Risk of Multiple Sclerosis in People Living with HIV: An International Cohort Study, 2023, McKAy et al

[EndME]

Risk of Multiple Sclerosis in People Living with HIV: An International Cohort Study

Abstract

Objective
There has been interest in a possible negative association between HIV and multiple sclerosis (MS). We aimed to compare the risk of MS in a cohort of individuals living with HIV to that in the general population.

Methods
Population-based health data were accessed for 2 cohorts of HIV-positive persons from Sweden and British Columbia, Canada. Incident MS was identified using MS registries or a validated algorithm applied to administrative data. Individuals with HIV were followed from 1 year after the first clinical evidence of HIV or the first date of complete administrative health data (Canada = April 1, 1992 and Sweden = January 1, 2001) until the earliest of incident MS, emigration, death, or study end (Canada = March 31, 2020 and Sweden = December 31, 2018). The observed MS incidence rate in the HIV-positive cohort was compared to the expected age-, sex-, calendar year-, income-specific, and region of birth-specific rates in a randomly selected sample of >20% of each general population. The standardized incidence ratio (SIR) for MS following the first antiretroviral therapy exposure (“ART-exposed”) was also calculated.

Results
The combined Sweden-Canada cohort included 29,163 (75% men) HIV-positive persons. During 242,248 person-years of follow-up, 14 incident MS cases were observed in the HIV-positive cohort, whereas 26.19 cases were expected. The SIR for MS in the HIV-positive population was 0.53 (95% confidence interval [CI] = 0.32–0.90). The SIR for MS following the first ART exposure was 0.55 (95% CI = 0.31–0.96).

Interpretation
This international population-based study demonstrated a lower risk of MS among HIV-positive individuals, and HIV-positive ART-exposed individuals. These findings provide support for further exploration into the relationship among HIV, ART, and MS.


https://onlinelibrary.wiley.com/doi/full/10.1002/ana.26840

 

[Hutan]

There is a substantial decrease of risk of MS in the HIV positive women, but the numbers of people with HIV going on to get MS are very small, even in men (and men constituted the majority of the samples).

In sex-specific analyses, the SIR for MS incidence following the first ART exposure was significantly reduced for women with HIV (SIR = 0.25, 95% CI = 0.06–0.98), but not for men with HIV (SIR = 0.72, 95% CI = 0.39–1.35).

Nevertheless, these counteracting processes led to the hypothesis that HIV, by reducing peripheral CD4+ T cell counts, modifies the pathogenesis of MS.5 In contrast to this line of reasoning, it is noteworthy that HIV positivity has been linked to a heightened incidence of other autoimmune diseases,14, 15 perhaps related to the chronic activation of CD8+ cells.16

The suggestion that ART might alter MS risk appears to have partly stemmed from a series of case reports of persons with comorbid HIV and MS.5 These reports included observations of limited MS disease activity and disability progression, which led to speculation that ART exposure might translate to a lowered MS risk.5 Possible mechanisms for the effectiveness of ART in reducing MS disability, or even MS risk, include the inhibition of human endogenous retroviruses or Epstein–Barr virus.5, 17, 18 With regard to EBV, it is known that individuals with HIV have a higher risk of EBV-related Hodgkin's lymphoma than individuals without HIV. Since the advent of ART though, whereas the risk of Hodgkin's lymphoma has remained higher, the prognosis has markedly improved in persons living with HIV.19, 20

A difference in risk for HIV and MS by region of origin is a conceivable explanation for the low risk of MS in persons with HIV. Because HIV is more prevalent in certain regions, including Sub-Saharan Africa,25 whereas MS occurs with greater frequency in countries further from the equator.26 There is a high proportion of people born in Sub-Saharan Africa in the Swedish HIV cohort, and we were able to take this into account by stratifying the analyses by region of birth.

They took country of birth into account, but didn't take length of time living there, or years there during childhood into account.

Further work on the relationship between ART use and MS risk is warranted. However, our findings might also motivate a more concerted effort to ascertain whether ART use, or specific ART combinations, could beneficially alter subsequent MS disease progression. In the face of limited research resources, this line of inquiry may yield a more immediate clinical benefit, addressing the major unmet need to develop better treatment strategies aimed at preventing or ameliorating the unrelenting progression in MS.35