AIDS "Patient Zero" Was Wrongly Accused

For many years, it was believed that the first outbreak of AIDS in the U.S. was triggered by just one person, dubbed "patient zero". That belief was popularized by Randy Shilts's best-selling book And The Band Played On, published in 1987. Patient zero was allegedly Gaetan Dugas, a French-Canadian flight attendant who was thought to have picked up H.I.V. in Haiti sometime in the late 1970s. Mr. Dugas died of AIDS in 1984. After his death Mr. Dugas was vilified by the media; a 1987 New York Post headline called him "The Man Who Gave Us AIDS".

The myth of "patient zero" persisted for almost 20 years. It wasn't until 2014 that careful detective work provided convincing evidence that HIV actually arrived in New York City around 1971 and was well established in the U.S. before Mr. Dugas became infected. And just recently, DNA analysis of a sample of Mr. Dugas's stored blood confirmed that he was not the infamous "patient zero", if indeed there ever was one.

Mr. Dugas was not the villain he was made out to be, despite the fact that he continued to be sexually active after he became infected. He deserves our belated apology.

Transplanting HIV-Positive Organs

If all goes according to plan, there will soon be a significant increase in the number of human organs available for transplantation. That's because the United Network for Organ Sharing (UNOS), the system that oversees organ transplants in this country, has given final approval to begin transplanting organs from HIV positive donors into HIV recipients.

Twenty years ago, HIV-positive patients were not considered good candidates for organ transplantation because they were not expected to live very long. But over the years better treatment of HIV has meant that HIV-positive patients can live nearly a normal life. So although HIV-positive people are now eligible for organ transplants, there are not nearly enough HIV-negative organs available to satisfy a rapidly growing demand. (Traditionally, organs from donors who test positive for HIV are rejected because of the fear of transferring HIV to the recipient.)

Prior to 2013 it was illegal to even conduct research using HIV-positive organs. Then in 2013 the government passed the HIV Organ Policy Equity (HOPE) act, allowing such research for the first time. The research showed conclusively that HIV-positive organs could be effectively and safely transplanted into HIV-infected recipients. The first such transplant is likely to occur within months. The availability of HIV-infected organs dramatically increases the pool of organs available to HIV-positive recipients (they will now be eligible for organs that HIV-negative recipients are not). It will also improve the situation for potential recipients who are not HIV-positive, because there will be fewer HIV-positive recipients competing for the available HIV-negative organs.

It's win-win for all potential organ recipients, regardless of HIV status. The government should be congratulated for their vision on this one.

An HIV-Preventing Drug Exists, But Isn't Being Used

Back in 2012, the FDA approved the first drug for the prevention of HIV infection in otherwise healthy persons who might be at risk for infection due to exposure to an infected partner. The drug, called Truvada, prevents HIV infections 92% of the time, meaning that it could sharply reduce the number of new HIV infections if it were widely used. That turns out to be a big "if", for hardly anyone seems to be using the drug.

The drug's manufacturer, Gilead Sciences, Inc., has made a lot of money ($1.8 billion in 2014) from the use of the drug to treat HIV-infected patients. But it has made no effort to market Truvada for use in healthy persons solely for the purpose of preventing HIV infection. The company says that it just isn't profitable to market the drug for HIV prevention. And as a result of a lack of marketing, many physicians and nurses are simply unaware that the drug has been approved and is available for HIV prevention. According to the Centers for Disease Control and Prevention (CDC), one in three primary care doctors and nurses have never even heard of the potential use of Truvada for what is called preexposure prophylaxis (PrEP).

Lesson learned: government health officials will have to take the greater role in educating primary care physicians and nurses about Truvada for PrEP. Health officials in New York are already doing so according to the CDC, and as a result the number of NY medicaid beneficiaries receiving PrEP more than quadrupled between 2014 and 2015.

Truvada is Not Popular Among Men at Risk for HIV Infection

Back in September of 2012 the FDA approved the first daily pill for the prevention of HIV infection in persons at risk (see "First Drug Approved for HIV Prevention").  The drug was hailed as a potential life-saver for healthy (uninfected) partners of HIV-infected persons and for healthy individuals who, by virtue of their behavior, felt that they were at risk of HIV infection.  In other words, healthy gay men.  Health officials had hoped that the drug might put a serious dent in the more than 50,000 new HIV infections in the U.S. every year.

Alas, it just isn’t working out that way.   According to an analysis by researchers at Gilead Sciences, Truvada’s manufacturer, only about 1,400 new prescriptions for Truvada were written in 2013.  Surprisingly, nearly half of the new users were women.

Why are healthy gay men at risk for HIV infection not rushing to try Truvada?  A recent New York Times article describes some of the possibilities, including the drug’s price (about $1,000 per month), inadequate education and marketing, and supposedly even the stigma of being called a “Truvada whore”.  Whatever the reason, health officials (and Gilead Sciences) must be disappointed with the fact that new prescriptions represent less than 3% of the annual number of new HIV infections.   This drug is not yet reaching the people for whom it is intended…

An Anti-HIV Protein in Human Milk

The HIV virus that causes AIDS is present in the milk of HIV-infected mothers, yet only about 10% of infants who nurse from HIV-infected mothers get infected. In the past it was thought that ingestion is simply a poor route to HIV infection. Now it turns out there’s another reason – human milk contains a protein that latches onto the surface coating of the virus, preventing it from infecting the infant. The protein, called Tenascin-C, normally plays a role in wound healing and fetal development. Its antiviral properties are apparently just a lucky coincidence; it couldn’t have evolved during the course of human evolution to combat HIV, because HIV didn’t exist until recently.

Will Tenascin-C become an important weapon in the fight against HIV infection? Probably not. HIV-infected mothers are already given antiretroviral drugs and they already have Tenascin-C in their milk, so purified Tenascin-C might not add much of a benefit to them or their infants. And it’s unlikely that Tenascin C would work if it were to be given intravenously to patients with established HIV infections. Nevertheless, the finding that a natural human protein can inactivate the HIV virus before it infects the host is leading to renewed hope that a drug with similar properties could be developed. An AIDS-free world may just be within our reach.

Should Healthy People be Screened for HIV Infection?

According to the Centers for Disease Control (CDC), 25% of people who are infected with HIV do not know they are infected. Apparently these people are causing 80% of all new HIV infections. The available research suggests that if they knew they were infected they would make healthier choices in order to maintain their own health and protect the health of those they love. In the long run, that would reduce the rate of new HIV infections and ultimately lower our national health care costs.

At least that’s the logic behind the idea that all adults should routinely be tested for HIV infection. The American College of Physicians and Surgeons currently recommends that all persons older than 13 years should be tested. The CDC largely agrees, but adds that testing is not warranted in persons older than 64 or in populations with an HIV prevalence of less than 0.1%. However, the U.S. Preventive Services Task Force (USPSTF) does not yet recommend routine HIV screening of all persons; it recommends screening only patients “at increased risk”. As a result, routine screening for HIV infection is not yet commonplace.   It boils down to money; without a recommendation by the USPSTF, insurance companies are unlikely to pay for HIV tests in healthy people. 

Physicians groups and the CDC argue that patients don’t necessarily tell their physicians if they are at increased risk of HIV infection, so it’s nearly impossible to tell who is at increased risk. In addition, it’s hard for a physician to know the actual percentage of HIV in the patient’s population.

But now it appears that the USPSTF is considering changing its recommendation. The Task Force issued a draft document on Nov. 20 that, if approved, will recommend that all persons aged 15-65 be routinely screened for HIV infection. The draft document is available for public comment until Dec. 17.

Would routine screening for HIV infection be a good idea? You decide. You can comment on the USPSTF’s draft recommendation if you wish by going to to the USPSTF’s web page on the subject.

A Home Test for HIV

The first in-home HIV test kit became available last month in retail stores nationwide. The test kit, called OraQuick, was approved by the FDA in July, but it took until October to ramp up production and launch a nationwide sales effort.

The kit is designed to test a sample of oral fluid for antibodies to HIV in under 45 minutes. The kit has a reported false positive rate (identifying a person as HIV-infected when in fact he/she is not) of only 0.02%, or 1 in 5,000 persons. However, it has a false negative rate (failure to identify an HIV-infected person as infected) of 8%, meaning that HIV infection will be missed in 1 in 12 infected persons. The reason for the higher false negative rate is because the test detects the human antibodies that develop in response to HIV infection, not the HIV virus itself, and it takes several months after initial infection for these antibodies to develop.

A similar test has been available in doctors’ offices for some time. Nevertheless, health officials are hailing the home test as an important step forward in the fight against HIV-AIDS. The hope is that the availability of an inexpensive home test will encourage more people to test themselves for HIV infection, and then to seek treatment if they test positive.

First Drug Approved for HIV Prevention

For the first time, the U.S. Food and Drug Administration (FDA) has approved a drug specifically for the prevention of sexually-acquired HIV infection. The drug, called Truvada, is currently being used in combination with other drugs in the treatment of existing HIV infections.

Not everyone is happy about the FDA’s decision. The main concern is that using the drug in a large number of uninfected individuals could increase the risk of the HIV virus becoming resistant to the drug. To reduce that possibility, the FDA is asking health professionals to prescribe the drug only to high at-risk individuals (such as partners of HIV-infected persons) who have been tested for HIV and are currently negative. In addition, individuals who are taking the drug should be retested every three months to ensure that they remain negative, because Truvada alone is not recommended for HIV-infected individuals. But retesting for HIV status every three months is asking a lot in terms of compliance by health professionals and patients.

Health officials will be watching closely for any signs of the development of resistance of the HIV virus to Truvada. Whether or not patients on Truvada actually comply with the HIV re-testing recommendation will be of interest, too.

Setback for Vaginal Gel Against HIV

Last year a study reported that a vaginal gel containing 1% tenofovir (an anti-HIV drug) was partially effective in preventing HIV infection in at-risk women in Africa (see this blog Sept. 5, 2010). Researchers were particularly interested in developing a gel against HIV because it would be a prevention method controlled by women, rather than by men. The study was hailed by a breakthrough by AIDS researchers, and several large follow-up studies were undertaken to to confirm the findings.

The results have been very disappointing. One of the follow-up trials was halted recently when it became clear that the vaginal gel was not going to be effective in reducing the rate of HIV infection in what was thought to be a similar group of at-risk women. (See also the PBS report.) Researchers are scratching their heads and trying to work out the differences between this and the previous study to see if they offer any clues as to why the recent trial failed. In the meantime, another study is still ongoing.

But let's put the disappointment in perspective. This is the scientific process at work. Hypotheses are made and tested, findings repeated and confirmed (or not confirmed), hypotheses modified and tested again….its a continuous process that brings us closer to the truth through repeated success and failure, trial and error. We’ll just have to wait for the next instalment in this ongoing saga. In the meantime, don’t expect a vaginal gel against HIV infection to hit the market any time soon.

Preventing HIV Infection

Nearly three years ago on this blog (see “A Daily Pill Against HIV Infection”, Aug. 10, 2008) I reported that research was underway to determine whether HIV infection could prevented in healthy people by giving them AIDS drugs before they became infected, not after. It’s called pre-exposure prophylaxis (PrEP), and according to a news release from the CDC, there is now convincing evidence that it works!

In one study by researchers from the University of Washington in conjunction with the CDC, a daily pill comprised of two known AIDS drugs (or a placebo) was given to nearly 5,000 “discordant couples” in Kenya and Uganda (one partner HIV-infected, the other not). Uninfected partners who took the daily pill had a 73% lower chance of becoming infected, compared to those who received the placebo. The study was stopped early because the results were so clear-cut that it was deemed unethical to continue withholding the drug from the control group. A second study by the CDC of 1,200 sexually active young adults in Botswana revealed that those who took a daily PrEP pill had a 63% lower chance of infection, compared to those who did not.

Given these recent findings, PrEP is likely to become a new standard of prophylaxis for healthy, at-risk individuals who request it. However, it should be noted that the PrEP pill has not yet been tested in pregnant women, so it may not be for everyone.

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 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.