A Way to Cure HIV Infection?

Modern HIV treatment drugs suppress an active HIV infection well enough that an HIV-infected person can live a relatively normal life. But they don’t cure an HIV infection because some viruses lie dormant inside living cells, out of reach of suppressive drug therapy. For that reason, high-cost suppressive therapy needs to be continued throughout the life of the patient, just so the drug is present whenever viruses do come out of hiding. What is needed is a way to get rid of the latent viruses lying dormant inside cells, once and for all.

A new approach is anti-latent therapy – therapy designed to prevent dormant viruses from staying dormant and hidden. The idea is to force any remaining dormant viruses to become active again so that they can be targeted and killed by suppressive therapy. A combination of anti-latent therapy and suppressive therapy just might wipe out an HIV infection completely. At least, that’s the idea.

A Daily Pill Against HIV Infection

First came the news that several AIDS vaccine trials had to be halted because the vaccines just didn’t work. Then last week the CDC admitted that number of people newly infected with HIV in the U.S. each year is nearly 40% higher than previously reported. Is there ANY good news on the AIDS front?

Well, yes…..maybe. A document released this month by the AIDS Vaccine Advocacy Coalition describes a potentially powerful new HIV prevention method called pre-exposure prophylaxis (PrEP.) It’s a simple notion, really – that a daily pill consisting of one or more of the current AIDS treatment drugs might prevent HIV infection from occurring in the first place. There are at least seven clinical trials of PrEP either planned or underway using the drugs tenofovir and emtricitabine, both of which are already approved for treating people who are currently HIV-positive.

No one knows for sure whether PrEP will work, but there are some promising signs that it might. But even if PrEP does prevent HIV infection, there would still be the issues of access and cost. In order to prevent HIV infection the drug would need to be available to a lot of healthy people, rather than just the few who are already infected.

A report on the status of PrEP research and some of the issues related to its use in AIDS prevention can be accessed at www.avac.org/prep08.pdf.

HIV/AIDS Incidence Revised Upward

The number of new HIV infections per year in the United States has been grossly underestimated for the past 20 years, according to an article published in today’s Journal of the American Medical Association (“Estimation of HIV Incidence in the United States.” JAMA 300:520-529, August 6, 2008.) The new estimate for HIV incidence is 56,300 new cases in 2006, 40% higher than previously reported by the CDC. The new data also show that the incidence of HIV has not declined at all since 1991, in sharp contrast to the previously estimated 50% decline since that time (compare Figure 1 in the JAMA article with Figure 9.24 in Human Biology, 5th ed., taken from official CDC data available at the time.) The total number of people living with HIV/AIDS is also expected to be revised upward, but those numbers will not be available until later this year.

How could the numbers have been so far off? For one, the new data are based on better testing methods that more precisely differentiate new HIV infections from long-standing ones. In addition, HIV infection rates are notoriously hard to come by, especially back in time. Even the new estimates are based on extrapolations using data from only 22 states. The CDC does the best it can do with limited data; the rest is an educated estimate.

Officials emphasize that this does not mean that there actually were more new cases of HIV – rather, we now have better estimates of the actual rates of new infection that existed at the time, regardless of whether or not they were accounted for. Nevertheless, some Democrats are criticizing the Bush administration for not doing enough to combat HIV/aids in this country. Senator Waxman of California released a statement last week in which he pointed out that the CDC budget for prevention has actually shrunk by 19% since 2002, and that the president recently requested a reduction in funding for HIV prevention at the CDC. Given that the incidence of HIV has not declined at all over the past 15 years, Senator Waxman may have a valid concern.

Students may react with a "So what are we supposed to believe, when even scientists can't get it right?" attitude. They'll need convincing that this kind of "flip-flop", as it would derisively be labeled in politics, is actually a normal part of a healthy scientific process.

AIDS Vaccine Tests Halted

Two trials of promising AIDS vaccines have been halted in recent months because the vaccines didn't work. Worse yet, they may have nearly doubled the subjects’ chances of contracting AIDS. It’s an enormous setback for the AIDS vaccine, and no one saw it coming.

The National Institutes of Health, which funded the two studies, will be meeting this week to reexamine its entire AIDS vaccine program, currently funded at nearly $500 million per year. But the findings from the two halted vaccine trials were so disastrous that scientists now seriously doubt that an AIDS vaccine could be ready in the next few decades. It may depend on whether any new hypotheses come out of the new findings, and whether (and how much) NIH decides to fund AIDS vaccine research in the future. No one is giving up just yet, but an AIDS vaccine has certainly proved to be a more difficult challenge than was expected. Way back in 1984, federal officials predicted that an AIDS vaccine would be ready in three years.

See an article available online in The Washington Post March 21 entitled “Vaccine Failure Is Setback in AIDS Fight”. The article could be used as a springboard for a class discussion about the process of scientific inquiry; how new hypotheses are oftentimes developed out of the failure of old ones. You can almost see that happening in the speculation in the article about the causes of the vaccine’s failure.

AIDS proteins

The AIDS virus can only make about 15 proteins on its own. In order to reproduce, it must rely on its ability to force its human host cell to make all of the other proteins it needs. And with the use of a new genetic screen, researchers at Harvard University have identified at least 273 of these human proteins. Knowing precisely which human proteins the virus needs may lead to techniques for growing the virus in the laboratory for research purposes, or ways to block one or more of these key proteins in humans without disrupting the human body very much.

Instructors who are especially interested in how viruses reproduce may wish to read the full research article (Science online January 10; "Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen") and comment on its findings in class. The article itself is too difficult for entry-level students.

AIDS Vaccine Fails in Clinical Trials

This week Merck announced that it was halting test vaccinations of human volunteers with its promising new AIDS vaccine when preliminary findings showed that the drug was not going to be effective in preventing HIV infection. The vaccine was already in Phase II testing (Phase I – is it safe? Phase II – does it work?), meaning that Merck had already invested a lot of time and money in it. Details of the vaccine and its failure can be found on Merck’s website (http://www.merck.com/) under “Research and Development News”.

In Human Biology, 5th ed. (p. 215) we mention that a vaccine may be the only real hope of conquering AIDS once and for all. The failure of Merck's vaccine is a setback for AIDS research and for Merck, to be sure. But Merck’s vaccine was not the only AIDS vaccine under development; currently there are about 30 AIDS vaccines already in either Phase I or Phase II trials in humans.

And kudos to Merck for knowing when to give up this time! Perhaps they learned a lesson from their fiasco with Vioxx (see the Current Issue in Human Biology pp. 184-185). This is how good science is supposed to work - without bias based on financial interest.