Chronic Pain in HIV

Abstract

The evolution of therapeutics for and management of human immunodeficiency virus-1 (HIV-1) infection has shifted it from predominately manifesting as a severe, acute disease with high mortality to a chronic, controlled infection with a near typical life expectancy. However, despite extensive use of highly active antiretroviral therapy, the prevalence of chronic widespread pain in people with HIV remains high even in those with a low viral load and high CD4 count. Chronic widespread pain is a common comorbidity of HIV infection and is associated with decreased quality of life and a high rate of disability. Chronic pain in people with HIV is multifactorial and influenced by HIV-induced peripheral neuropathy, drug-induced peripheral neuropathy, and chronic inflammation. The specific mechanisms underlying these three broad categories that contribute to chronic widespread pain are not well understood, hindering the development and application of pharmacological and nonpharmacological approaches to mitigate chronic widespread pain. The consequent insufficiencies in clinical approaches to alleviation of chronic pain in people with HIV contribute to an overreliance on opioids and alarming rise in active addiction and overdose. This article reviews the current understanding of the pathogenesis of chronic widespread pain in people with HIV and identifies potential biomarkers and therapeutic targets to mitigate it.

Keywords: HIV; HIV-1 proteins; chronic widespread pain; inflammation; peripheral immune cells; peripheral neuropathy.

Figure 1.

Pro-inflammatory M1 macrophages release pro-algetic cytokines, IL-1β, IL-6, and TNF-α. However, pro-resolution M2 macrophages release anti-inflammatory cytokines, IL-10, and anti-algetic endogenous opioid peptides Met-enkephalin, dynorphin A, and β-endorphin. IL: interleukin; TNF: tumor necrosis factor; TGF: transforming growth factor.

Figure 2.

HIV-1 proteins, gp120, Tat, and Vpr along with the antiviral drugs increase the release of pro-inflammatory and pro-algetic cytokines, IL-1β, IL-6, and TNF-α from M1 macrophages, which contributes the development of chronic pain in HIV. IL: interleukin; TNF: tumor necrosis factor.