Tuesday, 12 September 2017

HIV ninja versus MS

In Vivo. 2017 Sep-Oct;31(5):1041-1046.

Multiple Sclerosis and Subsequent Human Immunodeficiency Virus Infection: A Case with the Rare Comorbidity, Focus on Novel Treatment Issues and Review of the Literature.

Skarlis C, Gontika M, Katsavos S, Velonakis G, Toulas P, Anagnostouli M.

Abstract
BACKGROUND:

The comorbidity between Multiple Sclerosis (MS) and Human Immunodeficiency Virus (HIV) infection is particularly rare. Only a few cases of comorbidity of Clinically Definite(CD)-MS and HIV have been documented worldwide, while the potential beneficial role of antiretroviral therapy regarding MS activity has long been an area of debate.

CASE REPORT:

We present a 36-year old male, bearing a diagnosis of CD-MS for twelve years. He had been treated for ten years with interferon-beta-1b, when he voluntarily discontinued therapy, claiming clinical stability. One year later he was diagnosed positive for HIV and he started and continued only on efavirenz/emricitabine/tenofovir-disoproxil fumarate (ATRIPLA®), remaining relapse-free until today.

CONCLUSION:

This fact, in combination with the unique pharmaceutical composition of the drug, which contains a component similar to a newly-approved agent for MS, dimethyl fumarate, prompted us to review the literature regarding this rare comorbidity and to suggest that the role of the antiretroviral therapy should be further explored in MS.



Having both HIV and MS, you're either the most unluckiest person to be alive - having two incurable chronic disorders in one lifetime; or the un/luckiest person on the face of this Earth according to this report!!! Depending on your social ideology, that's Murphy's Law or Karma. 

The global prevalence of HIV is 0.8% and of MS is 33 per 100,000; the two together, however, consist of only a few published cases in the literature. Thankfully, the treatment of both disorders has come a long way. Although, this is not to say that we know what to do in instances where the two occur together or simultaneously.

Skarlis et al., report that having HIV on top of MS may possibly be a good thing for your MS (warning: not to be interpreted literally!), and that antiretroviral drugs (HAART) may have positive impact on MS disease activity. They present a case of 36y old man with a 12y history of active MS (but not highly active MS; annualized relapse rate of 0.44, EDSS progression of 0.22), before being diagnosed with HIV. He was previously on IFN-1b, which he stopped himself two years prior to his HIV diagnosis. His antiretroviral regimen consisted of efavirenz/emricitabine/tenovir-disproxil fumarate (not certain whether there is any bioequivalence between the latter and the licensed dimethylfumarate for MS, i.e. does this drug regimen have an immunomodulatory component?). The authors state that after almost three years on HAART, the subjects annualized relapse rate was 0.24, with an EDSS progression of 0.14, and stable imaging appearances.

In their discussion, they report of similar cases in the literature where the MS remained clinically stable on HAART alone; albeit all relapsing remitting cases. Raising the possibility of some interesting deductions. Is the immunodeficiency caused by HIV the explanation for the lack of disease activity as far as the MS is concerned? HIV specifically targets CD4+ T cells - is this relevant, and possibly a protective factor in the development of MS? Moreover, there is the HERV (Human Endogenous Retroviruses) hypothesis in MS; could the antiretroviral medications used to treat HIV be also suppressing the HERVs? I feel this raises more questions than answers.

Of course, this is not the whole story, in fact, there is a resurgence of some autoimmune disorders with HIV; including rheumatoid arthritis, systemic lupus erythematosus, anti-phospholipid syndrome, vasculitis, primary biliary cirrhosis, polymyositis, Grave's disease and idiopathic thrombocytopenic purpura...

11 comments:

  1. Well NDG you already said in the last paragraph what I would express in the comment, I have read in the medical literature and I know patients with HIV who started having autoimmune disorders after infection with the virus.
    So I think it's more likely an immunomodulatory action of HAART that ends up benefiting in the treatment of MS as well.

    Has any study ever looked at the action of HAART on B cells, and especially memory B cells?

    Now of course all this needs to be elucidated and prove ...

    ReplyDelete
    Replies
    1. Here's the link https://www.msif.org/news/2015/01/19/exploring-relationship-hiv-ms/
      Probably need to redesign our Charcot study

      Delete
    2. In vertical transmission of HIV there's evidence that early establishment of HAART allows normal development and maintenance of memory B cells. But in adults there is depletion of specific memory B cells in the 1st phase of infection and HAART doesn't reseatablish them - interesting

      Delete
  2. Yet, Raltegravir (an antiretroviral medicine currently used to treat HIV) and GNbAC1 Retroviral have failed at trials as possible treatments. I think there is a third one of this concept that has failed too. I think cancer treatments hold better promise.

    (To blog: Please continue keeping us updated as much as you do!)

    ReplyDelete
    Replies
    1. I think we need to redo that one (INSPIRE - raltgravir)...

      Delete
  3. HIV infects vital cells in the human immune system such as helper T cells (specifically CD4+ T cells), macrophages, and dendritic cells.[4] HIV infection leads to low levels of CD4+ T cells through a number of mechanisms, including pyroptosis of abortively infected T cells,[5] apoptosis of uninfected bystander cells,[6] direct viral killing of infected cells, and killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells.[7] When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections.

    Hiv is a T cell story is this why it supress ms?

    If you take antiviral the efects is to save those cd4 t cells ,you should have disease activation then ?

    One more think i didnt know hiv can also infect microglia

    https://en.wikipedia.org/wiki/HIV

    Obrigado

    ReplyDelete
    Replies
    1. There is very little in terms of cell type which the HIV virus doesn't affect. It does affect Bcells by interacting with their CD21 surface receptor and the same receptor is also found on follicular dendritic cells which are antigen presenting cells, but interestingly affects the way the function - ineffective antibody production, irreversible loss of memory B cells which is associated with poor responsiveness to Tcell dependent and independent antigen presentation. The latter may be equally relevant than just a Tcell disease. It is why vaccines are ineffective in HIV, the immune just doesn't establish any memory.

      Delete
    2. NDG and this is what I would ask above, in addition to HAART being able to act specifically on HIV-infected B cells, since HIV also infects them, the virus itself can destroy B cells from memory, so that that was causing MS, the "notorious" antigen or even another virus to momentarily disappear.

      Delete
    3. That we don't know. HIV coinfection simply educates us about the immune system and autoimmunity.

      Delete

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