Map of life expectancy at birth from Global Education Project.

Monday, August 11, 2008

Scientific Wrap-up

Whew. As always, my flight was late and I got into Boston at 2:00 am. It's okay, I expected that. Had time to digest everything now so I'm going to do some overall takes on the conference. This the first installment, on the state of the science of HIV.

I'm sorry to say that in spite of the cheerleading and optimistic spin, it's pretty grim.

First, Anthony Fauci (Director of NIAIDS, the NIH unit that funds HIV research) made it absolutely clear that in his opinion, there is no effective preventive vaccine anywhere in the foreseeable future. Reading between the lines, I would venture that he believes it to be ultimately impossible. He said the best we can hope for in the next 25 years is a vaccine that would be partially protective for people who happen to have the right genetic makeup. That, in my view, would be useless. You could never market it because all it would accomplish is to give people a false sense of security. Fauci said, unequivocally, that he will not approve funding for any HIV vaccine trials at this time.

The difficulties in creating an HIV vaccine are already well known. (The most important obstacle is that the protein that forms the envelop of the HIV virion hides from the immune system behind a screen of sugar molecules, but there are further difficulties as well.) The news is that the strategies people hoped might get around them have unequivocally failed. That's all folks: the HIV vaccine story is over for the time being.

Equally discouraging is the prospect for a cure. A cure for HIV would mean that the infected individual could live disease free and without risk of infecting others, without needing continual treatment. The reason HIV is incurable is a bit complicated if you don't already know the basics, but let me try to make it simple.

As you know, the genetic instructions that control the cell are contained in DNA in the chromosomes. RNA in the cell ordinarily carries those instructions from the nuclear DNA out into the cytoplasm, where proteins are synthesized, and also does the work of protein synthesis. Most viruses contain DNA, and when they enter the cell, their own DNA hijacks the cell's machinery. But HIV is different, it's a retrovirus. It does not contain any DNA, but rather RNA. When HIV enters a cell, it's own RNA first produces an enzyme called reverse transcriptase, which then causes HIV's genetic code to be written into the nuclear DNA of the host. The viral DNA residing in the host's DNA is called a provirus.

We are usually told that HIV disease is all about the infection of CD4+ cells, which are turned into factories for producing virus particles, called virions, which constitute the "viral load" in the blood plasma. Antiretroviral drugs control this process. However, they do nothing about the reservoir of proviruses, which exists in non-active CD4+ cells, but also in other cells of the body including the meninges (the membrane surrounding the central nervous system), macrophages (cells that go around scouring up debris) and now, it appears, just possibly lymphatic stem cells. These latter cells continually renew themselves and also produce new lines of infected T cells. That is why, no matter how long you have been taking anti-retrovirals, and no matter how long you have had undetectable viral load, if you stop taking the ARVs, the virus will reappear.

So, the advances are incremental: better understanding of exactly how to use antiretroviral drugs, the possibility of topical "microbicides" (really a misnomer) that women could use in vaginal inserts to prevent becoming infected, better post-exposure prophylaxis. That's about it. Oh, they're also talking about pre-exposure prophylaxis, basically meaning that people expecting to be exposed could take ARVs, but that strikes me as a very bad idea, frankly.

If extraterrestrials had engineered this little particle to maximally mess with us, they could not have done a better job. As we confront the future of the HIV pandemic, it is essential to get this absolutely clear, whether you like it or not:

No vaccine. No cure. Not next year. Not next decade. Never say never, but best to plan for never because nobody knows when, or how. That's where it's at.

No comments: