People with HIV are less likely to develop multiple sclerosis than the general population, but more data are needed to establish whether receipt of antiretroviral therapy (ART) influences the reduced risk, according to a recent population-level study.
The international team of researchers used data from patient cohorts in British Columbia and Sweden to compare the incidence of MS among those with and without HIV. They also sought to assess how taking ART influenced MS risk in these patients.
In total, 18,773 people with HIV in British Columbia and 10,390 with HIV in Sweden were included in the study (Ann Neurol 2024;95[3]:487-494). In both areas, participants were mostly male (British Columbia, 79.9%; Sweden, 65.9%), on average were diagnosed with HIV in their late 30s (British Columbia, 39.4 years of age; Sweden, 35.5 years), had a lower income (British Columbia, 31.9% in lowest income quintile; Sweden, 37.6% in lowest income quintile) and had received at least one dose of ART (British Columbia, 87.8%; Sweden, 93.8%).
After standardizing age, sex, year, socioeconomic status and global geographic region of birth, the incidence of MS in those with HIV was significantly lower than expected based on data from the general population (standardized incidence ratio [SIR], 0.53; 95% CI, 0.32-0.90). They found 14 cases of MS among those with HIV, but statistically, 26.19 were expected. This held when looking at women only (SIR, 0.28; 95% CI, 0.09-0.88), but not necessarily men only (SIR, 0.70; 95% CI, 0.39-1.27).
To Elaine Kingwell, PhD, a senior research fellow at the University College London, who led the study, the fact that “the lower risk for MS was found in two distinct populations of people living … in Sweden and Canada” lends credence to the results.
Given the speculation that receipt of ART may influence MS risk, symptomatology and progression, the researchers also sought to examine whether MS incidence differed in patients during periods of ART exposure versus nonexposure. ART exposure time included all the person-time contributed by patients after their first receipt of ART.
However, because most participants had received ART, the results in the ART-exposed subanalysis were like those seen in the full participant sample (SIR, 0.55; 95% CI, 0.31-0.96). And the limited amount of person-time during which patients were not exposed to ART contributed to a relatively imprecise estimate of SIR for this nonexposure period (SIR, 0.46; 95% CI, 0.12-1.85).
“More than 90% of the people living with HIV in this study had been treated with ART, so we were unable to separate the effects of the virus from the effects of ART,” Dr. Kingwell told Infectious Disease Special Edition. In addition, she pointed out that “we cannot assume a causal relationship between the virus or ART and MS,” based on the study design used.
“Additional studies are needed to determine if ART might influence MS risk, or if ART has any effect on MS disease course,” Dr. Kingwell said. Related research is underway, Dr. Kingwell said, citing ongoing research by groups in Norway and Boston “assessing the effects of tenofovir on shedding of Epstein-Barr virus [EBV] in people with MS.” She suggested that “results of trials such as these might provide further support for trials of ART as a treatment for MS.”
The trial out of Boston (ClinicalTrials.gov Identifier: NCT05957913) is led by Michael Levy, MD, PhD, an associate professor at Harvard Medical School and the research director for the Division of Neuroimmunology and Neuroinfectious Disease at Massachusetts General Hospital, and his colleague Natalia Drosu, MD, PhD, a postdoctoral fellow at Massachusetts General Hospital. “I think [the association between HIV and MS risk] has been of interest for a while now,” Dr. Drosu told IDSE. It “brings up the question of, ‘Well, is it the HIV or is it the drug [that is influencing MS risk]?’ And these epidemiological studies keep suggesting we need to answer that question,” she said.
Dr. Levy explained that, with this epidemiological evidence of a link between HIV positivity and MS risk, additional data suggesting that EBV is linked to MS pathology, and previous research by Dr. Drosu showing “some HIV medications have activity against EBV,” they “embarked on a study to target EBV with tenofovir in MS patients” to understand how the HIV drug affects EBV viral load.
“We’re still at the very beginning of this” area of research, Dr. Levy said. “We still have to prove that EBV is driving MS and that targeting EBV is useful in MS” from a clinical standpoint.
The study was funded by MS Canada and the Canadian Institutes of Health Research. Drs. Drosu, Kingwell and Levy reported no relevant financial disclosures.
This article is from the October 2024 print issue.