Children With HIV at Higher Risk of Drug Resistance

About 1 in 8 children infected with HIV experiences triple-class virological failure -- meaning the virus becomes resistant to multiple drugs -- within five years of starting antiretroviral treatment, a European study shows.

That drug failure rate is higher than in adults and highlights the challenge of maintaining viral load suppression in young patients who begin antiretroviral therapy so early in life, the researchers said.

Virological failure occurs when drugs can no longer reduce the amount of HIV in a patient's blood, according to the U.S. National Institutes of Health.

The study included more than 1,000 HIV-positive children in several European countries. The children, who were infected with HIV via their mother before or at birth, were under 16 years of age and began treatment with three or more drugs between 1998 and 2008.

Along with an overall 12 percent rate of triple-class virological failure, the researchers also found that children who began antiretroviral treatment at an older age were more likely to experience failure.

One expert said that the higher rate of virological failure may be tied to lower rates of drug adherence by kids.

"HIV is a dynamic infection in which billions of virus particles are produced each day in the bodies of HIV infected persons," explained Dr. Bruce Hirsch, attending physician in Infectious Disease at North Shore University Hospital in Manhasset, N.Y. "Though each particular virus dies off in less than a day, the high rate of production and the high mutation rate requires that three active anti-viral medicines be present in the blood stream continuously for years."

"Growing up is hard to do," Hirsch added, and "taking unpalatable medications every day is hard on young kids."

But there are potential solutions.

"Easier to take combinations, better tasting syrup versions would help children cope with this infection," Hirsch said.

The study's authors agreed. "There is continued need for strategies to promote optimum drug adherence in children, caregivers and young people to minimize the likelihood of triple-class virological failure, and for development of suitable new drugs and formulations to optimize the treatment of children with treatment failure," wrote Ali Judd and colleagues at the Medical Research Council Clinical Trials Unit in London.

The study appears online April 19 in The Lancet. health.usnews.com

More information

The New Mexico AIDS Education and Training Center has more about HIV and children.

Launch of the Rome Statement for an HIV Cure

Members of the Advisory Board for a global scientific strategy “Towards an HIV Cure” today launched the Rome Statement for an HIV Cure calling for an acceleration of HIV cure research. The announcement was made at the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011) currently being held in Rome.

Recent scientific advances in HIV research have led to a re-emergence of interest and optimism in prospects of at least a functional cure for HIV. The development of a functional cure which, without completely eliminating the virus from the body, would permanently suppress its replication and considerably diminish viral reservoirs, possibly leading to the long-term remission of patients.

Under the auspices of the International AIDS Society, a group of internationally recognized scientists and stakeholders is guiding the development of a global scientific strategy “Towards an HIV Cure”. The strategy aims at building a global consensus on the state of HIV reservoirs research and defining scientific priorities that need to be addressed by future research to tackle HIV persistence in patients undergoing antiretroviral therapy. The strategy will be presented at the XIX International AIDS Conference (AIDS 2012) which will be held in Washington DC from 22-27 July 2012. (1)

The International Scientific Working Group is co-chaired by Professor Françoise Barré-Sinoussi, IAS President-Elect and 2008 Nobel Laureate for Medicine, and Professor Steve Deeks, University of California, San Francisco (UCSF) and Positive Health Program (AIDS Program) at San Francisco General Hospital. The working group works closely with an advisory board composed of leading advocates and major research stakeholders in HIV cure, including representatives of people living with HIV and funders and clinicians from high prevalence settings. The Advisory Board is co-chaired by Prof. Barré-Sinoussi and Dr. Jack Whitescarver, Associate Director for AIDS Research and Director of the Office of AIDS Research at the National Institutes of Health.

“While there is certainly a high level of interest being expressed about finding a functional HIV cure (2), it can only be achieved through an increased and concerted international effort engaging not only the scientific community but all stakeholders involved in the HIV/AIDS response and global health,” said Professor Barré-Sinoussi.

“Partnership and collaboration are critical to the efforts to find an HIV cure,” said Dr. Whitescarver. “We need not only the finest minds but the very best in scientific alliances.”

Today’s Rome Statement for an HIV Cure lists the following three key objectives:

• recognizing the importance of developing a safe, accessible and scalable HIV cure as a therapeutic and preventive strategy against HIV infection and to help control the AIDS epidemic.
• committing to stimulating international and multidisciplinary research collaborations in the field of HIV cure research.
• encouraging other stakeholders, international leaders and organizations to contribute to accelerating HIV cure research through their own initiatives and/or by endorsing this statement and supporting the alliance that the Advisory Board is building.

Board members, including co-chairs Professor Barré-Sinoussi and Dr. Whitescarver, have officially endorsed the statement.

Individuals and organisations wishing to sign the statement can do so by clicking here

Ends

Notes to Editors:

(1) For a complete list of Towards an HIV Cure Advisory Board and Working group members www.iasociety.org/Default.aspx?pageId=559

(2) Functional cure some HIV genetic material remains in the body, but the patient’s immune defence fully controls any viral rebound, allowing patients to be free of antiretroviral treatment; Sterilizing cure no HIV genetic material can be found in the body, HIV infection is eradicated. Given the nature of HIV - a retrovirus infecting the host immune system – and current knowledge and tools, a functional cure is more likely to be achieved.

About the signatories:

amfAR:

amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested nearly $325 million in its programs and has awarded grants to more than 2,000 research teams worldwide.

ANRS:

The Anrs (National Agency for Research on AIDS and Viral Hepatitis) is the leading organization for research on the HIV/AIDS and hepatitis epidemics in France, and a leader in the fight against these diseases in limited resource settings. In 2009, the Anrs had a budget of 44 million euros (62 million US dollars) from the French government, over 95% of which was allotted to research projects.

EATG:

EATG is a community organisation that promotes the interests of people living with HIV/AIDS. EATG’s mission is to achieve the fastest possible access to state of the art medical products, devices and diagnostic tests that prevent or treat HIV infection, and to improve the quality of life of people living with HIV/AIDS in Europe.

IAS:

The International AIDS Society (IAS) is the world's leading independent association of HIV professionals, with 16,000 members from 196 countries working at all levels of the global response to AIDS. Our members include researchers from all disciplines, clinicians, public health and community practitioners on the frontlines of the epidemic, as well as policy and programme planners. The IAS is the host of the IAS Conference on HIV Pathogenesis, Treatment and Prevention held in Rome July 17-20, 2011. The IAS is also the custodian of the biennial International AIDS Conference, which will be held in Washington D.C., USA, from 22 to 27 July 2012.

ITPC:

ITPC is the only international coalition of people living with HIV/AIDS and their supporters solely devoted to advocacy on HIV/AIDS treatment access. It is a broad coalition of people working in and for the community in their own countries and with strong expertise in HIV/AIDS treatment and related issues. As a community voice, it has been successful in communicating the concerns of people living with HIV/AIDS who need treatment to governments, United Nations agencies, pharmaceutical manufacturers, and other public and private bodies that influence the progress of the establishment, scale-up and sustainability of HIV/AIDS treatment programme.

NIH:

The U.S. National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, behavioral and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. F
or more information about NIH and its programs, visit www.nih.gov.

Sidaction:

Sidaction, a France-based NGO, is a diverse coalition of individuals and organizations from France and from developing countries. Dedicated to fundraising, advocacy, and technical assistance to fight HIV/AIDS in France and in 29 low and middle income countries, Sidaction raises private funds to promote cutting-edge scientific research and to improve access to prevention, care, treatment, and support programs.

TAG:

The Treatment Action Group is an independent AIDS research and policy think tank fighting for better treatment, a vaccine, and a cure for AIDS. TAG works to ensure that all people with hiv receive lifesaving treatment, care, and information. iasociety.org

Mayor Gray Releases Annual Report Showing Progress on Addressing HIV/AIDS, STDs, Hepatitis and TB in DC

Today, Mayor Vincent C. Gray and Department of Health (DOH) officials released the District of Columbia HIV/AIDS, Hepatitis, STD and TB Epidemiology Report 2010 Update.

"Our newest update on the state of the HIV epidemic gives new inspiration to our efforts as One City – government and community working together – to fight HIV/AIDS in the District of Columbia. We are getting people diagnosed earlier and into care and treatment faster for their health, thereby reducing the chances that others will get infected," said Mayor Gray. "I look forward to the recommendations of the Mayor’s Commission on HIV and AIDS to strengthen our response and do more to improve the health of District residents."

In line with the National HIV/AIDS Strategy, the Update highlights progress the District has made to reduce the burden of the disease on District residents:

Increasing Access to Care and Improving Health Outcomes

• More than 75% of persons in DC entered into care and treatment within three months of their HIV diagnosis. This is a steady increase from the 58% in 2005.
• Average CD4 count at diagnosis increased again from 352 in 2008 to 361 in 2009. Overall, there has been an increase of 71% from 211 in 2004.
• The number of persons testing late declined by nearly 10% -- from 53.3% to 44.0% -- in 2008.
• The proportion of persons progressing from HIV to AIDS decreased again to 24.2% in 2008, cut nearly in half from 47% in 2004.
• The number of deaths among persons with HIV/AIDS decreased by more than half, from 326 in 2005 to 153 in 2009.

Reducing New Cases

• In 2009, there were 755 new cases of HIV/AIDS and 16,721 persons are living with HIV/AIDS in the District of Columbia or 3.2% of all District residents.
• From 2008 to 2009, there was a leveling of the number of new chlamydia and gonorrhea cases, which holds promise for a slowing in new infections.
• DC made more progress toward its goal of TB elimination, with another decrease in cases from 54 in 2008 to 41 in 2009.

• DC made more progress toward its goal of TB elimination, with another decrease in cases from 54 in 2008 to 41 in 2009.

Health disparities remain a challenge in the District, with an overall disproportionate impact of HIV and STDs among African Americans. The Update shows new emerging disparities among other population groups. The proportion of new AIDS cases among older adults (ages 50 years old and older) has increased from 19% in 2005 to 26% in 2009. Older adults had the highest rates of late testing, at more than 70% -- compared to 44% among all ages. A greater proportion of Hispanics between 20 and 29 years of age were diagnosed with AIDS than whites and blacks. A higher proportion of Hispanics were late testers (64% compared to 44% among all racial groups). Adolescents (ages 15 to 19 years old) continue to comprise the largest proportion of chlamydia (40%) and gonorrhea (34%) cases. Women now represent a higher proportion of TB cases, increasing from 36% in 2005 to 59% in 2009.

Mayor Gray also released a new study on drug use and HIV, Injection Drug Use: IDUs and HIV Infection in DC. The study showed a high rate of HIV (13%) among active drug users. It also reported that one out of five study participants had shared needles with partners and three-quarters shared "works" (other items related to intravenous drug use, including cookers, cotton swabs and water), which can lead to HIV infection. Most of the study participants were older and had been using drugs for 30 years. In addition, more than 90% reported that they had been told they had hepatitis C. The study did highlight the success of needle-exchange programs in providing services to active drug users. The study recommends increasing the availability of free needles, more targeted outreach to younger and newer injection drug users and women, and enhanced efforts addressing co-infection of HIV and hepatitis C.

The District of Columbia, through DOH and in collaboration with other DC government agencies and community partners, has a strong record of accomplishment. DC continues to increase HIV testing, supporting 110,000 tests in 2010 -- nearly triple the number from 2006. New demonstration projects have started or are about to start for HIV testing in the Department of Motor Vehicles and in income-maintenance centers. Since 2007, DOH has doubled the number of residents receiving free HIV medications. DC distributed 4 million free condoms in 2010. DC reached 5,000 young people with free voluntary STD testing. In 2010, DC’s comprehensive needle-exchange programs removed 320,000 needles, enrolled about 1,300 new clients, provided HIV testing to 1,600 people and linked 241 to drug treatment.

Select the following links to upload and read the District of Columbia HIV/AIDS, Hepatitis, STD and TB Epidemiology Report 2010 Update* and Injection Drug Use: IDUs and HIV Infection in DC*.

Evidence Shows NTD Control Can Help in the Fight Against HIV/AIDS

There is a growing body of evidence revealing the connection between neglected tropical diseases (NTDs) and HIV/AIDS, prompting experts to call for greater integration of national NTD treatment programs with HIV/AIDS initiatives.

Emerging evidence and treatment recommendations are the subject of a new editorial entitled "Linking Global HIV/AIDS Treatments with National Programs for the Control and Elimination of the Neglected Tropical Diseases," published in the open access journal Public Library of Science Neglected Tropical Diseases (PLoS NTDs). In the article, authors Julie Noblick, MPH; Richard Skolnik, MPA; and Peter Hotez, MD, PhD review the links between NTDs and HIV/AIDS and propose ways to take advantage of the accumulating evidence that shows how HIV/AIDS can be affected by NTDs.

Geographically, areas of high NTD infection are often the same areas that have high prevalence rates of HIV/AIDS. Studies from the past twenty years have shown different ways that HIV/AIDS can be exacerbated by various NTD co-infections. For example, recent studies have shown that deworming has an association with decreased HIV viral loads and/or elevations in CD4 counts, and also that maternal helminth infections increase the risk of maternal-to-child HIV/AIDS transmission. "We are particularly concerned about the associations between female genital schistosomiasis, a common condition in sub-Saharan Africa, and a 3-4 fold increased risk for HIV/AIDS," said Dr. Peter Hotez, President of the Sabin Vaccine Institute.

Based on the evidence, the authors of the paper call for a variety of actions aimed at fighting HIV/AIDS through control of NTDs. They advocate integration of the delivery of anti-retroviral drugs with NTD control and elimination programs; research to monitor and evaluate the success of NTD and HIV/AIDS cross-treatment; and the promotion of integrated control and implementation of new strategies.

While the article focuses on the benefits to HIV/AIDS treatment by NTD control, the authors believe that the proposed actions will help reduce overall NTD rates as well. "Integrating programmatic control measures for HIV/AIDS and NTDs would be a mutually beneficial course of action," Ms. Noblick said. "Not only could we expect improved health outcomes for people living with HIV/AIDS, but working with established global HIV/AIDS prevention and treatment programs also creates an opportunity to both increase the scale of NTD control operations and to elevate the level of attention paid to these traditionally neglected maladies."

Ms. Noblick also expressed hope for expansion of these latest strategies beyond national levels. "Since the initiation of NTD control measures would be based on careful prevalence mapping," she stated, "it would be fair to say that progress will emerge on the regional level as well. Treating NTDs should become standard practice in HIV/AIDS care." (sciencedaily.com)

Amount of HIV in Genital Fluid Linked to Transmission

Findings shed light on virus' spread and may advance prevention efforts, researchers say

By Randy Dotinga

In a development that could enhance HIV-prevention research, a new study of heterosexual couples confirms that the risk of transmitting HIV rises with the level of the virus in semen and cervical fluid.

The finding -- that more virus translates to higher likelihood of transmission -- hasn't been proven to this extent before, said study lead author Dr. Jared M. Baeten of the University of Washington in Seattle.

"This confirms what we had thought about the biology of HIV," he said, "and it gives us new information about genital levels of HIV being particularly important, even independent of blood levels."

For the study, researchers obtained samples of genital fluid from 2,521 heterosexual couples living in seven African countries. Most were married and living together. At the start of the two-year study, one partner in each couple was infected with HIV, the AIDS-causing virus, and none was taking anti-HIV drugs.

Over the course of the study, published April 6 in the journal Science Translational Medicine, 78 partners became infected within the relationship.

The researchers compared cervical and semen fluid samples from partners who transmitted the virus with samples from men and women who didn't transmit the virus and found that the risk of HIV transmission approximately doubled with each specified HIV increase in genital fluids. (In a few cases, HIV transmission occurred without any sign of the virus in genital fluids, although it was in the blood.)

The results are "really useful for figuring out new research studies looking at new strategies," said Baeten, an assistant professor of global health and medicine. "You can develop strategies that reduce HIV levels only in the genital tract, not in the blood, like microbicides."

The study is useful for a couple of reasons, said Dr. Peter A. Anton, director of the Center for HIV Prevention Research at University of California Los Angeles, who co-wrote a commentary accompanying the study. Not only does it suggest a way of determining who is most likely to infect a partner, it also enables researchers to study those who didn't infect the people they had sex with.

This can help researchers better understand "the natural protections that the penis, the vagina and the rectum have that we want to make sure we preserve," he said. The study "is highlighting what we need to look at going forward," he added.

Still, the study, which Anton said was "really well done," has some limitations. It only looked at heterosexual couples and not at people at higher risk of becoming infected with HIV, such as sex-trade workers and gay men.

And the study doesn't examine how often HIV-positive people with no detectable virus in their blood transmit the disease to their partners. Anti-HIV drugs can often reduce the level of HIV in blood to zero, while the virus hides in other parts of the body.

Worldwide, more than 7,000 new HIV infections are diagnosed daily, according to background information in Anton's commentary. In the big picture, these new findings can only do so much to curb the rate of HIV infection, he said.

Noting that many HIV-positive people are unaware they have the disease, Anton said, "The biggest issue in transmission is that many people don't know their status."businessweek.com

More information

For more about HIV/AIDS, visit the U.S. National Library of Medicine.

SOURCES: Jared M. Baeten, M.D., Ph.D., University of Washington, Seattle; Peter A. Anton, M.D., professor of medicine and director, University of California Los Angeles, Center for Prevention Research, David Geffen School of Medicine, Los Angeles; April 6, 2011, Science Translational Medicine

HIV vaccine technologists edge nearer to effective designs

A vaccine symposium held at the sixth International AIDS Society conference in Rome heard how designers are slowly developing HIV vaccines designed to overcome problems that had prevented the generation of an effective vaccine in the past.

Barbara Ensoli of the Italian Istituto Superiore di Sanitá outlined the barriers to success in a field which has seen only three large efficacy trials in humans in the last 15 years.

Vaccine trials past and present

In 2003, a trial of a first-generation vaccine, AIDSVAX, a simple vaccine made from HIV proteins and designed to generate antibodies to the virus, failed to demonstrate efficacy. The problem with HIV is that the antibodies that are generated naturally (and also in response to a conventional vaccine) do not contain the virus’s enormous capacity to proliferate and mutate its way round the antibody response.

In 2007 STEP, a trial of a more complex vaccine consisting of HIV components encased in the shell of another virus (a ‘vector’, designed to take it into cells), also failed. This second-generation vaccine was designed to simulate the other branch of the immune system and generate cells that destroy HIV-infected cells. It too failed, and there is some evidence that it may have made some people who already had immunity to the viral shell more vulnerable to HIV.

In 2009 RV144, a trial using a composite vaccine of a ‘prime’ dose of a vector vaccine plus a ‘boost’ dose of the original AIDSVAX finally produced a weakly positive result. It reduced HIV infections by 31% compared with placebo, though it was not effective against people more likely to have had multiple HIV exposures and protection faded with time. This reinvigorated the search for a vaccine, though Barbara Ensoli commented that it was still unclear how the vaccine generated an immune response.

Because of this, no large efficacy trials are currently being conducted until developers are more confident that they have something that generates an effective response.

Barbara Ensoli said that there were currently about 50 trials of 42 vaccine candidates taking place worldwide, though 40 of these trials were small phase 1 safety trials. There were 22 trials of vaccines using viral vectors (plus or minus other boost doses), ten using artificially-generated DNA, three using HIV proteins, two using replicating viral vectors which spread the vaccine from cell to cell (an approach with some safety concerns), and a handful of miscellaneous candidates. Twenty-eight used a multiple-dose prime-boost design.

Promising results – a review

The most promising results in recent years have been seen in animal studies, though the STEP vaccine is an example of one that produced positive results in some animal studies but failed in humans.

A vaccine consisting of the HIV cell-entry protein gp41 inside an artificial vector, dosed twice as an intramuscular infection then twice as a nasal spray, protected five monkeys from vaginal challenge with 13 doses of the monkey/human spliced virus SHIV (Barnett 2008). The interesting thing about this vaccine was that it did not produce antibodies to SHIV in the blood, but only in the mucous membranes lining the vagina – a potential ‘vaccine microbicide’.

A vaccine reported on aidsmap consisted of SIV (monkey HIV) components packaged inside an actively replicating vector consisting of the shell of the common CMV virus (Hansen). This vaccine, given to 26 monkeys, did not protect them from SIV infection but in 13 of the monkeys resulted in an infection characterised by a low viral load – which gradually turned into a situation in which there was no detectable virus in their bodies. This, if achieved in humans, would essentially be a ‘vaccine cure’. But we need to understand why only half of the monkeys responded and why – and actively replicating vaccines are potentially dangerous.

A vaccine consisting of the two HIV components tat and env inside another actively-replicating viral vector produced a similar effect, preserving the CD4 count and bringing the viral load down to undetectable in five monkeys, and down by a factor of 10,000 in the other three out of eight infected with a highly pathogenic variety of SHIV (Demberg). By comparison, monkeys receiving placebo maintained viral loads of a million and their CD4 count crashed to 10 cells/mm³ within two months. A phase 1 trial of a human version of this vaccine in 50 people is planned.

How to generate antibodies

The most elusive but potentially effective goal in HIV vaccine development is to design a vaccine that would produce what are called broadly neutralising antibodies (BnAbs). These are antibodies that neutralise a wide variety of different viral strains – in contrast with most anti-HIV antibodies, whether vaccine-generated or natural, which are too specific to types the virus soon mutates away from. Broadly neutralising antibodies have been isolated from the blood of some people who control HIV naturally and even reproduced in the laboratory, but how to design a vaccine that induces the body to generate then has been a huge challenge.

Susan Zoller-Pasner of the New York University School of Medicine described how her team was developing vaccines by analysing which parts of the HIV surface protein, env, were ‘highly conserved’. These are parts of the protein that cannot mutate without affecting viral viability. They were developing vaccines based on highly-conserved sequences from two of the prominent ‘bulges’ on the surface of the env protein, the V3 and V2 loops. The ‘V’ in these terms stand for ‘variable’ as they are amongst the areas of HIV most quick to mutate away from immune surveillance, but in fact there are sequences that are common to nearly all strains and should in theory generate BnAbs. An antibody response to the V2 loop appears to be part of what gave the RV144 vaccine its efficacy.

So far they have managed to generate test-tube responses that protect against 50% of a panel of viruses susceptible to neutralisation, they’ve yet to succeed against more evolved viruses that shrug off antibodies. The important thing, however, is that Zoller-Pasner’s team has found a way to rationally design vaccines that may generate BnAbs, rather than rely on serendipity.

In connection with this work, Susan Barnett, senior scientist at the drug company Novartis, described further details of the intramuscular and intranasal vaccine described above, which induced a protective mucosal response in monkeys. This work has led on to developing HIV protein-based vaccines which are now going to be used as the ‘boost’ for in the vaccine intended to be used in the follow-on to the RV144 trial.

The company are going to produce 50,000 of an artificially-generated composite viral envelope protein isolated from 22 different subtypes of HIV to use in the follow-on vaccine.

DNA vaccines

David Weiner of the University of Pennsylvania described the latest steps in the development of a different kind of vaccine – DNA vaccines. These vaccines do not employ any naturally occurring component, however adapted, but consist of ring-shaped packages of artificial sequences of DNA. DNA vaccines are relatively simple to manufacture but so far have had poor immunogenicity in humans; it is difficult to get cells to mount a string reaction to the DNA and difficult to get the DNA into the cells in the first place. He described how his team is developing technologies to increase the amount of DNA produced, using immune-stimulating chemicals to provoke cells into reacting to the DNA, and even using electrical stimulation of the same type used in in vitro fertilisation to ensure the vaccine becomes incorporated into cells that can then produce anti-HIV antibodies.

A number of phase 1 studies of DNA vaccines had produced long-lasting immune responses in humans – partly because there is no viral vector that the immune system can ‘get used’ to – and more studies of what will hopefully prove to be increasingly potent DNA vaccines are planned. (aidsmap.com)

References

Ensoli B Preventative and therapeutic HIV vaccines: where we stand now and what we foresee. Sixth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Rome, symposium presentation TUSY0102, 2011.

Zoller-Pasner SB Env-based vaccines. Sixth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Rome, symposium presentation TUSY0103, 2011.

Barnett SW Antibody-mediated vaccines protection against HIV: the critical path to next phase of proof of concept HIV vaccine trials. Sixth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Rome, symposium presentation TUSY0104, 2011.

Weiner D DNA vaccines. Sixth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Rome, symposium presentation TUSY0105, 2011.

Barnett SW et al. Protection of macaques against vaginal SHIV challenge by systemic or mucosal and systemic vaccinations with HIV-envelope. AIDS 22(3):339-48, 2008.

Hansen SG et al. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature, early online publication, doi:10.1038/nature10003, May 2011.

Demberg T et al. A Replication-Competent Adenovirus-Human Immunodeficiency Virus (Ad-HIV) tat and Ad-HIV env Priming/Tat and Envelope Protein Boosting Regimen Elicits Enhanced Protective Efficacy against Simian/Human Immunodeficiency Virus SHIV89.6P Challenge in Rhesus Macaques. Journal of Virology 81(7):3414-3427, 2007.

View the details of, and some presentations from, the vaccine symposium on the conference website

Scientists Use Live Bacteria to Fight HIV

A novel topical microbicide could provide a “live bioshield” to protect women against HIV

Scientists at Osel Inc. and the National Cancer Institute (NCI) have developed a new way to prevent HIV infection by genetically enhancing the ability of naturally occurring vaginal bacteria to block viral transmission. Bioengineered bacteria introduced into the vaginal cavity of macaques—a commonly used experimental primate— reduced the transmission of simian HIV (SHIV) by nearly two thirds.

The novel approach takes advantage of lactobacilli, which are beneficial bacteria that play an important role in vaginal health and help protect women against a variety of sexually transmitted infections. The Osel team engineered the common strain Lactobacillus jensenii to pump out therapeutic quantities of the HIV inhibitor cyanovirin-N, which is a protein originally discovered by NCI scientists screening natural substances for antiviral activity.

In a study just published online in advance of publication in the Nature journal Mucosal Immunology, the team showed that vaginal administration of Lactobacillus expressing CV-N to rhesus macaques could reduce the transmission of SHIV (a virus developed for research that combines critical components of HIV with the ability to infect monkeys) by 63 percent after repeated challenges with virus. A reduction in the viral load was also seen in infected macaques that received the Lactobacillus product, called MucoCept.

“We were excited to see this reduced rate of transmission in the macaque model,” said Dr. Laurel Lagenaur, the leader of the Osel team. “Because this Lactobacillus strain is likely to colonize women at a higher rate than macaques, we could see an even bigger reduction in the rate of HIV infection when this product is tested in women. The lactobacilli themselves are also beneficial to vaginal health.”

The scientists believe their approach could provide an affordable and durable method for reducing the continuing worldwide epidemic of HIV, which currently infects more than two million people every year. A major advantage of the novel approach of a live bioshield such as MucoCept is that it would provide sustained protection; women would not need to apply it frequently or immediately before sexual intercourse.

“This approach has potential as a novel ‘natural’ approach to prevent HIV,” said Dr. Salim S. Abdool Karim of Centre for the AIDS Programme of Research In South Africa (CAPRISA) at the University of KwaZulu-Natal, who co-led a study establishing proof-of-concept for microbicides using tenofovir gel. “Data in women are eagerly awaited.” Dr. Karim was not involved in the current study.

"It's exciting to be working on a prevention for HIV that people could actually afford,” said Dr. Dean H. Hamer, chief of the Gene Structure and Regulation Section at the NCI and senior author of the study. “While there is much interest in the recent results with PrEP [pre-exposure prophylaxis], it's important to realize that the cost of the required antiretroviral drugs is prohibitive in the real world.”

The engineered lactobacilli in MucoCept constitute an ideal microbicide because the organisms naturally colonize the vagina—unlike the strains found in dairy products or food supplements— and they continuously produce the HIV inhibitor. Upon administration of MucoCept as a vaginal suppository, these bacteria can take up residence and potentially protect the user for weeks at a time.

The Osel group is hoping to start human trials of MucoCept within the next several years following completion of product development and safety testing.

These studies were funded by the National Institutes of Health, under federal grants from NIAID and DMID. The MucoCept HIV project has also been supported by CONRAD-GMP, IPM, USAID, and the Bill and Melinda Gates Foundation. (positivelypositive.ca)

REFERENCE: Mucosal Immunology; Advanced Online Publication July 6, 2011
http://www.nature.com/mi/journal/vaop/ncurrent/full/mi201130a.html

About Osel, Inc.
Osel Inc. is a biopharmaceutical company with a proprietary technology platform to develop next-generation probiotics as pharmaceutical products. In addition to MucoCept, Osel is developing an unmodified Lactobacillus crispatus product, LACTIN-V, as a natural antimicrobialsparing intervention to prevent several common urogenital infections in women, including recurrent urinary tract infections (RUTI) and bacterial vaginosis. LACTIN-V was recently shown to reduce the rate of recurrent urinary tract infection in women by about one-half (Stapleton et al., Clin Infect Dis. 52:1212-1217, May 2011), which compares favorably to antimicrobial prophylaxis, the current standard of care for RUTI. MIYA-BM, containing the novel probiotic bacterium, Clostridium butyricum MIYAIRI 588, is an oral product in clinical development for the prevention of antimicrobial-associated diarrhea and Clostridium difficile infection. For further information, visit www.oselinc.com.

Media Contact
Dr. Laurel Lagenaur—Telephone: 650-964-1420—e-mail: llagenaur@oselinc.com

SOUTH AFRICA: Prisons expand HIV services

Obtaining HIV treatment in jail is becoming easier as about 9 percent of South African prisons now offer antiretroviral (ARV) drugs in-house.

Leeuwkop Prison, north of Johannesburg, where minimum-security prisoners tend horses and cattle and raise crops, is the latest jail to launch its own antiretroviral clinic - one of 22 such in-house HIV treatment centres, according to the Department of Correctional Services’ 2010 annual report.


The prison has also begun providing inmates with condoms, as have others, including Johannesburg Prison in the city’s largest township, Soweto, said Gauteng correctional services spokesperson Simphiwe Kondleka.

According to South Africa’s Institute for Security Studies, the country’s 240 correctional facilities house 160,000 prisoners - a third more than they were originally designed for.

At Leeuwkop, 13 percent of the 4,500 prison population are HIV-positive. Although the HIV prevalence among Leeuwkop’s prisoners is not far off South Africa’s national HIV prevalence rate of about 18 percent, limited studies among some of the country’s prisons have found HIV prevalence rates of as high as 45 percent.


“Correctional services are a microcosm of the country; what we see in our country will be found in our facilities – even disease patterns,” noted Nontsikelelo Jolingana, chief deputy commissioner (CDC) of development and care for the Department of Corrections.

According to Jolingana, the department is also working to accredit at least three more facilities in Gauteng province.

Changing of the guard

Just five years ago, South African courts ordered the government to take steps to provide all prisoners with access to treatment. The judgment followed a court case involving 13 HIV-positive inmates and the AIDS lobby group, the Treatment Action Campaign.

Before the Leeuwkop ARV clinic was launched, the prison’s more than 300 HIV-positive inmates on treatment had to be shuttled to an inner-city Johannesburg health facility, posing major logistic and security problems for correctional services.

“The prison’s clinic benefits the whole process – it increases access to treatment and care, and compliance with treatment for prisoners,” said Gloria Lekubu, regional HIV and AIDS coordinator for Correctional Services in Gauteng.

Lekubu added that not only would the clinic mean fewer security risks but also that the Department of Correctional Services would save money it previously had to pay the Department of Health for treating prisoners in public clinics.

The Department of Correctional Services dedicates about 10 percent of its annual budget to prisoner care, which includes access to medical services.

For HIV-positive inmates such as Prince, it also takes a lot of stress out of treatment. “In South Africa, there’s an overcrowding of prisoners, which makes it difficult for us to get treatment,” he told IRIN/PlusNews. “In a day, there may be 30 to 40 of us who need to go to the clinic, and there’s a shortage of [correctional staff].

“The new clinic means I will be counselled in time, I will see a doctor in time and there won’t be a shortage of ARVs.”
Balancing act

South African health NGO, the Aurum Institute, helped finance and design the clinic, said Gillian Gresak, deputy director of HIV and Tuberculosis treatment, balancing security concerns and infection-control measures.

According to the World Health Organization’s Stop TB department, overcrowding, poor nutrition, and high alcohol and drug use in prisons, make prisoners very susceptible to developing active TB, with the rate of new TB infections on average 23 times higher than in the general population.

Inadequate TB control measures are another risk factor. Typically, many health facilities keep windows open to prevent TB infection, which can be spread by coughing, but in many prisons, windows were not designed to open, Gresak told IRIN/PlusNews.

Another infection control measure, the use of ultraviolet lights indoors, was also ruled out as the lights could be dissembled and used as weapons, added Aurum operations manager Joyce Lethoba.

Ultraviolet lighting has been shown to reduce TB transmission by up to 70 percent in hospital wards by killing the bacteria that causes TB.

Instead, Aurum designed outdoor waiting rooms much like those pioneered by Médecins Sans Frontières in its HIV/TB clinics in South Africa’s Western Cape. With a separate area to collect potentially infectious sputum samples, the waiting rooms allow for maximum ventilation with minimum security risks, Lethoba added.

Aurum has been in talks with the Department of Correctional Service to support the establishment of future prison clinics in the province. (plusnews.org)

Early initiation of HIV therapy would save money, lives of South Africans

Model compares outcome of following WHO recommendations with outcome from current policy

If the South African government followed a recent recommendation by the World Health Organization to start antiretroviral therapy (ART) for HIV-infected residents earlier in the progress of the disease, the policy shift would start saving the country money after 16 years and would extend thousands of lives for dozens of years, according to a new study.

In 2009, the WHO recommended that people start ART when a key measure of immune system strength, the CD4+ cell counts, reaches a concentration of 350 per microliter of blood. South Africa has instead decided to stick with the old standard of waiting until only 200 cells per microliter remain, reflecting a more compromised immune system.

"South Africa, the country with the most people living with HIV/AIDS in the world, has not yet adopted the WHO treatment initiation criteria," said Mark Lurie, a Brown University epidemiology professor and senior author of the study published online July 20 in PLoS One. "We used a mathematical model to predict the impact of adopting the new WHO guidelines on HIV prevalence, incidence, and cost. We found that changing the treatment guidelines would have a profound impact on HIV incidence. It would require, over five years, an additional 7 percent investment, resulting in 28 percent more patients receiving HIV treatment. After 16 years, the cumulative net costs reach a break even point."

In addition, the models developed by Lurie's team show South Africa saving more than 120,000 life-years by 2040. Life-years are determined by multiplying the number of people who will still be alive by the number of years of extra longevity.

The reason why the higher up-front investment in ART ultimately would save South Africa money and lives, the authors wrote, is because more aggressive ART treatment would curb the epidemic's spread. Reduced infectivity from the drugs would outweigh the longer period of time in which HIV-infected people would be alive and therefore able to spread the virus.

"While initial costs of adopting the new guidelines will be greater because of the increased number of people now eligible for treatment, in the long run costs would be saved because of the reduced number of new infections," they wrote.

The researchers tested and refined their model by comparing it with actual data from the Hlabisa Treatment and Care Programme, where ART was rolled out in the South African province in 2004, and other data from the Africa Centre for Health and Population Studies, a collaborator in the study. The model accurately predicted recent HIV prevalence and other epidemiological characteristics. They then used it, along with assumptions based on theirs and others' research, to simulate the economics and demographics of the country's future epidemic, comparing what would happen if people received treatment according to the WHO or according to current South African policy.

"Our paper provides further evidence that starting treatment earlier in generalized epidemics like South Africa simply makes sense," Lurie said.

Source: Brown University

Amount of HIV in Genital Fluid Linked to Transmission

Findings shed light on virus' spread and may advance prevention efforts, researchers say

By Randy Dotinga

In a development that could enhance HIV-prevention research, a new study of heterosexual couples confirms that the risk of transmitting HIV rises with the level of the virus in semen and cervical fluid.

The finding -- that more virus translates to higher likelihood of transmission -- hasn't been proven to this extent before, said study lead author Dr. Jared M. Baeten of the University of Washington in Seattle.

"This confirms what we had thought about the biology of HIV," he said, "and it gives us new information about genital levels of HIV being particularly important, even independent of blood levels."

For the study, researchers obtained samples of genital fluid from 2,521 heterosexual couples living in seven African countries. Most were married and living together. At the start of the two-year study, one partner in each couple was infected with HIV, the AIDS-causing virus, and none was taking anti-HIV drugs.

Over the course of the study, published April 6 in the journal Science Translational Medicine, 78 partners became infected within the relationship.

The researchers compared cervical and semen fluid samples from partners who transmitted the virus with samples from men and women who didn't transmit the virus and found that the risk of HIV transmission approximately doubled with each specified HIV increase in genital fluids. (In a few cases, HIV transmission occurred without any sign of the virus in genital fluids, although it was in the blood.)

The results are "really useful for figuring out new research studies looking at new strategies," said Baeten, an assistant professor of global health and medicine. "You can develop strategies that reduce HIV levels only in the genital tract, not in the blood, like microbicides."

The study is useful for a couple of reasons, said Dr. Peter A. Anton, director of the Center for HIV Prevention Research at University of California Los Angeles, who co-wrote a commentary accompanying the study. Not only does it suggest a way of determining who is most likely to infect a partner, it also enables researchers to study those who didn't infect the people they had sex with.

This can help researchers better understand "the natural protections that the penis, the vagina and the rectum have that we want to make sure we preserve," he said. The study "is highlighting what we need to look at going forward," he added.

Still, the study, which Anton said was "really well done," has some limitations. It only looked at heterosexual couples and not at people at higher risk of becoming infected with HIV, such as sex-trade workers and gay men.

And the study doesn't examine how often HIV-positive people with no detectable virus in their blood transmit the disease to their partners. Anti-HIV drugs can often reduce the level of HIV in blood to zero, while the virus hides in other parts of the body.

Worldwide, more than 7,000 new HIV infections are diagnosed daily, according to background information in Anton's commentary. In the big picture, these new findings can only do so much to curb the rate of HIV infection, he said.

Noting that many HIV-positive people are unaware they have the disease, Anton said, "The biggest issue in transmission is that many people don't know their status."

More information

For more about HIV/AIDS, visit the U.S. National Library of Medicine.

(businessweek.com)

SOURCES: Jared M. Baeten, M.D., Ph.D., University of Washington, Seattle; Peter A. Anton, M.D., professor of medicine and director, University of California Los Angeles, Center for Prevention Research, David Geffen School of Medicine, Los Angeles; April 6, 2011, Science Translational Medicine

The 'pariahs' who tamed AIDS

This World AIDS Day, some 30 years after the epidemic began, we should recognize how the hard work of thousands of dedicated scientists transformed the most dreaded disease of the late 20th century into a chronic, manageable condition.

AIDS has been tamed in the Western world — perhaps the greatest triumph of the pharmaceutical industry.

Back in 1994, the disease had reached an awful nadir. The number of US deaths from AIDS reached 41,699 that year, a new high. With no vaccines or effective drugs available, the death rate was 100 percent.

Just two years later, the cover of Newsweek asked if we were seeing "The End of AIDS?" The number of deaths that year was below 20,000 and falling. This number has stabilized and is now about 18,000 a year.

And it was largely due to the much-maligned drug companies, waging a campaign that is arguably among the most impressive in medical history in its scope, scientific sophistication and outcome.

Behind the scenes, pharmacologists worked feverishly to uncover the secrets of HIV and look for potentially helpful therapies. Using state-of-the-art technologies in drug design, virology and biotechnology, the industry delivered a revolutionary series of novel therapies that not only halted the disease, but also actually reversed it.

In 1987, we had only one specific AIDS therapy — AZT, an old drug that was marginally effective at best. But in 1995, Hoffman-La Roche (now Roche) received FDA approval for a drug called saquinavir, the first member of a new class of drugs called protease inhibitors (PIs). The PIs attacked HIV by a completely different mechanism than AZT — making possible the use of "AIDS cocktails," in which two or more drugs are given together. Within 10 years, nine more PIs were approved, as well as eight other new AIDS drugs.

These drugs were the end-result of painstaking research. The industry average is to get just one new, marketed drug out of every 5,000 to 10,000 new chemical compounds. A good chemist will synthesize only about 50 such compounds a year.

These figures only hint at the degree of difficulty involved in discovering a new drug and the number of people required to do the research. The extent of the manpower devoted to AIDS research during the first two decades of the disease was mind-boggling.

Yet we now have 22 different AIDS drugs in seven distinct classes, with each class using a different mode of action against HIV. Some are meant to replace older, more toxic drugs; some just work better and some function to "salvage" patients for whom conventional therapy has failed.

Among the most dramatic developments is the decreased pill burden. Fifteen years ago, AIDS patients had to take 30 to 40 pills a day. But in 2006 collaboration between Gilead and Bristol-Meyers Squibb yielded a single, life-saving pill called Atripla, which is taken just once a day.

Drug companies are often portrayed as "evil" or "greedy," but they actually make very little money on AIDS drugs, as do the scientists who work for them. The big payoff was for the patients: Hospitalization for AIDS is drastically decreased, and the projected life span of patients receiving modern AIDS treatments now ranges from 63 (in the United States) to 77.7 years in Germany (compared to 78.1 years for those not infected). This kind of life expectancy would have been considered science fiction a decade ago.

Although universities and government made significant contributions, the campaign against HIV was waged primarily by the pharmaceutical industry -- the only one with the knowledge and resources to develop new drugs.

Never before has a virulent, fatal disease been so rapidly brought to heel. Instead of the usual drug-company bashing, today calls for at least a quiet "Thanks." (New York Post )

Josh Bloom worked in the pharmaceutical industry for more than two decades before joining the American Council on Science and Health in September as the group's di rector of public health.

New Trends In HIV Cure Research

Researchers speaking on the final day of the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011) focused on the growing interest in the scientific path to an HIV Cure. Discussions around an HIV cure have been growing over the past 12 months and are now gaining momentum with the establishment of an International AIDS Society (IAS) convened working group concentrating its initial efforts on establishing a global scientific strategy. A number of abstracts have featured research on a cure at the conference in Rome, which has been attended by over 5,000 researchers, clinicians and community leaders since Sunday.

"Fifteen years ago, even the most optimistic members of the scientific community were silent about the prospect of an HIV cure or vaccine," said IAS 2011 International Chair and IAS President, Elly Katabira. "Today, there is a reemergence of hope that the long-term remission of an infected individual is a realistic objective. The IAS is proud to be leading the coordination of the research effort and we look forward to the unveiling of the global scientific strategy at the XIX International AIDS Conference (AIDS 2012) in Washington next year."

Researchers also highlighted the need to scale up programmes that could more effectively address both the issues of injecting drug use linked HIV transmission and the still unacceptably high mortality rates amongst pregnant women and young children in sub-Saharan Africa and Southeast Asia.

"While these may be scientifically exciting times we just cannot afford to take our eyes off the huge gaps that still remain in the roll-out of effective prevention and treatment programmes in many countries," said Stefano Vella , IAS 2011 Local Co-Chair and Research Director at the Istituto Superiore di Sanità (ISS). "There needs to be more solid and courageous leadership in the efforts to reduce HIV infection amongst injecting drug users. For too long this vulnerable group has been left at the margins of HIV prevention programmes, and that approach is simply no longer sustainable.

"Similarly, we are never going to reach the Millennium Development Goals on maternal and child health as long as nations, international donors and agencies do not step up to the mark. Yes, there have been marked improvements over the past decade but there are still too any women and children needlessly dying. Care, prevention and treatment need to be scaled up in many developing countries and it needs to start happening now."

The final Plenary Session united three fields of research that are each calling for a scale up of commitment and resources to more effectively drive policy implementation:

Ending HIV Transmission in Drug Users by 2015:

Nora Volkow (United States), Director, National Institute on Drug Abuse (NIDA), remarked in her plenary speech that although injecting drug use is the most commonly recognized drug use related vector for transmission of HIV, non-injecting drug use can also increase the likelihood of HIV transmission through intoxication that alters judgment and prompts greater risk taking. Drug use also affects the course of the infection by damaging the immune system (e.g., opiates, alcohol), through drug interactions with HAART (e.g., alcohol), or through compromised compliance with HIV treatment regimes, all of which can worsen clinical outcomes.
Access to comprehensive interventions including drug abuse treatment, needle exchange programmes (NEP), and community outreach are effective HIV prevention strategies for drug users. Research shows that proactively seeking out drug users to test them for HIV and engaging them in both drug use and HAART treatment (for those who test positive) can improve patient outcomes and prevent HIV transmission and incidence at population level.

Caring for Mothers and Children: Towards the Millennium Development Goals

In her plenary remarks, Philippa Musoke (Uganda), of the Department of Pediatrics and Child Health, Makerere University, argued that although progress had been made in reducing maternal and child mortality in most regions of the world, in most countries this improvement remains inadequate to meet the Millennium Development Goals (MDGs) 4 and 5 by 2015.

In sub-Saharan Africa, HIV infection contributes significantly to the morbidity and mortality of women and children. Without antiretroviral therapy, HIV-infected children have a very high mortality with 50 per cent dying by two years of age. Over the last decade the reductions in maternal and child mortality in sub-Saharan Africa and Southeast Asia have been related to implementation of prevention of mother-to-child HIV transmission (PMTCT) programmes.

Further scale-up of PMTCT programmes and coverage is critical to improving the lives of infected women and children. In addition, education of the girl child, empowering women to be economically independent and the provision of family planning services are critical to improving maternal health and survival. Strengthening national Maternal, Newborn and Child Health (MNCH) programmes for the provision of antenatal and postnatal care for all pregnant women, increased immunization coverage rates, exclusive breastfeeding and nutritional support for all infants remains a priority.

Towards an HIV Cure

Eric Verdin (Belgium), Professor of Medicine, University of California, concluded the morning plenary by stating that the eradication of HIV would require the elimination of persistent HIV during suppressive therapy.

The source of persistent HIV in patients on HAART suppressive therapy is a current topic of debate. Recent studies of treatment intensification have showed persistent viremia may arise from several different sources, including latent HIV in resting CD4 T cells.

HIV eradication strategies currently focus on small molecules that activate viral transcription in CD4+ T cells. These include inhibitors of histone deacetylases and nuclear factor kappa B activators. medicalnewstoday.com
Source:
Lindsey Rodger
International AIDS Society

Atazanavir safe and effective for HIV/HCV patients with cirrhosis

Michael Carter

Atazanavir (Reyataz) is a safe and effective option for HIV-positive patients who are co-infected with hepatitis C virus (HCV) and who have liver cirrhosis, investigators report in an online advance publication in the journal AIDS.

“Our study demonstrated the safety and adequate tolerance of atazanavir-based regimens in HCV-HIV-1 coinfected patients, even when used in the worst clinical situations”, comment the investigators, adding “there were no episodes of hepatoxicity, and virological and immunological efficacy was adequate.”

Many patients with HIV are co-infected with hepatitis C, and liver disease is an important cause of illness and death in these patients.

The protease inhibitor atazanavir has been shown to be effective when taken as part of antiretroviral therapy in both treatment-naive and treatment-experienced individuals. The usual dose of the drug is 300mg boosted by 100mg of ritonavir (Norvir) once daily. However, the drug can cause bilirubin levels to increase, and in some patients this leads to the development of non-dangerous jaundice.

There is little information about the safety and efficacy of atazanavir when used as a component of antiretroviral therapy for co-infected patients with advanced liver disease.

Investigators in Madrid therefore performed a retrospective study involving 34 co-infected patients with cirrhosis. The patients were followed for a year and the impact of atazanavir treatment on their liver function, viral load and CD4 cell count was monitored.

Most of the patients (80%) were male, and their mean age was 43.

A quarter of patients had a Child-Pugh class B or C score – which is associated with a poorer prognosis – and 21% of patients had decompensated cirrhosis.

All but one of the patients were treatment experienced and median baseline CD4 cell count was 238 cells/mm³. On entry to the study, 41% of individuals had an undetectable viral load.

Three-quarters of patients were treated with atazanavir boosted by ritonavir. The investigators suggest that nearly a quarter of patients were treated with unboosted atazanavir because their doctors feared intolerance of ritonavir.

The patients were monitored at three-monthly intervals for one year. The median duration of atazanavir therapy was 437 days and a total of 551 person-months of treatment were available for analysis.

Therapy was well tolerated, and only six individuals stopped taking atazanavir. Two patients with advanced cirrhosis died because of gastrointestinal bleeding.

Bilirubin increased by a mean of 0.72 mg/dl. The investigators described this increase as “surprisingly mild” and only 9% of patients developed jaundice. However, higher mean increases were recorded in individuals with Child-Pugh class B or C (mean 1.03 mg/dl). No new cases of hepatic decompensation were observed during the study.

The median MELD (Model for End-stage Liver Disease) stage increased from 10.6 to 11.9 at month twelve, which was significant (p = 0.02). However, the investigators note, “no patient changed the pretreatment situation (transplant allocation) after atazanavir introduction.”

After a year of therapy with atazanavir 79% of patients had an undetectable viral load and 80% had a CD4 cell count above 200 cells/mm³.

These outcomes lead the investigators to write “the usual dose of atazanavir seems to be adequate with good tolerance and efficacy.”

They conclude, “our study emphasizes the safety of atazanavir-based regimens in HCV-HIV-1 co-infected patients with cirrohsis…boosted or unboosted atazanavir could be considered a safe option in patients with cirrhosis in the clinical setting.” (aidsmap.കോം)

Reference

Rodriguez JM et al. The use of atazanavir in HIV infected patients with liver cirrhosis: lack of hepatotoxicity and no significant changes in bilirubin values of MELD score. AIDS 25: online edition, DOI: 10. 1097/QAD.0b01333283466f85, 2011

After 30 years, war on AIDS at 'moment of truth'

By Boris Bachorz (AFP)

NAIROBI — With the war on AIDS nearing its 30th anniversary, the UN on Thursday declared "a moment of truth" had come for new strategies to address the campaign's failures and brake costs that were now unsustainable.

"We have a unique opportunity to take stock of the progress and to critically and honestly assess the barriers that keep us shackled to a reality in which the epidemic continues to outpace the response," UN Secretary General Ban Ki-moon said in a report issued in Nairobi.

The 30th anniversary of AIDS is generally recognised as June 5.

It marks the date in 1981 when US epidemiologists reported on mysterious cases of fatal pneumonia among young gays. In 1983, French scientists pinned the cause on a new pathogen, the human immunodeficiency virus (HIV), which destroyed the immune system in heterosexuals and homosexuals alike.

"AIDS has claimed more than 25 million lives and more than 60 million people have become infected with HIV," Ban said in his progress report on the disease.

"Each day, more than 7,000 people are newly infected with the virus, including 1,000 children. No country has escaped the devastation of this truly global epidemic."

Ban said there had been many pluses over the past three decades, notably getting AIDS drugs to more than six million badly-infected people in poor countries.

But at this point, "the HIV response faces a moment of truth," he said.

Among the problems he highlighted was "a wholly unsustainable" rise in costs and a flatlining in resources, which have remained at under 16 billion dollars a year since late 2007.

More and more people are becoming infected, which means they will eventually join the numbers of patients who eventually need AIDS drugs, a treatment that has to be taken daily for the rest of one's life.

Ban spelt out ways by which countries could meet a target set last December 1 on World AIDS Day, of "zero new infections, zero discrimination and zero AIDS-related deaths" by 2015.

"Of course progress has been frustratingly taking a long time," he admitted at a press conference.

But, he added, "I am sure that by 2015 we will have a much greater progress in our common efforts in fighting against HIV."

He called on member states to carry out a "prevention revolution," in which member states would commit to reducing sexual transmission of HIV by 50 percent by 2015.

Approaches should include new methods that have been validated by science, such as the use of male circumcision, which reduces the risk of female-to-male infection by around 60 percent. In the past two years, more than 200,000 men have been circumcised in 13 countries with a high prevalence of the HIV.

In the pipeline are promising trials involving a vaginal microbicide, to help women fend off HIV infection, and the use of AIDS drugs as a prevention against the virus, rather than treatment for it.

Ban also urged countries to ensure that all 13 million people who will need drugs by 2015 have access to them.

But a massive effort will be needed to brake the upward trajectory in costs, using smart but effective methods, he said.

The report called for a 50-percent reduction in fatalities from tuberculosis, the leading cause of death among people with HIV, and for the elimination of the transmission of HIV from infected mothers to their babies.

"It is a grave global injustice that 370,000 newborns contract HIV in low- and middle-income countries each year, while vertical transmission has been virtually eliminated in high-income countries," Ban said.

The UN chief also called for a bonfire of the regulations that targeted people with HIV. He urged member states to commit to reducing by half the number of countries with HIV-related restrictions on entry, stay and residence.

The appeal is the third major initiative on AIDS to be launched by the United Nations in the past decade.

The two previous ones were the "Three by Five" goal of providing three million people with AIDS drugs by the end of 2005, and the objective of universal access to these drugs by the end of 2010.

Both initiatives fell short of their mark although the UN says they generated momentum, especially in building medical infrastructure in poor countries. (hostednews/afp/article)

Ending HIV Organ Donation Ban Could Eliminate Transplant Waiting List for People With HIV

Ending a decades-old ban on using organs from HIV-positive donors could completely eliminate the current waiting list for organs among HIV-positive people needing transplants, according to a study published online March 28 in the American Journal of Transplantation.

The ban on organ donation was put in place in the 1980s around the same time as bans were put in place to prohibit people with HIV from donating blood. At that time, people with HIV were also excluded as viable candidates for receiving organ transplants. This is because most experts believed that the organs should go to people with a better chance of survival.

In the late 1990s, however—with the introduction of potent combination antiretroviral (ARV) therapy—survival for people living with HIV increased substantially, effectively ending arguments that they were less likely to live than their HIV-negative counterparts. However, the lack of available organs means that many people—both HIV positive and HIV negative—die waiting for an organ from a matched donor.

Dorry Segev, MD, PhD, and his colleagues from Johns Hopkins University in Baltimore believed that the wait for organs among people with HIV might be shortened considerably if HIV-positive people were allowed to donate their organs to other people living with the virus. In fact, given the dearth of available organs in South Africa, doctors in that country have begun transplants between HIV-positive donors and recipients there with good results.

To determine what the impact would be if the U.S. Congress were to overturn the organ donation ban and thus allow donation to other HIV-positive people, Segev’s team pulled data from two large registries of people with HIV—the Nationwide Inpatient Study and the HIV Research Network. They then estimated the number of deaths by HIV-positive people in those studies where viable organs might have been available for transplantation.

The number of such deaths was similar between the two studies, 534 each year between 2005 and 2008 in the Nationwide Inpatient Study and an average of 494 each year between 2000 and 2008 in the HIV Research Network. This number, according to Segev and his colleagues, would be sufficient to provide donor organs to every HIV-positive person put on transplant waiting lists each year. Of course, no organs from HIV-positive people would go to HIV-negative people in need of transplants should the congressional ban be over-turned. If people with HIV don’t need organs from HIV-negative donors anymore, however, those organs would then become available to HIV-negative people on waiting lists.

“If this legal ban were lifted, we could potentially provide organ transplants to every single HIV-infected transplant candidate on the waiting list,” Segev explains. “Instead of discarding the otherwise healthy organs of HIV-infected people when they die, those organs could be available for HIV-positive candidates.”

Opening up the donor pool to HIV-positive people is not without risks. It is technically possible for an organ to be mislabeled and passed onto someone who is HIV negative. It is also possible that the strains of virus in the person donating the organ could be more virulent or drug-resistant than the strains carried by the person receiving the transplant. The authors write, however, that given the desperate need of those awaiting transplants and the number who die before a matched organ becomes available, such risks should be made on a case-by-case basis by physicians—and not limited by a law that arbitrarily forbids all donations by HIV-positive donors. (aidsmeds.com)

Watch for malnutrition risk in children with HIV after starting ART

Carole Leach-Lemens

One in nine HIV-infected children with advanced illness was hospitalised with severe malnutrition within 12 weeks of starting antiretroviral and these children had a 15-fold increased risk of dying within the first six months compared to those children not hospitalised, Andrew Prendergast and colleagues reported in the ARROW study published in the advance online edition of AIDS.

The high frequency of new cases of severe malnutrition in children after starting antiretroviral therapy (ART) is not easy to explain say the researchers, and they warn that health care workers need to be alert for the condition, especially in children who are already malnourished.

Treatment programmes for children also need to integrate HIV and malnutrition care, and look at whether nutritional supplementation before starting treatment can protect against development of severe malnutrition once ART begins.

Antiretroviral Research for Watoto (ARROW) is an open-label, randomised trial of induction-maintenance and monitoring strategies for antiretroviral treatment in 1207 HIV-infected children with a median age of 6 (3-17) in three hospitals in Uganda and one in Zimbabwe recruited from March 2007 to November 2008.

HIV infection and malnutrition among children in resource-limited settings cannot be separated. HIV prevalence is high in children with severe malnutrition. The risks of dying are three times greater in HIV-infected children with severe malnutrition than in uninfected children with severe malnutrition.

In resource-poor settings HIV infected children are likely to be seriously ill and severely malnourished when they present for care. Studies show 5-10% early death in children starting ART in these settings

The two primary clinical manifestations of severe malnutrition are:

• non-oedematous (no swelling) malnutrition (marasmus) and
• oedematous (oedema or build up of swelling in the tissues or circulatory system) malnutrition (kwashiorkor and marasmic kwashiorkor).

The authors note that while marasmus is most often associated with HIV-infected children anecdotal reports suggest that oedematous malnutrition can occur in children soon after starting ART.

The authors wanted to better understand the effect of SM on early death in children soon after starting ART. They looked at the frequency of hospitalisations and change in CD4 percentages 12 weeks after the start of ART and death and change in Z score by six months.

Severe malnutrition (SM) in this study was defined as one or more of:

• Kwashiorkor: 60-80% of weight for age with oedema
• Marasmus: <60% of weight for age without oedema
• Marasmic kwashiorkor: <60% of weight for age with oedema.

Children were assessed for SM before enrolment. Children with SM before enrolment got 2-8 weeks of supplementary feeding.

At enrolment children began cotrimoxazole prophylaxis and started abacavir, lamivudine and either nevirapine or efavirenz. Children randomised to an induction-maintenance therapy also got zidovudine in the first 36 weeks. Children were followed up every four weeks for clinical evaluation, height and weight and CD4 count and percentage measurements.

After starting ART children were hospitalised for SM if they developed oedema, loss of appetite and/or concurrent infections needing treatment.

No child had oedema before starting ART.

3.2% (39) of children were hospitalised for SM, 20 with oedema (11 kwashiorkor and 9 marasmic kwashiorkor); 19 had marasmus.

The median time from starting ART to hospital admission for those with swelling (oedema) was 26 days (IQR: 14-56) and for those without (marasmus) was 28 days (IQR: 14-36).

74% (29) of children with SM admitted to hospital had underlying infections. Similar proportions were seen in children with oedematous malnutrition or with non-oedematous malnutrition.

Children hospitalised for SM had significantly lower baseline weight-for-age, height-for-age, weight-for-height and mid-upper arm circumference than those not admitted.

Among the 220 (18%) children with advanced illness 7.3% (95% CI: 3.8-10.7) developed kwashiorkor and 3.6% (95% CI: 1.2-6.1) developed marasmus within three months.

The authors highlighted that over half of the children hospitalised for SM developed oedema after starting ART. While marasmus is more common in HIV-infected children their findings support anecdotal evidence from sub-Saharan Africa suggesting starting ART may play a role in this contrary finding.

They suggest that since many children in resource-poor settings will start ART at an advanced stage it is wise for treatment programmes to anticipate oedematous malnutrition.

While the reasons for the onset of kwashiorkor are unclear, the authors offer several suggestions, which may not be mutually exclusive:

1) The decline in immune activation and increase of CD4 cell count after starting ART may result in the development of oedema.

2) The onset of kwashiorkor shortly after starting ART may be yet another presentation of immune reconstitution inflammatory syndrome (IRIS).

3) Onset of oedema may be a manifestation of refeeding syndrome, a range of metabolic and physiological disturbances that can occur when food is introduced after a period of starvation. Refeeding syndrome might occur as a result of an increased appetite after starting antiretroviral therapy, itself a widespread phenomenon according to anecdotal reports.

4) It may be a form of ART toxicity specific to malnourished children. Severe manifestations of well-known toxicities are more common in HIV-infected people with very low nadir CD4 cell counts. In those with oedematous malnutrition the median CD4 count was 2.5, an extremely low level.

Death rates among children hospitalised with SM were high. At six months the death rates were 32%, 20% and 1.7% among children hospitalised with marasmus, kwashiorkor and not hospitalised, respectively (p<0.001).

“There is an urgent need to understand better the complex interplay between malnutrition, infection and immunodeficiency” the authors note.

The authors conclude “integration of HIV/malnutrition services and further research to determine optimal ART timing, role of supplementary feeding and antimicrobial prophylaxis are urgently required.” (aidsmap.com)

Reference

Prendergast A et al. Hospitalisation for severe malnutrition amongst HIV-infected children starting antiretroviral therapy in the ARROW trial. AIDS, Advance online publication, March 2011 DOI: 10.197/QAD.0b013e328345e56b

Gay men reduce their risk behaviour after HIV diagnosis, studies find, but disagree on how much

Two studies presented at last month’s 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) both found that gay men diagnosed with HIV considerably reduce the amount of sex they have that could pass on their infection.

However the two studies disagreed on how much men reduced their risk behaviour, and for how long they sustained this reduction.

The two prospective cohort studies, from Amsterdam and San Francisco, did not look at gay men’s behaviour over the same time frames so cannot be directly compared.

The Amsterdam study followed a group of 206 initially HIV-negative gay men and monitored the sexual risk behaviour of those who acquired HIV from four years before the date of diagnosis to four years afterwards. They were thus able to determine what the men’s baseline behaviour had been before diagnosis.

As a long-established cohort, it was also able to compare the behaviour of men diagnosed before HIV combination therapy came along (1984-1995) and after (1996-2008).

The San Francisco study only followed the risk behaviour of its 237 subjects from the date of diagnosis, but followed behaviour out to twelve years after diagnosis.

In addition, while the Amsterdam study only monitored the prevalence in unprotected anal intercourse (UAI) regardless of partners’ HIV status, the San Francisco study looked at rates of anal intercourse (AI) with all partners and partners of negative or unknown HIV status as well as rates of unprotected insertive anal intercourse (UIAI – the kind of sex most likely to transmit HIV) with partners of known and unknown status.

It also conducted a second analysis in which it took account of the effect of viral suppression by regarding unprotected sex by men with viral loads below 500 copies/ml as representing zero risk of transmission.

Amsterdam

In Amsterdam, it was found that HIV diagnosis produced an immediate fall in the amount of unprotected anal intercourse men had. Before diagnosis 68% of men had had UAI (defined as “not (always) using a condom during anal sex”) in the previous year. One year after diagnosis this had reduced to 38% and thereafter the proportion of men who had UAI continued to decline more slowly: four years after diagnosis it was 32%.

In the post-HAART era, however, post-diagnosis UAI rates decreased a lot less and started to increase again after the first post-diagnosis year. The proportion of men who had had UAI in the previous year was 61% four years before diagnosis, 72% at diagnosis, 53% one year post-diagnosis, then back to 61% four years after diagnosis.

San Francisco

The San Francisco study presented an apparently very different pattern of behaviour. This study counted the number of partners men had had in the previous three months. This was ten at diagnosis but then declined to seven two years after diagnosis. It then increased again to 8.5 five years after diagnosis and then declined again, reaching 3.5 ten years after diagnosis.

This absolute decline in the number of partners could be accounted for by age and the acquisition of primary partners, but it was notable that the proportion of sex with partners of negative or unknown HIV status followed a similar pattern of initial decline, then resurgence, then final decline. At diagnosis the men in the study had averaged six partners in the last three months of negative or unknown HIV status (60% of all partners); two years after diagnosis it was 2.5 partners (36% of all partners); five years after diagnosis it was back to 6.25 partners (69% of all partners), but by year ten it was down to one partner (29% of all partners).

Note that this was all anal sex, protected or not. In the case of unprotected insertive anal sex (UIAI, the behaviour most likely to pass on HIV) it declined from four UIAI partners in the last three months at baseline to one five years after diagnosis, and then very slowly increased to 1.5 at year ten. The proportion of insertive sex that was unprotected became larger than the proportion with negative or unknown-status partners nine years after diagnosis, perhaps indicating that by this time the majority of men were only having UIAI with other men known to have HIV.

The majority of UIAI was with other HIV-positive partners throughout. The number of partners of negative or unknown status with whom the men had UIAI declined from 1.8 in the last three months at baseline to 0.57 after a year and was only 0.14 after five years.

The researchers calculated that even without taking viral suppression into account, this meant that the San Francisco men reduced the risk of their passing on HIV by 71% a year after diagnosis, 87% two years after diagnosis, and 92% five years after. If the proportion with viral loads under 500 was taken into account, then gay men reduced their chance of passing on HIV by 97% after two years and maintained that reduction in risk.

Comparing the two

It’s difficult to compare the two studies directly because but there is not one single measure they use in common. The proportion of men in the Amsterdam study who had unprotected anal sex in the post-HAART era only declined by 20% a year after their HIV diagnosis, whereas the San Francisco men had reduced the amount of insertive unprotective sex they had by nearly 50% at this point. They had reduced UIAI by 75% four years after diagnosis, by which time the UAI levels in Amsterdam men were back almost to baseline.

These figures do not, however, take account of the possibility of “strategic positioning”: the San Francisco men might be having a higher proportion of sex that was unprotected, including with negative or unknown-status partners, if, post-diagnosis, the majority of that sex was as the passive partner. We can’t tell from this study.

It is noticeable that, in the San Francisco study at least, the majority of the reduction in the risk of transmission was due to behaviour change, rather than the reduction in infectiousness due to decreased viral load. (aidsmap.com) Gus Cairns

References

Heijman RLJ et al. Changes in sexual behaviour after HIV diagnosis among MSM who seroconverted before and after the introduction of ART. Eighteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 1034, 2011.

Vallabhaneni S et al. Seroadaptive tactics adopted by HIV-positive MSM can contribute to profound and sustained reductions in HIV transmission risk following HIV diagnosis. Eighteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 1038, 2011.

Test-and-treat not enough to control HIV epidemic in the US

Michael Carter

Only 19% of HIV-positive individuals in the US have an undetectable viral load, and this means that a “test-and-treat” strategy by itself will not be enough to control the country’s HIV epidemic, investigators argue in the March 15^th edition of Clinical Infectious Diseases.

Late diagnosis, low levels of referral and retention in specialist HIV care, and sub-optimal adherence to antiretroviral therapy all undermined the potential for test-and-treat to eradicate transmission of the virus.

“This review demonstrates that incomplete engagement in HIV care is common in the United States and that incompletely engaged individuals account for the largest proportion of HIV-infected individuals with detectable viremia,” comment the investigators, who believe their findings “have direct implications for test-and-treat programs, because disengaged individuals continue to contribute to the ongoing transmission of HIV infection.”

The investigators also estimated that even in the best-case scenarios over a third of HIV-positive individuals in the US would still have a detectable viral load and therefore be at risk of transmitting the virus to others.

Prof. Joep Lange in his accompanying editorial described the small proportion of US patients with an undetectable viral load as “shocking.” He argued that “combination prevention” was the best hope of controlling the epidemic.

Improvements in HIV treatment and care mean that many HIV-positive patients now have a realistic hope of a normal prognosis. To have the best hope of this outcome individuals need to have their infection diagnosed early, utilise specialist HIV care services, initiate antiretroviral therapy at the optimum time, and have high levels of adherence to their treatment.

Another advantage of antiretroviral therapy is its impact on infectiousness. Patients who have an undetectable viral load when taking HIV treatment are at very low risk of transmitting the virus to others. Therefore, a test-and-treat strategy has been advocated as a way of not only improving the life-expectancy of patients already infected with the virus, but also as a way of controlling the epidemic.

Investigators from the US wished to see if this approach to prevention was realistic.

There are approximately 1.1 million HIV-infected individuals in the US, and HIV incidence in the country is steady at around 56,000 new infections each year.

Rates of HIV testing in the US have increased in recent year, but approximately a fifth of all infections are still undiagnosed. The investigators note that undiagnosed individuals “cannot engage in treatment that reduces morbidity and mortality, may participate more often in high-risk HIV transmission behavior, and have a higher risk of transmitting HIV to others than do those who are aware of their HIV infection.”

Failure to link patients with specialist care after their diagnosis is also common. The investigators found that 25% of newly-diagnosed individuals were not successfully linked to HIV care within six-twelve months of their diagnosis, and between 10%-20% of patients remained unengaged in care three to five years after their diagnosis.

Rates of retention in care were also found to be far from perfect. “50% of known HIV-infected individuals are not engaged in regular HIV care,” comment the investigators, adding “poor engagement in care is associated with poor health outcomes, including increased mortality. In addition, these individuals contribute to ongoing transmission in the community.”

But being in care did not guarantee that patients would receive optimum therapy. The investigators calculated that on the basis of current guidelines, 80% of in-care patients were eligible for antiretroviral therapy. However, approximately 27% of individuals either declined this treatment or failed to initiate it for some other reason.

Moreover, results from cohort studies suggest that between 4% - 6% of patients stop taking their HIV therapy each year.

Newer anti-HIV drugs are powerful, have generally mild side-effect profiles, and forgiving adherence requirements. Nevertheless, the researchers found that between 13% - 22% of patients taking antiretroviral therapy still have a detectable viral load and are at risk of transmitting the virus to others.

After taking into account all these factors the investigators calculated that only 210,000 HIV-positive patients in the US have an undetectable viral load. These patients constitute just 19% of the HIV-infected population in the US.

“With > 80% of HIV-infected individuals in the United States having detectable HIV viremia, it is not surprising that the incidence of HIV infection has not decreased in the United States despite almost 15 years of widespread access to antiretroviral therapy,” comment the investigators.

However, they also found that even in a best-case scenario, a test-and-treat strategy would not be sufficient to control the HIV epidemic.

They write: “Diagnosis of 90% of HIV infections, achievement of 90% engagement in care, treatment of 90% of engaged individuals, and suppression of viremia in 90% of treated individuals could lead to considerable improvements in the proportion of HIV-infected individuals in the United States with undetectable viral loads. However, even in this ideal scenario, approximately 34% of HIV-infected individuals will remain viremic, with the potential to spread HIV infection to others.”

The researchers therefore conclude, “complete eradication of HIV infection through test-and-treat programs is unlikely.”

Nevertheless, they believe that “incremental improvements in methods to overcome the greatest care challenges today in the United States – undiagnosed HIV infection and inadequate engagement in HIV care – will improve the care of HIV-infected populations and decrease the incidence of HIV infection in the future.”

In his accompanying editorial, Prof. Lange suggests that the study shows the limitations of a test-and-treat approach.

He writes: “It is unlikely that ‘test and treat’ strategies by themselves, even if vigorously and comprehensively pursued, will be sufficient to end the epidemic. It should be clear that ‘combination HIV prevention’, using a mix of available prevention tools, including ‘test and treat’ strategies, in a context-specific manner based on knowledge about local, national, and regional epidemics, is the way forward.” [aidsmap.com/]

Reference

Gardner EM et al. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis 52: 793-800, 2011 (click here for the free abstract).

Lange JMA. “Test and Treat”: is it enough? Clin Infect Dis, 52: 801-02, 2011