Pilot Award Recipient: Blair Spence, MD

Antiretrovirals and neurocognition in HIV infected women

August 14, 2018

The human immunodeficiency virus (HIV) infects the brain soon after infection and can cause cognitive (mental) difficulties for infected persons. These difficulties may be mild or severe, but as better treatments for HIV have become available the severity of these cognitive difficulties have decreased. However, it is still common to see these difficulties in both men and women living with HIV. Several reasons have been proposed to explain this include direct effects of the HIV virus itself, toxic effects of HIV medications, or the inability of HIV medications to reach the brain. There are studies that show protease inhibitors, a type of medication used to treat HIV, may cause damage to the brain. Use of these medications may contribute to the continued observation of cognitive difficulties in men and women treated for HIV. This study will determine if the women enrolled in the Women’s Interagency HIV Study (WIHS) currently taking or have previously taken protease inhibitors or other medications used to treat HIV are more likely to develop cognitive difficulties. It will also determine if a long history of taking these medications makes women living with HIV more likely to have cognitive difficulties and/or have more severe difficulties.

In addition, because cognitive difficulties are so common in men and women living with HIV, biomarkers (blood tests) are needed to predict who will develop cognitive difficulties. Earlier diagnosis could help doctors give treatments or other interventions to patients sooner. β-Amyloid, a protein that can be tested for in the blood, is being studied in the blood and spinal fluid of HIV uninfected patients as a test for cognitive difficulties. Recent studies showed that certain HIV medications may cause higher levels of this protein. This study will use the stored samples from the WIHS to test for β-Amyloid in women living with HIV, and see if the levels are different in women taking certain HIV medications and/or can be used to predict which women will develop cognitive difficulties. Finally, prior studies showed that variations in the genetic make-up found in certain parts of your DNA (termed “genes”) may predispose patients to develop cognitive dysfunction or have unwanted side effects to certain drugs. These gene differences have been studied extensively in patients with Alzheimer’s type dementia, a disease that causes cognitive difficulties in adult patients. This study will use the WIHS database to evaluate the women for the presence of several of these gene differences that have been seen in non-HIV infected patients with cognitive difficulties. These genetic abnormalities may be linked to worse health outcomes or the development of gene differences in women exposed to protease inhibitors. This information may help doctors tailor the type of medication they give to their patients.

This study is especially relevant to the District of Columbia (DC) as there are currently 12,964 residents living with HIV by the latest report from the DC Department of Health HIV/AIDS, Hepatitis, STD, and TB Administration. In this population of individuals living with HIV, over 16% are age 60 or above and 27% are over the age of 50. In persons living with HIV, older age is associated with an increased risk of cognitive difficulties. More research is needed in this aging population about the potential causes of these difficulties. Findings will be communicated to the public in the form of a scientific manuscript as well as a presentation at a scientific meeting. Findings will also be communicated to the community with presentations to community groups including members of the Women’s Interagency HIV Study community action board.