HIV DNA in circulating monocytes as a mechanism to dementia and other HIV complications

Abstract

It is broadly accepted that HIV DNA in lymphoid and myeloid cells persists despite combination antiretroviral therapy. Recognized as the Achilles heel to HIV eradication, the role of these peripheral reservoirs in HIV morbidity is less well developed. The burden of HIV DNA in peripheral mononuclear cells is linked to HIV disease outcomes such as time to AIDS diagnosis, survival, and CD4 T-lymphocyte counts. Monocytes are a minor HIV DNA reservoir, and the burden of HIV DNA in these cells appears to be linked to dementia, suggesting that residual infection in this subset is linked to tissue-related HIV complications. Since monocytes are likely involved in trafficking virus to the brain, there is a strong mechanistic link underlying this discovery. Herein, we summarize our current understanding of monocyte HIV DNA and central nervous system dysfunction in humans. We present a model to understand these relationships and suggest possible treatment approaches to be tested.

Figure 1.

A model of brain injury in HIV. Activated monocytes transmigrate the blood-brain barrier resulting in inflammation, oxidative stress, and neuronal injury.

Figure 2.

HIV DNA content in various monocyte blood cell subsets in individuals with HAD vs. normal cognition (NC). (A) HIV DNA is higher in individuals with HIV-associated dementia (HAD) (left) compared with individuals with NC in the CD14+CD16+ subset. (B and C) In CD14⁺/CD16^– (B) and CD14^– (C) subsets, the amount of HIV DNA does not differ between individuals with HAD (left) and individuals with NC.

Figure 3.

HIV DNA in circulating monocytes in a naïve cohort and 6 and 12 mo following highly active antiretroviral therapy. HIV DNA remains elevated in dementia but not nondementia cases.