Tag Archives: HIV

Bacteria Therapy: Cure for HIV?

Bacteriophage

Bacteriophage

Just a thought…

The article above in Popular Science is very interesting to me because I wonder whether reverse phage therapy or bacteria therapy would work in HIV. In phage therapy, viruses that kill bacteria are used to kill infectious drug resistant bacteria. If we could use bacteria instead to invite infectious viruses and then clear the bacteria post infection, we can in turn clear the viruses.

In case of HIV, initially I had thought that we could possibly engineer a bacteria to express receptors such as CCR5 or CXCR4 that would lure HIV to infect them instead of CD4+ T cells. These bacteria would also express receptors that would facilitate the opsonization process (clearing of pathogens by immune cells).

Engineered Bacteria

Engineered Bacteria

However, there major obstacles in this process. First, the interaction of CD4 with other molecules expressed by our cells can prove to be a major obstacle. Next, the bacteria may generate immune response and may be cleared too soon before it can actually circulate in the body. Third, it may cause immune activation which is not necessarily advantageous to a patient. Fourth, how will these bacteria be administered? Fifth, depending the route of administration, they may not clear HIV from hard to reach areas such as gut and brain. Finally and possibly the most importantly, it will not clear latent infections. One more: there will still be CD4+ cells that will be infected…how are we going to deal with them?

Although these questions persist and not being able to answer any one of these questions may render the whole process uneffective, it is important to think about phages in HIV. Despite the fact that there are thousands of papers on HIV and hundreds on phages, to my knowledge, there is not a single scientific literature that has investigated the possible role of the phages in HIV infection/pathogenesis. Therefore, despite various challenges, investigating the the beneficial use of phages in HIV could lead us to a novel way of tackling the HIV epidemic.

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AIDS: a photographer’s and an economist’s perspectives

There is so much information about HIV/AIDS in the net but still this pandemic is on the rise. I tried to explain what a conventional website such as Wikipedia does not tell you about HIV/AIDS in my previous article. I am including a few links here to assist you better understand the havoc it has caused. The second link is an economist’s perspective on HIV. It is a very different thinking about the pandemic, none like I have ever heard before.

A Photographer’s perspective: A short talk accompanied by photographs of Kristen Ashburn

An Economist’s perspective: Emily Oster on AIDS in Africa

(Materials were obtained from TED)

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HIV/AIDS: What the Wikipedia does not tell you

The Chinese name their years after animals. There are years of the dogs, lions and even dragons. From that perspective, the year 2008 was the year of the viruses. If the naming was to be based on the Nobel Prize in Medicine, one half of which was awarded to “Harald zur Hausen for his discovery of “human papilloma viruses causing cervical cancer” and the other half jointly to Françoise Barré-Sinoussi and Luc Montagnier for their discovery of “human immunodeficiency virus””.

Not only this year but also the last few decades probably can be considered “the decades of viruses.” In fact, particularly of one virus– HIV, for all the havoc it has caused worldwide. Despite the billions of dollars spent and thousands of scientists, sociologists, and medical personnels working desperately under the pressure of high competition (in case of scientists) there is no cure for HIV. Many attempts to make vaccines have failed and scientists are back to the drawing board to tackle this menace. If there were a riddle for HIV, it would probably sound like this:

Its only me, its only me,
Millions of men are carrying me,
Millions more have been killed by me,
Thousands of men are chasing me,
Two decades of studying,
No cure from the wraths of me,
Its only me, its only me!

This riddle I just made…if I were to ask Gollum this riddle he probably would not know…but it still probably is barely mediocre…and that’s why I have a day job. In fact, I am one of those thousands of men chasing the HIV. For the last two years I have worked in HIV research and so, I am ebullient to jot down my thoughts despite the fact that I am no expert. A good review of HIV encompassing its history up to the treatment can be found in Wikipedia. I am only going to tell you about a few things that you cannot find in Wikipedia and some recent development in HIV research. If anyone is interested in finding any sort of detailed statistics on HIV you can visit the UNAIDS/WHO Global HIV/AIDS Online Database

History

There were a bunch of historical essays published in the journal Science (29 Nov, 2002 issue) two of which are particularly interesting from the context of HIV discovery. The first essay is written by Luc Montagnier, one of the Nobel awardees, who describes the first hand experience of discovering the HIV in his lab. This article is followed by another essay by Robert Gallo. It sucks that such prominent journals like science is not accessible to the public but pornography is. That tells a lot about why kids are not interested in science….the lower case ‘s’.

Anyway, although the Nobel was awarded to the French discoverers, the first two retroviruses (HTLV-I and HTLV-II) were indeed, discovered in Gallo’s lab in the USA. Furthermore, there was also some collaboration between these two groups while investigating the HIV but later the collaboration ended when Gallo discarded a joint conference scheduled between his lab and Montagnier’s lab to side with the US government to claim the discovery first and to develop the patent rights and totally forgot his French collaborators. Gallo did not have the world “loyalty” in his dictionary.

In his Science essay Gallo puts all the blame on an unnamed freelance journalist and U.S. Dept of Health and Human Services Secretary Margaret Heckler. “The scientific achievements were overshadowed by a dispute between the United States and France over the patent rights to the blood test, and a temporary disagreement among the scientists,” Gallo says in the paper. That keeps me wondering why he did not mention the French group in that press conference. Was he trying to hoard all the glory to himself? Or may be he credited the group and still there was a controversy? Only Gallo or Heckler knows. This suggests there can be…I correct myself….there are bigger dramas in scientific world than Hollywood itself!

Who discovered HIV is probably a mute point now except for the glory of Nobel and a relatively small and insignificant amount of $$ from the Nobel group…yes it is insignificant for the achievement of a lifetime…even failing car company CEOs get ten times that EACH YEAR! In the real world no one cares about who discovered it. Do you? I don’t. But there is a growing curiosity in everyone because HIV is no longer limited to Africa or to the gay community. It can infect anyone.

HIV has severely affected sub-Saharan Africa where it continues to be the leading cause of death. Lack of knowledge and lack of a social support system has lead to the modern day pandemic of HIV. In an article in August 9, 2008 issue of The Lancet, Merson et al. wrote a very good and comprehensive summary of history of HIV and how the lack of knowledge and social support system has fueled the pandemic. Even though HIV pandemic was recognized in 1981 (that was 27 years ago!) by the US Centers of Disease Control, everyone thought it was limited to gay men and peoples of the third world living in penury. Most of the world and their political and religious leaders were in denial of the fact that HIV was spreading in an unprecedented rate. To know more about HIV’s history and about social issues related to HIV two papers are a must read: Merson et al. and Gupta et al., both published on the Lancet (vol. 372, August 30, 2008)

While the leaders turned their back to the pandemic, a few people took it into their hands to start some social support programs to ameliorate the pandemic. In 1982, Bay Area Physicians for Human Rights, a San Francisco doctors group, were the first to issue education materials to the general public. Their efforts were followed by many local and international agencies in various parts of the US, South America, Europe and Africa which condemned prejudice against the HIV infected people and initiated a social network to provide care and support for the HIV infected patients. It was only in 1987 that WHO launched its Global Program on AIDS (GPA) which reached out to every single constituencies including activists, community groups, NGOs, and HIV/AIDS patients. GPA was shortly replaced by UNAIDS. Despite the increasing efforts of UNAIDS and other organizations, worldwide prevention efforts have not been sufficient to reduce the HIV infection rates.

Transmission

Sadly, despite so much literature on how is it transferred there is still a huge void on people’s understanding of how HIV is transferred. “Oral sex is safe; it’s only vaginal sex and anal sex (men are screwed both ways) that HIV is transferred.” “Using condoms can prevent HIV.” “Magic Johnson is doing okay with HIV. Why can’ I even if I were to be infected?” “There are antiretroviral (ART) drugs now and there will be vaccines in near future.” All these are fallacies. No unprotected sex is safe, INCLUDING ORAL SEX. There will soon be papers that will demonstrate this fact. Condoms do not provide 100% protection either. One can be on ART and live long like Magic but ART does not work on everyone and there are thousands who fail ART treatment. Even if the treatment is successful one is not cured and will have to endure a lot of hassles just to live. Can you imagine being sick all the time, contracting flu every season, contracting bacterial and fungal infection easily? How about the possibility that you may not be able to have a kid? Life with HIV is very grim so the best way to prevent it is to stay safe.

Two decades have passed and there is yet no cure for HIV. Merck was probably the closest to developing a vaccine but the failure of STEP, the Merck vaccine trial, was such a big blow not only to Merck but to the entire scientific world that they have returned back to the drawing boards. Now some scientists such as Norman Letvin of Harvard think that HIV vaccine is not possible at all and instead we should think about stopping disease progression.

Not everyone thinks like Letvin though and after the failure of Merck vaccine scientists have started thinking about alternative ways of generating HIV vaccines. Evolutionary biologists have long known about endogenous retroviruses,the viruses that were once infectious but millions of years ago they somehow got incorporated in our genome and toady they exist in dysfunctional state in the genome. One idea is to figure out a way to endogenize HIV like its ancient relatives.

In addition, the Nixon group reported in the journal Plos Pathogens that immune response against the endogenous retrovirus may help in getting rid of HIV infected cells. One way that can happen is by killer cells killing HIV infected cells expressing endogenous retroviral protein on the surface. Another way is more direct: sometimes endogenous proteins are so similar to HIV proteins that the killer cells that recognize these endogenous proteins can also recognize HIV infected cells and kill them. Whoa! Don’t get too excited yet because not many scientists think this will be enough to get rid of HIV from an infected person. Even if turns out to be enough, a lot more work still needs to be done in this area for any commercial product to come out in the market.

There is still hope though. Steve Deeks at UCSF has found patients called “Non-Term Non Progressors” that incredibly control HIV and immunodeficiency for a very long time without any medications. Only about 5-15% of HIV infected patients fall in this category. Even remarkable are those people known as “elite controllers” that can control the virus for over 25 years without any medications. Deeks is studying these patients and trying to decipher what causes them to be so successful in the battle against HIV.

Scientists have insinuated various factors that may play a role in viral control. While some immune cells have been thought to play a role in this immunity, host genetics has also been shown to play a part in controlling HIV. For example, HLA B57 (B5701 in Caucasians and B5703 in Africans) and HLA-B27 alleles may play a role in HIV. Furthermore, in addition to the CCR5 delta 32 mutation other CCR5 mutations along with CCL3L1 gene polymorphisms may play a role in HIV resistance and/or control.

Therefore, a holistic look at all components, both immunological and genetic factors need to be considered while thinking about HIV vaccines. We are entering the era of personalized medicines and gene therapy. May be we will find one or a combination of genes that can protect us from HIV.

Images: Worldwide data on HIV infected people by countries (obtained from Merson et al, the Lancet, vol 372, Aug 09, 2008) Click on the images to download the original size.

hiv

hiv2

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Variation in DARC Gene Causes More Suscesptibilty to HIV in Peoples of African Descent

“People with the Duffy protein carry on their red cells and in their circulatory system a larger amount of immune molecules known as chemokines, which confers protection against HIV. In addition, the Duffy protein can act as a sponge and soak up infectious HIV particles, providing additional protection against the virus. People who have a variation of the gene – which includes a large proportion of people of African descent – don’t carry the Duffy protein, and are therefore at higher risk of getting infected when exposed to HIV.”

Entire Article

Scientific Journal

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The Role of Human Endogenous Retroviruses (HERV) in Human Immunology and Evolution

Retrovirus Lifecycle

Retroviruses are not only important in immunity of an organism but also with thier evolution. Some retroviruses, known as endogenous retroviruses, have even been successful to get incorporated into our genome and represent roughly 8% of human genome. Last month, a colleague of mine at UCSF in collaboration with University of Toronto published a paper in Plos Pathogens regarding the role of Human Endogenous Retroviruses on HIV infection.

The collaborating team found increased levels of HERV production in HIV-1 infected patients and showed that HIV-1 virus causes expression of HERV particles on cells which are recognized by cytotoxic immune cells. These HERV specific cytotoxic (CD8 T cells) that recognize HERV may end up increasing immune response against HIV-1 virus. The increased immunity by HERV can be indirect or direct. The cells that are expressing HERV are killed by immune cells and thus the HIV replicating inside these cells are also killed. This is the indirect effect of HERV on HIV. Also, some of the HERV proteins, very similar to HIV-1 proteins causes some cytotoxic immune cells to recognize cells expressing HIV-1 proteins and kill them directly. Thus, there is a serious potential of using HERV for vaccines.

This news must have been very big because the article was featured by The San Francisco Chronicle and CBC news of Canada. I even found the same work quoted by Michael Specter in a recent issue of The New Yorker. Interestingly Michael’s article, although in a non scientific journal is one of the best reviews on HERV that I have ever read.

 

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