News (Updated February 21, 2010)

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AIDS vaccine effects may wear off, researchers say

Maggie Fox, Health and Science Editor

WASHINGTON

Fri Feb 19, 2010

Credit: Reuters/Kham  

HIV-positive women are seen in a social center in Ba Vi district, outside Hanoi, November 30, 2009.

WASHINGTON (Reuters) - An AIDS vaccine that appears to have worked at least partly in Thailand may only temporarily protect patients, with the effects starting to wane after a year or so, researchers reported on Thursday.

Health

That may explain why results of the experimental vaccine have been so difficult to interpret, said Dr. Nelson Michael, a colonel at the Walter Reed Army Research Institute of Research in Maryland, who helped lead the trial,

Michael's team is trying to find out how or why it might have worked. They surprised the world last September when they showed the experimental vaccine cut the risk of infection by 31 percent over three years.

"It is very likely that this vaccine only worked for a short period of time," Michael said in a telephone interview.

"It is a weak, a modest effect but something that we can build on."

The vaccine is a combination of Sanofi-Pasteur's ALVAC canarypox/HIV vaccine and the HIV vaccine AIDSVAX, made by a San Francisco company called VaxGen and now owned by the nonprofit Global Solutions for Infectious Diseases.

Michael told the Conference on Retroviruses and Opportunistic Infections in San Francisco that it may be possible to design a trial that will show better whether the vaccine can really help people.

Part of the problem, he said, was that the 16,000 Thai volunteers who tested the vaccine were not at especially high risk of AIDS infection.

He said he would work with Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, to design trials in Asia or Africa.

According to the United Nations, more than 33 million people are infected with the fatal and incurable virus, with 2.7 million new infections every year.

Even a vaccine that protected for just a year would be useful, Michael said.

"Is that ideal?" No," Michael said. "But it is true there are vaccines like the flu vaccine where you have to get them every year."

Within the next few weeks, Michael said studies will also start to try to find clues from the blood of the vaccinated volunteers.

"Everyone wants to know why this worked and what lab measurements we could take that could predict this," he said.

Results will take roughly a year, he said, but labs all over the world will be looking for so-called correlates -- measurements such as antibody levels that will show whether a vaccine has affected the immune system in the desired way.

"It is what I call an all-hands-on-deck exercise," he said.

The AIDS virus has killed 25 million people since it was identified in the 1980s. Cocktails of drugs can control HIV but there is no cure. In 2007, Merck & Co ended a trial of its vaccine after it was found not to work, and in 2003, AIDSVAX used alone was found to offer no protection, either.

(Editing by Eric Walsh)

Blanket HIV testing 'could see Aids dying out in 40 years'

Health officials consider routine checks followed by lifetime course of drugs for everyone with the virus

Ian Sample Science correspondent in San Diego

guardian.co.uk, Sunday 21 February 2010

People who test HIV-positive could be put on a lifetime course of anti-retroviral drugs under a new strategy being considered by health officials. Photograph: Krista Kennell/ZUMA/Corbis

Health officials are considering a radical shift in the war against HIV and Aids that would see everyone tested for the virus and put on a lifetime course of drugs if they are found to be positive.

The strategy, which would involve testing most of the world's population for HIV, aims to reduce the transmission of the virus that causes Aids to a level at which it dies out completely over the next 40 years.

Brian Williams, professor of epidemiology at the South African Centre for Epidemiological Modelling and Analysis in Stellenbosch, said that transmission of HIV could effectively be halted within five years with the use of antiretroviral drugs (ARVs).

"The epidemic of HIV is really one of the worst plagues of human history," Williams told the American Association for the Advancement of Science meeting in San Diego.

"I hope we can get to the starting line in one to two years and get complete coverage of patients in five years. Maybe that's being optimistic, but we're facing Armageddon."

Major trials of the strategy are planned in Africa and the US and will feed into a final decision on whether to adopt the measure as public health policy in the next two years.

The move follows research that shows blanket prescribing of ARVs could stop HIV transmission and halve cases of Aids-related tuberculosis within 10 years.

More than 30 million people are infected with HIV globally and two million die of the disease each year. While ARVs have been a huge success in preventing the virus from causing full-blown Aids, scientists estimate only 12% of those living with the infection receive the drugs.

The disease is overwhelmingly prevalent in sub-Saharan Africa, which accounts for a quarter of all HIV/Aids cases globally. Half of these are in South Africa.

In general epidemics, a person with HIV infects between five to 10 others before succumbing to complications of Aids. Treating patients with ARVs within a year of becoming infected can reduce transmission tenfold, enough to cause the epidemic to die out.

In the trials, people will be offered HIV tests once a year, either as routine when they visit their GP, or through mobile clinics in more remote regions. Those testing positive will be put on a lifetime course of ARVs.

"Over the past 25 years we have saved the lives of probably two to three million people using antiretroviral drugs, but almost nothing we have done has had any impact on transmission of the disease," Williams said. "We have stopped people dying but we haven't stopped the epidemic."

If patients take ARVs when they should, the amount of virus in their bodies can fall by 10,000 times, to a level at which they are extremely unlikely to pass the virus on.

"The question is, can we use these drugs not only to keep people alive, but also to stop transmission and I believe that we can. We could effectively stop transmission of HIV in five years." Scientists estimate that the cost of implementing the strategy in South Africa alone will be $3bn-$4bn a year. The world currently spends $30bn (£19.4bn) a year on Aids research and treatment, a figure that some experts believe will double over the next decade.

Sub-Saharan Africa has seen a dramatic rise in cases of tuberculosis among HIV patients, who are also susceptible to other infections because their immune systems are weakened.

"If you factor in all of the costs, in my opinion, doing this would be cost saving from day one, because the cost of the drugs would be more than balanced by the cost of treating people for all of these other diseases and then letting them die," Williams said.

"We're killing probably half a million young adults every year in the prime of their life just at the point where they should be contributing to society and the cost of that to society is enormous," he added. "The only thing that's more expensive than doing this is not doing this."

HIV patients in southern Africa are more likely to take ARVs when they should than people living in developed countries, according to health officials. The finding gives doctors hope that the blanket administering of drugs might suppress the virus enough that it dies out naturally.

Last year, scientists reported marginal success of a HIV vaccine following a large scale trial in Thailand. The vaccine benefited only 31% of those who received it. A vaccine is generally regarded as worthwhile if it protects more than 70% of those treated.

HIV versus HIV: New Strategy, Say Experts

Submitted by Amit Pathania, 02/20/2010

Scientists are resurrecting the controversial approach which was dismissed in the case of HIV; where vaccines against many viruses are made from deactivated versions of those viruses.

VIRxSYS, from Gaithersburg, Maryland, is planning on injecting people with a HIV vaccine made of the deadly virus itself, only that it is a deactivated version instead.

Their plan is going to be carried after a string of successful tests of a similar vaccine against SIV - also known as simian HIV - in monkeys.

"We said 'let's use HIV against itself', and that's what we're doing", New Scientist quoted Gary McGarrity, VIRxSYS's vice president of scientific and clinical affairs, as saying.

Describing how they vaccinated monkeys, and then six months later injected them with SIV, VIRxSYS researchers said, “Within weeks of receiving the injection of SIV, concentrations of the virus had fallen by at least 95 per cent in those treated. After a year, when the trial ended, these concentrations remained low, whereas untreated monkeys became progressively sicker as their immune systems were depleted by the virus”.

The AIDS virus, which infects 33 million people globally and has killed 25 million, is mostly passed sexually. In Africa, women account for more new cases than men. More than often, they are infected by their husbands.

New Scientist quoted Gary McGarrity, VIRxSYS's vice president of scientific and clinical affairs, as saying, "We said 'let's use HIV against itself', and that's what we're doing".

H1N1 Meets HIV

by Tim Horn

February 18, 2010

People with HIV are generally no more likely to experience severe complications of H1N1 influenza virus than people not infected with HIV, according to studies reported on Wednesday, February 17, at the 17th Conference on Retroviruses and Opportunistic Infections (CROI). However, studies presented here also paint a conflicting picture regarding the ability of H1N1 vaccines to spark sufficient immune responses against the virus in people with HIV hoping to avoid the novel influenza virus still circulating the globe.

Though H1N1 continues to spread in regions throughout the world, it has not resulted in the high number of serious complications, hospitalizations and deaths many public health experts initially feared. In fact, according to a February 12 report from the U.S. Centers for Disease Control and Prevention (CDC), the proportion of deaths attributed to pneumonia and influenza continues to decrease and is now lower than expected for this time of year.

Questions remain, however, regarding the effects of H1N1 in people living with HIV. HIV-positive people are still considered to be at high risk for H1N1-related complications, according to the CDC, yet little data have been available to either confirm or refute this rightfully cautious assumption. What’s more, little information has been reported regarding the effectiveness of H1N1 vaccination in people living with HIV.

Answers to these questions surfaced at CROI in the form of several poster presentations—many of which were submitted as “late-breakers.”

Risk of Complications and Death

Three studies reported at CROI suggest the clinical presentation of H1N1 in people living with HIV is not distinct from that reported in HIV-negative individuals, although the risk of serious disease and death appears higher than average in HIV-positive individuals with advanced HIV disease.

According to Ariel Campos-Loza, MD, and his colleagues at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) in Mexico City, H1N1 virus infection was infrequent in HIV-positive patients followed in the clinic during the initial epidemic wave (April through June 2009). What’s more, HIV-infected patients represented only a small fraction of all H1N1 cases seen at INCMNSZ.

Campos-Loza said that the rates of hospitalization, mechanical ventilation and survival were similar between HIV-positive and HIV-negative patients who had H1N1. Among 11 HIV-positive patients with H1N1, only three were hospitalized and one died—all of whom had AIDS. In contrast, mild influenza occurred in patients with CD4 counts above 300. “Late stage of HIV disease and poor HIV control may influence the severity and outcome of H1N1 in HIV-infected individuals,” he said.

A second study, reported by Esteban Martinez, MD, and his colleagues of the Hospital Clinico Provincial de Barcelona, concluded that HIV infection did not make H1N1 influenza more severe, nor did H1N1 have a major effect on HIV infection.

Except for higher rates of gastrointestinal symptoms among people living with HIV—37 percent versus 18 percent—clinical features of H1N1 were similar between HIV-positive and HIV-negative patients cared for at the hospital between April and December 2009. In fact, pneumonia and respiratory failure were less common among HIV-positive people than those who were HIV negative. People living with HIV with confirmed H1N1 were also less likely to be admitted to the hospital and recovered more rapidly than HIV-negative individuals with H1N1.

Of note, HIV-positive individuals were much more likely to be prescribed Tamiflu (oseltamivir), likely because of increased vigilance among health care providers caring for people living with HIV believed to be at a higher risk for H1N1-related complications.

H1N1 infection did not appear to have an effect on HIV disease progression. CD4 cell counts and viral loads documented at the time of H1N1 diagnosis were unchanged four to six weeks later.

Data presented by Gustavo Reyes-Teran, MD, and his colleagues at the Instituto Nacional de Enfermedades Respiratorias (INER) in Mexico City painted a slightly more grim picture, likely because many of the HIV-positive people at INER were receiving care for underlying respiratory diseases, including Pneumocystis pneumonia and tuberculosis. Of 27 HIV-positive, H1N1-positive patients seen during the initial months of the Mexico City epidemic, 14 required hospitalization and six died. “Opportunistic infections mask symptoms and [X-ray] signs of influenza, resulting in delayed [H1N1] treatment,” Reyes-Teran said.

He also noted that some HIV-positive patients had H1N1 virus detectable in their lungs after standard five-day courses of Tamiflu. This, he feared, may increase the risk of developing H1N1 drug resistance, which can potentially be spread to others.

H1N1 Vaccine Immune Responses

The H1N1 vaccine is recommended for all HIV-positive people. Yet little is known about its effectiveness—notably its ability to induce a sufficient antibody response to H1N1—in people with HIV, who are generally less likely to experience robust immune responses to vaccines compared with HIV-negative individuals. Three studies at CROI presented conflicting data on this topic.

Kate Sullivan, MD, of the University of Pennsylvania School of Medicine and her colleagues evaluated the immune response to an inactive H1N1 vaccine in 120 HIV-positive individuals. All but one patient were receiving antiretroviral (ARV) therapy.

Thirty of the patients enrolled had H1N1 antibody levels consistent with protection against infection, likely because of previous exposure to the virus. Among the 89 participants without evidence of previous exposure to H1N1, only 61 percent developed antibody levels capable of defending against H1N1 three weeks after receiving the vaccine. In comparison, about 95 percent of those between 18 and 60 years old, and 79.2 percent of those older than 60, in the general population achieve a sufficient antibody response to H1N1 within three weeks post-vaccination.

Sullivan’s group noted that non-responders had lower CD4 counts and had undetectable viral loads for a shorter period of time than responders. Among those who didn’t have a sufficient immune response, the average CD4 count at the time of vaccination was 394 cells, compared with 501 cells among vaccine responders. And the duration of undetectable viral loads was 19 months among non-responders, compared with 31 months among vaccine responders.

Sullivan said that one way to potentially increase efficacy is to use vaccines containing adjuvants—compounds that help prime the immune system to better respond to antigens in vaccines. None of the H1N1 vaccines available in the United States use adjuvants, because of limited data regarding safety and efficacy.

Unfortunately, a poster presentation by Markus Bickel, MD, and his colleagues at Goethe University Hospital in Frankfurt indicated that an adjuvanated H1N1 vaccine may not make a great deal of difference.

According to Bickel, only 69 percent of the HIV-positive people who received an adjuvanated vaccine in his clinic developed sufficient antibody responses to H1N1 within three weeks. Those who did respond tended to be younger (45 versus 49 years old) and have a higher CD4 count (532 versus 475 cells).

Interestingly, a French study conducted by Odile Launay, MD, of the Hôpitaux de Paris and her colleagues found higher rates of antibody responses to H1N1, using both non-adjuvanated and adjuvanated vaccines. About 95 percent of HIV-positive patients receiving the adjuvanated vaccine had sufficient antibody responses after three weeks, compared with 77 percent of patients receiving the non-adjuvanated vaccine.

Bickel and Launay both question whether a second dose of an adjuvanated or non-adjuvanated H1N1 vaccine might further increase the antibody response rates in people living with HIV. Unfortunately, no one has conducted studies to explore this possibility.

New HIV-Associated Tuberculosis Vaccine Proved Successful In African Trial

By Abby Horstmann
Published: Feb 18, 2010

In a press release by Dartmouth Medical School on January 29th, researchers reported on the successful creation of a vaccine for HIV-associated tuberculosis. Immunization with the vaccine was found to reduce the rate of tuberculosis (TB) infection by 39 percent.

The study, dubbed the DarDar Health Study, was a 7-year collaboration among groups in the United States, Zambia, Finland, and Tanzania.

Currently, TB is the leading cause of death among HIV-positive individuals in developing countries, and is responsible for approximately half of all the deaths worldwide of people with AIDS.

Almost immediately after contracting HIV, all patients are at an increased risk for TB infection. The CDC estimates that one third of HIV patients are also coinfected with TB.

Therefore, the invention of a vaccine against HIV-associated tuberculosis has been a priority, and the successful results of this study represent a significant achievement in the worldwide effort to prevent tuberculosis in HIV-infected individuals.

The novel vaccine used, Mycobacterium vaccae (MV), is known as an inactivated, whole-cell vaccine. Vaccines of this type are comprised of entire MV cells that have been killed prior to injection.

Researchers treated 2,000 HIV-positive patients in Tanzania with either the vaccine or placebo, all of whom had received the current TB vaccine, Bacille Calmette-Guerin (BCG), during childhood.

Along with increased protection against contracting TB, patients treated with the experimental vaccine experienced no negative effects on HIV viral load or CD4 cell count (white blood cell count).

The next steps are to establish a manufacturing scheme to provide enough of the vaccine for additional trials and eventually, clinical use. Experts expect the production and distribution of the vaccine to be relatively inexpensive.

HIV illness 'delayed by' herpes drug aciclovir

A common treatment for herpes can delay the need for HIV drugs in people with both infections, say US researchers.

A study of 3,300 patients in Africa found aciclovir reduced the risk of HIV progression by 16%, The Lancet reports.

Although a "modest" effect, the researchers said the cheap treatment was a simple way of keeping people with HIV healthy for longer.

One expert said it was important to note that aciclovir did not seem to make HIV patients less infectious.

The researchers from the University of Washington, Seattle, concentrated on people infected with HIV-1 - the most common type of infection.

It is known that most people who are infected with HIV-1 are also infected with herpes simplex virus type 2 (HSV2), or genital herpes.

Previous studies have shown that keeping the herpes virus suppressed reduces HIV levels but it was unclear whether this would slow down the disease.

Those in the trial were either given a twice daily dose of aciclovir or a dummy pill and then they were monitored for two years.

At the end of the study, 284 people on aciclovir had either started taking HIV medication, had a drop in CD4 count suggesting they should be on medication or had died. The comparable figure for patients taking the placebo was 324.

Use of aciclovir treatment did not reduce HIV transmission to their heterosexual partners.

More options

The researchers pointed out that HIV treatment with antiretroviral drugs would probably have a greater effect on reducing HIV disease progression than was seen with aciclovir.

But the herpes treatment may provide an additional option for individuals who have not reached medical thresholds for initiating antiretroviral therapy.

"Further investigation is needed to establish if suppression of this herpes virus has a role in HIV-1 treatment for people not eligible for antiretroviral therapy."

Study leader, Dr Jairam Lingappa, said: "While the HIV disease ameliorating effect we have observed is modest, it could add one more tool to help people with HIV infection stay healthy for longer."

Gus Cairns, editor of HIV Treatment Update, said: "It's nice to see a positive result in this field.

"There are biological reasons to believe that treating people's herpes could make them less likely to acquire HIV, or less likely to transmit it if they already have it, but results of trials testing the idea have been disappointing.

"Now at least we find that aciclovir, a very cheap, non-toxic and widely-available drug, can prolong the time some patients may be able to stay off the more expensive, and sometimes toxic, HIV drugs."

He added that the delay in HIV progression seen in the study may translate into a year or two off HIV medications.

"The only reservation I have is that aciclovir doesn't appear to make people less infectious, whereas the HIV drugs certainly do."

Phase II HIV Gene Therapy Trial Has Encouraging Results

ScienceDaily (Feb. 19, 2010) — Researchers from the University of Pennsylvania School of Medicine presented the results from an ongoing Phase I/II open-label clinical trial of Lexgenleucel-T at the 16th Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco, CA on February 18. Lexgenleucel-T is a cell and gene therapy product being investigated for the treatment of HIV infection. The current study examined the effect of Lexgenleucel-T infusions in HIV-1 infected individuals prior to being taken off their antiretroviral treatment (HAART) regimens as part of the study design's scheduled treatment

In the study, seven of eight evaluable subjects experienced a decrease in viral load set point and one subject experienced prolonged, complete control of HIV viremia for more than 14 weeks in the absence of HAART. Viral load set point is the HIV RNA value specific for each infected individual in absence of anti-retroviral drug control. Higher viral load set point is correlated with more rapid disease progression to AIDS.

"We are excited to see these responses using autologous transfer of CD4+ T lymphocytes genetically modified with VRX496TM, a HIV-based lentiviral vector encoding for a RNA antisense targeting HIV env. These are subjects who were taken off of their antiretroviral treatment and are showing a better control of their infection as demonstrated by reduced viral load set points," said Pablo Tebas, M.D., director of the Adult AIDS Clinical Trials Unit, who presented the results at CROI. "Further study is needed to see whether these types of results will translate into a delay in disease progression."

In the current study, several administrations of Lexgenleucel-T, each comprising approximately 1010 autologous CD4+ T cells transduced ex vivo with VRX496TM, were administered to 17 HIV-1 infected subjects who were fully suppressed on HAART. Each subject received three to six separate infusions over a period up to 13 weeks. Six weeks after the last infusion, eligible subjects underwent a scheduled treatment interruption to evaluate timing to HIV RNA recrudescence, changes in viral load set point and changes in CD4 T cell count. Of the 17 subjects who received infusions, 13 (76%) underwent the scheduled treatment interruption. Eight of these 13 subjects (62%) were evaluable for the efficacy endpoint. Overall, 7 of 8 (88%) of the evaluable subjects had a decrease in viral load set point ranging from -0.26 to -0.98 Log10. One subject maintained a complete control of HIV RNA viral load below the limit of detection (50 copies/ml) and a CD4+ cell count greater than 1200 cells/µL for over 14 weeks.

"It is notable that all patients on the protocol had elevated CD4+ counts after treatment with Lexgenleucel-T," said Carl June, M.D., professor of Pathology and Laboratory Medicine. "Achieving a complete control of HIV recrudescence following HAART interruption for over 14 weeks is, indeed, remarkable."

Pablo Tebas, MD, David Stein, MD, Gwendolyn Binder, PhD, Larisa Zifchak, RN, Angelo Seda, RN, Jean Boyer, PhD, Faten Aberra, MD, Ronald Collman, MD, Gerard McGarrity, PhD, Bruce Levine, PhD and Carl June, MD, are all co-authors of this study. The study was funded by the NIH, NIAID. Drs. Tebas, Zifchak, Boyer, Aberra and Colman are affiliated with the Center for AIDS Research at the University of Pennsylvania, Philadelphia. Drs. Binder, Levine, June, and Boyer are affiliated with the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia. Drs. Stein and Seda are affiliated Jacobi Medical Center, Bronx, New York. Dr. McGarrity is an employee of VIRxSYS Corporation, Gaithersburg, Maryland. VIRxSYS is the owner of the Lexgenleucel-T therapy. No author on this study other than Dr. McGarrity is affiliated with VIRxSYS in any capacity beyond their roles as clinical collaborators on this project.

Merck Sharpe and Dohme report success from HIV drug Isentress 

19/02/2010

Merck Sharpe and Dohme has published clinical trial data from a recent phase III study of its HIV drug Isentress, which it believes demonstrates the treatment's benefits.

Results from the 96-week study showed that patients trialled using Isentress instead of the alternative treatment efavirenz suffered less impact on their lipids and fasting blood sugar.

Dr Edwin de Jesus, who oversaw the study, stated that these findings were important given the role played by lipid and glucose levels and body composition in the management of HIV.

The Merck Sharpe and Dohme drug's advantages were further underlined by a separate phase II study which showed that it is equally as effective as efavirenz in maintaining viral load suppression to undetectable levels.

Earlier this week, the pharmaceutical company published data from a clinical trial of its human papillomavirus treatment Gardasil, with the firm welcoming the findings as evidence of Gardasil's effectiveness in both male and female patients.

Future of AIDS gels may lie in drugs, experts say

Feb 20 2010

By Maggie Fox, Health and Science Editor

WASHINGTON (Reuters) - The quest for a cream or gel to prevent AIDS infection has narrowed to using powerful HIV pills that are already on the market, scientists say.

AIDS experts have long been searching for a microbicide -- a cream, gel or vaginal ring that women or men could use as a chemical shield to protect themselves from sexual transmission of the deadly and incurable virus.

Several substances have been tried unsuccessfully but experiments presented this week at the Conference on Retroviruses and Opportunistic Infections, a scientific meeting of AIDS experts, suggested HIV drugs might hold the key to making such gels work.

"The next wave of compounds is all going to be based on antiretroviral drugs," Dr. John Moore of Weill Cornell Medical College in New York told reporters.

Moore 's team tested Pfizer's new drug maraviroc, sold under the brand name Selzentry. It is in a new class of drugs called CCR5 entry inhibitors, designed to stop the human immunodeficiency virus from getting into human cells using a type of cellular doorway or receptor named CCR5.

"The CCR5 inhibitors are compelling candidates as an alternative because these drugs are not being used for treatment in, for example, Africa," Moore said.

That means there is less risk of resistance developing -- when viruses evolve to get around the effects of drugs.

Moore 's team took a unique approach to formulating their experimental microbicide using Selzentry.

"We found a friendly physician, scrounged a tablet, ground it up," Moore said. "I assure you it actually works very well," he told the San Francisco meeting.

Tests in monkeys showed it would protect a female from sexual transmission for about four hours. "You couldn't apply these gels in the morning and have protection in the evening," Moore said.

A vaginal ring with a time-release formula may work better for longer-term protection, Moore said.

The approach is affordable, he said. "A single maraviroc tablet, about 300 mg, retailing for about $15 on the Internet, contains enough drug to fully protect around 15 macaques. That is broadly going to be applicable to women."

Laura Guay of the Elizabeth Glaser Pediatric AIDS Foundation said the approach sounds reasonable. Her group supports the development of microbicides to protect women and by extension their children.

"The hope is by putting antiretrovirals into the microbicide, you can prevent the virus from either entering or replicating," she said in a telephone interview.

Last year researchers found Gilead Sciences Inc.'s drug Truvada also might work as a microbicide. But a gel made by Massachusetts-based Indevus Pharmaceuticals that did not include an HIV drug failed in human trials.

The AIDS virus, which infects 33 million people globally and has killed 25 million, is mostly passed sexually. In Africa women account for more new cases than men and are often infected by their husbands.

Abstinence and condom use are not options for women trying to have children, but a microbicide would be. Microbicides using HIV drugs would represent a large new market for the companies that make the drugs, which are currently now used only to treat infection.

(Editing by Alan Elsner)

Health workers often decline TB treatment

Amy Norton

Feb 16, 2010

NEW YORK (Reuters Health) - Hospital and nursing-home employees who are infected with latent tuberculosis may often decline drug therapy to prevent the disease from becoming active, a new study suggests.

The study, which followed patients with latent TB at 32 U.S. and Canadian medical clinics, found that 22 of 53 healthcare workers who were offered treatment declined to take it.

Of all 720 patients in the study, 17 percent refused drug therapy to ward off active TB.

Compared with other study patients, healthcare workers -- all employees of a hospital or nursing home -- were nearly five times as likely to decline treatment, according to findings published in the medical journal Chest.

Latent TB refers to a chronic, but symptomless and non-contagious, infection with TB bacteria; it is detected through tuberculin skin testing. Such TB infections are common throughout the world because in most people, the immune system is able to suppress TB bacteria. Up to 15 million Americans are estimated to have latent TB infection.

The danger with latent TB is that it can become active; active TB usually attacks the lungs, causing symptoms such as a severe cough, chest pain and weight loss. It can also spread through the air from person to person.

The U.S. Centers for Disease Control and Prevention (CDC) recommends treatment of latent TB in people who are at high risk of progressing to active infection, including people whose immune systems are compromised -- due to HIV or immune-suppressing medications, for instance.

Treatment is also recommended for people who could easily spread the disease if it becomes active -- such as prison inmates and patients and employees at hospitals and nursing homes.

It's not clear why healthcare workers in this study were more likely than other people to decline drug treatment. One possibility is that they felt their risk of developing active TB was not significant, according to lead researcher Dr. C. Robert Horsburgh Jr., of the Boston University School of Public Health.

The average risk of developing full-blown TB disease is roughly one in 20, Horsburgh told Reuters Health in an email.

"It may also be that they are more concerned about side effects of the medicines used to treat latent TB," he said, "since they see side effects of medications every day in the patients they take care of."

Treatment of latent TB lasts for months. The standard therapy is a drug called isoniazid, usually prescribed as a nine-month course. Another option is a four-month regimen of a medication called rifampin.

The more common side effects of isoniazid include stomach upset and diarrhea; the drug has also been linked to cases of sometimes severe liver damage. Rifampin may cause symptoms such as stomach upset, nausea and headache.

In their study, Horsburgh and his colleagues found that healthcare workers, besides being more likely to decline treatment, were at increased risk of failing to complete treatment. Of the 209 prescribed treatment, 125 did not finish the full course.

Residents of congregate settings -- nursing homes, shelters and prisons -- were also at increased risk of not completing drug treatment.

One factor that did boost treatment compliance overall, however, was shorter therapy.

Most study patients who accepted treatment were placed on nine months of isoniazid, but those given four months of rifampin were more likely to complete treatment -- about 65 percent did, versus roughly 45 percent of those on isoniazid.

The implication, according to Horsburgh's team, is that shorter courses of therapy would encourage more patients to comply. They point out, though, that the effectiveness of the four-month rifampin therapy has not yet been tested in large clinical trials.

An ongoing clinical trial is testing the effectiveness of a three-month course of isoniazid plus another drug, rifapentine.

"I hope that new regimens of three months...or less will be shown to be effective and will replace the current regimens," Horsburgh said.

The study was funded by the CDC; one of the co-researchers has received grants from Pfizer, which makes the TB drug Mycobutin (rifabutin), and Oxford/Immunotec, which makes a blood test for TB.

SOURCE: Chest, February 2010.

Excitement grows over Gilead's HIV combo Quad

18 February 2010

Gilead Sciences has presented impressive mid-stage data on its new four-drug HIV therapy which the company hopes will grab huge market share.

The company has announced Phase II results at the Conference on Retroviruses and Opportunistic Infections in San Francisco showing that Quad, a single pill containing Gilead’s investigational drugs elvitegravir and cobicistat with Truvada (emtricitabine and tenofovir), exhibited antiretroviral activity comparable to that of Atripla, which combines Truvada with Bristol-Myers Squibb’s Sustiva (efavirenz). The data showed that after 24 weeks, the proportion of patients who achieved HIV RNA (viral load) less than 50 copies/mL was 90% in the Quad arm and 83% in Atripla patients and discontinuation rates due to adverse events were comparable among both groups.

Norbert Bischofberger, Gilead 's chief scientific officer, said ”we are excited about these results and look forward to working with the US Food and Drug Administration to finalise the Phase III clinical programme for the Quad and cobicistat”. His enthusiasm was shared by Calvin Cohen, principal investigator and director of research at the Community Research Initiative of New England.

He said that “simplified treatment regimens of co-formulated, fixed-dose medicines have become the standard of care in HIV therapy because they can help patients adhere to dosing schedules”. He added that “these positive efficacy and safety results indicate that the Quad has the potential to become an important new treatment option”.

In the fourth quarter, sales of Truvada were up 19% to $670.7 million, and were surpassed for the first time by Atripla, which leapt 50% to $697.8 million. Gilead and some analysts believe Quad could achieve similar blockbuster status.

HIV transmission among male partners

A team of scientists, led by a virologist from the University of California , San Diego 's Center for AID Research (CFAR), has discovered the origin of strains of human immunodeficiency virus (HIV) among men who have sex with men. The study, which may be important in developing prevention strategies for HIV, will appear in Science Translational Medicine on February 10, 2010.

"If we want to stop the HIV epidemic, then we must know the mechanisms by which HIV uses human sex to spread," said principal investigator Davey Smith, MD, MAS, associate professor of medicine in UCSD's Division of Infectious Diseases and in the Veterans Affairs San Diego Healthcare System, and director of the CFAR Viral Pathogenesis Core.

It is known that most HIV infections worldwide result from exposure to the HIV virus in semen, made up of seminal cells and the fluid around these calls, called seminal plasma. HIV virus particles contain RNA and exist in the plasma, while infected seminal cells contain HIV DNA.

Using a method of comparing genetic characteristics, called phylogenetic analysis, the researchers studied a group of men who had sexually transmitted their HIV virus to other men. Phylogenetic models allow researchers to estimate the dates of origin of various groups of viruses; in this way the team was able to determine the source of rapidly mutating HIV viruses by analysing the viral sequences extracted from the blood and semen of HIV transmitting partners. The team found that recipients shared a more recent common ancestor with virus from the seminal plasma than with virus found in the seminal cells of their source partner.

"Until now, it had not been established whether HIV RNA or DNA is transmitted during sex," said Smith. "By analysing the genetic differences between these two forms and the virus that was ultimately transmitted to newly infected individuals we found that it was the HIV RNA form present in seminal plasma that was transmitted."

"The findings from this study will help direct prevention strategies to address the virus in the seminal plasma," Smith said. "By knowing the origin of the transmitted virus, scientists may be able to develop new vaccines, vaginal microbicides and drugs to prevent the spread of sexually transmitted HIV."

Smith notes that because the study involved pairs of men who have sex with men, the findings do not comment directly on HIV transmission to women. "Since the vast majority of women are infected with HIV by exposure to the virus in semen, HIV RNA in the seminal plasma is the likely culprit, but this needs to be confirmed," he said.

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