The Nature study highlights just how tough it could be to develop a vaccine that keeps pace with the changing nature of the virus.

The researchers showed HIV was able to adapt rapidly to counter human genes controlling immune system molecules that can target it for destruction.

However, they stressed this would not affect the impact of anti-HIV drugs.

HIV has already killed 25 million people, and an estimated 33 million are currently infected.

However, HIV does not kill all people at the same rate. On average, without treatment it takes 10 years for the infection to progress to Aids, but some people develop the disease within 12 months, while others do not do so for more than 20 years.

The rate of progress is tied to genes which control production of key immune system molecules called human leucocyte antigens (HLAs).

Humans differ in the exact HLA genes they have, and even small differences can have a big impact on how quickly Aids develops.

The researchers examined HIV genetic sequences and HLA genes in over 2,800 people in countries, including the UK, Australia, South Africa, Canada and Japan.

‘Escape’ mutations

They found mutations that enabled HIV effectively to neutralise the effect of a particular HLA gene were more frequent in populations with a high prevalence of that specific gene.

For example, a HLA gene called B*51 is particularly effective at controlling HIV – unless the virus is carrying an “escape” mutation in its genetic make-up.

The researchers found that in Japan, where the B*51 gene is common, two-thirds HIV-positive people without the gene carry HIV armed with the “escape” mutation.

In contrast, in the UK, where the gene is much less common, just 15%-25% of this group of patients are infected with HIV which carries the same key mutation.

Lead researcher Professor Philip Goulder, of the University of Oxford, said similar effects were seen for every HLA gene examined.

He said: “This shows that HIV is extremely adept at adapting to the immune responses in human populations that are most effective at containing the virus.

“This is high speed evolution that we’re seeing in the space of just a couple of decades.

“The temptation is to see this as bad news, that these results mean the virus is winning the battle.

“That’s not necessarily the case. It could equally be that as the virus changes, different immune responses come into play and are actually more effective.

“The implication is that once we have found an effective vaccine, it would need to be changed on a frequent basis to catch up with the evolving virus, much like we do today with the flu vaccine.”

Big challenge

Jo Robinson, of the HIV charity Terrence Higgins Trust, said: “HIV is a complex virus which is constantly changing.

“This kind of research suggests that if we’re able to create a vaccine that works against HIV, the virus will always be one step ahead.

“In that case we’d be in a situation where we need to constantly update the HIV vaccine, a bit like we see with a different flu vaccine each year.”

Keith Alcorn, of the HIV information service NAM, said: “These findings indicate the enormous challenge involved in developing a vaccine against HIV.

“People need to be aware that the research required to develop a successful vaccine may take decades, during which the virus will continue to evolve, as this research shows.”

Rapid HIV evolution avoids attack

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The 42-year-old American living in Germany received the transplant to treat his leukemia, not the HIV itself.

But, it appears the transplant has wiped out the deadly disease.

“The patient is fine,” said Dr. Gero Hutter of Charite Universitatsmedizin Berlin in Germany. “Today, two years after his transplantation, he is still without any signs of HIV disease and without antiretroviral medication.”

The gene mutation is known as CCR5 delta32 and is found in 1 percent to 3 percent of white populations of European descent.

News of the case was first reported in November.

FOXNews.com

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But now that patients with the AIDS virus are living longer, doctors are discovering a new set of complications: People with HIV have a much higher risk of developing certain cancers — lung, liver, head and neck, to name a few — and doctors fear a cancer epidemic among this group could be coming.

Researchers in Maryland, home to one of the nation’s largest AIDS populations per capita, are among the leaders in an effort to solve what has become something of a medical mystery.

“We’re seeing people we have treated successfully for HIV at much higher risk” for cancer, said Dr. Kevin J. Cullen, director of the University of Maryland’s Greenebaum Cancer Center. “The reasons aren’t fully understood.”

New research presented Tuesday by a Johns Hopkins epidemiologist at a national cancer conference shows that patients with HIV are twice as likely as the general population to get any of the cancers not previously linked to the disease. Previous studies have put the risk of developing certain cancers as much as tenfold higher for those with HIV.

There are some hypotheses for why this is so: HIV patients are simply living long enough to get cancer diagnoses; their immune systems are weakened by disease or injured by antiretroviral drugs; those with HIV are more likely to engage in high-risk behaviors. One prominent researcher wonders whether HIV drugs themselves could be a carcinogen.

What scientists learn about cancer and the immune system could have ramifications not just for those with HIV but also for everyone else.

“We’re really at the first stages of systematically looking at the epidemic and fully looking at cancer,” said Dr. William A. Blattner, an associate director of the University of Maryland’s Institute of Human Virology. “Before, you died from AIDS, so you didn’t have time to develop cancer. … The unusual observation is the cancers are occurring at a much younger age.”

Some of the most common cancers being seen among those with HIV are the ones known to be caused by viruses — such as anal and head and neck cancers, which have been linked to the human papillomavirus, and liver cancer, which has been linked to hepatitis.

One theory is that HIV depresses the immune system, allowing cancer-causing viruses to take hold.

Certain cancers have long been associated with HIV and AIDS. Kaposi’s sarcoma, non-Hodgkins lymphoma and cervical cancer — all linked to viruses — were seen from the earliest days of the AIDS epidemic. It’s the other cancers that are today being seen in much greater numbers, now that HIV in the United States has become a long-term, manageable condition not unlike diabetes.

“There’s a real concern about all these cancers and what they portend,” said Dr. Mark Wainberg, director of the McGill University AIDS Center in Montreal. “Obviously, we don’t want to have an epidemic of cancers in long-term HIV-infected people.”

Meredith Shiels, the author of the paper presented Tuesday at the American Association for Cancer Research meeting in Prince George’s County, Md., said it is possible these cancers might have been seen sooner if antiretroviral drugs had come along years earlier. “Perhaps if they had lived longer, we would have seen this 10 years ago,” said Shiels, a doctoral candidate at the Johns Hopkins Bloomberg School of Public Health.

Some researchers have suggested that cancers are developing regularly in all of us but that the immune system is able to keep most of them in check. The immune system of a person with HIV might not be able to perform this function as well.

At the same time, HIV patients who get cancer don’t always have the weakest immune systems, further confounding researchers.

Researchers at Hopkins and the National Cancer Institute, meanwhile, have been studying the elevated risk of lung cancer in patients with HIV.

In November 2003, Dr. Malcolm Brock, a Johns Hopkins thoracic surgeon, and others noticed that every week at the hospital, there seemed to be another HIV patient being diagnosed with lung cancer. “Finally, we said, ‘Something is going on,’” he recalled last week at a conference on HIV and cancer at the University of Maryland School of Medicine.

Johns Hopkins Hospital has a database of about 12,000 patients with lung cancer going back to 1950. In there, researchers found 80 HIV-positive lung cancers, which turned out to be by far the largest such population in any one place — a large enough group to begin studying.

The increased risk of lung cancer in people with HIV, Brock said, is three to five times that for the general population. The risk remains high, he said, even when controlled for smoking. The patients who are appearing at Hopkins, he said, have more late-stage lung cancer, appear to smoke less and are significantly younger than other lung cancer patients. The median age among HIV-positive lung cancer patients is 46; among others it is 64.

“These patients die and they die quickly,” Brock said. The average time from HIV diagnosis to lung cancer diagnosis is six years, he said.

“The deaths here were overwhelmingly cancer-related,” he said. “They were not due to AIDS.”

ajc.com

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Speaking to lawmakers in Santiago, the health minister, Álvaro Erazo, said that in about half of the cases there was no evidence that anyone tried to reach the patients. “There is no justification for that,” Mr. Erazo told members of Chile’s Congress.

The health minister’s admission came just weeks after his predecessor, María Soledad Barría, was forced to resign after revelations that a hospital in Iquique, in the north, had failed to notify dozens of patients that they were H.I.V.-positive. Two people in the hospital later died from complications of AIDS.

Mr. Erazo was summoned before Congress to give a report on the notification problems.

With Thursday’s revelations, the scandal is deepening.

Mr. Erazo told the lawmakers that some of the notification problems resulted from a lack of coordination between the National AIDS Commission and the Health Ministry, and that epidemiological security “was not functioning.”

The Central Metropolitan Health Service in Santiago, the capital, said Thursday that it would open an investigation into the causes of the 107 cases of patients’ not being notified under its jurisdiction. It expected to have results in two weeks.

Two groups dealing with AIDS in Chile, Asosida, a coalition of nongovernmental groups, and Vivo Positivo, said in a joint statement on Wednesday that the notifications scandal was “the worst health crisis that the country has been through in the last several years.” The groups added that the negligence had been “a flagrant violation of human rights and of the right to life.”

Cecilia Sepúlveda, the dean of the School of Medicine at the University of Chile, estimated that about 40,000 people in Chile do not know that they are infected with H.I.V.

Meanwhile, the government said it was making an intense effort to locate and inform the patients of their status. Mr. Erazo vowed it would be done in as confidential a manner as possible.

But that did not appear to be happening in every case. A 28-year-old man in Puerto Montt, a city south of the capital, told Radio Cooperativa in Santiago that two health officials came to his workplace in an ambulance two weeks ago and, in the presence of his boss, told him he was H.I.V.-positive. The following day, he said, his boss told him not to return to work.

Mr. Erazo, responding on Thursday to the claims of the man from Puerto Montt, told lawmakers that “clearly there is a legitimate concern about safeguards and technical capabilities.” If what the man said was true, he said, “it would be disgraceful.”

The brewing scandal is the latest challenge for President Michelle Bachelet’s center-left coalition government, which has endured a series of protests and scandals in recent months that have emboldened right-wing rivals before next year’s presidential race.

Pascale Bonnefoy reported from Santiago, and Alexei Barrionuevo from Rio de Janeiro.

NYTimes.com

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The patient, a U.S. citizen living in Germany, was suffering from advanced leukemia and HIV two years ago when Huetter treated the cancer with a bone-marrow transplant at Berlin’s Charité hospital. As a side experiment, he inserted the bone marrow of a donor naturally resistant to HIV, the virus that causes AIDS. (Researchers have long known that about 1% of Europeans carry a genetic mutation that makes their cells resistant to HIV infection.) Bone marrow produces the cells that HIV attacks. So, the thinking went, inserting marrow that produces HIV-resistant cells might endow the patient with a means to repel the infection. Twenty months after the transplant, Huetter says, the man shows no signs of carrying the virus. (See stories of people surviving with HIV.)

Is this a viable cure for HIV? Not by a long shot. Even Huetter says bone-marrow transplants, which kill about a third of patients, are so dangerous that “they can’t be justified ethically” in anything other than desperate situations like late-stage leukemia. Nor is it clear that Huetter’s claim to have cured his patient is yet justified. HIV has a frustrating ability to hide in hard-to-detect “reservoir” cells in various parts of the body. Current antiviral drugs, for example, can lower a patient’s “viral load” to the point that HIV is undetectable in his or her bloodstream. But as soon as such patients are taken off antivirals, the virus comes storming back.

Huetter’s patient has not received antivirals for two years and remains virus-free even in the known HIV hiding spots of brain and rectal tissue, according to Huetter’s tests. But many researchers remain skeptical about whether these tests have been thorough enough. Dr. Andrew Badley, director of the HIV and immunology research lab at the Mayo Clinic, told the Associated Press, “A lot more scrutiny from a lot of different biological samples would be required to say it’s not present.”

But there might be a glimmer of hope in the case. If the transplant does prove to have been a success and can be replicated, researchers say gene therapists might one day be able to re-engineer a patient’s cells to change their bone morrow the same way a transplant does, except without the dangers. Such a breakthrough, if it proves possible, would be “decades rather than years away,” according to Ade Fakoya, a London-based clinician and senior adviser to the nonprofit Aids Alliance. The treatment would also likely prove too expensive to implement in developing countries where HIV rates are highest, although some proponents of gene therapy say it could eventually be done cheaply through an injection, as with vaccines. (Read a TIME cover story on AIDS.)

Ron Noble of the British AIDS charity Avert says recent setbacks for research into an AIDS vaccine, along with multiple false hopes in the search for a cure, have caused many in the HIV activism community to view Huetter’s experiment warily. For many AIDS activists, bone-marrow transplantation is a loaded procedure that evokes a traumatic past: before antivirals were widely introduced in the 1990s, it was one of the aggressive and often fatal procedures doctors tried in their desperate effort to halt the epidemic; some of these transplants even used marrow harvested from baboons.

In light of that pessimism about curing HIV in patients, Huetter’s announcement was barely discussed at a major international HIV conference in Glasgow today, according to Fakoya, who was attending the event. He said greater attention was paid to more prosaic methods of defense, such as early identification and testing programs. “I’m in the conservative camp — I don’t think there will be a cure,” he says. “But if you look at antiviral treatment, data was provided at this conference confirming that you can live 30 years on [antiviral-drug] therapy, especially if it’s initiated soon after infection. We are getting to a stage where HIV can be managed as a chronic illness. Now, that’s not great, but I have a feeling it’s the best we can do for the foreseeable future.”

TIME

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The killer T-cells, dubbed “assassin” cells, were able to recognize other cells infected by HIV and slow the spread of the virus in lab dishes.

If the approach works in people, it might provide a new route of treating infection with the deadly human immunodeficiency virus, the researchers in the United States and Britain said.

“Billions of these anti-HIV warriors can be generated in two weeks,” said Angel Varela-Rohena of the University of Pennsylvania, who helped lead the study.

In a second, unrelated report, researchers testing Dutch biotechnology firm Crucell NV’s experimental AIDS vaccine said it prevented infection in six monkeys.

The animals were infected with a monkey version of HIV called SIV, and the vaccine used a virus that is dangerous to use in humans, so it is not ready for human tests.

But, writing in the journal Nature, Dr. Dan Barouch of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston and colleagues said it shows there is still hope for developing a vaccine against AIDS.

The AIDS virus, which infects 33 million people globally, is especially hard to fight. Like all viruses, it hijacks cells in its victims, forcing them to become little viral factories and make more virus.

ESCAPE AND EVADE

HIV is even more insidious, attacking immune system cells called CD4 T cells, which help mount a defense. It can also disguise itself to escape CD8 killer cells, also known as cytotoxic T lymphocytes or CTLs.

“CTLs are crucial for the control of HIV infection. Unfortunately, HIV has an arsenal of mutational and nonmutational strategies that aid it in escaping from the CTL response mounted against it by its host,” the researchers wrote in their report, published in the journal Nature Medicine.

One good defense allows HIV to hide a protein called HLA-I-associated antigen.

Varela-Rohena and colleagues took T-cells from an HIV patient and created a genetically engineered version that recognizes this deception.

“It is possible to improve on nature when it comes to preventing HIV CTL escape,” they wrote.

Not only could the engineered T-cells see HIV strains that had escaped detection by natural T-cells, “but the engineered T cells responded in a much more vigorous fashion so that far fewer T-cells were required to control infection,” Penn’s James Riley, who also worked on the study, said in a statement.

“In the face of our engineered assassin cells, the virus will either die or be forced to change its disguises again, weakening itself along the way,” added Andy Sewell of Britain’s Cardiff University.

Perhaps having to mutate will weaken the virus, the researchers said.

They plan to test the T-cell treatment in HIV patients next year.

“We have managed to engineer a receptor that is able to detect HIV’s key fingerprints and is able to clear HIV infection in the laboratory,” said Bent Jakobsen, chief scientific officer at Adaptimmune Ltd, a British company launched in July that owns the rights to the technology. “If we can translate those results in the clinic, we could at last have a very powerful therapy on our hands.”

Reuters

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The review is the most comprehensive analysis of the subject to date. It encompasses data from 15 studies conducted in seven countries, involving more than 53,000 men, most of whom were Caucasian and approximately half of whom were circumcised. The authors concluded that being circumcised reduced a man’s risk of acquiring H.I.V. by 14%. That finding was statistically nonsignificant, but the authors say it should be regarded as a launching point for future trials. “This study gives us a more complete picture than we’ve ever had before,” says Gregorio Millett, the study’s lead author and a senior behavioral scientist at the Centers for Disease Control and Prevention (CDC). “The next step is to design better quality studies to see if there is an association we aren’t detecting.”

One such question, says Millett, is whether circumcision can reduce infection rates among the subset of men who have only insertive sex with other men, as opposed to those who have only receptive sex or both. Millett’s review suggested that among the former group, circumcision lowered H.I.V.-infection risk by 29%, a finding that also showed statistical nonsignificance. But targeting that distinct population in future studies may prove useful for distilling the specific effect of circumcision — and perhaps for future public-health strategies. “For every insertive man who is protected, there might be a receptive man who isn’t infected, for the same reason why women get protected…in other words, from a herd-immunity phenomenon,” says Dr. Sten Vermund, director of the Institute for Global Health at Vanderbilt University School of Medicine, who co-authored an editorial in the current issue of J.A.M.A.

Circumcision is believed to lower H.I.V. transmission in several ways. The inner surface of the foreskin is rich with cells that are more vulnerable to H.I.V. than cells on other parts of the penis; because they are also closer to the epithelial surface and at higher risk for tears during intercourse, they increase susceptibility to infection. Removal of the foreskin further lowers men’s odds of developing genital ulcers (from diseases such as syphilis), which in turn lowers their vulnerability to H.I.V. during intercourse. In theory, circumcision should be protective for all men who participate in insertive sex, including heterosexual men and men who have sex with men.

But researchers note that circumcision is no cure, and no substitute for safe-sex measures such as using condoms. Millett’s analysis found that in studies conducted before 1996 — before the advent of highly active antiretroviral therapy — circumcision was associated with a statistically significant 53% reduction in H.I.V.-transmission risk, which is on par with the 48% to 60% reduction in infection rates reported by the 2007 trials in Kenya, South Africa and Uganda that studied heterosexual men. After 1996, however, when antiretroviral (ARV) drugs turned H.I.V. into a condition that people lived with rather than died from, the protective effect of circumcision became nonsignificant, Millett found. The widespread belief that ARVs could prevent H.I.V. transmission led to an increase in risky sexual behavior, outbreaks of sexually transmitted infections and increasing rates of H.I.V., which, the study’s authors say, may have diminished the relative effectiveness of male circumcision.

“Nobody should frame male circumcision as some sort of panacea,” says Vermund. “But it may prove to be one more tool in the toolbox…if you can add it to behavioral risk reduction, prompt diagnosis and access to care, it may be the combination needed to really knock the socks off the H.I.V. epidemic.”

New Debate Over Circumcision, HIV Reduction – TIME

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The report, published in the British medical journal The Lancet, says 3m self-injecting drug users worldwide could now be HIV-positive.

In nine countries, more that 40% of drug users were infected.

The authors are concerned about the lack of data from Africa and say the risk factors that have helped spread HIV in this way exist on the continent.

They said there was a “pressing need” to address the problem.

The scientists behind this study, frmo the University of New South Wales in Australia, carried out a wide-ranging review of published data.

They concluded that both the numbers of injecting drug users and the prevalence of HIV infection among them are on the increase.

The virus is spread mainly by the use of shared needles.

In some countries in South East Asia, Latin America and Eastern Europe the rates of infection among injecting users are above 40%. In Estonia it is more than 72%.

But some countries have maintained very low rates of infection, such as the UK – where the rate is 2.3% – New Zealand and Australia where only 1.5% of injecting drug users are HIV-positive.

Needle exchange

Researchers say that this was due to the swift introduction of needle exchange programmes in the 1980s.

The report says that there is a clear mandate to invest in HIV prevention programmes such as needle exchanges and drug substitution treatments.

There is also a clear need for education to help prevent the spread of infection in countries where injecting drug use is common but where the virus has not yet become widespread among users.

“The high prevalence of HIV among many populations of injecting drug users represents a substantial global health challenge,” the authors say.

Michael Carter, of the HIV information service NAM, said the report provided “striking evidence” to support the provision of needle exchange programmes.

He said: “The UK has historically low rates of HIV amongst injecting drug users because we put health promotion first.

“Compare this to the HIV prevalence in countries which have resisted the provision of needle exchanges in the misguided belief that they ‘encourage’ drug use.”

Mr Carter added there was good evidence that IDUs can do very well on anti-HIV treatment – but often stigma and discrimination meant that they were denied potentially life-saving drugs.

Ailsa Spindler, of the charity Terrence Higgins Trust Scotland, said: “There is a long way to go globally in tackling IDU, its causes and its effects on health, including HIV transmission.”

She said health among IDUs was “relatively good” in the UK, but the number of new HIV diagnoses among the group had increased gradually over the past five years.

BBC NEWS | Health | HIV rates among drug users rising

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The last stage of HIV infection is AIDS (acquired immunodeficiency syndrome). The AIDS virus is transmitted in bodily fluids such as blood, semen and breast milk with sexual contact being the most common method of transmission. The use of contaminated needles and blood transfusions can also cause infection.

Recently, the U.S. Centers for Disease Control and Prevention (CDC) reported that 56,300 people in the U.S. become infected with HIV annually, which far surpasses previous estimates of about 40,000. The CDC has now found that HIV has the heaviest impact on men who have sex with men (MSM). This group of men includes gays, bisexuals and men who have an occasional sexual encounter with other men.

In a new report from the CDC the authors write, “The male-to-male sexual contact transmission category represented 72 percent of new infections among males, including 81 percent of new infections among whites, 63 percent among blacks, and 72 percent among Hispanics.” The report explains that more than half of the new infections in 2006 were among gay and bisexual men, with 46 percent among whites, 35 percent among blacks and 19 percent in Hispanics. However, among the overall U.S. population, more blacks are affected at more than 45 percent.

Kevin Fenton, MD, PhD, director of the CDC’s division of HIV/AIDS, said at a news conference, “The number of new HIV infections among young black men who have sex with men is alarming.” Similarly, Richard Wolitski, PhD, acting director of the CDC’s division of HIV/AIDS Prevention said that the astonishingly heavy impact of HIV on African-American women is no less alarming.

The CDC now sees the need to intensify prevention efforts targeting the black community as the report read, “The alarming number of new infections among young black MSM underscores the need to ensure that each new generation has the knowledge and skills to prevent HIV infection beginning early in their lives.” Additionally, the CDC wrote, “African-Americans make up 12 percent of the total U.S. population, yet represented 45 percent of new HIV infections in the United States in 2006.”

Other findings listed in the report include that 27 percent of new infections are among girls and women with high-risk sexual contact with men, which causes 80 percent of new infections. The authors also noted, “Among females, 61 percent of infections were in blacks, 23 percent were in whites, and 16 percent were in Hispanics.”

The bottom line of the facts are that young black men, ages 13 to 29, who have sex with men get HIV more often than any other age or racial group and African-American men are six times more likely to get HIV than are white men. In addition, African-American women are 15 times more likely to get HIV than white women.

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