**3. Conclusion**

explanation for this protective effect may be HIV-induced immunodeficiency targeting a wide continuum of immune cells and signal transduction pathways involved in MS pathogenesis. Alternatively, antiretroviral medications used against HIV may target other viruses involved

**Figure 2.** Protective inverse relationship between MS and HIV: HIV infection leads to reduced MS risk, which may be attributed to constant suppression of the immune system by HIV-induced immunodeficiency targeting diverse spec‐ trum of immune cells and signal transduction pathways involved in MS pathogenesis, and/or antiretroviral drugs used

The big puzzle of whether and when to start HIV therapy in MS patients remains blurred. Previous studies based on case report and data linkage studies presumed that protective infection was conferred against MS development due to ART treatment rather than HIV infection *per se*. However, in neither case has systematic description been offered about the individuals who were treated with ART and those who were not [27]. There are still different opinions on early [35] and late treatment options due to different aspects such as side effects and drug resistance [36]. Therefore, no clear-cut approach exists on starting ART. In these studies, nothing has been mentioned about exposure to antiretroviral medications and its duration [27]. Moreover, HIV and MS are often misdiagnosed due to the presence of MS-like symptoms in HIV; therefore, focus should be on targeted treatments of MS patients with HIV and vice versa. To fully understand the mechanism behind the apparently MS-protective phenotype of HIV infection, the most plausible research approach would be analysis of data on HIV patients with MS or vice versa and the details on influence of cotreatment with

Due to the presence of immune-inflammatory characteristics in MS, treatments targeting T lymphocyte activation may play a significant role. There is growing evidence that favors suppression of MS pathology by employing anti-HIV therapy, and it has prompted one trial in MS patients for the drug Raltegravir (Isentress) [37] used in HIV treatment and also an immunoglobulin G4 monoclonal antibody called GNbAC1 [4, 38–40] against HERV proteins. The association between HIV and MS can be exploited to replace conventional treatment options for MS by formulating new safe, effective, and long-term therapeutic alternatives. Further investigations are mandatory to provide a deeper insight into the mechanism of action

to treat the infection, thus preventing MS progression or treating it completely.

antiretroviral medications and disease-modifying treatments (DMTs).

in MS pathogenesis such as, HERV and herpes.

190 Trending Topics in Multiple Sclerosis

Despite the extensive research on MS, its exact etiology remains hard to pin down. Neverthe‐ less, epidemiological findings across the globe suggest its association with specific retroviruses endogenous to humans. Regardless of the paucity of reports on HIV and MS association, this finding appears to be crucial in the etiology of MS. A comprehensive understanding of this link is needed to elucidate the complex interactions between HIV and MS and also to exploit HIV's protective role in order to develop treatments for MS. Research that unscrambles the relation between the two would, at the same time, provide new insights into the etiopatho‐ genesis of MS and provide therapeutic targets and strategies.

Nevertheless, additional studies on mechanisms of interaction between HIV and MS are required to determine the underlying mediators of this protective association and eventually endow insight into the disease pathogenesis as well as its management. To date, the studies in this milieu hitherto are insufficient, and there is extreme need for an extensive upsurge in large-scale conclusive molecular and epidemiological studies. It is noteworthy that this chapter further enlightens the acuity of an association between HIV (or its treatment) and a reduced risk of developing MS; however, it is flagrant that this association needs to be examined skeptically in order to gain deeper insight into this enigmatic relationship. The need of hour is to establish precisely whether having HIV, being treated for HIV with antiretroviral drugs, or a combination of the two reduces the risk of developing MS, which will certainly open the door for developing better and more promising treatment options for MS.
