Among new HIV treatment recommendations, all adult patients should be offered antiretroviral therapy

Among new HIV treatment recommendations, all adult patients should be offered antiretroviral therapy

WASHINGTON, D.C. – Included in the 2012 International Antiviral Society-USA panel recommendations for human immunodeficiency virus (HIV) patient care is that all adult patients, regardless of CD4 cell count, should be offered antiretroviral therapy (ART), according to an article in the July 25 issue of JAMA, a theme issue on HIV/AIDS. Other new recommendations include changes in therapeutic options and modifications in the timing and choice of ART for patients with an opportunistic illness such as tuberculosis.

Melanie A. Thompson, M.D., of the AIDS Research Consortium of Atlanta, presented the findings of the article at a JAMA media briefing at the International AIDS Conference.

"Since the first antiretroviral drug was approved 25 years ago, improvements in the potency, tolerability, simplicity, and availability of ART have resulted in dramatically reduced numbers of opportunistic diseases and deaths where ART is accessible," according to background information in the article. "New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for ART in HIV-infected adults in resource-rich settings."

Dr. Thompson and colleagues with the International Antiviral Society-USA panel conducted a review of the medical literature to identify relevant evidence published since the last report (2010), as well as data that had been published or presented in abstract form at scientific conferences in the past 2 years. The revised guidelines reflect new data regarding recommendations of when to initiate ART, new options for initial and subsequent therapy, ART management in the setting of special conditions, new approaches to monitoring treatment success and quality, and managing antiretroviral failure.

Among the primary recommendations of the panel are that treatment is recommended for all adults with HIV infection. The researchers found that there is no CD4 cell count threshold at which starting therapy is contraindicated, but the strength of the recommendation and the quality of the evidence supporting initiation of therapy increase as the CD4 cell count decreases and when certain concurrent conditions are present. Patients should be monitored for their CD4 cell count, and also HIV-1 RNA levels, ART adherence, HIV drug resistance, and quality-of-care indicators.

Initial regimens that are recommended include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). "The aim of therapy continues to be maximal, lifelong, and continuous suppression of HIV replication to prevent emergence of resistance, facilitate optimal immune recovery, and improve health" the authors write. Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions, including cardiovascular disease, reduced kidney function, or tuberculosis.

The primary reasons for switching regimens include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Switching regimens in virologically suppressed patients to reduce toxicity, improve adherence and tolerability, and avoid drug interactions can be done by switching 1 or more agents in the regimen. "Confirmed treatment failure should be addressed promptly and multiple factors considered," the researchers write.

"Although it is crucial to intensify efforts to find a cure for persons who are already infected and an effective vaccine for those who are not, many of the tools needed to control the HIV/AIDS pandemic are already at hand. Critical components of the tool kit to eradicate AIDS include expanded HIV testing, increased focus on engagement in HIV care, early and persistent access to ART, and attention to improving ART adherence. These must occur in the context of strategies to address social determinants of health, including the elimination of stigma and discrimination," the authors conclude.

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(JAMA. 2012;308[4]:387-402. Available pre-embargo to the media at http://media.jamanetwork.com)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
To contact Melanie A. Thompson, M.D., email drmt@mindspring.com, or contact Donna Jacobsen, Executive Director of IAS-USA at DJacobsen@iasusa.org or 415-544-9400.

AIDS Conference Returns to U.S. For First Time Since 1990

Published on Jul 20, 2012 by PBSNewsHour

Ray Suarez talks to Dr. Diane Havlir, U.S. Co-Chair of AIDS 2012 and Professor of Medicine at the University of California, San Francisco and Joseph Elias, Global Village Coordinator, about the AIDS Conference being held in Washington D.C. and how the gathering hopes they can 'begin to end the AIDS epidemic.'

HCV Weekend Reading - HIV i-Base and TAG "2012 Pipeline Report"

Hello folks,

Most weekends this blog offers up a few substantial links to relevant HCV information, research and education, click here for previous "Weekend Reading" articles.

This weekend I am especially excited to point readers to the new "2012 Pipeline Report" by HIV i-Base and TAG.

Officially, The International AIDS Conference taking place in Washington, D.C. begins tomorrow, and runs through July 27.  Over the next few weeks the public will have the opportunity to read daily highlights and press releases available at the conference website. 

However, today in Washington HIV i-Base (U.K.) and Treatment Action Group (TAG) (U.S.)  released the comprehensive - 2012 Pipeline Report, authors Polly Clayden, Simon Collins, Colleen Daniels, Nathan Geffen, Mark Harrington, Richard Jefferys, Coco Jervis, Karyn Kaplan, Erica Lessem, Tracy Swan; report on drugs in development and preventive technologies for HIV, hepatitis C (HCV), and Tuberculosis (TB).

The report is ready to view at the new website launched today by "TAG".

In the US, patient advocacy groups like TAG, continue to be the critical component in the fight against  HIV, HCV and TB.  I want to express my gratitude for the many years of  pipeline reports, fact sheets, clinical trial guides, research, and advocacy that Tag has provided us with.

The press release from  HIV i-Base and Tag discussing the new report is listed below, along with links to all the invaluable information.

For the HCV community, there is a particular article written by Tracy Swan and Karyn Kaplan you won't want to miss; Hepatitis C Drug Development Goes from Pony Ride to Rocket Launch.

The in depth report includes some of the following topics; HCV drug resistance, DAA drug-drug interactions, nucleosides and nucleotide polymerase inhibitors, HCV protease inhibitors, the next generation of drugs, HCV quad therapy, SVR-4 ,SVR-12, interferon free therapy, ABT-450/r, ACH-1625, BI 201335, BMS-650032, BMS-790052, danoprevir, genotypes 1-4, GS-7977 formally/PSI-7977, GS-9256, lambda, MK-7009, TMC435 and much more....

Links:

The 2012 Pipeline Report: HIV, Hepatitis C Virus (HCV), and Tuberculosis (TB) Drugs, Diagnostics, Vaccines, and Preventive Technologies in Development by Polly Clayden, Simon Collins, Colleen Daniels, Nathan Geffen, Mark Harrington, Richard Jefferys, Coco Jervis, Karyn Kaplan, Erica Lessem, and Tracy Swan is available online at:

http://www.treatmentactiongroup.org/pipeline-report/2012

and as an interactive web report at:

http://www.pipelinereport.org.

Table Of Contents

Introduction and Executive Summary

The Antiretroviral Pipeline

The Pediatric Antiretroviral Pipeline

Retrofitting for Purpose: Treatment Optimization

Preventive Technologies, Research Toward a Cure, and Immune-Based and Gene Therapies

Hepatitis C Drug Development Goes from Pony Ride to Rocket Launch

Hepatitis C (HCV) Treatment Access: Spotlight on Thailand/Asia

The Tuberculosis Diagnostics Pipeline

The Tuberculosis Treatment Pipeline

The Tuberculosis Vaccine Pipeline

Acknowledgments

Press Release:

HIV i-Base/Treatment Action Group 2012 Pipeline Report Reveals

Deep Gaps between Scientific Promise and Program Delivery

– Recent Advances in Biomedical HIV, Hepatitis C Virus (HCV), and Tuberculosis (TB) Prevention and Treatment Are Not Reaching Those Who Need Them Most –

– Political Leaders Continue to Break Domestic, Global Health Commitments –

WASHINGTON, D.C., July 21, 2012 – On the eve of the XIX International AIDS Conference in Washington, D.C., a new report by HIV i-Base (U.K.) and Treatment Action Group (TAG) (U.S.) reveals the deepening gulf between new scientific advances that make it possible to prevent, treat, and in some cases cure people living with HIV, hepatitis C virus (HCV), and tuberculosis (TB), and access to these where they are most needed. According to Polly Clayden of i-Base and Mark Harrington of TAG, “the abundance of promising advances documented in this year’s i-Base/TAG 2012 Pipeline Report may seem unattainably out of reach to many of the millions of people who need them most. It will be the task of the activists, implementers, policy makers, and scientists attending this year’s International AIDS Conference...to work together to turn the tide so that everyone who needs high-quality treatment and prevention interventions for the global HIV, hepatitis C virus (HCV), and tuberculosis pandemics receives them.”

Pointing to the recent dramatic demonstration that earlier anti-HIV therapy can reduce transmission of the virus by 96% among stable sexual partners with differing HIV status, Clayden and Harrington comment, “Three papers published in the past year provide the scientific, public health, and policy framework for accelerating the response to the HIV pandemic such that within a few years the spread of HIV can be reversed, saving millions of lives and billions of dollars, using existing antiretroviral therapy earlier and more broadly around the world. The only thing holding us back is the lack of economic and political leadership at the highest levels.”

The authors point out that while 7 million people are receiving lifesaving HIV treatment, the new scientific results indicate that up to 27 million more will need such therapy to realize the promise of earlier treatment for both individuals and public health. More preliminary results also suggest that targeting HIV prophylaxis for high-risk HIV-negative individuals can also prevent transmission, when administered in well-organized and comprehensive prevention programs, as indicated by the U.S. Food and Drug Administration (FDA) approval, earlier this month, of the first two-drug combination licensed for HIV prevention. Still more preliminarily, a single patient, Timothy Brown, has been cured of HIV infection after receiving an immune system transplant with stem cells genetically resistant to HIV. Brown has remained off HIV treatment for more than five years with no ongoing HIV replication detected.

There are many promising new HIV therapy candidates in the pipeline, as indicated in Simon Collins’s article on adult antiretrovirals, with at least 15 new drugs and combinations in phase II and III studies. In her article on the pediatric HIV pipeline, Polly Clayden demonstrates that some sponsors have made significant progress in more rapidly developing new drug options for children living with HIV. “Accelerating the regulatory approval gap between rich countries and poor ones, and between adult HIV approvals and pediatric availability, is one of the most important recommendations in this year’s Pipeline,” commented Clayden. “Children and people in developing countries should be given the best chance for durable responses to therapy, with 21st-century drugs, not forced to take second-class, toxic, and inferior drugs from the 1990s just because they are cheaper or were developed first.”

Nathan Geffen of South Africa’s Treatment Action Campaign (TAC) emphasizes the many years that can elapse needlessly between approval of new HIV drugs in Europe and America and their availability in countries such as South Africa, which has both the world’s largest HIV epidemic and its largest HIV treatment program. He points out that regulatory inefficiency by South Africa’s Medicines Control Council (the country’s equivalent of the FDA) delays both the opening of critical clinical trials and the approval of safer and more effective new drugs.

Richard Jefferys covers this year’s groundbreaking FDA review of Truvada for preexposure HIV prophylaxis (PrEP), HIV cure research, and the ongoing struggle to discover and develop safe and effective vaccines to prevent HIV transmission. For the first time in three decades, there are concrete indications that progress is at hand in biomedical HIV prevention, vaccination, and cure.

Moving to the hepatitis C virus (HCV) pandemic, which affects over 160 million people worldwide and is the leading cause of death among people with HIV in America and Europe, Tracy Swan and Karyn Kaplan provide a sweeping overview of the explosive developments in HCV combination therapy and cure, with over 25 direct-acting antivirals (DAAs) in development for HCV. Last year’s regulatory approvals of the first two protease inhibitors to treat HCV marked the cutting edge of a tidal wave of new DAAs, oral treatments for HCV that can cure more cases than ever before, sometimes without the former therapy backbone of peginterferon alfa, which is both expensive (over US$20,000/year) and highly toxic. The HCV DAA revolution makes it possible for the first time to envisage eradication of HCV—which has no natural animal hosts, and can be cured in some cases in just a few months with two or three DAAs—in the coming two decades. Swan and Kaplan caution that currently infrastructure and reimbursement mechanisms to cover treatment and care costs for people with HCV are lacking almost everywhere, and must be rapidly expanded to treat and cure the millions who are living with HCV.

Tuberculosis research has undergone a renaissance, particularly in TB drugs and regimens, but hardly a revolution (unlike HCV). Erica Lessem shows significant progress in new TB drug and regimen development, with two new drugs—bedaquiline from Janssen and delamanid from Otsuka—being filed with regulators for accelerated approval to treat drug-resistant forms of TB; the first two novel combination studies in decades having been started by the TB Alliance; and a two-drug, twelve-dose, curative regimen newly recommended by the U.S. government for prevention of latent TB infection (LTBI). As slow progress in TB diagnostics and vaccine research reveals, investment in TB research is far too low to permit rapid progress.

“We call on political leaders worldwide to step up implementation of new scientific discoveries to bridge the global and domestic prevention and treatment gaps,” concluded Clayden and Harrington.

# # #

The 2012 Pipeline Report: HIV, Hepatitis C Virus (HCV), and Tuberculosis (TB) Drugs, Diagnostics, Vaccines, and Preventive Technologies in Development by Polly Clayden, Simon Collins, Colleen Daniels, Nathan Geffen, Mark Harrington, Richard Jefferys, Coco Jervis, Karyn Kaplan, Erica Lessem, and Tracy Swan is available online at:
http://www.treatmentactiongroup.org/pipeline-report/2012
and as an interactive web report at:
http://www.pipelinereport.org.

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Hair samples from infants show exposure to anti-HIV drugs in the womb and during breast-feeding

Hair samples from infants show exposure to anti-HIV drugs in the womb and during breast-feeding

Researchers from the University of California, San Francisco (UCSF) and Makerere University in Uganda have used hair and blood samples from three-month old infants born to HIV-positive mothers to measure the uninfected babies' exposure—both in the womb and from breast-feeding—to antiretroviral medications their mothers were taking. The results, they said, are surprising.

"We found high levels of exposure to three antiretroviral medications in the hair samples of HIV uninfected infants at twelve weeks of life," said study senior author, Monica Gandhi, MD, MPH, associate professor of medicine at the UCSF Division of HIV/AIDS at San Francisco General Hospital and Trauma Center (SFGH).

"From looking at plasma level data at the same time point, we believe that transfer of two of the medicines from mother to baby occurs exclusively in the womb and transfer of the third medication occurs both in the womb and through breastfeeding."

The findings could lead to new ways to protect infants from HIV transmission and to better understand the development of toxicities and resistance to the drugs, the researchers said.
A single plasma level of a medication reflects drug exposure over approximately 24 hours. Measuring the concentrations of antiretrovirals in a small hair sample reveals exposure over the past month. The team therefore measured both plasma and hair levels of medications in babies whose mothers were taking HIV medications to get a better idea of when drugs are being passed from mother to baby. "Since fetuses start growing hair in the womb, hair sampling gives us an opportunity to examine exposures to drug before birth," said Gandhi.

UCSF researchers have pioneered the use of hair sampling for measuring antiretroviral levels. The procedure is now a standard measure in many research studies, equivalent in HIV clinical care to measuring hemoglobin A1C to monitor average blood glucose levels in patients with diabetes.
In the study, the team took hair and blood samples from two groups of HIV-positive mothers, all of whom breast-fed their infants. For 45 mother/infant pairs, the mothers' antiretroviral regimens included a protease inhibitor, lopinavir, boosted by ritonavir, another antiretroviral medication. The other 64 mothers were on an efavirenz-based regimen.

Infants in the lopinavir group had levels of the drug in their hair that measured 87 percent of the levels found in their mothers' hair. The levels of ritonavir were about 45 percent of the levels found in their mothers' hair. When the researchers looked at the drug levels in the blood drawn from the mothers and infants at 12 weeks, they found the expected levels of lopinavir and ritonavir in the mothers, but none of either in the blood of the infants.

"The inability to find drug in the infants' blood at 12 weeks tells us that the lopinavir and ritonavir in their hair is not due to recent exposure, so breast-feeding did not transfer these drugs to the infants. Our conclusion is that the lopinavir and ritonavir were transferred to the babies in the womb, and lopinavir at quite a high level," said Gandhi.

In the efavirenz group, researchers found infant drug levels in hair samples that were about 40 percent of the levels found in their mothers. Additionally, they found that infants had levels in their blood that were about 15 percent of what was found in their mothers.
These findings indicate a moderate transfer of efavirenz both in the womb and during breastfeeding said Gandhi.

"Our findings, as we verify them, will have important implications. One, being able to measure drug exposures of fetuses in the womb and during breast-feeding can help us understand how to better protect infants from HIV transmission from HIV-positive mothers during pregnancy, birth and after birth. Antiretroviral medications are delivered prophylactically to HIV-positive mothers and newborns to prevent transmission, and fetuses derive protection from transmission if their HIV-positive mothers are on an antiretroviral regimen," she said.

"Second, the development of resistance to antiretroviral medications in infants is an important issue. HIV develops resistant mutations after fairly low levels of exposure to the class of medications to which efavirenz belongs, non-nucleoside transcriptase inhibitors (NNRTIs). Additionally, hair sampling for antiretroviral exposure levels will ultimately help us monitor toxicities associated with these medications in infants."

Using hair to measure exposure to antiretrovirals has advantages in that it is a painless, bloodless, biohazard-free method of collecting a stable specimen from HIV patients. It measures drug exposure over time and has been shown to be more predictive of treatment response than the "snapshot" of exposure provided by a single plasma level of medication.

Gandhi said that researchers are finding hair sampling to be a very useful tool in several settings. One use is in resource-limited settings where collecting, storing and handling blood draws is difficult and expensive. Hair is snipped, wrapped in foil and needs no refrigeration.

Another setting is in monitoring drug exposures in uninfected people. Researchers have been using the technique to measure adherence/drug levels in some of the pre-exposure prophylaxis trials, where high-risk uninfected patients take antiretrovirals to prevent getting infected with HIV. Non HIV-infected individuals cannot be monitored for adherence to antiretrovirals like HIV-infected individuals (where levels of HIV in the blood are measured routinely to indicate how well they are taking their pills) so hair levels provide a novel and reliable indicator of adherence.

A third setting is for monitoring prenatal exposures. Hair sampling is the only way currently to measure how much antiretroviral exposure fetuses are getting in the womb long-term. Cord blood measurements of antiretrovirals at birth, which are expensive and cumbersome to collect, still only reflect exposure to the babies over the short-term. And collecting hair levels is a much easier technique for monitoring drug exposure levels in infants, especially when compared to blood draws.
This work will be presented at 11:15 a.m. ET on Saturday July 21, 2012 during the 4th International Workshop on HIV Pediatrics, which takes in Washington, D.C. preceding the XIX International AIDS Conference. A poster presentation of the same data, titled, "Lopinavir and efavirenz concentrations in paired hair samples as a marker of cumulative exposure among postpartum women and breastfeeding infants in Tororo, Uganda" will be unveiled at the XIX International AIDS Conference at 3:00 p.m. ET on Sunday, July 22, 2012.

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Study co-authors include Jane Achan, Deborah Cohan, Frances Aweeka, Julie Mwesigwa, Yong Huang, Albert Plenty, Edwin Charlebois, Theodore Ruel, Veronica Ades, Tamara D. Clark, Paul Natureeba, Moses R. Kamya, and Diane V. Havlir (principal investigator of the study), from the Infectious Diseases Research Collaboration, UCSF-Makerere University, Tororo, Uganda.

The National Institute of Child Health and Human Development, the Office of AIDS Research, the National Institute of Allergy and Infectious Diseases, and the President's Emergency Plan for AIDS Relief provided funding for this research.

The UCSF Division of HIV/AIDS at San Francisco General Hospital and Trauma Center is affiliated with the AIDS Research Institute (ARI) at UCSF. UCSF ARI houses hundreds of scientists and dozens of programs throughout UCSF and affiliated labs and institutions, making ARI one of the largest AIDS research entities in the world.

UCSF is a leading university dedicated to advancing health worldwide through advanced biomedical research, graduate level education in the life sciences and health professions, and excellence in patient care.

http://www.eurekalert.org/pub_releases/2012-07/uoc--hsf071212.php