June 2007: New amfAR Grants to Optimize HIV Treatment
June 20, 2007 - amfAR, The Foundation for AIDS Research, will grant almost $1.2 million for 10 new research projects aimed at increasing understanding of the social and biological factors that influence the treatment of HIV/AIDS, Dr. Rowena Johnston, amfAR’s vice president of research, announced today.
Among those projects is a study exploring the potential benefits of maraviroc, a new antiretroviral drug expected to be approved by the FDA soon. Maraviroc works by blocking the cell surface protein CCR5 and thus preventing the virus from entering cells. amfAR funded research 10 years ago that played a leading role in spurring the development of maraviroc.
The drug also has the potential to prevent disease progression by reducing the activation state of the immune system, said Dr. Nancy Shulman of Stanford University and the Palo Alto VA Medical Center, who received the grant.
“Immune activation has been implicated in promoting HIV disease,” she said. “If maraviroc can decrease HIV disease both by blocking HIV entry into cells as well as decreasing immune activation, this could have implications for broadening the use of maraviroc – even in patients who might otherwise seem to be unsuitable candidates for the drug.”
amfAR will also fund several projects related to the social factors contributing to HIV infection, including one that examines how stigma associated with HIV affects the level of care that patients receive.
“Although progress has been made over the past 25 years in protecting the rights of people with AIDS, the stigma associated with being HIV positive can still contribute to lower quality health care in those with HIV infection,” Dr Johnston said. New research funded by amfAR and being conducted by Dr. Jennifer Sayles of the University of California, Los Angeles aims to identify factors that contribute to HIV-related stigma in women, with the long-term goal of improving the quality of their health care.
Also being funded by amfAR are several projects concerning recent recommendations by the U.S. Centers for Disease Control and Prevention (CDC) that HIV testing be included in routine medical care. The recommendations have raised questions about how best to implement testing among wide-ranging populations.
Dr. Marya Gwadz of the National Development and Research Institutes will study the impact that the recent recommendations will have on homeless youth. These young people are at particularly high risk for HIV infection and yet they are often not tested for the virus or do not return for test results.
And Dr. Roland Merchant, based at Brown University in Providence, RI, will compare the perceptions and success of current opt-in HIV testing procedures to the opt-out recommendations advanced by the CDC, in a study that will inform the implementation of the new recommendations around the United States.
“Despite the sophistication of health care in the United States, physicians are still grappling with overarching issues of identifying and appropriately caring for HIV positive populations,” Dr. Johnston said. “amfAR’s most recent research funding promises to make valuable contributions to optimizing the treatment of HIV infection.”
The recipients of this $1.2 million round of funding and their projects are:
Marya Gwadz, Ph.D.
NDRI USA Inc., New York, NY
Recent changes in HIV testing recommendations – Impact on youth at risk: Homeless youth are at particularly high risk of HIV infection and yet are often not tested for the virus or do not return for test results. Because the CDC has recently recommended that all people be tested for HIV, Dr. Gwadz plans to study how often homeless youth are tested, which factors influence their decision to be tested, and how HIV test counseling and access to medical care might change testing practices among homeless youth. Results of her studies will be used to design and test interventions aimed at increasing HIV testing rates in this population.
Elias Haddad, Ph.D.
Université de Montréal, Quebec, Canada
Impact of PD-1 on the establishment and maintenance of the HIV-1 reservoir: The PD-1 molecule has recently been shown to be associated with the reduced ability of certain immune cells to survive and proliferate during HIV infection. Dr. Haddad will test the hypothesis that PD-1, which is present in increased amounts in immune cells specialized to fight HIV, is also involved in the establishment and/or maintenance of the HIV reservoir. This reservoir contains HIV that is resistant to both antiretroviral therapy as well as the immune system’s efforts to destroy it, and so constitutes the major barrier to curing HIV infection. Discovering the role of PD-1 in establishing and maintaining the reservoir may lead to new therapies designed to eradicate the virus from the body.
Stephen Kent, M.D.
University of Melbourne, Melbourne, Australia
Establishment of the HIV reservoir during acute infection: The HIV reservoir, where HIV persists during the entire course of infection beyond the reach of the immune system or antiretroviral therapy, is the major hurdle that needs to be overcome in order to cure HIV infection. Scientists believe the reservoir is established during acute infection and so the most effective interventions aimed at eradicating it might have to be applied very early during infection. Dr. Kent plans to study the nature of the virus strains that become part of the reservoir, as well as the timing of the reservoir’s establishment, in order to gain a better understanding of how interventions designed to cure HIV infection must work.
Lori Leonard, Sc.D.
Johns Hopkins School of Public Health, Baltimore, MD
How to test – policy and practice after the CDC recommendations: The CDC has recently recommended that all patients seeking medical care be routinely tested for HIV. Dr. Leonard plans to investigate how doctors and adolescent patients implement these findings in a clinic in Baltimore, and how the low-income and mostly minority adolescents in that clinic respond to the implementation of these new testing guidelines. Via surveys and interviews, Dr. Leonard will gather information that will inform other regions around the United States on how to best implement the CDC testing recommendations.
Roland Merchant, M.D., M.P.H., Sc.D.
Brown University, Providence, RI
CDC HIV testing guidelines – unresolved ethical concerns: In response to CDC recommendations that all patients seeking medical care be routinely tested for HIV, Dr. Merchant and colleagues will conduct surveys of clinicians, advocates and patients regarding their concerns and experiences of opt-in versus opt-out HIV testing. Patients will be asked about their perception of coercion, how well they understand informed consent, and their knowledge of various HIV-associated risk factors and prevention. This study will lead to a greater understanding of the potential benefits and pitfalls, as well as outstanding ethical concerns, involved in the roll-out of routine HIV testing.
Robert Remien, Ph.D.
Research Foundation for Mental Hygiene Inc, New York, NY
Acute HIV Infection awareness and entry into care among high risk populations: The risk of transmitting HIV to others is particularly high during the first few months of HIV infection and as such represents an important time for counseling newly infected people as well as their partners. Dr. Remien will interview at-risk populations from community-based organizations, as well as physicians and test counselors, in order to develop an educational program aimed at raising awareness of the importance of acute HIV infection and promoting behavioral skills to minimize harm to both newly infected people as well as their partners.
Jennifer Sayles, M.D.
University of California Los Angeles, Los Angeles, CA
The impact of stigma on access to HIV treatment and care: The stigma associated with being HIV positive can be compounded by gender, race, poverty and other factors, all of which can contribute to lower quality of health care in those with HIV infection. Less is known about the contributions of these factors to health care quality in women compared to other populations. Dr. Sayles plans to test the validity of a new measure of HIV-related stigma in women, with the long-term goal of identifying factors that might guide future interventions to improve quality of health care in HIV-positive women.
Nancy Shulman, M.D.
Stanford University and Palo Alto VA Medical Center, Palo Alto, CA
Immunologic benefits of CCR5 inhibitor intensification: The new antiretroviral maraviroc works by blocking the cell surface protein CCR5 and thus preventing the virus from entering cells. Dr. Shulman postulates that the drug might also prevent disease by reducing the activation state of the immune system. Immune activation has been implicated in promoting HIV disease – if maraviroc can decrease HIV disease both by blocking HIV entry into cells as well as by decreasing immune activation, this could have implications for using maraviroc even in patients who might otherwise seem to be unsuitable candidates for the drug.
Christina Meade, Ph.D./Mentor: Steven Safren, Ph.D.
Harvard Medical School, Belmont, MA
Impulsivity, drug abuse, and HIV medication adherence – an fMRI study: While it is well known that drug abusers tend not to adhere as well to antiretroviral therapy as those who do not use drugs, the cognitive and biological mechanisms linking drug abuse with poor adherence are not completely understood. Dr. Meade, who has won several pre-doctoral awards and has been invited to present her work at several conferences around the world, will use functional MRI brain scans to compare the brain functioning of cocaine abusers and those with no history of drug abuse while they conduct a cognitive test designed to measure decision making processes. The results of her studies may be used to design interventions to improve adherence to antiretroviral therapy among drug users.
Miranda Xhilaga, Ph.D./ Mentor: Sharon Lewin, Ph.D.
Monash University, Melbourne, Australia
Viral persistence in MGT of RT-SHIV infected macaques on HAART: Sexual transmission remains the leading cause of new HIV infections, and many cases are due to the presence of HIV in semen. The extent to which the virus can survive and persist in semen when the patient is taking antiretroviral therapy is unclear. Dr. Xhilaga, the recipient of several previous graduate and postdoctoral awards, including the prestigious Fellows Award for Excellence in Research, will conduct systematic studies in several regions of the male genital tract of monkeys, testing the ability of the virus to persist during the early stages of infection and in the presence of antiretroviral therapy. Her studies will determine the importance of the reservoir of virus in semen as a target for therapies aiming to cure HIV infection.