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HIV, Hi-Tech, and Hope By Dr. Derek Lowe 04/02/2002


No one who keeps up with the news needs to be reminded of the slow-motion HIV disaster. Looking at the statistics, though, it's as if there are two separate diseases.

In most of the developed world, it's has taken a fearful toll (and continues to) but the spread of the retrovirus isn't close to the most pessimistic early projections.

But for the flip side, just look at the HIV-endemic areas of the world, where the virus has had an easier time spreading among the population. In sub-Saharan Africa and southeast Asia, there are areas with climbing infection rates, and areas where they're terribly high already. The arguments about how this took place have been endless - it's likely an intersection of medical infrastructure, culture, and some sheer bad luck, with the mix varying from country to country.

There's no end to the ideas of what to do about it, either. These fall into three broad categories: behavioral, pharmacological, and immunological. Unfortunately, each of these operate under the old engineer's constraint: "Good, Fast, Cheap -- pick two."

The behavioral category (telling people how not to spread the infection) is relatively cheap, and is of course being done right now (fast.) But it the amount of good it does is variable (and debatable.) Uganda is probably the success story of this approach, actually reducing the seropositive level in its population. But that's counterbalanced by other (unfortunately larger) regions of Africa where less has been done, and what's been done is less effective.

J. Y. Kim of Harvard Medical School, testifying last month to a Senate subcommittee, pointed out an estimate that 90% of Africans understand how HIV is transmitted, but only 10% of them report using condoms. In some areas, he said, the disease is so widespread that there's not much that behavior changes could accomplish; the damage is already done. Look, for example, at countries like Botswana or Swaziland, with some 30% (or more) of the entire population seropositive.

The pharmacological category is also available now (fast), and could certainly help (good.) But it sure isn't cheap. Not only is there the inherent cost of the newer medications, but the public-health cost of administering them properly is substantial. Epidemiologically, you could be better off not administering drug therapy rather than doing it poorly or incompletely. Otherwise, you run the risk of merely gardening the retrovirus, encouraging drug resistance and making the problem even worse. What we don't know is how much drug therapy affects HIV transmission. It would seem logical that reducing viral load would make patients less infectious, but we really don't know how that plays out in reality yet.

These comments apply to the various protease inhibitor combination therapies. The latest generation of agents - integrase inhibitors and CCR5 antagonists - have yet to prove themselves on large scale. Their new mechanisms of action have to be good news, though, on the principle that the more distinct modes of attack, the better. Their effects on resistance and virus transmission are also unknown.

That takes us to the third category: vaccination. That could stop transmission in its tracks, if all goes well, and do a vast amount of good. And it would surely be cheaper than drug therapy - after all, you don't have to be vaccinated several times a day. But we're not going to have one any time soon, unfortunately. The most optimistic estimates put a vaccine close to ten years out.

It seems to be largely accepted in the HIV therapeutic world, though, that this is our best hope. Going even further than transmission, studies in primates (with the related SIV) suggest that a vaccine might even knock down the disease in those already infected, providing the sort of benefit that the drug therapies do now. I'll go into details on some of the vaccines that are under development in my next column -- it's been a very difficult ride so far, since none of the clear and obvious vaccination methods have really worked. But the research in this area is intense, and it's starting to bear fruit.

So where does that leave us? There have been (and will continue to be) huge debates about what sort of education and public health programs slow the spread of the disease. And the same goes for the debates on administering drug therapy in developing countries -- how to do it, how to pay for it. Neither of these approaches is going to stop the epidemic; all they can do is slow it down. Unfortunately, though, slowing it down is all that we can really hope for until a vaccine is ready. It's a terrible position to be in. We could start by making sure that everyone realizes that this is where we really are.


Derek Lowe is a medicinal chemist with 12 years of experience at major pharmaceutical companies. He conducted PhD and postdoctoral work were on natural products synthesis and free radical chemistry. Lowe has worked on drug discovery projects targeted against schizophrenia, Alzheimer's disease, diabetes, osteoporosis and other diseases. He edits the Lagniappe website

-- (, April 07, 2002


Condoms? Do you eat the candy with the wrapper on?

-- (, April 07, 2002.

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