+CLICK. (The University of Texas School of Public Health)

+CLICK was developed by Christine Markham, Ph.D., and Ross Shegog, Ph.D., assistant professors of behavioral sciences. The game’s usability and credibility were assessed by HIV-positive (HIV+) youth at a Texas Children’s Hospital clinic. Results from the study were published in the May issue of AIDS Care.

According to the World Health Organization, adolescents and young adults ages 13-24 account for 40 percent of new HIV infections worldwide and almost half of all HIV infections in the United States. Many HIV+ youth engage in risky sexual behaviors, according to Markham.

“We wanted to create +CLICK so that we could help educate youth on the importance of making proper, healthy decisions to protect their relationships and themselves as well as help to reduce transmission of the HIV virus,” said Markham, lead investigator of the study.

The game was developed as an adjunct to the youths’ traditional clinic-based self-management education.

The small sample size of 32 study participants included 62.5 percent females and 37.5 percent males. Of those participants, 56.2 percent contracted the virus through birth and 43.8 percent became infected through sexual contact.

Markham and Shegog worked with Mary Paul, M.D., associate professor of pediatrics at Baylor College of Medicine, and Amy Leonard, M.P.H., research coordinator at Baylor College of Medicine, to develop the material presented in the interactive lessons.

Replicating a shopping mall, study participants travel through lessons on abstinence, condoms and contraception, and also watch video clips from experts and peers who are also HIV+. +CLICK is designed to target four behaviors: choosing not to have sex; disclosing HIV status to a potential partner; using condoms correctly and consistently; and using an effective method of birth control along with condoms.

Participants were able to play several of the game’s lessons in approximately 15 minutes during their regularly scheduled clinic visits. “Participants were very receptive and enthusiastic about playing the game,” said Leonard. “They also liked that they were able to ask the clinicians questions about what they learned on the lessons.” Credibility of the game was trusted by 93.8 percent of the participants and 84.4 percent of users found the game to be very easy to use and would tell others about +CLICK, according to the study.

A prototype of the game was used for the study. The game, which is in the last stages of development, is tentatively scheduled to be available to the public in approximately six months. In addition, the research team is working to create a similar web-based game that will focus on medication adherence for HIV+ youth.

This study was funded by the Baylor College of Medicine-University of Texas at Houston Center for AIDS Research.

The University of Texas
Health Science Center
At Houston

EMBL researchers provide the as yet closest look at the structure of immature HIV.

Lattice maps for immature HIV particles. The 3D computer reconstruction shows the immature Gag lattice of HIV that matures to form the protein shell of the infecious virus. Maps are shown in perspective such that hexamers on the rear surface of the particle appear smaller. The side of the particle toward the viewer lacks ordered Gag. (John Briggs/EMBL)

Scientists at the European Molecular Biology Laboratory (EMBL) and the University Clinic Heidelberg, Germany, have produced a three-dimensional reconstruction of HIV (Human Immunodeficiency Virus), which shows the structure of the immature form of the virus at unprecedented detail. Immature HIV is a precursor of the infectious virus, which can cause AIDS. The study, published in the 22-26 June online edition of PNAS, describes how the protein coat that packages the virus’ genetic material assembles in human cells. Drugs that block this assembly process and prevent the virus from maturing into its infectious form are considered a promising therapeutic approach. HIV consists of an RNA molecule that carries the genetic information of the virus and is surrounded by protective protein and membrane layers. During infection the virus deposits its genetic material into a human cell where it reprogrammes the host cell machinery to generate many copies of the viral genome and initiates the production of a viral protein called Gag. In the immature virus, many copies of Gag interact to form a roughly spherical lattice that encloses the virus’ genetic material.The virus then leaves the cell with the help of proteins of the host and infects new cells.

A simplified representation of HIV’s lifecycle. For a detailed description please refer to page 2. (John Briggs/EMBL)

Using a method called cryoelectron tomography researchers in the groups of John Briggs at EMBL and Hans-Georg Kräusslich at the University Clinic Heidelberg generated the as yet highest resolution 3D computer reconstruction images of the immature Gag lattice. The results suggest a simple model of HIV formation in human cells: multiple Gag proteins interact to form a hexameric lattice that grows with an inherent curvature and that incorporates new proteins stochastically. Several further steps in which Gag is cleaved by an enzyme are necessary to transform this immature lattice into its mature, infectious form.

Briggs and his team are now working on producing an even higher resolution structure of the protein lattice to gain a more detailed understanding of the virus’ assembly and maturation processes, which may eventually help to find weak points that could be targeted by drugs.

Cryoelectron tomography is a technique with which a sample is instantly frozen in its natural state and then examined with an electron microscope. Images are taken from different directions and assembled into an accurate 3D reconstruction by a computer.

Source Article: Briggs, J.A.G. et al. Structure and assembly of immature HIV. PNAS online, 22 June 2009

European Molecular Biology Laboratory (EMBL)

(Université de Montréal)

The study was led by Dr. Rafick-Pierre Sékaly, of the Université de Montréal. Dr. Jean-Pierre Routy of the Research Institute of the McGill University Health Centre (RI-MUHC) and scientists from the National Institutes of Health (NIH) and the University of Minnesota in the United States also collaborated on the investigation. To date, anti-AIDS treatments have been stymied by “HIV reservoirs” – immune system cells where the virus hides and where existing HAART treatments cannot reach. The researchers successfully identified the cells where HIV hides and the “stealth” mechanisms that allow the virus to escape existing treatments. This breakthrough opens the way towards innovative therapies that are completely different from current approaches.

“Our results argue in favour of a strategy similar to the one used against leukemia, which is targeted chemotherapy, associated with a targeted immune treatment. This would make it possible to destroy the cells containing a virus, while giving the immune system time to regenerate with healthy cells,” says Dr. Rafick-Pierre Sékaly, a professor at the Université de Montréal, researcher at the Centre Hospitalier de Université de Montréal (CHUM), director of INSERM 743 and scientific director of the Vaccine and Gene Therapy Institute of Florida.

“For the first time, this study proves that the HIV reservoirs are not due to a lack of potency of the antiretroviral drugs, but to the virus hiding inside two different types of long life CD4 memory immune cells,” explains Dr. Jean-Pierre Routy, a hematologist with the MUHC, researcher in infection and immunity at the RI-MUHC and professor of hematology at McGill University. “There are several types of HIV reservoirs, each necessitating a different treatment to eliminate them.”

Nicolas Chomont and Rafick-Pierre Sékaly of the Université de Montréal with McGill University’s Jean-Pierre Routy. (Université de Montréal)

Indeed, once the virus is hidden in these reservoir cells, it becomes dependent on them: if the cell lives, the virus lives, but if the cell dies, so does the virus. As such, destroying these immune cells will allow for the elimination of the resilient or hidden parts of the virus. Existing HAART treatments destroy the viruses circulating in the body, yet cannot reach those hidden in reservoir cells.

“We now have brand-new options to fight HIV,” concludes Nicolas Chomont, a postdoctoral intern at the Université de Montréal’s Department of Microbiology and Immunology and one of the co-authors of this study. “The combination of fundamental and clinical approaches led to amazing results that allow us to elucidate another mystery of this virus of a thousand faces.”

These new therapeutic options will require many more years of research before they are validated and become a reality for patients. However, this study represents an invaluable work plan that will provide a map for many laboratories around the world.

Partners in research
This study was funded by the American Foundation for AIDS Research (amfAR), the National Institutes of Health, the Canadian Institutes of Health Research and the FRSQ-AIDS and Infectious Diseases Network.

About the study
The study, “HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation,” published in Nature Medicine, was coauthored by Rafick-Pierre Sékaly, Elias K. Haddad, Nicolas Chomont, Mohamed El Far, Petronela Ancuta, Lydie Trautmann, Francesco A. Procopio, Bader Yassine-Diab and Geneviève Boucher of the Université de Montréal and Centre Hospitalier de Université de Montréal (CHUM), Jean-Pierre Routy, Mohamed-Rachid Boulassel and Georges Ghattas of the McGill University Health Centre (MUHC) and McGill University, Brenna J. Hill, Daniel C. Douek and Jason M. Brenchley of the National Institutes of Health, U.S.A., and Timothy W. Schacker of the University of Minnesota, U.S.A.

On the web
About the Université de Montréal’s Faculty of Medicine
About the Research Centre of the Centre Hospitalier de Université de Montréal
About the Research Institute of the McGill University Health Centre
About McGill University
About INSERM
About Vaccine and Gene Therapy Institute of Florida

Université de Montréal

In the first study of the impact of social tolerance levels toward gays in the United States on the HIV transmission rate, the researchers estimated that a constitutional ban on gay marriage raises the rate by four cases per 100,000 people.

“We found the effects of tolerance for gays on HIV to be statistically significant and robust – they hold up under a range of empirical models,” says Hugo Mialon, an assistant professor of economics.

“Laws on gay marriage are in flux and under debate,” added Andrew Francis, also an assistant professor of economics, citing the recent decision by the California Supreme Court to uphold a ban on same-sex marriage. “It’s a hot issue, and we are hoping that policymakers will take our findings into account.”

The study used data from the General Social Survey (GSS), which has tracked the attitudes of Americans during the past four decades. The economists calculated that a rise in tolerance from the 1970s to the 1990s reduced HIV cases by one per 100,000 people, and that laws against same-sex marriage boosted cases by 4 per 100,000.

“Intolerance is deadly,” Mialon said. “Bans on gay marriage codify intolerance, causing more gay people to shift to underground sexual behaviors that carry more risk.”

Outstanding law and economics paper of the year

Francis and Mialon previously did an analysis of the optimal penalty for sexually transmitting HIV. Published in March of 2008, the study was recently named outstanding paper of the year by the editors of the American Law and Economics Review.

The two researchers developed a game theory model for sexual behavior, which demonstrated that laws in some states regarding the sexual transmission of HIV are generally inefficient at slowing the spread of the disease.

In Georgia, for instance, failing to inform a partner that you are HIV positive prior to having sex is a felony punishable by up to 30 years in prison. The same penalty can apply even if the person who is HIV positive uses precautions such as a condom during sex, and even if the sexual partner does not contract HIV. The law does not apply, however, to people who do not know that they are HIV positive and transmit the virus.