consultant.