It is always difficult, and is a necessarily subjective process, to cull from various sources and limit the detail while offering such coverage.
Today’s Newsletter is longer; however, please note it contains more scientific content… The opening day’s content is more announcement-like.
Again, the official sources for this information (as suggested by the Conference organizers) are:
- The Live Conference Blog
- News Releases
- Clinical Care Options
- Rapporteur summaries
For more in-depth information on these and other subjects arising from this Conference, please visit: http://www.ias2009.org/
This Newsletter summary will continue daily through and including Thursday, July 23rd.
MAIN HALL
MAIN HALL (CLOSE UP OF STAGE)
PLENARY HALL
Biomedical Prevention – Microbicides, Vaccines, Circumcision and PrEP
In his plenary presentation, Dr. Ronald Gray summarized the results of the 28 completed biomedical HIV prevention trials of STD control, microbicides, pre-exposure prophylaxis (PrEP), HIV vaccines and male circumcision. Of these trials, only four, including three of male circumcision, have reported significant efficacy. According to Dr. Gray, one of the
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conclusions to be drawn from positive and negative results is that phase III prevention trials are difficult, expensive and time-consuming. Ultimately, according to Dr. Gray, researchers will need to more carefully screen candidate interventions prior to trials and may need to conduct fewer trials, but with a greater investment in rigor and quality. Dr. Gray is Robertson Professor of Reproductive Epidemiology in the Department of Population, Family and Reproductive Health at the Johns Hopkins Bloomberg School of Public Health.
ELITE CONTROLLERS
People with AIDS may have viral loads of several hundred thousand copies per milliliter. In contrast, the viral loads of elite controllers range from a scant 50 down to levels so small that even the most sensitive tests can't detect them. Doctors know these people have the virus only because separate tests have revealed the presence of antibodies to HIV in their systems. In other words, elite controllers aren't HIV-free; they may still be able to pass the virus to others, in whom it may be deadly.
Early on, researchers discovered that elite controllers aren't infected with a less virulent strain of the disease. But little else about their condition is certain.
Since 2006, Walker and his colleagues have been organizing an international contingent of more than 250 researchers and more than 200 physicians who have elite controllers as patients. Initially funded by a gift from the Mark and Lisa Schwartz Foundation and recently boosted by a $22 million grant from the Bill & Melinda Gates Foundation, the International HIV Controllers Study is working to identify elite controllers, collect samples of their blood and DNA, and distribute the samples to labs for analysis.
Vaccines normally work by introducing a dead or harmless piece of virus that stimulates the adaptive immune system to attack. In that way, the body builds defenses capable of destroying the real virus. But AIDS has resisted every effort to develop a vaccine.
The MIT team wants to know whether the T cells in elite controllers have special properties. The answer will require a much more detailed understanding of how T cells function. So the team has developed a system to trap a single T cell along with a single cell infected with HIV. That allows researchers to watch T cells attacking infected cells and to compare the action of elite controllers' cells with those of patients whose HIV has progressed into AIDS.
One clue may already have emerged. In the Dec. 19 issue of the journal Immunity, researchers at the National Institute of Allergy and Infectious Diseases concluded that the killer T cells of elite controllers killed 68 percent of infected cells in an hour, compared with just 8.1 percent for those with AIDS.
One theory about elite controllers holds that they possess special genetic traits, beyond any differences in their immune systems, that better equip them to battle AIDS. Geneticist Paul de Bakker of Brigham and Women's Hospital in Boston is combing through the human genome to find those characteristics. It's a daunting endeavor. The genome comprises 3 billion coded pieces of information that determine who a person is. Some 99.9 percent of these pieces are the same in all people, but there are points of difference known as single nucleotide polymorphisms (SNPs, pronounced "snips").
GRACE Shows Similar Treatment Response Rates in Women and Men on Prezista Treatment
July 20, 2009
By Tim Horn
Long-awaited 48-week data from the Gender, Race and Clinical Experience (GRACE) study indicate that Norvir (ritonavir)–boosted Prezista (darunavir) can be used in women and men with similar safety and efficacy outcomes. Reported by Kathleen Squires, MD, of Jefferson Medical College in Philadelphia and her colleagues on Monday, July 20, at the Fifth International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town, GRACE also documented higher rates of study discontinuation among women, underscoring the need for further investigation into ways to better retain women in clinical trials.
Prezista, combined with low-dose Norvir, has been approved in the U.S. as a protease inhibitor option for treatment-experienced patients, as well as first-time treatment takers and HIV-positive children between the ages 6 and 17.
About 66 percent of the women enrolled were black, compared with 51.4 percent of the men. Hispanics/Latinos accounted for 20.9 percent and 25.4 percent, respectively. The average length of infection upon entering the study was about 11 years; in addition, 58.5 percent of the women and 64.8 percent of the men had used at least two protease inhibitors before enrolling in GRACE. Average CD4 counts at study entry were 210 cells in the women, compared with 175 cells in the men.
The rate of treatment discontinuation was higher in women (32.8 percent) compared with men (23.2 percent). This difference was statistically significant, meaning it was too great to have occurred by chance. The primary reasons for study discontinuation were loss to follow-up and side effects; however, there were no trends toward a specific type of side effect driving discontinuations in either group.
Men experienced a slightly better CD4 cell recovery compared with women after 48 weeks in the ITT analysis: gains of 89 versus 68 cells, respectively. But in the less stringent analysis, women faired better with a 131 CD4 cell gain, compared with a 104 cell gain among men.
The number of men and women who developed new HIV resistance mutations while participating in GRACE was small, according to data still being analyzed. Two (7.4 percent) women, compared with two (1.2 percent) men, were found to have a new major protease inhibitor-resistance mutation after experiencing virologic failure.
Overall, 90.2 percent of the women and 83.1 percent of the men experienced at least one adverse event, the majority of which were mild-to-moderate in severity. In total, 46.7 percent of women and 43.0 percent of men experienced at least one adverse event considered by Squires’s group to be at least possibly related to the use of Prezista/Norvir.
The most common side effects were nausea (24.4 percent of the women versus 14.1 percent of the men), diarrhea (16.4 versus 22.5 percent, respectively), upper respiratory tract infections (11.1 versus 7.7 percent, respectively) and vomiting (11.5 percent versus 6.3 percent). Interestingly, serious adverse events were less common among women compared with men: 16.4 percent versus 22.5 percent, respectively.
In conclusion, Squires pointed out that the GRACE study successfully enrolled a high proportion of women and is, to date, the largest North American study to assess sex-based differences in the efficacy and safety of an ARV regimen. Overall, she said, the data reported suggest that Prezista/Norvir can be used in women and men with similar safety and efficacy outcomes.
DART study
A major study has shown that HIV treatment can be successful in resource-limited settings without laboratory monitoring.
The DART study involved over 3300 adults in Uganda and Zimbabwe. All were starting HIV treatment for the first time.
Half the patients were randomised to change to second-line antiretroviral therapy if their CD4 count fell, the others switching if they developed a serious HIV-related illness.
Similar proportions of patients in the clinical monitoring arm (87%) and laboratory monitoring arm (90%) were alive after five years.
There were no differences in toxicity rates between the two arms.
Direction of Obama government HIV policy
Presentations from senior US HIV officials have given some clues about the priorities of the Obama administration.
These include:
Continued PEPFAR funding
Earlier HIV treatment
Exploring the concept of 'treatment as prevention'.
Abacavir and heart attack: debate continues
Two new studies have found no connection between treatment with abacavir (Ziagen, also in the combination pills Kivexa and Trizivir) and an increased risk of heart attack.
The first study involved over 19,000 US veterans with various HIV treatment histories. The first set of results showed that abacavir was associated with a modest 17% increase in the risk of heart attack. But when the researchers controlled for other risk factors, this association was weakened.
Of note, the investigators found that patients with kidney disease, which can increase the risk of cardiovascular disease, were more likely to be given abacavir. They believe that this could be an explanation for the association between treatment with the drug and heart attack.
A second smaller study was conducted in Spain. It involved 300 patients and showed that treatment with abacavir did not affect levels of bio-markers that can predict an increased risk of heart attack.
'Treatment as prevention' must not violate human rights
A plenary session at the conference was told that expanded HIV testing and treatment as prevention must not be coercive or violate human rights.
Mathematical models have predicted that increasing the number of individuals diagnosed with HIV and on antiretroviral therapy has the potential to significantly slow the pace of the epidemic.
But human rights organisations said that testing for HIV must not be coercive. They also emphasised the importance of having properly trained counsellors, and linking testing to treatment and education.
MORE DETAILS ON A STORY QUOTED YESTERDAY:
South Africa begins AIDS vaccine trial, cuts funds
AP – Dr Danielle Crida, left, demonstrates how a new Aids vaccine is administrated on a trail subject, Wanda …
By MICHELLE FAUL, Associated Press Writer Michelle Faul, Associated Press Writer – Mon Jul 20, 5:26 pm ET
CAPE TOWN, South Africa – South Africa launched a high-profile trial of an AIDS vaccine created by its own researchers Monday, a proud moment in a nation where government denial, neglect and unscientific responses have helped fuel the world's worst AIDS crisis.
After a government official lauded the project at a ceremony at Cape Town's Crossroads shantytown, the scientist leading the research said state funding had been halted.
The contrast between Monday's hopeful vaccine launch and the revelation of funding cuts raised questions about whether the government was backsliding on its pledge to combat AIDS.
Anna-Lise Williamson, an AIDS researcher at the University of Cape Town, told The Associated Press the clinical trial would continue with U.S. money. But she said South Africa's Department of Science and Technology had pulled its funding in March, while the project's other sponsor, the state electricity utility Eskom, did not renew its contract when it expired last year.
Neither government spokesmen nor Eskom immediately returned calls seeking comment about funding cuts.
The South African vaccine was developed at the University of Cape Town and targets the specific HIV strain that has ravaged South Africa. It is also undergoing safety tests at a trial involving 12 volunteers in Boston that began earlier this year, said Sarah B. Alexander, spokeswoman for the HIV Vaccine Trials Network at the Fenway Institute, an AIDS treatment center where the trial is under way.
The safety trials started in the U.S. to allay any criticism the United States was collaborating on an AIDS vaccine that might be seen as using Africans as guinea pigs, she said.
In its vaccine initiative, the government decided it was important to target the HIV subtype C strain that is prevalent in southern Africa "and to ensure that once developed, it would be available at an affordable price," said Anthony Mbewu, president of South Africa's government-supported Medical Research Council, which shepherded the project.
Some 250 scientists and technicians worked on the vaccine's development.
Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Disease and a leading AIDS researcher, was in South Africa for the trial launch and said the South African scientists received more money from his institute's research fund than any others in the world, outside the United States. The U.S. also paid to produce the vaccine.
He called it "the most important AIDS research partnership in the world."
But, he warned: "There are extraordinary challenges ahead," referring to the years of testing needed now that South Africa has reached the clinical trial stage.
Monday's launch was put on by the South African AIDS Vaccine Initiative, the lead program of the government-backed Medical Research Council. The deputy ministers of health and science were both at the event and praised the initiative.
Aaron Motsoaledi, a medical doctor who became health minister in May, has promised to try to strengthen AIDS prevention campaigns that were weakened for years by red tape and mixed messages from policy makers.
Getting people onto treatment, not earlier treatment, must be priority, conference warned
Monday, July 20, 2009 2:00 AM
Filed under: Conference news, Starting treatment news, IAS 2009
Debates about whether to start treatment at a CD4 count of 350 in developing countries ignore the fact that current programmes are doing very badly at retaining patients in care after diagnosis or starting people on treatment before they become seriously ill, Dr Francois Venter, President of the South African HIV Clinicians Society told the Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention on Monday.
Speaking during a conference symposium on when to start treatment, Dr Venter pointed out that the current average CD4 count at which patients start treatment in South Africa is 87 cells/mm3.
Despite a huge increase in the number of people who undergo HIV testing – up to one-quarter of South African adults took a test in the past year, according to 2009 research by the Human Sciences Research Council – the average CD4 count at which patients in his Johannesburg clinic start treatment has not moved above 80 to 100 cells since 2004, Dr Venter said.
“We are still doing a terrible job of retaining patients in care, and we need to start looking harder at retention in care,” he said. “Are you delivered into a package of care that looks after you [after diagnosis]?” he asked.
A large number of patients were dying while waiting for the results of diagnostic tests and while undergoing treatment-preparation counselling, or during acute opportunistic infections.
He also expressed concern about the implications of recent findings on the inflammatory effects of HIV infection for developing countries. “Cardiovascular disease is not usually seen as an African problem, but death-certificate analysis in South Africa recently revealed that diabetes and hypertension were among the most frequent causes of death.”
Similarly, South Africa is seeing overlapping epidemics of HIV and obesity. Potent cardiovascular risks may lead to a high rate of cardiovascular disease in people with HIV, Dr Venter argued. He also drew attention to the high rate of liver disease and hepatitis virus infection in the developing world, to data showing that uncontrolled HIV replication exacerbates liver damage, and to the high frequency of kidney disease in African-Americans with advanced HIV infection (people of African origin appear to have a high risk of HIV-associated kidney damage).
“The thing that filled me with fear [looking at the data on inflammation and HIV] was renal disease. Kidney transplants, dialysis, even prophylactic drugs to deal with proteinuria are difficult to obtain and expensive in this region.”
Eighty-four per cent of maternal deaths and 47% of postnatal infant infections occur at CD4 counts below 350, he noted.
“… one of the major obstacles to early treatment in the developing world is the current reliance on d4T (stavudine) in first-line treatment.
Starting treatment in the developed world
In the developed world national US, British and European guidelines now concur that treatment should be recommended to all patients with CD4 counts below 350.
While US cohort data suggest benefits to starting treatment before the CD4 count falls below 500, another major cohort analysis did not find an additional benefit to starting treatment at CD4 counts above 400, and an international randomised trial called START is currently recruiting patients to determine whether starting treatment at a CD4 count above 500 results in less death and illness than starting at the currently recommended threshold.
Dr Jose Gatell of Hospital Clinic, University of Barcelona, highlighted that current European AIDS Clinical Society treatment guidelines state that antiretroviral treatment should be considered for all diagnosed patients.
He warned “We cannot wait until completion of the START study to make decisions.”
But to achieve an extended period of healthy life, normalisation of CD4 counts needs to be achieved. Professor Gatell pointed to research showing that normalisation of CD4 counts for at least five years above 500 cells is necessary in order to eliminate the difference in mortality between people with HIV and the general population.
Nevertheless, a substantial proportion of patients continue to fail to reach this CD4 level with current treatment due to late initiation of treatment, he noted. Therefore all patients with a CD4 count below 350 should be offered treatment unless there is a specific contraindication.
RAPPORTEUR:
Track B
Session summary
MOAB2, Cardiovascular Disease: to HAART or not to HAART
________________________________________
Not surprisingly the session started with presentations related to the presumed role of abacavir in increasing the risk of cardiovascular events in patients with HIV infection, a topic that has been in the mind of clinicians, patients, and researchers since the original presentation of this data by the DAD group in 2007.
Bedimo et al. presented a large epidemiological study of the VA cohort that included more than 19000 participants. In this cohort the use of abacavir was marginally associated with an increased cardiovascular risk, and the association disappeared after adjusting for traditional risk factors, renal function (the main reason ABC is used instead of tenofovir) and HCV. Importantly, renal dysfunction was an additional strong predictor of cardiovascular risk.
RAPPORTEUR:
Track B
Session summary
MOSY3, Current Issues in Pharmacology and Toxicology
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Carr gave an update on changes of body composition (fat and bone) and their importance in the management of HIV infected individuals. The discontinuation of thymidine analogs consistently (and slowly) improves lipoatrophy, one of the most feared toxicities of HIV treatment. Tesomorelin decrease fat in patients with fat accumulation, but its benefits are transient. Bone is affected probably by all ART regimens, with bone loss after the initiation of therapy that is greater with some drugs (TFV). Although tenofovir appears not to decrease kidney function at the population level, once renal problems appear in a particular individual, they are only partially reversible. Hyperlipidemia and insulin resistance are also very common in HIV infected individuals and that was the focus of Dr. Currier who discussed different lipid lowering therapies, ART switch, and intensification strategies to manage it. She also discussed the effects of HIV infection itself, and of different classes of drugs, on insulin resistance and lipids. She noted that it is necessary to address both problems to decrease the incidence of cardiovascular disease
RAPPORTEUR:
Track B
Session summary
MOPDB1, Update on Diagnosing and Monitoring
________________________________________
In this symposium on advances in point of care diagnostic testing, Wee presented an elegant micro-fluidic system which is the size of a credit card for the quantification of HIV1 cDNA for neonatal diagnosis. With a 30 minute throughput, the data correlated well with a standard table top analyzer, with an R2 value of 0.997, and is well positioned for large scale testing.
In order to improve the accuracy and precision of viral load testing in reservoirs, Fiscus et al studied the Abbott m2000 RealTime HIV-1 viral load assay, which is standardized for plasma, in breast milk, dried blood spots (DBS), seminal plasma, and cerebrospinal fluid, and compared the results to plasma. Linear results were obtained for all fluids, and, compared to blood, recovery was near 100% for semen, CSF, and DBS, and roughly 50% for breast milk.
In contrast to the earlier presentations, an independent review of various rapid tests in 20 HIV negative and 200 HIV-1 individuals specimens by Payle et al result in high rates of false negative results with oral fluid and blood specimens. The highest false negatives were seen with the Oraquick oral fluid (11.9%), with false negative rates of 3-4% for Oraquick blood and Determine rapid blood tests, and the lowest rates with the Vikia and INSTI blood tests (<2%). The authors urged awareness of this variability and caution in the interpretation of these results.
Community
Session summary
MOSY1, When to Start
________________________________________
When to Start?
Monday July 20 11am
Josep Gatell from the University of Barcelona: The data on years of survival for people on HAART who started below 350 was acceptable (at 35 years) but patients needed to be above 500 T-cells for at least 4 years to have the same life expectancy as the rest of the population. Two thirds of Gatell’s cohort start below 350 T-cells and only half of that (53%) reach more than 500 after 3 years.
(NB: Elsewhere, Gatell is quoted as saying “… at least 5 years…”)
There is also now more evidence of higher risks of AIDS defining events for those who start under 350 and more results about the role the virus itself plays in chronic inflammatory responses in people with HIV. Viral replication is a main predictor of non-AIDS events. Evidence is mounting that people should start earlier when their T-cells are less than 500. This was particularly true for people with other health issues such as a higher cardiovascular risk, Hepatitis B or C and pregnancy.
Nevirapine May Be Option for Some Kids After Single Dose for MTCT
Author: Mark Mascolini
________________________________________
20 July 2009
Children exposed to single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission (MTCT) of HIV may be able to replace lopinavir/ritonavir with nevirapine in a first regimen after that regimen gets HIV replication under control, according to results of a randomized trial presented at the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention.
The investigators caution that more work must be done to confirm the findings and define which children may safely swap lopinavir/ritonavir for nevirapine. But if the results hold, the strategy would be a plus in low-income countries where many children are exposed to sdNVP and still become infected with HIV. Nevirapine is cheaper and easier to use than the protease inhibitors (PIs) lopinavir/ritonavir because it is formulated into a single pill with other antiretrovirals. Nevirapine may also have fewer long-term side effects than lopinavir/ritonavir.
http://www.clinicaloptions.com/HIV/Conference%20Coverage/Cape%20Town%202009.aspx
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