Question
What in your opinion, is the best known method for clearing HIV virus from reservoirs?
HIV continues to hide in reservoirs. Several methods have been proposed to clear latent virus. Interested in opinions on best practice, efficacy vs toxicity for methods proposed via immune manipulation.
All Answers (38)
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in my point of view, local herbs are more effective in case of HIV rather than chemical medicines.there are many herbs, effective antiviral properties. -
Attack the macrophage cells since they are the HIV reservoir cells. -
If you continue on a steady HAART, you can only hope that with time latent virus will diminish with the reservoir cells. other than that there is unfortunately no other way of doing it yet. -
Suicide strategy with virus specific drugs along with activation of latent viruses using HDAC inhibitors.
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Actually there are no known methods for clearing the HIV reservoir, although some promising strategies are being developed. Two heavily investigated approaches involve inducing HIV expression by activating the latently infected cells in various ways or heavily suppressing HIV replication by an enhanced drug regimen. Both have their merits but still have to prove effectiveness and address the big risks involved. -
- Actually , couple of years ago, a team of scientists succeeded in extracting the viral DNA from cells without damaging them. If this method is shown to be possible in a lab animal and later on humans without causing damage, it will be the way to go.
- An other way would be to destroy the reservoir by chemotherapy the way it was done in Berlin.
- Alternate version of suggestion number one. Although it is years away, it could be possible to construct a different Retrovirus that specifically attacks the HIV - DNA in infected cells, either by destroying the infected cell or HIV DNA. -
Addendum: It is not a matter if we can do it, but how good are our tools. A vaccine would stop the spread (and probably increase every other STD prevalence in the beginning :-) ), but i have not enough knowledge in immunology to see how it could eliminate the reservoir. Of course if you vaccinate everyone, and keep infected people under treatment, the reservoir will die out anyway a natural way after given time (of course not if someone invents a pill for immortality)
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Currently, there isn't any known method to clear the HIV reserviors. Some herb may be effective in control HIV infection. However, they were not specific to anti-HIV. So, in my opinion, they are also not useful in clear the reserviors.
I'm wondering if there is some medthod (like RNAse or RNAi) that could specifically destroy HIV RNA and intergrated DNA (provirus). That might work. -
patient's own stem cell repopulation of the marrow after bone marrow is wiped out by irradiation which will kill all macrophages/monocytes in circulation. Problems will be the microglia in the brain and having infected stem cells. -
Use HCT, see the website www.hivcure.in
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@ Joseph: this was done with the guy in Germany. Due to lymphoma they killed his immunesystem off and donated a new one with homozygot CCR5 mutation. So far as i have read, he is still cured of HIV.
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In my opinion Virus Clearing is out of Question. Because Cell mediated & Humoral mediated immunity Plays
Vary Imporatant role in hiv infection. And also when retoviral thearpy Starts we moniter Pt for Decrease in
Viral copies by Real time PCR. If we think Hypothetically If Steam Cells are cultured against the Hiv viral
Ag & Made to avilable in the form Injection .Then it is possible to tackle the Cell medaiated immunity
Against Hiv Viral Load. Whether Circulating or Virus in Reservoir. -
The conference on retroviruses and opportunistic infections (CROI) in Seattle this year had whole sessions dedicated to the latest strategies for purging the latent reservoir (http://retroconference.org/). -
Christian's suggestion about extracting viral DNA from infected host cells is interesting, but I am worried about the feasibility of this technique in humans especially given that you have about 40 million people infected with HIV world wide. I do more HIV vaccine research so this is really not my area, but can someone tell me how the virus maintains latency and conditions which promote virus to come out of latency? If we know the conditions that promote virus to come out of latency then one might be able to devise more targeted treatment to prevent or reduce the establishment of latent reservoirs.
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That is a vital question to answer, Danushka. Unfortunatly it is not known, to my knowledge, what factors cause reactivation of latent pro-viri.
I agree with some of Christian's earlier comments: the well known bone marrow transplant case out of Berlin is an extremely useful finding. It shows that it is indeed possible to clear HIV infection. As was alluded, however, bone marrow transplantation is quite risky and the procedure was not performed as an intentional HIV/AIDS treatment. Due to the risk involved in this procedure (and the relative effectiveness of antiretroviral therapies) it is unlikely to ever be approved as an HIV treatment.
Another possibility was mentioned by Christian; HIV provirus ablation with a viral vector. I came across this idea a good number of years ago, when I first learned of HIV's infectious processes. If HIV is so effective in avoiding immune surveillance following infection, is it not feasible to engineer a virus capable of doing the exact reverse? Theoretically, this would clear HIV proviri without damaging host cells significantly. While I agree that this type of treatment is likely a long way off, it may be interesting to note that Frank Buchholz, PhD, of the Max Planck Institute in Dresden, Germany, has taken some initiative by developing an enzyme that does appear to successfully excise HIV proviral DNA (Tre recombinase).
Regardless of the conventional thoughts regarding eradication of HIV from reservoir tissues, I think it is important to recognize that it is not yet clear where exactly this reservoir is. A daunting challenge in HIV virology is how to improve methods of detecting infectious HIV particles. After all, undetectable RNA levels means just that: undetectable. -
you can look at http://beta.news.yahoo.com/30-years-first-aids-cases-hope-cure-040149920.html. The example is Timothy Ray Brown of San Francisco, the first person in the world apparently cured of AIDS. His treatment isn't practical for wide use, but there are encouraging signs that other approaches might someday lead to a cure, or at least allow some people to control HIV without needing medication every day.
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It is impossible to eradicate HIV using ARV in ten years. We should find the new pathway, especially immunotherapy. -
Immune system replacement may work experimentally in highly restricted circumstances. It will not become a widely applicable approach. Even the Germany case remains to be seen in view of the long clinical latency of the disease. Personally I do not think that it is possible to eradicate HIV-1 as a general therapeutic means once a systemic infection is established. Dealing with peripheral circulation is relatively easy since the virus can be uniformly disseminated and detected. How can one be so sure that the virus is completely eradicated from all lymphoid tissues ? You even do not have credible assays to find the virus.
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I concur well with Zhiwei on the question of clearing definatelty the Lymphoid tissues is a standard which needs to be met before any claim of any means of viral clearing -
I think we have to find good histone deacetylases inhibiror to use in association with HAART
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Sounds good. What kind of purpose should/would it fullfill. Inactivation of the HIV Genom ?
I am not very knowledgeable about this molecule. -
The histone deacetylases inhibitor concept is wrong, when we target the HIV genome into host chromosome,the host DNA will get affected, it will be a failure like HAART what we thought in 1996.For this multiple drugs:multiple actions only will work out. The only way to eliminate reservoir is by stimulating CTL and it will all the reservoirs.This approach only possible in the human individuals.The one molecule histone deacetylases inhibitor will produce severe side effects than HAART and very soon it will get host resistance.It needs multiple approach, find www.hivcure.in
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Histone deacetylases play an important role in gene expression regulation and seem to be an interesting approach to be associated with other strategies. It will be necessary to find the best molecule to this funcion. I send an review about this.
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Indeed. Sounds interesting.
Stimulating CTL and eradicating the reservoirs in the brain is going to be great. Nothing better than a good old inflammatory reaction in an organ with limited expansion volume. -
Great discussion! Thanks everyone. Seems there are real challenges eg. efficacy vs toxicity. -
you are welcome :-D
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Dear Sigrid, I already read Dr. Margolis article,here he is only focusing on HIV DNA, he has not bother about the rest of 30000 genes of human genome,his research is about to disturb the human gene transcription and its control along with HIV latent DNA. If we inhibit the histone deacetylases, there wont be transcription control in human genome, already we could not control the transcription of oncogene, in the same manner the controlled transcription will be lost and leads to over expression of genes and naturally new problems will come along with cancers.In HDACs inhibitors we could only make the latent DNA to transcribe but we can not remove the latent DNA from the host chromosome, Did we ever heard the story of removing the gene after its own transcription or auto removal after transcription, is such a mechanism is there in our DNA?
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The best thing is to activate cell proliferation to eliminate latent infected cells.
Please the abstract of our paper (Virology 386 (2009) 160–167)
“Highly active antiretroviral therapy (HAART), although effective in improving the survival of HIV-1-infectedindividuals, has not been able to reconstitute the adaptive immune response. We have described the use ofnovel chemical agents to restore T-cell survival/proliferation by inducing cytokine production. Due to itscationic amphiphilic structure, these molecules appear to enhance immune restoration. In this study, weinvestigated the action of Riluzole (2-amino-6-trifuromethoxybenzothiazole) in HIV-1 infection. Riluzole isable to increase (effective dose from 1 to 1000 nM) the cell-survival of T cells from HIV-1-infected patientsand inhibit spontaneous apoptosis. The immunomodulatory effect of riluzole-sensitized cells was ascribed toendogenous type I interferon (IFN) derived from monocytes. Riluzole might be used for restoring the cell
survival of immunocompromised patients and eliminating latent infected cells upon HIV-1 reactivation.” -
Not having enough time to read your abstract, but do you get rid of T cells only? Because then there are macrophages and dendritic cells left to deal with.
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Not only T lymphocytes but monocytes/macrophages too. We obtained the same observations using dendritic cells derived HIV-1 patients (preliminary not published results).In our paper we reported that the effect is ascribed to endogenous type 1 interferon produced by monocytes. You can take in account that ype I IFN is induced by viral infections and also produced constitutively at low levels in haematopoietic tissues (monocytes/macrophages and dendritic cells).
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Ammar, this is an interesting approach. Can you upload more information?
Thanks -
In previous studies, we reported the ability of cationic small molecules as potential immunostimulants for HIV-1 infection (Achour, 2001; Achour, 2002). We have also reported the immunomodulatory effects of aminoperazine, a phenothiazine derivative able to increase the antigen-specific dendritic cell-proliferation (Lu et al., 2001).
Then we have shown that in treated cells, the small molecules Riluzole promotes an increase of viral RNA (Achour, 2009). Our data clearly indicate that these high levels of viremia do not necessarily lead to cell survival dysfunction. Our approach does not target latently HIV-1 infected cells directly. Nevertheless, this mean is aimed at enhancing cell survival to more rapidly and effectively eliminate latent cells upon reactivation of HIV-1 expression. Establishment of latency is driven by selection of cells that resist viral replication. Then, by maintaining the cell survival associated with a high viral expression an elimination of latent virus might be possible.
Regarding clinical practice, the combination of these molecules with HAART might represent a pharmacologic mean for HIV–1 eradication. Our approach could enhance immune restoration to more efficiently eliminate latent infected cells upon HIV-1 reactivation as suggested (Butera, 2000). Our findings, therefore, suggest that our described molecules could represent an important candidate for therapeutic aimed the elimination of latent infected cells in HIV-infected individuals. -
What is the status of testing in a clinical study of any of these compounds for HIV?
Are they available for license or can they just be repurposed for HIV? Would be interested in forming a company to explore further. -
see the website hivcure.in for Elimination of HIV from the reservoirs
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Stimulating CTL and eliminating foreign DNA bearing cells, Please visit www.hivcure.in
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Regarding this issue, there are two recent papers of great interest. One is a review and the other an original research study. -
This is the other paper.
