HIV May Protect Against Multiple Sclerosis

Megan Brooks

August 06, 2014

New research supports an association between HIV infection and a reduced risk for multiple sclerosis (MS).

Investigators at the Prince of Wales Hospital in Sydney, Australia, and Queen Mary University of London, United Kingdom, found that having HIV infection was associated with a greater than 60% reduced risk of developing MS.

It is unclear whether chronic immune suppression as a result of HIV infection and/or the antiretroviral drugs used to treat the infection are behind the association, the investigators note.

"If subsequent studies demonstrate there is a causal protective effect of HIV (and/or its treatment), and if the magnitude of it proves to be similar...this would be the largest protective effect of any factor yet observed in relation to the development of MS," the researchers, led by Julian Gold, MD, PhD, write.

The study was published online August 4 in the Journal of Neurology, Neurosurgery and Psychiatry.

First Statistical Link

In 2011, the researchers reported the case of a patient with MS and HIV infection whose MS symptoms resolved completely after starting antiretroviral therapy. The patient remained free of MS symptoms for more than a decade (Maruszak et al. Eur J Neurol. 2011;18:e110-11).

"We [published] this case because we realized that while there are well over 750,000 peer-reviewed papers in HIV and over 250,000 peer-reviewed papers in MS, there had never been a case yet described of a patient with both HIV and MS that had been treated with HIV antiretroviral drugs," Dr. Gold said in a podcast.

This initial case report led a group from Denmark to examine the association between MS and HIV using population-based databases. They found a reduced incidence of MS in HIV-positive adults compared with the general population (Nexo et al. Epidemiology. 2013;24:331-2).

But the incidence rate ratio for an HIV patient acquiring MS failed to reach statistical significance, possibly because of the relatively small numbers in both groups (5018 patients with HIV, and 50,149 control individuals).

The new study by Dr. Gold and colleagues back that of the Danish group but in a much larger sample (21,207 patients with HIV, and 5.3 million control individuals).

Overall, the rate ratio of MS in people with HIV, relative to those without HIV, was "highly statistically significant" at 0.38 (95% confidence interval [CI], 0.15 - 0.79), based on 7 observed cases of MS vs 18.3 expected cases, Dr. Gold noted.

The degree of protection seemingly conferred by HIV increased the more that time had elapsed between a diagnosis of HIV and a diagnosis of MS, the researchers say.

After more than 1 year following the first record of HIV, the rate ratio of MS was 0.25 (95% CI, 0.07 - 0.65), based on 4 observed MS cases and 15.8 expected cases.

And after more than 5 years from first HIV diagnosis, the rate ratio was 0.15 (95% CI, < 0.01 - 0.83), based on 1 observed and 6.7 expected cases of MS.

"The immune dysfunction caused by HIV may in some way be protecting people from getting MS," Dr. Gold said. It is also possible that antiretroviral medication used to suppress HIV may suppress other viral pathogens implicated in MS. "Unfortunately, neither this study nor any study design that is feasible at present can prove which mechanism may be correct," the researchers note.

Significant Contribution

Despite limitations inherent in the current study, the authors make a "significant contribution to the literature on whether there is an association between HIV and the development of MS," writes Mia L. van der Kop, of the University of British Columbia, Vancouver, Canada, and the Karolinska Institutet, Stockholm, Sweden, in a linked editorial.

"They have answered the call for a larger study and importantly, controlled for confounding to a greater extent than has been done previously. Their replication of previous findings, the magnitude of their effect size and the statistical significance of their results combine to provide further evidence to support the hypothesis that there is an association between HIV (or its treatment) and a reduced risk of MS," said Dr. van der Kop.

"However, additional work is required to move beyond hypothesis generation. A logical next step would be to directly examine the association between exposure to ART [antiretroviral therapy] and the development of MS," she concludes.

Dr. Gold and colleagues note that a pilot clinical study with the integrase inhibitor raltegravir (Isentress, Merck & Co, Inc) in patients with relapsing/remitting MS is now recruiting in the United Kingdom. The study was designed to test whether raltegravir is effective in preventing progression of MS, as determined by gadolinium-enhanced magnetic resonance imaging.

The authors report no relevant financial relationships.

J Neurol Neurosurg Psychiatry. Published online August 4, 2014. Full text, Editorial

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