For HIV-Positive Patients, Delayed Treatment A Costly Decision

February 27, 2011

HIV infected patients whose treatment is delayed not only become sicker than those treated earlier, but also require tens of thousands of dollars more in care over the first several years of their treatment.

"We know that it's important clinically to get people into care early because they will stay healthier and do better over the long run," says Kelly Gebo, M.D., M.P.H., an associate professor of medicine in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine and the study's senior author. "But now we know it's also more costly to the health care system for potentially decades and a serious drain on our limited health care dollars."

Gebo says her team's findings highlight the importance of motivating people who are at risk to seek HIV testing and of reducing the time between the first positive HIV test and the first visit to an HIV clinic for care.

Patients with HIV are living longer and healthier lives, thanks to advances in antiretroviral therapy, but those successes may erode when some wait too long into the course of their disease to get treatment whether because they don't know they are infected with HIV, aren't sure how to access the health care system or have competing needs like mental health or substance abuse issues.

Dr. Gebo and her team's research, published in the December issue of the journal Medical Care, reviewed medical records of 8,348 patients at nine HIV clinics across the United States between 2000 and 2007. They found that more than 43 percent of patients were considered late entrants into the health care system, presenting at a clinic with extremely weakened immune systems, characterized by having CD4 counts below 200. CD4 cells are keys to a healthy immune system healthy people have counts between 800 and 1,000. When CD4 cells are damaged, as they are by HIV, counts can fall dramatically, making patients more susceptible to infection and certain types of cancer.

Low CD4 counts "make it more likely that patients are going to have complications and more likely that their CD4 counts won't ever recover to normal levels even with antiretroviral treatment," Gebo says. Previous studies have shown that those who come to care late in the course of their disease have shorter survival and benefit less from antiretroviral therapy.

Gebo and her colleagues found that the average difference in cumulative treatment expenditures between early and late presenters ranged from $27,275 to $61,615 higher over the course of the first seven to eight years of treatment. Costs are higher for the late presenters because they tend to be sicker than early presenters, particularly the first year of treatment and the cost gap doesn't shrink over time, she says. Late presenters are hospitalized more often, need to be put on costly antiretroviral therapy and antibiotics, and often must be treated for other diseases that have been exacerbated by a weakened immune system.

The study was supported by the Agency for Healthcare Research and Quality and the National Institutes of Aging and Drug Abuse. Richard D. Moore, M.D., M.H.Sc., a professor of general internal medicine at Johns Hopkins, also contributed to the research.

Source: Johns Hopkins Medicine


The Control Of HIV, A Highly Promising Compound

February 14, 2011

A compound that can inhibit the transfer of HIV from one cell to another has been developed by researchers at the Institut de Biologie Structurale Jean-Pierre Ebel (CNRS/Université Joseph Fourier/CEA). It acts by saturating a receptor called DC-SIGN, which is used by HIV to ensure its transmission throughout the body. A patent has been filed for this compound, and an article on the subject will be published in ASC Chemical Biology on 19 March 2010.

Despite the major advances achieved in the control of HIV, this infection still causes millions of deaths each year. The search for new cellular targets for novel antiviral therapies remains an important challenge.

Researchers at the Institut de Biologie Structurale (CNRS /Université Joseph Fourier/CEA) have been working on a receptor called DC-SIGN which is found on the surface of dendritic cells: immune cells which are present in contact zones with the exterior, such as the skin or mucous membranes, and the first sites to encounter pathogens. DC-SIGN is implicated in the initial phases of HIV infection and constitutes a potential therapeutic target that has not yet been exploited.

What is the role of DC-SIGN? Under normal circumstances, it captures pathogens by recognizing certain characteristic oligosaccharides present on their surface. The pathogens are then internalized by dendritic cells that degrade them and present the fragments at their surface. These cells then move to lymphoid tissues where they trigger an immune response by the body, i.e. the production of T lymphocytes that can fight the pathogen. As for HIV, it uses DC-SIGN to ensure its transmission in an intact form to the T lymphocytes that it will infect. In particular, it attacks CD4+ T lymphocytes (carrying a molecule called CD4 that is susceptible to HIV) which are the principal target used by the virus to ensure its spread.

The researchers have developed a compound that can inhibit the HIV transmission process to CD4+ T lymphocytes. This tetravalent compound, endowed with four functional groups that mimic the oligosaccharides of pathogens, is recognized by DC-SIGN, which thus prevents HIV from using the receptor to travel to the lymphoid tissues. It has some particularly interesting properties; e.g. high solubility in physiological media, negligible cytotoxicity and a long-lasting effect (even after washing the cells, the inhibitory effect can persist for several hours). Furthermore, the simple structure of the compound means that its large-scale production could easily be envisaged.

Last but not least, DC-SIGN is also utilized by other pathogens to circumvent the immune system. The compound developed by the research team could also be used to inhibit infection by the hepatitis C, dengue, Ebola and SARS viruses, the Mycobacterium tuberculosis bacterium (which causes tuberculosis) and a number of parasites. It may even prove to be more effective in these cases than with HIV. This compound could therefore be added to the list of antiviral compounds designed on the basis of oside structures that exist in nature, the glycomimetics, such as Tamiflu which is used to control seasonal influenza.

Its efficacy has been proven in vitro to prevent the transmission of HIV from one cell to another. The researchers have protected their compound with a patent filed jointly by CNRS and Université Joseph Fourrier. The next step is to perform tests in animal models. Until they find a partner, or themselves set up a structure that can manage these activities, the researchers are continuing to enhance the efficacy of their compound to render it more specific to DC-SIGN and increase its interaction with this receptor.

Source: CNRS (Délégation Paris Michel-Ange)


HIV in People Who Use Drugs: Need to Focus on Conditions of Health Delivery That Create Treatment Interruptions

February 09, 2011

The Lancet Series on HIV in people who use drugs, published online July 20 and presented at the International AIDS conference in Vienna, reports that in order to improve access to antiretroviral therapy among injecting drug users (IDUs), health providers must focus less on the individual patient's ability to adhere to treatment, and more on conditions of health delivery that create treatment interruptions.

Among low-income and middle-income countries, almost half of all injecting drug users with HIV are in just five of these countries: China, Vietnam, Russia, Ukraine, and Malaysia. Access to antiretroviral treatment (ART) is disproportionately low in these countries -- IDUs make up two thirds of cumulative HIV cases in these countries, but only 25% of patients receiving ART. This third paper is by Daniel Wolfe, Open Society Institute, International Harm Reduction Development Program, New York, M. Patrizia Carrieri, of INSERM, France, and Donald Shepard, a health economist at Brandeis University's Heller School for Social Policy and Management.

Injecting drug users (IDUs) have successfully started ART in at least 50 countries, with evidence showing clearly that these patients can achieve excellent virological outcomes and with no greater development of drug resistance than other patients. Early adherence to ART is associated with long-term virological response, with behavioural support and provision of opioid substitution treatment (OST) increasing treatment success of ART in IDUs. Preliminary evidence suggests that increased ART provision to IDUs also reduces infectivity and HIV transmission, independent of needle sharing.

Not only is ART vital for saving lives and preventing transmission, but the evidence shows it is cost-effective. Data show clear benefits of targeting of ART to IDUs in areas with concentrated HIV epidemics (such as these five countries). Furthermore, the cost of drug dependence treatment is as little as one seventh that of addressing social and medical costs of untreated drug use.

"Our analysis focused on two treatments: provision of anti-viral therapy (ART) for and provision of methadone or buphenorphine for HIV-infected drug users. We found that both are highly cost-effective. Unfortunately, many barriers limit their use," said Shepard.

Systemic barriers to ART and OST provision include stigmatisation of IDUs in health settings, medical treatment separated by specialties, bans on treatment of active IDUs, hidden or collateral fees, and multiple requirements for initiation or modification of treatment for IDUs. In the five countries considered, fewer than 2% of IDUs have access to opiate substitution treatment.

Structural barriers to treatment provision result from wholesale criminalization of drug users. Barriers include sharing the names of IDUs seeking treatment with police, arrest and harassment of IDUs in or around clinical settings, and harassment of physicians who prescribe opioids. Even in Asian countries praised for initiation of OST programs, far greater numbers of IDUs are detained for years in "treatment and rehabilitation" settings that offer no medical evaluation, right of appeal, or evidence-based treatment or rehabilitation. ART and OST in these detention centres are largely unavailable. Incarceration of drug users, and interruption of ART and OST in prison, is also commonplace.

"Compared to detention policies in many countries, these treatments not only save lives, they also save money," said Shepard.

A necessary measure to improve ART coverage for IDUs is improved data collection, including an "equity ratio" to assess whether IDUs are receiving a fair share of antiretroviral treatment. The authors highlight that the Global Fund to Fight AIDS, Tuberculosis and Malaria, which between 2001 and 2008 has awarded about $180 million for HIV prevention in IDUs, does not ask grantees to detail IDU-related spending, even in countries where most of the HIV-infected population are IDUs. The U.S. President's Emergency Plan for AIDS Relief (PEPFAR), despite legal requirements to collect data about how many IDUs are reached through its programs, also fails to do so.

Other required improvements are integration of ART with OST and treatment for co-infections such as tuberculosis, and greater use of community-based treatment models and peer support.

In view of persistent human-rights violations and negative health effects of policing, detention, and incarceration, law and policy reform is needed to improve ART coverage of IDUs. The authors say that systemic improvements "are unlikely to succeed without action to resolve the fundamental structural tension between public health approaches that treat IDUs as patients and law enforcement approaches that seek to arrest them. Police registries, arbitrary detention, and imprisonment of people who have committed no crime apart from the possession of drugs for personal use are barriers to treatment and care that cannot be overcome by counselling, electronic reminders, or peer support."

They conclude: "A basic challenge remains in the reversal of social forces, including popular opinion, that portray IDUs as already dead or less than human, and so deserving of less-than-human rights. Resurrection of IDUs from this status is beyond the healing power of ART alone, although reformation of HIV treatment systems can help to emphasise that IDUs, including those actively injecting, are capable of making positive choices to protect their health and that of their communities," adding that referral to the 1948 Universal Declaration of Human Rights could guide an approach to improve treatment for IDUs and others vulnerable to HIV infection.

Story Source:

    The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Brandeis University, via EurekAlert!, a service of AAAS.


Circumcising Gay Men Would Have Limited Impact on Preventing HIV, Study Suggests

February 01, 2011

Adult circumcision has been proposed as a possible HIV prevention strategy for gay men, but a new study by the University of Pittsburgh Graduate School of Public Health presented at the XVIII International AIDS Conference suggests it would have a very small effect on reducing HIV incidence in the United States.

Circumcision is thought to reduce the risk of HIV transmission by removing cells in the foreskin that are most susceptible to infection by the virus. Clinical trials conducted in Africa have found it reduces the risk of HIV in heterosexual men, yet there is little evidence that it can reduce transmission among American gay men.

The study was based on surveys of 521 gay and bisexual men in San Francisco. Findings indicated that 115 men (21 percent) were HIV-positive and 327 (63 percent) had been circumcised. Of the remaining 69 men (13 percent), only three (0.5 percent) said they would be willing to participate in a clinical trial of circumcision and HIV prevention, and only four (0.7 percent) were willing to get circumcised if it was proven safe and effective in preventing HIV.

The researchers extrapolated these findings to the entire gay and bisexual male population of San Francisco, an estimated 65,700 people, and determined that only 500 men would potentially benefit from circumcision.

"Circumcision in the U.S. already is very common, making it applicable to a limited number of men as a potential HIV prevention strategy in adulthood," said Chongyi Wei, Dr.P.H., study author and post-doctoral associate, Pitt's Graduate School of Public Health. "Our study indicates that any potential benefit may likely be too small to justify implementing circumcision programs as an intervention for HIV prevention."

Study co-authors include H. Fisher Raymond, M.P.H., Willi McFarland, M.D., Ph.D., Susan Buchbinder, M.D., and Jonathan Fuchs, M.D., all of the San Francisco Department of Health. The study was funded by the Centers for Disease Control and Prevention.

Story Source:

    The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Pittsburgh Schools of the Health Sciences, via EurekAlert!, a service of AAAS.


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