Booster Shots

Oddities, musings and news from the health world

Category: AIDS

WHO recommends earlier treatment for HIV and a halt in use of Zerit

November 30, 2009 | 12:48 pm

In a sweeping revision of its guidelines for treating HIV infections, the World Health Organization said today that countries should begin drug treatment sooner, phase out the use of the antiviral drug stavudine and begin treating breastfeeding women.

The guidelines are designed to delay progression of the infection to AIDS, reduce undesirable side effects and minimize transmission of the virus.

"These new recommendations are based on the most up to date, available data," Dr. Hiroki Nakatani, the WHO's assistant director general for HIV/AIDS, TB, malaria and neglected tropical diseases,  said in a statement. "Their widespread adoption will enable many more people in high-burden areas to live longer and healthier lives."

In 2006, the WHO recommended that patients begin receiving antiretroviral therapy (ART) when their CD4 counts -- a measure of immune system strength -- had fallen to 200 cells per cubic millimeter of blood. By that point, however, the first signs of AIDS, such as opportunistic infections, had begun.

Studies reported since then have clearly demonstrated that starting therapy earlier delays progression to AIDS and keeps the person healthier longer. Early treatment also reduces the level of virus in the blood, thereby reducing its transmission to others. The new guidelines now recommend that treatment begin when the patient's CD4 level falls to 350 cells per cubic millimeter, regardless of whether symptoms have occurred.

Zerit, known generically as stavudine or d4T, was one of the first drugs used to treat HIV infections and is still one of the cheapest and most widely used medications for the disease, in large part because its patent expired in 2005 and several companies began making generic versions.

In 2006, about 80% of all patients in the developing world were receiving it as part of their cocktail of ART drugs. In that year, the WHO recommended that countries start cutting back on their usage of stavudine because of side effects, which include irreversible nerve damage and a loss of fat, a process called wasting.

Today, only about half of patients receive the drug, but new data about the side effects shows that that is still way too many. The WHO recommends that, instead of stavudine, patients receive either zidovudine (AZT) or Tenofovir (TDF), which are less toxic and equally effective.

Also in 2006, the agency recommended that ART be started in pregnant women in the third trimester to prevent mother-to-child transmission of the virus. At that time, the agency said, there was little evidence to suggest whether it was beneficial to continue treatment after birth while the mother was breastfeeding. However, in light of new findings, the WHO now recommends that ART be started in the 14th week of pregnancy and that it be continued until the mother stops breastfeeding.

"We are sending a clear message that breastfeeding is a good option for every baby, even those with HIV-positive mothers, when they have access" to ART, said Daisy Mafubelu, the WHO's assistant director-general for family and community health. If the new guidelines are implemented, the risk of transmission of the virus to infants could be reduced below 5%, she said.

An estimated 33.4 million people worldwide, two-thirds of them in sub-Saharan Africa, are HIV-positive. About 2.7 million people are newly infected each year.

-- Thomas H. Maugh II

On HIV and AIDS: Six assessments about where we go from here

November 25, 2009 | 10:45 am

Hiv The number of new HIV infections may be declining, but the battle is far from over.

In assessing how this country, and the world, should proceed, the journal Health Affairs offers up six HIV/AIDS policy briefs, part of an in-depth look at the issue:

HIV and AIDS: Past Successes, Future Opportunities

The Short-Term Costs of Fighting HIV/AIDS

The Long-Term Costs of Battling HIV/AIDS

Preventing HIV/AIDS

Battling HIV/AIDS: Value for Money

The Role of Science in the Fight Against HIV/AIDS

As the introduction notes:

"The articles in our issue demonstrate that the U.S. and other leading donor nations can take crucial steps now to shape the extent of the pandemic and to dramatically reduce its costs – both in terms of the treatment of those affected, and in overall human lives."

If HIV and AIDS have taken a backseat amid better publicized health-related concerns of late, now's the time to take stock.

Today's story in the Los Angeles Times: New HIV infections in decline

It begins: "The estimated number of new HIV infections each year has declined about 17% since 2001, but for every five people infected, only two begin treatment, according to a report from the World Health Organization and UNAIDS released Tuesday."

-- Tami Dennis

Photo: An HIV-positive woman receives treatment in a hospital recently in Merauke, West Papua, near Jayapura, Indonesia.

Credit: Ulet Ifansasti / Getty Images  

Cold virus may have caused 2007 AIDS vaccine trial failure

November 18, 2009 | 10:39 am

One of the biggest disappointments in AIDS research was the failure of Merck & Co.'s STEP trial of an experimental AIDS vaccine, which was terminated prematurely in 2007 when it became apparent that the vaccine seemed to increase the number of people who contracted HIV. Now, British scientists believe they have an explanation for why the vaccine failed, and it has little to do with HIV itself and more to do with the adenovirus that was used to produce the vaccine. The findings may have implications for other experimental vaccines, such as those against malaria and tuberculosis, that also used the adenovirus, as well as for gene therapy.

The adenovirus is what is known as a vector. It is used to carry genes from, in this case, the AIDS virus into cells in the body, where they can produce proteins that stimulate immunity to HIV. Merck used a vector called adenovirus serotype 5 (Ad5), from which they removed genes that could cause disease. Ad5 is very similar to adenoviruses that cause colds, and there's the rub, according to Dr. Steven Patterson of Imperial College London, who led the new study, appearing this week in the Proceedings of the National Academy of Sciences. Many of the patients in the study had previously been exposed to closely related adenoviruses and had built up immunity to the virus.

But that immunity did not simply destroy the vaccine vector. In addition, it attracted T cells that were meant to kill the virus to the mucosal membranes in the nose, mouth and genital areas. Those cells are the primary targets for HIV. "Our research suggests that the adenovirus-based HIV vaccine effectively instructs the cells that HIV infects to gather round exactly where HIV is likely to be introduced," Patterson said. "This is clearly worrisome for this kind of vaccine. Scientists are currently developing adenovirus-based vaccines to protect people from TB and malaria as well as HIV, but they may have to rethink those vaccines if the effect we describe in our new paper is a problem for all of them."

Patterson and his colleagues studied the phenomenon in laboratory dishes using samples obtained and frozen during the initial trials of the vaccine. Two other recent studies in humans concluded that the adenovirus was not the problem. But such negative results, Patterson said, can be difficult to interpret. In particular, those earlier studies looked for the T cells in the blood, and Patterson believes the simplest explanation is that the cells migrated out of the blood into mucosal tissues.

Merck responded that the researchers may be jumping to unwarranted conclusions. "It would be premature to suggest that this provides an explanation for the STEP results, and the implications for other vaccines or gene therapy are unclear," Dr. Michael Robertson, director of vaccines clinical research for the company, said in a statement.

— Thomas H. Maugh II

AIDS vaccine results questioned

October 11, 2009 | 10:45 am

U.S. Army and Thai researchers announced to great fanfare last month that a combination vaccine had produced a statistically significant 31% reduction in new HIV infections in a trial of more than 18,000 people in Thailand -- a modest rate, but the first vaccine results that suggested it may eventually be possible to produce a vaccine against the deadly infection, which has killed more than 25 million people worldwide. In an unusual approach, the researchers decided to make the results public in a news conference rather than wait for formal publication of their findings. The complete results have never been made public.

Now, however, a secondary analysis of the results have suggested that the vaccine was not quite as good as people had believed, reducing infections by only 24%, which was not statistically significant, according to researchers who spoke with Science magazine. The first analysis included all 16,000 people who participated in the trial and produced the promising results. The secondary analysis -- which was part of the protocol and is considered normal for all vaccine trials -- excluded patients who did not follow the experimental regimen. When that was done, the results were less convincing, according to experts who have seen the data.

The study was heavily criticized when it was launched three years ago because each component of the combination vaccine had failed in previous trials. But the National Institute of Allergy and Infectious Diseases, which largely funded the $120-million trial, hoped that it would provide some insight into the kinds of biological responses that must be provoked by a vaccine for it to provide protection. The researchers have subsequently been criticized for how they released the results, but they say that they feared the results would be leaked before they presented them and that they hoped to preempt such an event.

Of course, no one in the public has seen all the data yet. Full details of the trial are expected to be made public Oct. 20 at a meeting in Europe, and the researchers say they are writing a paper to be submitted to the New England Journal of Medicine. Meanwhile, all those who fervently hope for an HIV vaccine can do is wait for further revelations.

-- Thomas H. Maugh II

Women, don't count on male circumcision to protect against HIV

July 17, 2009 |  2:21 pm

Morecondoms Obviously, men shouldn't bank on circumcision to keep them safe either. But the results of a study released this week are especially disappointing for researchers who'd hoped it might reduce HIV transmission to women, thus helping fight AIDS in Africa. 

The premise was promising. Earlier research had indeed suggested that male circumcision might reduce the risk of transmission to the female partners of HIV-positive men.

That seems not to be the case.

The new study, of 922 Ugandan men with the virus, found that the female partners of circumcised participants were no less likely to contract the disease than the female partners of uncircumcised participants.

The removal of the penile foreskin does seem to protect men against HIV transmission from female partners. Just not women at risk from men.
Here's a summary of the study, published today in the Lancet.

Its interpretation is very straightforward: "Circumcision of HIV-infected men did not reduce HIV transmission to female partners over 24 months; longer-term effects could not be assessed. Condom use after male circumcision is essential for HIV prevention."

The report notes, "The trial was stopped early because of futility."

Here's a more readable story on the findings, courtesy of Reuters news agency.

And here's a fact sheet from the Centers for Disease Control and Prevention on male circumcision and HIV transmission. Of special note are the biological reasons that circumcision has been such a focus of concern:

Compared with the dry external skin surface, the inner mucosa of the foreskin has less keratinization (deposition of fibrous protein), a higher density of target cells for HIV infection (Langerhans cells), and is more susceptible to HIV infection than other penile tissue in laboratory studies. The foreskin may also have greater susceptibility to traumatic epithelial disruptions (tears) during intercourse, providing a portal of entry for pathogens, including HIV. In addition, the microenvironment in the preputial sac between the unretracted foreskin and the glans penis may be conducive to viral survival. Finally, the higher rates of sexually transmitted genital ulcerative disease, such as syphilis, observed in uncircumcised men may also increase susceptibility to HIV infection.

-- Tami Dennis

Photo: Use them -- if you can get them. Credit: Bryan Chan / Los Angeles Times

HIV is evolving at warp speed around the globe

February 25, 2009 |  1:13 pm

HIV, the virus that causes AIDS, is one of the fastest evolving entities known. That's why no one has yet been able to come up with a vaccine: The virus mutates so rapidly that what works today in one person may not work tomorrow or in others.

A study published today in the journal Nature confirms that dizzying pace of evolution on a global scale.

Iovxg6kn "It's very clear there's a battle going on between humans and this virus, and the virus is evolving to become unrecognized by the immune system," said Dr. Bruce Walker, director of the Ragon Institute at Massachusetts General Hospital in Boston and one of the researchers. "It does make clear what a huge challenge making a vaccine is."

HIV evolves to escape the immune system, much in the same way that bacteria mutate under pressure by antibiotics, Walker said. Researchers looked at HIV genetic sequences in the United Kingdom, South Africa, Botswana, Australia, Canada and Japan to see how they evolved in response to a key set of molecules in the human immune system called human leukocyte antigens. These key molecules direct the immune system to recognize and kill HIV and other infectious diseases.

Genes encoding human leukocyte antigens vary among humans, and even small differences can dramatically affect a person's response to HIV infection. For example, an adult infected with HIV will survive on average about 10 years without anti-HIV drugs before developing AIDS. But some people will progress to AIDS within a year, and others can survive without treatment for 20 years.

The study published online today found mutations occurred not just in individuals but on a population level. That is, if a particular genetic immune sequence was common in a population, the HIV mutation that evolved to escape it became the most common strain of HIV even in those without that particular human leukocyte antigen gene.

"What this study does is give an explanation for why there are different HIV strains in different parts of the world," Walker said. "The genetic makeup of people in different regions is influencing the virus in specific ways."

This would appear to be bad news for the director of the newly opened Ragon Institute, which was founded to develop vaccines for HIV and other infectious diseases.

But Walker saw the results as hopeful. Mutations often come at a cost to the virus, he said. They can actually make the virus less fit -- that is, less able to replicate as quickly or do as much damage. His challenge is to find what kind of pressure results in this kind of mutation.

In addition to the Ragon Institute, the study involved researchers from Oxford University in England, Kumamoto University in Japan and the Royal Perth Hospital and Murdoch University in Australia, who analyzed the genetic sequences of HIV and human leukocyte antigen genes in 2,800 people.

-- Mary Engel

Photo credit: Ricardo DeAratanha / Los Angeles Times

Today is World AIDS Day

December 1, 2008 |  4:58 pm

AIDS ribbon kite

Today is the 20th anniversary of the first World AIDS Day back in 1988. Worldwide, around 33 million people are infected with the virus -- an earlier estimate of 40 million was downgraded by the United Nations in its most recent report, due to revised sampling methods.

There were 2.7 million new infections in 2007 (the stats on which the report is based), and 2 million died of the virus. More than 1 million people are infected with HIV in the United States.

Around the Web:

Read the UNAIDS 2008 report on the global AIDS epidemic here. (The reports are published every two years.)

Here, at, are remarks by Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. Fauci notes that on the first World Aids Day in 1988, there was only one drug for treating those infected with the virus -- AZT -- and HIV fast became resistant to it. Now, Fauci notes, there are two dozen drugs that are taken in various combinations (reducing the chances that HIV will develop resistance.) Fauci notes that this makes it possible for people to live normal lives for at least a decade and maybe even live normal lifespans.

But Fauci notes that the drugs must be made available to far more people throughout the world -- less than one-third of people infected with the virus "in low- and middle-income countries" are getting these drugs, he notes.

Continue reading »

Another barrier to routine AIDS testing falls

September 29, 2008 |  4:55 pm

Another obstacle to routine screening for HIV is about to fall, this time for the Department of Veterans Affairs, the nation's largest provider of HIV care. You may recall that in 2006, the Centers for Disease Control and Prevention issued revised recommendations for testing adults, adolescents and pregnant women for the virus that causes AIDS.

Aids2 The new recommendations, while acknowledging that 38% to 44% of adults in the U.S. have been tested for HIV, are aimed at the approximately 25% of HIV-positive Americans who are unaware that they harbor the virus. So -- in bureaucratic lingo -- the CDC switched to an opt-out, rather than an opt-in, recommendation. What that means to people who go to hospitals, emergency rooms, clinics and other healthcare settings is that AIDS was to be treated like any other disease when it came to testing.

AIDS testing was to become more like Pap test screening for cervical cancer, or blood pressure readings to check out the heart. Patients have the right to say "no" to such screenings in a medical setting, but if they don't object -- or opt out -- a simple explanation from the physician acknowledged by the patient is enough to grant permission. The CDC said in 2006 that it was time to treat AIDS the same way. Specific signed consent for AIDS screening should no longer be required.

Since the early days of the AIDS epidemic in the 1980s, the disease had different rules from those of most others. Because of the stigma and potential for discrimination associated with the disease, along with the fact that until 1996, there was very little in the way of treatment to slow down the progression from HIV to AIDS to death, federal recommendations were that patients could not be subjected to testing for the disease unless they expressly asked to be tested -- or opted in.

But a CDC report found that of all HIV infections reported in 2004, 40% progressed from HIV-positive to AIDS within a year of diagnosis. That means they've been HIV-positive for a long time. Since the average time from infection with the virus to onset of the disease is about seven to nine years, a lot of infected people are out there, possibly spreading the disease without even knowing it. And the average survival rate is about 11 years longer when people with AIDS are diagnosed early.

The CDC wanted more people to know their HIV status, but that has meant that 20 states had to re-write their laws, eliminating a need for separate written consent for HIV testing. So far, 11 of the states with restrictive HIV-testing laws, including California, have passed new laws removing those barriers.

Now Congress has passed a law removing the barrier to opt-out testing from the VA, according to a news release from OraSure, maker of a rapid results HIV test. It's expected to be signed into law soon, meaning more veterans will be routinely screened.

It's been two years since the CDC recommended that adults 13 to 64 get routinely screened for HIV, according to an article in the Aug. 27 Journal of the American Medical Assn., and there are still problems. AIDS discrimination is still real, some insurers won't cover HIV-screening and many hospital emergency rooms simply don't have the time, personnel and resources to do routine screening on everyone who comes in the door.

But now there's one less barrier to identifying the 250,000 to 312,000 Americans who are HIV-positive and don't know it.

-- Susan Brink

-- Photo Illustration: Getty Images

AIDS in Africa. Exhibit offers a child's-eye view.*

August 14, 2008 |  6:55 pm

Aids1 Step out of your comfortable life and experience the devastation of AIDS in some of the hardest-hit areas in sub-Saharan Africa, from the point of view of a child.

Aidsbed1That's the purpose  of a traveling exhibit featuring a 2,340-square-foot replica of an African village. Tour the village while listening on headsets to a personal audio track telling the true stories of four children -- Kombo, Babirye, Emmanuel and Mathabo -- whose lives have been affected by AIDS.

The exhibit was inspired by the U.S. Holocaust Memorial Museum In Washington, D.C. There, visitors can see the displays while reading the personal story of an individual Holocaust victim.

The AIDS exhibit, sponsored by World Vision, makes a stop in Los Angeles from now until Aug. 26 at two locations.  Until Aug. 18, you can "Step Into Africa" at the Holman United Methodist Church, 3320 W. Adams Blvd. in Los Angeles. And Aug. 22-26 you can experience it at Calvary Community Church, 5495 Via Rocas, Westlake Village.

The exhibit will travel to 80 cities, and some 200,000 people are expected to see it.

Be prepared to spend some time. As the voice says through the headset: "The pace is relaxed. Much like life in Africa."

And while the exhibit is moving, it is not hopeless. As you can see and hear, there is music, joy and hope in the people of Africa, where 25 million people are infected with the AIDS virus.

Short of getting on an airplane to see the continent for yourself, the exhibit gives you a sense of what it is like to be in a village "alive with activity, but people say it has the smell of death," as the gentle African voice will tell you.

-- Susan Brink

Photos: Robert Coronado, World Vision. Top: Faces of those affected by HIV and AIDS in a church in Babirye's village. *Earlier version said the scene was at the exhibit. Below: Bed in a one-room hut.


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