**Association Between Multiple Sclerosis Risk and Human Immunodeficiency Virus Infection: Insights and Challenges**

Ehtishamul Haq, Insha Zahoor and Mushfiquddin Khan

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63828

#### **Abstract**

Multiple sclerosis (MS) is a convoluted autoimmune and inflammatory disease of the central nervous system (CNS) in which the protective myelin sheath is eroded and the underlying nerve fibers are damaged. There is no conclusive knowledge on the role played by different etiological factors in its development, and studies have shown that it primarily results due to complex interactions between the genetic, geographic and infectious components. Among the risk factors reported to have a possible role in MS development, retroviruses also appear to influence it. Studies suggest human immunodeficiency virus (HIV) infection to be inversely related to MS risk, but to date, the association between the two remains enigmatic. This protec‐ tive inverse association has become an area of active research and the most plausible explanations for this may be immune suppression and/or antiretroviral medica‐ tions. The purpose of writing this chapter is to provide background information on the unfathomable relationship between HIV infection and the risk of developing MS while at the same time providing description of the insights garnered from recent studies. While highlighting the application of ART (antiretroviral therapy) as budding future alternative for MS management, this chapter provides momentum for further studies.

**Keywords:** multiple sclerosis, etiology, human immunodeficiency virus, epidemiolo‐ gy, ART

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **1. Introduction**

Multiple sclerosis (MS) is a complex, debilitating neurologic disease characterized by demye‐ linationof axons inthebrainandspinal cordandcausedbyanimmune attackagainstthemyelin sheath. The disease is highly prevalent in North America and Europe (>100/100,000 inhabi‐ tants). According to the recently revised 2013 Atlas of MS published by the World Health Organization(WHO)andMultipleSclerosisInternationalFederation(MSIF)(http://www.atlas‐ ofms.org), the prevalence rate of 5–20 per 100,000 has been reported for India. Clinically, MS is characterized by a broad spectrum of symptoms [1]. It has autoimmune and inflammatory components, with intense effects on the communication between nerve cells within the brain and spinal cord [1]. The different types of MS vary in terms of severity, prevalence, and degree of progression [2, 3]. The most common phenotype is relapsing remitting (RR) MS, followed by secondaryprogressive (SP) andthenprimaryprogressive (PP).Lessprevalentphenotypeshave also been reported [2]. MS pathology is characterized by inflammatory plaques caused by demyelination of axons in the central nervous system (CNS). Due to the presence of immuneinflammatory characteristics in MS, treatments targeting T lymphocyte and natural killer (NK) cell activation seem to play a significant role [4].

With intangible and enigmatic etiology having both genetic and environmental backgrounds, MS offers a profound conundrum. Yet, despite incomplete understanding of the basic mechanisms behind its pathogenesis, a growing body of evidence suggests heterogeneous etiology of MS with multiple environmental factors contributing to its development [5–7]. Various studies suggest that intricate interactions between genetic factors and environmental factors elicit it; thus, genetically susceptible individuals who encounter a number of environ‐ mental and epigenetic factors are at higher risk (**Figure 1**) [8, 9].

**Figure 1.** Multiple sclerosis as a complex neurological condition affecting CNS: The etiology of MS is unknown and enigmatic; however, it has a profound role of numerous environmental and genetic components, and multiplex inter‐ actions between them lead to its development, thus making it a multifactorial and polygenic heterogeneous disease.

Some risk factors, which have been studied in various populations, include geographic location [10, 11], wheat consumption [11, 12], dairy product consumption [13, 14], fish intake [15], animal fat intake [15], high ultraviolet radiation [16–18], vitamin D deficiency [19], and viral infection [20–22]. The likely association between genetic and infectious components in MS development is shown by the human endogenous retroviruses (HERVs) [23, 24]. Although many viruses have raised suspicions as responsible for MS, not all studies confirm their etiologic role. Thus, each virus has chalked up another obstruction in the MS conundrum. There is escalating evidence suggesting a retroviral connection to MS risk, and the most noteworthy among them is human immunodeficiency virus (HIV). Studies suggest HIV infection to be inversely related to MS risk [25–27] but, to date, the association between the two remains enigmatic [28]. The purpose of this chapter is to provide an overview of the insights garnered from recent studies on the association between HIV and MS risk. While highlighting this association, the main objective of this chapter is to provide an impetus for future studies aimed at precisely establishing the mechanism behind the impact of HIV on MS.
