Gene therapy clears HIV from human body

A person with HIV who didn't take antiretroviral drugs for three months remained free of the virus, thanks to a groundbreaking gene therapy. The success raises the prospect of keeping HIV in check permanently without antiretrovirals.

The gene therapy works by locking the virus out of the CD4 white blood cells it normally infects. Of six people with HIV given the treatment, one cleared the virus completely and another two saw 10-fold drops in circulating virus.

"We're over the moon to have seen that in this small phase I study," says Jeff Nichol, executive vice president for research at Sangamo BioSciences, the company in Richmond, California, that is developing the treatment. "Having one virus-free patient and 10-fold reductions in another two is amazing."

Most importantly, analysis of data from the six patients, and from four others in a separate trial, revealed the secret of the more successful outcomes, paving the way for the therapy to work better in future.

Zinc fingers

To deliver the treatment, doctors remove blood from the patient and isolate CD4 and other white blood cells. Specialised molecular "scissors" called zinc finger proteins enter the cells and sabotage a gene called CCR5, which makes a protein that helps HIV to enter cells. It is unclear what role CCR5 plays normally, although researchers know that cells can survive without it – and will remain uninfected by HIV.

These cells are then returned to the patient in the hope that they will multiply and provide a permanent source of cells immune to HIV, potentially locking out HIV completely. The link between CCR5 and HIV was first suggested in 1996. 

The concept was first tested inadvertently in Germany in 2006, when a person with leukaemia who was also HIV positive received a bone marrow transplant that happened to come from someone whose blood cells couldn't make CCR5 proteins. The patient was HIV-free by 2008.

Most people have two working copies of CCR5, one from each parent. The patient who did best in the Sangamo trial already had one defective copy, which is thought to explain why the therapy worked better in him than in the others. 

Further analysis showed that after the treatment he had twice as many cells in which both copies of the CCR5 gene had been sabotaged than any other trial participant.

The two patients who saw 10-fold reductions in circulating virus also had more doubly sabotaged cells than the three who didn't respond as well.

Double sabotage

The secret to making the treatment work best, Sangamo says, is therefore to eliminate both genes in as many cells as possible. If only one is sabotaged, cells can still make enough CCR5 protein to allow the virus to invade. In doubly sabotaged, or "bi-allelic" cells, there is no way in.

"The way forward is to get as many bi-allelic cells as possible back into the patient," says Nichol.

In the light of the findings, Sangamo has plans to try depleting the patient's native blood system with drugs before returning the altered cells. 

Depletion causes blood cells to multiply faster than normal to compensate for the shortage, resulting in a more rapid expansion of the numbers of HIV-resistant bi-allelic cells.

Nichol's colleagues presented the results on Sunday at the Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago.

New potent and broadly effective antibodies against HIV found

A team of researchers at and associated with the International AIDS Vaccine Initiative (IAVI), The Scripps Research Institute, the biotechnology company Theraclone Sciences and Monogram Biosciences Inc., a LabCorp company, report in the current issue of Nature the isolation of 17 novel antibodies capable of neutralizing a broad spectrum of variants of HIV, the virus that causes AIDS.

The new antibodies, large protein molecules that bind to pathogens and flag them for destruction, were isolated from blood serum samples collected in a continuing global search for broadly neutralizing antibodies (bNAbs) launched by IAVI.

They should provide researchers with a new set of targets for the design of vaccine candidates that can elicit similar antibodies to protect people from contracting HIV. Some of the bNAbs blocked HIV infection of cells as much as 10 to 100 times as potently as previously discovered bNAbs.

“Most antiviral vaccines depend on stimulating the antibody response to work effectively,” said Dennis Burton, a professor of immunology and microbial science and director of the IAVI Neutralizing Antibody Center at The Scripps Research Institute in La Jolla, Calif. Professor Burton, one of the senior authors of the study, is also a member of the Ragon Institute, in Cambridge, Mass.

“Because of HIV’s remarkable variability, an effective HIV vaccine will probably have to elicit broadly neutralizing antibodies. This is why we expect that these new antibodies will prove to be valuable assets to the field of AIDS vaccine research.”

Only a minority of people who are HIV-positive begin to produce bNAbs after several years of infection. Animal studies suggest that such antibodies could block HIV infection if they were elicited by a preventive vaccine.

Researchers prize bNAbs because their structural and biochemical analysis can reveal how to achieve a preventive vaccine. Specifically, scientists expect that they can use information about how bNAbs bind to HIV to construct immunogens—the active ingredients of vaccines—that elicit similar antibodies.

The potency of bNAbs matter because a highly potent antibody could confer such protection at relatively low levels.

“Solving the neutralizing antibody problem is perhaps the greatest challenge facing the field today,” said IAVI’s chief scientific officer, Wayne Koff. “IAVI concluded many years ago that unlocking the information stored in bNAbs was going to be essential to the fulfillment of our mission—ensuring the design and development of broadly effective AIDS vaccines.

This is why we support several laboratories around the world that are designing novel vaccine candidates on the basis of what we’re learning from such antibodies. We have no doubt that these new bNAbs will contribute a great deal to our own immunogen design efforts and, we hope, those of other researchers working on AIDS vaccines.”

In that regard, the new bNAbs are encouraging. Many of them bind hitherto unknown molecular structures, or epitopes, on the surface of HIV. This means that they could significantly broaden the target options researchers have in designing vaccines to elicit similar antibodies.

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Acne drug prevents HIV breakout

Acne drug prevents HIV breakout

Johns Hopkins scientists have found that a safe and inexpensive antibiotic in use since the 1970s for treating acne effectively targets infected immune cells in which HIV, the virus that causes AIDS, lies dormant and prevents them from reactivating and replicating.

The drug, minocycline, likely will improve on the current treatment regimens of HIV-infected patients if used in combination with a standard drug cocktail known as HAART (Highly Active Antiretroviral Therapy), according to research published now online and appearing in print April 15 in The Journal of Infectious Diseases.

"The powerful advantage to using minocycline is that the virus appears less able to develop drug resistance because minocycline targets cellular pathways not viral proteins," says Janice Clements, Ph.D., Mary Wallace Stanton Professor of Faculty Affairs, vice dean for faculty, and professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine.

"The big challenge clinicians deal with now in this country when treating HIV patients is keeping the virus locked in a dormant state," Clements adds. "While HAART is really effective in keeping down active replication, minocycline is another arm of defense against the virus."

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AIDS virus can hide in bone marrow

The virus that causes AIDS can hide in the bone marrow, avoiding drugs and later awakening to cause illness, according to new research that could point the way toward better treatments for the disease. Finding that hide-out is a first step, but years of research lie ahead.

Dr. Kathleen Collins of the University of Michigan and her colleagues report in this week's edition of the journal Nature Medicine that the HIV virus can infect long-lived bone marrow cells that eventually convert into blood cells.

The virus is dormant in the bone marrow cells, she said, but when those progenitor cells develop into blood cells, it can be reactivated and cause renewed infection. The virus kills the new blood cells and then moves on to infect other cells, said.

"If we're ever going to be able to find a way to get rid of the cells, the first step is to understand" where a latent infection can continue, Collins said.

In recent years, drugs have reduced AIDS deaths sharply, but patients need to keep taking the medicines for life or the infection comes back, she said. That's an indication that while the drugs battle the active virus, some of the disease remains hidden away to flare up once the therapy is stopped.

One hide-out was found earlier in blood cells called macrophages. Another pool was discovered in memory T-cells, and research began on attacking those.

But those couldn't account for all the HIV virus still circulating, Collins said, showing there were more locations to check out and leading her to study the blood cell progenitors.

Finding these sources of infection is important because eliminating them would allow AIDS patients to stop taking drugs after their infection was over. That's critical in countries where the treatment is hard to afford and deliver.

"I don't know how many people realize that although the drugs have reduced mortality we still have a long way to go," Collins said in a telephone interview. "That is mainly because we can't stop the drugs, people have to take it for a lifetime."

The research was funded by the National Institutes of Health, Burroughs Wellcome Foundation, University of Michigan, Rackham Predoctoral Fellowship, National Science Foundation and a Bernard Maas Fellowship.

Drug Resistant HIV spreading globally

Drug resistant HIV is striking back against the antiretroviral drugs that keep it largely in check in rich countries, thanks both to its over-exposure to the major drugs and to individuals who don't realise (or care) they're infected and so spread resistant strains to new partners.

Its not new
Drug-resistant strains of HIV have already been documented in San Francisco and elsewhere in the US, and Europe. Now a model of their transmission, based on studies of gay San Francisco men, forecasts a rapid upsurge in the next five years.

What's more, as access to antiretroviral therapy is expected to expand in poorer countries, they could experience a rise in resistance too, predicts Sally Blower of the University of California, Los Angeles, lead author on the analysis.

Cocktail of resistance
Currently, people with HIV tend to be given a cocktail of drugs, making it less likely that resistance will emerge. That's because even if a strain evolves resistance to one of the drugs, it will still succumb to the others.

Short Term Thinking
However, the virus can evolve resistance nonetheless. Currently, about 15 per cent of new infections in San Francisco are from resistant strains, some of them resistant to all three major classes of drug used to combat the virus.

To see how this might increase in future, Blower's team created a model of HIV transmission that predicts how and when resistant strains will emerge. When they fed in data from San Francisco, it correctly predicted how drug-resistant HIV has already evolved and spread among gay men there over the past 20 years. It also predicted how quickly it will spread globally.

Full article here .....

Journal reference: Science, DOI: 10.1126/science.1180556

AIDS /HIV and Circumcision: Reduces microbial neighbourhood

A flap of foreskin isn't the only thing missing after a circumcision. Microbes that call the penis home disappear, too, which could explain why the procedure reduces a man's chance of contracting HIV.

"The microbes change dramatically," says Lance Price, a microbiologist at the Translational Genomics Research Institute in Flagstaff, Arizona, whose team identified thousands of microbes on the penises of 12 HIV-negative men. All had participated in a clinical study in Uganda which showed that circumcision halves the chances of getting the virus.

The team discovered a total of 38 families of bacteria on the men's penises before circumcision, and 36 a year after. But the make-up of these communities had swung. Gone were a diverse population of bacteria intolerant of oxygen and linked with vaginal infection; now there was a more homogenous air-loving lot, more typical of other patches of skin.

Price thinks that some of the expelled bacteria provoke an immune reaction on an uncircumcised penis, causing specialised immune cells to shuttle HIV throughout the body.

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UN: Yao Ming in campaign to fight HIV stigma in China

UNAIDS said Friday it had launched a campaign to address rampant discrimination against people living with HIV in China, with the help of Chinese NBA megastar Yao Ming.

The campaign, launched with China's health ministry, will see posters and videos of Yao and his fans, including some with HIV, displayed on giant screens in 12 cities across China, the United Nations agency said in a statement.

People who are HIV positive in China experience high levels of stigma and discrimination.

According to a report by UNAIDS, a quarter of medical staff and over a third of government officials and teachers developed negative and discriminatory attitudes towards people living with HIV after learning their status.

More than 12 percent of people with HIV had also been refused medical care at least once since they tested positive, UNAIDS said in their China Stigma Index report emailed to AFP.

"These results really underscore the importance of ensuring health care professionals receive appropriate training to reduce stigma and discrimination and increase their ability to provide appropriate services to people living with HIV," UNAIDS executive director Michel Sidibe said in the statement.

The report was based on a survey of more than 2,000 people living with HIV in China and is the first of its kind in the Asian nation.

It also found that more than 34 percent of those of working age had stopped working as a result of being HIV positive and over 55 percent had chosen not to attend social gatherings or had isolated themselves from family and friends.

"Building understanding and care from society as a whole for people living with HIV, together with eliminating discrimination, are key elements of the AIDS response," Huang Jiefu, China's vice minister of health, said in the statement.

The campaign will also see more than 30,000 posters distributed across China, the statement said.

China's health ministry estimates that at the end of 2009, 740,000 people were living with HIV in the country, and according to the latest data, 48,000 were infected this year, according to UNAIDS.

Indonesian militants call for sharia law to stop HIV

Jakarta (AFP) Nov 29, 2009 - Several hundred hardline Muslim protestors staged rallies in Indonesia Sunday to urge the government to prevent the spread of HIV by implementing Islamic law.

Ahead of World AIDS Day on December 1, members of the Hizbut Tahrir group took to the streets in several cities including Jakarta, Solo, Yogyakarta and Makassar.

"We urge everybody to support the application of sharia in an Islamic caliphate so that, God willing, all of us will be free from the HIV/AIDS threat," Hizbut spokeswoman Febrianti Abassuni said in a statement. In the capital, more than 200 female demonstrators urged the government to close down brothels and ban condoms, which they said encouraged "free sex and unhealthy behaviour".

One banner read: "Prostitutes, drug users and homosexuals are the agents of immorality." Around 270,000 Indonesians are estimated to be infected with HIV, and AIDS has claimed about 8,700 lives in the Muslim-majority nation of 228 million people, according to the UNAIDS agency.

Does Experimental Vaccine helps prevent HIV infection

For the first time, an experimental vaccine has prevented infection with the AIDS virus, a watershed event in the deadly epidemic and a surprising result.

Recent failures led many scientists to think such a vaccine might never be possible.
The vaccine cut the risk of becoming infected with HIV by more than 31% in the world's largest AIDS vaccine trial of more than 16,000 volunteers in Thailand, researchers announced Thursday.

Even though the benefit is modest, "it's the first evidence that we could have a safe and effective preventive vaccine," said Col. Jerome Kim. He helped lead the study for the U.S. Army, which sponsored it with the National Institute of Allergy and Infectious Diseases.

The institute's director, Dr. Anthony Fauci, warned that this is "not the end of the road," but said he was surprised and very pleased by the outcome.

"It gives me cautious optimism about the possibility of improving this result" and developing a more effective AIDS vaccine, Fauci said. "This is something that we can do."

Even a marginally helpful vaccine could have a big impact. Every day, 7,500 people worldwide are newly infected with HIV; 2 million died of AIDS in 2007, the U.N. agency UNAIDS estimates.

"Today marks an historic milestone," said Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition, an international group that has worked toward develping a vaccine.

"It will take time and resources to fully analyse and understand the data, but there is little doubt that this finding will energize and redirect the AIDS vaccine field," he said in a statement.

Woman Contracts Gorilla HIV: Proof of Direct Connection between SIV and HIV /AIDS

A new strain of HIV has jumped from gorillas to humans.

So far, only one person, a 62-year-old French woman from Cameroon, has been reported to be infected with the virus.

It very closely resembles strains of Simian Immunodeficiency Virus (SIV) recently discovered in western gorillas in the wild.

"It would be surprising if there aren't many more" human cases, says David Robertson, a bioinformaticist at the University of Manchester, UK who analysed the virus's DNA along with colleagues in France.

"We don't think this is a direct gorilla-to-human transmission." It is more likely to be the result of eating 'Bush meat', plus transmission via sexual activity.

Drug hope

Until 2004, the infected woman lived in a suburb of Cameroon's capital city Yaoundé, where she didn't come into contact with apes or eat their meat, SIV's primary route to humans. This means that she probably acquired the infection from another human, likely through sexual contact.

AIDS

The woman hasn't yet shown any sign of a compromised immune system, the hallmark of AIDS but tests on laboratory-cultured human cells suggest that the virus can replicate in the same white blood cells as other strains of HIV. However, the new virus should be susceptible to anti-retroviral drugs that slow the growth of other strains of HIV, Robertson says.

SIV

Based on its genetic sequence, the virus appears most closely related to a number of SIV strains collected recently in gorilla faecal samples from forests in Cameroon. These viruses also resemble "group O" strains of HIV, which infect far fewer people than other strains of HIV, most of them in Cameroon.

Original source

The discovery of a gorilla virus in humans could suggest that some of these group O viruses came from gorillas, Robertson says, but it's also possible that the virus originated chimpanzees and was transmitted independently to gorillas and to humans.

"Until we do more sampling we're also guessing a little bit," Robertson concedes.

HIV Vaccine still a Fantasy? Research continues

FEARS that HIV vaccines may encourage infection with the virus have largely been laid to rest. This could revive the search for a vaccine.

In September 2007, pharmaceutical company Merck halted its STEP trial of an HIV vaccine because it appeared to work no better than a placebo.

The Cold Virus

Then it emerged that recipients of the vaccine who had previously caught the cold virus were more likely than those who hadn't to be infected with HIV, sparking fears that the vaccine made HIV infection more likely.

Loaded with HIV Genes

The vaccine consisted of a deactivated cold virus loaded with three HIV genes that were supposed to stimulate immunity. The fear was that participants with immune systems primed to fight the cold virus produced a surge of CD4 cells following injection with the vaccine, and that these cells provided ideal targets for HIV if the recipient was subsequently infected by the virus. "The vaccine may have added fuel to the fire," says Dan Barouch of the Beth Israel Deaconess Medical Center in Boston.

It Didn't Provoke Strong Immunity

Neither research team can explain why people with the cold virus antibodies were more likely to be infected with HIV. But Adrian Hill, a virologist at the University of Oxford, thinks this arose by chance, and that the vaccine failed simply because it didn't provoke strong enough immunity to HIV. The work should ease fears over other HIV vaccines, says Barouch.

Chimps can Transmit SIV to Humans (HIV)

The discovery that chimpanzees can develop an AIDS-like illness after infection with simian immunodeficiency virus (SIV), may have implications for future AIDS research and the prevention of HIV infection.

Until now, it was thought that SIV infection in chimps did not result in disease. However, after following 94 wild chimps in Gombe Stream National Park in Tanzania for nine years, Beatrice Hahn, of the University of Alabama at Birmingham, and colleagues have shown that SIVcpz, the virus that jumped from chimps to humans as HIV-1, can and does cause an AIDS-like illness.

Over the 9 years of the study, SIVcpz infection caused an increased risk of mortality. "Up to 41 per cent in adults and 100 per cent in infants, and lower birth rates," says Hahn, "but we need longer-term follow-up to determine what proportion of infected animals develop an AIDS-like illness."

Unique opportunity
Hahn suspects that compared to HIV-infected humans, a greater proportion of SIV-infected chimps do not go on to develop fatal disease. "But this is not simple to test because chimpanzees don't just walk into clinics and give you a blood sample."

However, Hahn hopes that future research into animals which have long-term infection without developing an AIDS-like illness will yield insights that will enable us to better tackle HIV infection.

Unique Opportunity
The team believes that these findings provide a unique opportunity to compare the disease-causing mechanisms of two closely related viruses – SIVcpz and HIV-1 – in two closely related species. Such work has also already yielded information on mortality rates, prevalence and routes of spread of HIV and SIV.