Tuesday, 5 August 2014

HIV infection linked to lower multiple sclerosis risk

#MS research HIV infection linked to lower MS risk

Gold J, Raph Goldacre R, Hubert Maruszak, Giovannoni G, Yeates D, Goldacre M. HIV and lower risk of multiple sclerosis: beginning to unravel a mystery using a record-linked database studyJ Neurol Neurosurg Psychiatry 2014;0:1–4. doi:10.1136/jnnp-2014-307932 1

Objectives: Even though multiple sclerosis (MS) and human immunodeficiency virus (HIV) infection are well-documented conditions in clinical medicine, there is only a single case report of a patient with MS and HIV treated with HIV anti-retroviral therapies. In this report, the patient’s MS symptoms resolved completely after starting combination anti retroviral therapy and remain subsided for more than 12 years. Authors hypothesised that because the pathogenesis of MS has been linked to human endogenous retroviruses, anti-retroviral therapy for HIV may be coincidentally treating or preventing progression of MS. This led researchers from Denmark to conduct an epidemiological study on the incidence of MS in a newly diagnosed HIV population (5018 HIV cases compared with 50 149 controls followed for 31 875 and 393 871 person-years, respectively). The incidence ratio for an HIV patient acquiring MS was low at 0.3 (95% CI 0.04 to 2.20) but did not reach statistical significance possibly due to the relatively small numbers in both groups. Our study was designed to further investigate the possible association between HIV and MS. Methods We conducted a comparative cohort study accessing one of the world’s largest linked medical data sets with a cohort of 21 207 HIV-positive patients and 5 298 496 controls stratified by age, sex, year of first hospital admission, region of residence and socioeconomic status and ‘followed up’ by record linkage.
Results Overall, the rate ratio of developing MS in people with HIV, relative to those without HIV, was 0.38 (95% CI 0.15 to 0.79).
Conclusions HIV infection is associated with a significantly decreased risk of developing MS. Mechanisms of this observed possibly protective association may include immunosuppression induced by chronic HIV infection and anti-retroviral medications.




Following the case of an HIV positive man with MS, whose MS symptoms appeared to disappear for more than 12 years after anti-retroviral treatment for HIV, a Danish research team attempted to find out if anti-retroviral drugs might treat or slow the progression of MS. Their results suggested this might be a possibility, but the numbers were too small to reach statistical significance, prompting the ProfGs to carry out a much larger comparative study.

Team G paired up with Ben Goldarce's dad and they did this by looking at episodes of hospital care between 1999 and 2011 in England.

In all, more than 21,000 people infected with HIV were treated during this period as were almost 5.3 million people treated for minor conditions or injuries who were not infected with HIV. The development of MS was tracked in all the participants for an average of between 6.5 and 7.5 years, in the context of the actual number of cases versus the expected number of cases in the population.

Compared with those who did not have HIV, those who did were 62% less likely to develop MS, based on 7 actual diagnoses of MS during that period versus the 18 that would be expected to develop. The degree of protection seemingly conferred by HIV seemed to increase the more time elapsed between a diagnosis of HIV and one of MS.

After more than a year between the two, HIV positive patients were 75% less likely to develop MS, based on four actual diagnoses versus the 16 that would be expected; after more than five years this increased to 85%, based on one actual case versus the 6.5 that would be expected.

The findings back those of the Danish researchers, but with the crucial difference being that they are statistically significant.

These findings are speculative rather than definitive because the study is observational, added to which there is no information on whether the HIV positive participants had taken anti-retroviral drugs, or for how long. The demographics of HIV and MS in UK are not identical but this study does look at very big numbers of people. 

Whilst we do not advocate unsafe sex or picking up the HIV virus in the off chance it does your MS good 

ProfG Down Under said “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.” HIV infection itself may stave off the development of MS or it could be that anti-retroviral drugs, prescribed to dampen down the proliferation of the virus may also have the same effect on MS.

So the ProfGs have put their mouth where Merck USA's money is and are investigating the effect of raltegrovir in early multiple sclerosis in the now fully recruited INSPIRE trial as part of the Charcot Project


Why not get it from the Horse's Mouth (or should this be the Kangeroo's mouth) and listen to ProfG Down Under on "Inside Health"  (Get it ONLINE (This link will work in UK, elsewhere not sure) or on the radio) on Tuesday 5th August 2014

STOP PRESS!!
Inside Health is on BBC Radio 4 Tonight at 21.00 BST, repeated tomorrow at 15.30 BST.
Sorry for the confusion!!

The story has cropped up in unusual places

CoI  Members of TeamG are authors of this work.

25 comments:

  1. The risk is not as low as people who are EBV negative

    ReplyDelete
  2. Thanks for posting this story on Good News Tuesday. The real question is whether the drugs are having the effect. Thanks to Profs G, we may get some indication next year. Does this put. prof Mouse out of a job ie no more need for rEAE?

    ReplyDelete
    Replies
    1. Lets wait and see if the trial works before we start with our UB40.

      If there is a cure for MS it is likely to aid the newly diagnosed the most and we will still have to think about can we turn back the clock for those with existing damage......

      Have the current crop of drugs..stopped EAE......not really, although we have not really worked on projects dealing with the peripheral immune response for the past 10 years or more.

      Will I hang up my boots..maybe....or maybe adapt and move on.....

      The question is what would pharma do?.

      No more need for beta interferon and copaxone etc....no more MS pharma, ECTRIMS becomes a little meeting in a nice place, with no free lunch...or anything free....would they adapt and move on.

      Delete
    2. You'll find another job mouse. I see you working in a shop selling vinyl records or reconditioned electric guitars. No Prof G to boss you around. No mice cages to clean out.

      Delete
    3. Thanks for the tip..I'll get my pliers and lemon oil at the ready

      Delete
    4. There will always be parkinsonism/strokes/peripheral nerve disease/dementia to treat for you Dr. G.

      By the way, I am the American at kaiser whom you asked to look at our patients with concomitant multiple sclerosis and HIV. We are working on pulling the charts, and I will review them and let you know if there are any interesting findings. We were very busy working on other projects recently.

      Delete
  3. Thanks for this - great to see the work being done in this area. hope to listen later courtesy of iplayer

    ReplyDelete
    Replies
    1. A quick note to say that Inside Health is on BBC Radio 4 tonight at 9pm BST not 3 pm as previously stated and repeated tomorrow at 3.30 pm.

      Delete
    2. It is permanently available as a download at www.bbc .co .uk/ podcasts/ series/ medmatters

      Delete
  4. The effect is not significant when controlled for ethnicity. What is the association seen in other diseases? Michael Goldacre says this is not seen just for MS.

    ReplyDelete
    Replies
    1. Michael and his big mouth:-), you will be able to see the effect in other conditions when the papers are published. Today's news is about MS.

      Delete
    2. Where did this "effect is not significant when controlled for ethnicity" come from? what does it mean?

      Delete
    3. Indeed. Old news :-). Caucasians have a higher risk of MS than other ethnicities, British HIV population is probably skewed towards MSM and ethnic minorities, both of which are maybe not the top candidates for MS. Control for those and ... yeah

      Delete
    4. Yes the ethnicity group does not have enough people in the sample

      Delete
    5. anon 8:37, are 'caucasians' an ethnic group? social constructs aside, the research applies to UK HIV population - 'predominantly made up of caucasian men.' <(:¬}>

      Delete
    6. Mouse Doc

      plz don't tell me that the Profs G have been comparing apples with oranges........

      Delete
  5. There is no mention of EBV in the article. I thought Prof G thought that EBV was the cause. Has he switched to HERVs? Couldn't you have done a survey of the main HIV treatment centres in the UK, Australia, Denmark and asked three questions: How many HIVers are being treated with antiretrovirals in your centre? How many of them have MS? How many had been diagnosed with MS before before starting antiretrovirals? This would give a feel for any impact antiretrovirals were having. Could also ask for any observations they have with regard to HIV infection / treatment / MS. I'm sure a charity like the Terence Higgins Trust would help.

    ReplyDelete
    Replies
    1. Good comments

      ProfG Down-Under is an international expert on HIV from Australia. He is director of the World Health Organization (WHO) Collaborating Centre and Director of the Albion Street Centre in Sydney, Australia, a centre established to provide services for people with HIV.

      I believe he has trawled the world literature HIV centres etc and the answer is unusually few people with HIV have MS,

      If you trawl through the blood you may see how EBV may be a trans activator of HERV which lie silent in the human genome but can be re awkened to produce virus.

      Delete
  6. So, is raltegrovir an antiretroviral drug used to treat HIV? Don't we need to understand the different types of antiretroviral drugs and allow people with ms to try them, starting with the ones likely to have a lesser impact on the overall functioning of the immune system? Again, those of us who have this condition have a heightened sense of urgency. Thanks for yet another informative post. (Sorry about my lack of knowledge about medicines etc).

    ReplyDelete
  7. http://www.jimmunol.org/content/193/4/1544.full.pdf?with-ds=yes
    HIV-1 infection increases HERV-K expression and the protein may be a target for an Ab vaccine. Much research has shown the relation between EBV infection and subsequent expression of HERV-W in MS leading to immune dysfunction. Using anti-retrovirals to limit HERV production is one possibility but has there been any research on Ab targeting of HERV-W Ag?

    ReplyDelete
    Replies
    1. Yes look up the name Perron-H and you will find..there are clinical studies ongoing

      Delete
  8. It was interesting reading the latest article about a person having HIV lowered the risk of getting MS. I said year ago to many people that the cure for MS is AIDS. The reason being the two diseases cannot coexist. AIDS suppresses the immune system. MS is a overactive immune system. The two working against each other AIDS would win out every single time. But who in their right mind would infect themselves with AIDS? Although research seems a lot closer to solving and treating AIDS than they do MS.

    I feel MS is a chronic infection triggered by a bacteria infection. But it could also be connected with a virus. Mainly EBV. Interesting to know that chronic infections can actually cause CCSVI! One thing I have always wondered about is leaky gut syndrome. And the bacteria that is living in the gut and it hides itself by creating biofilm. I do not believe MS is a autoimmune disease. The body does not attack itself for no reason. There is always a trigger. The body can see what we cannot. I am happy that people are you are helping. The MS society has let us down with their fixed ways and little hope. Keep up the good work.

    Signed a MS sufferer.

    ReplyDelete
  9. What about the INSPIRE trial that should be completed by now? The BBC anecdote fuelled my curiosity.

    ReplyDelete
    Replies
    1. We too are as intrigued as you are. Results will be posted here when announced.

      Delete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.