New report now available: HCV Drugs and Vaccines Development Status – 2017

07 February 2017

Antiviral InteliStrat Inc. has prepared for scientists and decision makers a unique, exhaustive review of the HCV research and development field as it is in early 2017 (See Table of Contents below).

 

The HCV Drugs and Vaccines - Development Status 2017 report (pdf format) is now available on the "Documents" page of the website.

The report represents a comprehensive yet concise analysis of the HCV preventive and therapeutic efforts pursued by the pharmaceutic industry globally with a focus on the products, both approved for patients’ treatment and currently in development. HCV Drugs and Vaccines - Development Status 2017 is based on information collected in our proprietary Database, which represents the most complete collection of data on antiviral drugs and vaccines currently available on the market.

HCV Drugs and Vaccines - Development Status 2017 offers a balance of scientific, corporate and market information needed to support and complement any organization’s in-house activities related to:

  • Competitive intelligence
  • Benchmarking
  • Pharma’s current pipeline (the report includes about 115 organizations in the domain)
  • Market and research evolution and trends (the report includes novel targets)
  • Potential collaborations and partnerships
  • Global HCV markets, products and strategies

 

Contact us for details: info@antiviralintelistrat.com

 Table of contents, HCV Report Mar2017

The Challenges of Poliovirus Eradication, by J.Yelle

12 January 2017

Following the successful efforts to wipe out the virus of Smallpox (Variola virus) that started in the 1950s and officially realized their goal in 19803, the World Health Organization (WHO) made a commitment in 1988 to eradicate Poliovirus and poliomyelitis and achieve a Polio-free world by 2000. This ambitious project proved to be much more challenging than initially anticipated. While many of its objectives have been met (including the effective eradication of one of Poliovirus antigenic types from human populations) and the virus has been eliminated from the vast majority of countries around the globe, there is still work to do to complete this mission.

see complete publication in Journal of Virology & Human Retrovirology, Medcrave Publishing Group:

Jocelyn Yelle (2016) The Challenges of Poliovirus Eradication. J Hum Virol Retrovirol 3(4): 00102. DOI: 10.15406/jhvrv.2016.03.00102

The Urgent Need for Broad-Spectrum Antiviral Drugs, by J. Yelle

18 March 2015

During the last decades, human populations have been exposed to several new viral pathogens such as Ebola and Marburg viruses, Lassa fever virus, SARS- and MERS- Coronaviruses, Hantaviruses, Kyasanur Forest virus and others, often with disastrous consequences.

see complete publication in Journal of Virology & Human Retrovirology, Medcrave Publishing Group:

Jocelyn Yelle (2015) The Urgent Need for Broad-Spectrum Antiviral Drugs. J Hum Virol Retrovirol 2(2): 00032. DOI: 10.15406/jhvrv.2015.02.00032

The 2014 Ebola Virus Outbreak in West Africa: Current Perspectives for Prevention and Treatment

15 December 2014

In 2014, West Africa has been the scene of the worst Ebola virus outbreak in history, with no end in sight. This health crisis is reportedly associated with an outlier strain of Zaire Ebola virus. While the first infections were reported in December of last year, the number of cases has literally exploded during the summer months of 2014, affecting mainly Guinea, Liberia and Sierra Leone, with a few cases in Mali, Nigeria and Senegal.

see complete publication in Journal of Human Virology & Retrovirology, MedCrave Publishing Group: 

Jocelyn Yelle (2014) The 2014 Ebola Virus Outbreak in West Africa: Current Perspectives for Prevention and Treatment. J Hum Virol Retrovirol 1(4): 00024. DOI: 10.15406/jhvrv.2014.01.00024

MERS Coronavirus: Current Status, by J. Yelle

28 July 2014

Recently, a new virus started to infect certain individuals in the Middle-East. It was soon identified as a previously unknown coronavirus that caused severe respiratory disease with a high rate of mortality. This virus, MERS-CoV, is still closely watched by health authorities as it has the potential to evolve and cause a major epidemic.

In early May 2014, the Centers for Disease Control and Prevention (CDC) announced the first case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection in the USA. Reportedly, the patient flew from Saudi Arabia to the United Kingdom (UK) and then to Chicago on April 24, before travelling by bus to Indiana. The patient started experiencing respiratory symptoms on April 27, according to the CDC, and laboratory tests confirmed that he was infected with the MERS-CoV.

see complete publication in Journal of Human Virology & Retrovirology, MedCrave Publishing Group: 

Jocelyn Yelle (2014) MERS Coronavirus: Current Status. J Hum Virol Retrovirol 1(3): 00010. http://dx.doi.org/10.15406/jhvrv.2014.01.00010

A New Era in the Treatment of Chronic HCV Infection

08 June 2011

In May 2011, the FDA has approved two new drugs to treat chronic hepatitis C (HCV) infection. The two drugs, Boceprevir (Victrelis) from Merck & Co. and Telaprevir (Incivek) from Vertex (in collaboration with Tibotec), both act as inhibitors of HCV's protease enzyme. This is the first time in the last 20 years that a new type of drugs is approved for treating HCV infection.

The current standard treatment for chronic HCV infection, a combination of pegylated Interferon alpha and Ribavirin, generates a long list of adverse drug reactions in patients and eliminates infection in only 50 to 60% of those infected with the viral genotype 1, the most common HCV subtype present in the US and many other countries. Many patients cannot tolerate the treatment and are left without viable options.

The newly approved drugs represent a different approach in managing HCV infection, targeting viral enzymes that are needed for replication, a strategy known as STAT-C (Specifically Targeted Antiviral Therapy for HCV). Other drugs acting as enzyme inhibitors are currently being developed by various companies and are expected to revolutionize the treatment of chronic HCV infection in the coming years.

While Boceprevir and Telaprevir will first be used in combination with the standard treatment for chronic HCV infection, most experts believe that future drugs or drug "cocktails" will eventually replace Interferon and Ribavirin, offering more user-friendly treatment options to patients. Already, drug combinations targeting more than one type of HCV enzymes and free of Interferon and Ribavirin are being evaluated in Phase II clinical trials. The whole HCV research arena has been re-energized in recent years, due in large part to the impressive success of enzyme inhibitors developed for treating HIV/AIDS.

The future looks a lot brighter for HCV-infected patients.

New Treatments Available Soon for HCV Infection

03 May 2011

On April 27 and 28, the FDA's Antiviral Drugs Advisory Committee reviewed all available data presented to support approval of two new molecules developed separately by Merck & Co. (initially by Schering-Plough) and Vertex Pharmaceuticals for the treatment of chronic HCV infection.

The two compounds, Boceprevir (Victrelis) from Merck, and Telaprevir (Incivek) from Vertex, belong to a new family of drugs acting as inhibitors of HCV protease. Both drugs have been granted priority review by FDA in the US and by EMEA in Europe earlier this year. After reviewing the data last week, the FDA's advisory committee voted unanimously to recommend regulatory approval of each of the two drugs. The new compounds are expected to be used in combination with current standard therapy (pegylated Interferon and Ribavirine) for treating people chronically infected with HCV genotype 1. FDA's final decision on approval is expected around mid-May.

The current treatment for chronic HCV infection is less than perfect with a success rate of about 50-60% with viral genotype 1 and a long list of serious side effects that are often unbearable for patients. The perspective of new drugs for treating chronic HCV infection is seen as a major breakthrough in the management of this disease.

Source: Merck's Press Release, April 27, 2011; Vertex' Press Release, April 28, 2011

HIV can use ribonucleotides to replicate inside macrophages

01 February 2011

In a paper published in Journal of Biological Chemistry (Dec. 10 issue), Kennedy et al. from University of Rochester Medical Center and Emory University reported evidence that HIV has developed an original strategy to replicate efficiently in non-dividing macrophages despite the absence of substantial amounts of deoxyribonucleotides in these cells.

Deoxyribonucleotides are usually required for reverse transcription of the single-stranded RNA genome of HIV into double-stranded DNA. In non-dividing, terminally differentiated macrophages, the pools of deoxyribonucleotides are very low compared to the ones inside activated CD4+ T-lymphocytes, another cell target for HIV. Despite this, HIV is known to replicate inside macrophages.

Kennedy et al. showed in their paper that HIV's reverse transcriptase enzyme, in the presence of reduced amounts of deoxyribonucleotides, can use ribonucleoside triphosphates as substrates in macrophages to perform viral genome replication. This property seems to be shared by other Lentiviruses as well. This work has major implications in the design of novel types of drugs derived from ribonucleosides instead of deoxyribonucleosides to inhibit HIV replication in non-dividing cells and offers new avenues for eliminating HIV from reservoirs in the body.

Reference: Kennedy et al., J. Biol. Chem. 285(50): 39380-39391, Dec. 2010 (free access on PubMed)

World AIDS Day 2010 and status of the epidemic

03 December 2010

UNAIDS and the WHO have just released their annual AIDS epidemic update. Here are some figures are comments taken from their report, which can be downloaded from the UNAIDS website at  http://www.unaids.org/globalreport/Global_report.htm .

 

"The  overall growth of the global AIDS epidemic appears to have stabilized. The annual number of new HIV infections has been steadily declining since the late 1990s and there are fewer AIDS-related deaths due to the significant scale up of antiretroviral therapy over the past few years. Although the number of new infections has been falling, levels of new infections overall are still high, and with significant reductions in mortality the number of people living with HIV worldwide has increased."


ESTIMATED PEOPLE LIVING WITH HIV (GLOBALLY)

Year 2009     Adults + Children      33,300,000 (31,400,000 low estimate - 35,300,000 high estimate)
                        Adults                          30,800,000 (29,200,000 low estimate - 32,600,000 high estimate)
   
                        Women (15+)            15,900,000 (14,800,000 low estimate - 17,200,000 high estimate)
                        Children (0-14)            2,500,000 (1,600,000 low estimate - 3,400,000 high estimate)


ESTIMATED AIDS-RELATED DEATHS (GLOBALLY)

Year 2009     Adults + Children        1,800,000 (1,600,000 low estimate - 2,100,000 high estimate)
       


ESTIMATED ORPHANS DUE TO AIDS (GLOBALLY)

Year 2009    Orphans (0-17) currently living        16,600,000 (14,400,000 low estimate - 18,800,000 high estimate)
       

The following section represents the original Introduction chapter of the report, without the charts.

 

 

More than 5 million people are now receiving HIV treatment

In 2009 alone, 1.2 million people received HIV antiretroviral therapy for the first time—an increase in the number of people receiving treatment of 30% in a single year. Overall, the number of people receiving therapy has grown 13-fold, more than five million people in low- and middle-income countries, since 2004. Expanding access to treatment has contributed to a 19% decline in deaths among people living with HIV between 2004 and 2009. This is just the beginning: 10 million people living with HIV who are eligible for treatment under the new WHO guidelines are still in need.


HIV prevention works—new HIV infections are declining in many countries most affected by the epidemic
In 33 countries, HIV incidence has fallen by more than 25% between 2001 and 2009. Of these countries 22 are in sub-Saharan Africa. The biggest epidemics in sub-Saharan Africa—Ethiopia, Nigeria, South Africa, Zambia, and Zimbabwe—have either stabilized or are showing signs of decline.

However, several regions and countries do not fit the overall trend. In seven countries, five of them in Eastern Europe and Central Asia, HIV incidence increased by more than 25% between 2001 and 2009.

These figures demonstrate that positive behaviour change can alter the course of the epidemic—while stigma and discrimination, lack of access to services and bad laws can make epidemics worse. In both cases, the effects are often profound.

Among young people in 15 of the most severely affected countries, HIV prevalence has fallen by more than 25% as these young people have adopted safer sexual practices. Similar to treatment access, the room for continued improvement on this success is great. Young people’s knowledge about HIV is increasing but needs to grow further.


Virtual elimination of mother-to-child transmission of HIV is possible

In 2009, an estimated 370 000 children [220 000–520 000] contracted HIV during the perinatal and breastfeeding period, down from 500 000 [320 000–670 000] in 2001.

Although this is a significant reduction, HIV continues to weigh heavily on maternal and child mortality in some countries. But in South Africa, which achieved almost 90% coverage of treatment to prevent mother-to-child transmission of HIV, transmission to infants has been drastically reduced. In many communities, countries and regions of the world, however, access to services to halt mother-to-child transmission needs to be scaled up.

In 2009, UNAIDS called for the virtual elimination of mother-to-child transmission of HIV by 2015. In the 10 most severely affected countries, this is a realistic aim and can be achieved with significantly increased action to implement proven strategies to eliminate HIV transmission to young people.


Women and girls need support

Slightly more than half of all people living with HIV are women and girls. In sub-Saharan Africa, more women than men are living with HIV, and young women aged 15–24 years are as much as eight times more likely than men to be HIV positive. Protecting women and girls from HIV means protecting against gender-based violence and promoting economic independence from older men.


Human rights are increasingly a part of national strategies

Human rights are no longer considered peripheral to the AIDS response. Today, the vast majority of countries (89%) explicitly acknowledge or address human rights in their national AIDS strategies, with 92% of countries reporting that they have programmes in place to reduce HIV-related stigma and discrimination.

At the same time, however, criminalization of people living with HIV still presents significant challenges to the AIDS response. More than 80 countries across the world have laws against same-sex behaviour, and the free travel of people living with HIV is restricted in 51 countries, territories and areas. Such laws are not only discriminatory and unjust—they also drive HIV underground and inhibit efforts to expand access to life-saving HIV prevention, treatment, care and support.

Financing the response is a shared responsibility

Increasingly, countries with heavy HIV burdens are assuming their responsibilities to resource the response to the degree that their means permit. Domestic expenditure is the largest source of HIV financing globally today, accounting for 52% of resources for the HIV response in low- and middle-income countries. Improving financing for the global response will require ongoing efforts to mobilize domestic resources among countries that appear to be under-investing in the HIV response, increasing the efficient use of funds for HIV and other related health and development programmes, and increasing external aid in a global environment of constrained resources.


A fragile progress

Despite extensive progress against a number of indicators on the global scale, many countries will fail to achieve Millennium Development Goal 6: halting and reversing the spread of HIV.

Having more than 5 million people receiving treatment is a major public health achievement—but still represents only 35% of the people who need HIV therapy now, according to WHO guidelines issued in early 2010. Reaching the two thirds of people who need treatment, but are not yet receiving it, and financing this expansion in access to HIV therapy will require a continued and expanded global commitment to providing high quality HIV care for all.

Knowledge of the epidemic and how to prevent HIV infection has increased among young people aged 15–24 years—people frequently at the highest risk for infection. Six countries have achieved greater than 80% condom use at last higher-risk sex among males, and two countries have achieved this high level of condom use among females.

Young people still lack knowledge and, importantly, often lack the tools they need to practice HIV risk-reduction strategies, however. Many people still lack ready access to condoms and lubrication, and people who inject drugs also lack sufficient access to sterile needles.


A new vision

Fulfilling the UNAIDS vision of zero new infections will require a hard look at the societal structures, beliefs and value systems that present obstacles to effective HIV prevention efforts. Poverty, gender inequity, inequity in health and the education system, discrimination against marginalized people, and unequal resource pathways all affect—and often slow—the HIV response.

In a world that has had to learn to live with an evolving and seemingly unstoppable epidemic over the course of three decades, UNAIDS’ vision of zero discrimination, zero new infections and zero AIDS-related deaths poses a challenge. But it is not a hopeless challenge. The vision of eliminating the toll that HIV imposes on human life can be made real using the knowledge and resources available today. Planners, programme administrators and implementers must make a sustained and dedicated effort to use the best social and scientific knowledge available. Strengthened programming using the latest knowledge and best practices to deliver effective prevention, treatment and care services to people in need, or at risk, is highly effective.

Building social coalitions to reduce vulnerability to HIV infection supports individuals and strengthens communities. Safeguarding the health of mothers and infants and optimizing infant feeding provides a strong basis for the growth of new generations. Investing in health care and social support systems, working to eliminate violence against women and girls and promote gender equality and working to end stigma and discrimination against people living with HIV and members of other marginalized groups help to provide social environments that are effective against the spread of HIV and promote more general mental and physical well-being. And in providing HIV-specific services with an awareness of other health and social issues and forging appropriate linkages, the response to HIV can make an important contribution to global health.

The Millennium Development Goals are intertwined. Without achieving substantive progress towards the HIV-specific Goal 6, few other Goals are likely to be reached; likewise, without integration and significant progress towards most other Goals being made, Goal 6 will probably not be achieved.

Stopping infections, saving lives and improving the quality of life of people living with HIV have always been at the heart of the global AIDS response. The successes and continuing challenges described in this report should serve as catalysts for continued action.

 

See complete report at  http://www.unaids.org/globalreport/Global_report.htm

WHO declares end to the H1N1 Swine Influenza pandemic

19 August 2010

The World Health Organization (WHO) announced in a virtual press conference on August 10, 2010 that the H1N1 (so-called "Swine") Influenza pandemic that started in 2009 has officially ended. The world is now entering the post-pandemic phase, according to WHO's Emergency Committee.

Here is an abstract of the Director-General's (Dr. Margaret Chan) opening statement at the virtual press conference:


"The world is no longer in phase 6 of influenza pandemic alert. We are now moving into the post-pandemic period. The new H1N1 virus has largely run its course.

As we enter the post-pandemic period, this does not mean that the H1N1 virus has gone away. Based on experience with past pandemics, we expect the H1N1 virus to take on the behaviour of a seasonal influenza virus and continue to circulate for some years to come.

In the post-pandemic period, localized outbreaks of different magnitude may show significant levels of H1N1 transmission.

Globally, the levels and patterns of H1N1 transmission now being seen differ significantly from what was observed during the pandemic. Out-of-season outbreaks are no longer being reported in either the northern or southern hemisphere. Influenza outbreaks, including those primarily caused by the H1N1 virus, show an intensity similar to that seen during seasonal epidemics.

Recently published studies indicate that 20–40% of populations in some areas have been infected by the H1N1 virus and thus have some level of protective immunity. Many countries report good vaccination coverage, especially in high-risk groups, and this coverage further increases community-wide immunity.

Pandemics, like the viruses that cause them, are unpredictable. So is the immediate post-pandemic period. There will be many questions, and we will have clear answers for only some. Continued vigilance is extremely important, and WHO has issued advice on recommended surveillance, vaccination, and clinical management during the post-pandemic period.

Based on available evidence and experience from past pandemics, it is likely that the virus will continue to cause serious disease in younger age groups, at least in the immediate post-pandemic period. Groups identified during the pandemic as at higher risk of severe or fatal illness will probably remain at heightened risk, though hopefully the number of such cases will diminish.

In addition, a small proportion of people infected during the pandemic, including young and healthy people, developed a severe form of primary viral pneumonia that is not typically seen during seasonal epidemics and is especially difficult and demanding to treat. It is not known whether this pattern will change during the post-pandemic period, further emphasizing the need for vigilance.

As I said, pandemics are unpredictable and prone to deliver surprises. No two pandemics are ever alike. This pandemic has turned out to be much more fortunate than what we feared a little over a year ago.

This time around, we have been aided by pure good luck. The virus did not mutate during the pandemic to a more lethal form. Widespread resistance to oseltamivir did not develop. The vaccine proved to be a good match with circulating viruses and showed an excellent safety profile.

Thanks to extensive preparedness and support from the international community, even countries with very weak health systems were able to detect cases and report them promptly.

Had things gone wrong in any of these areas, we would be in a very different situation today."



Source: WHO Director-General's statement on Pandemic (H1N1) Influenza, virtual press conference held on Aug. 10, 2010

Addendum
Composition of the seasonal Influenza vaccine for 2010-2011 (FDA website):

  • Influenza strain A/California/7/09 (H1N1)-like, representing the viral strain responsible for the 2009 pandemic
  • Influenza strain A/Perth /16/2009 (H3N2)-like
  • Influenza strain B/Brisbane/60/2008-like

The influenza vaccine composition to be used in the 2010-2011 influenza season in the U.S. is identical to that recommended by the World Health Organization on February 18, 2010, for the Northern Hemisphere's 2010-2011 influenza season.

Tenofovir gel reduces risk of HIV and HSV infection in a clinical trial

20 July 2010

On July 19, 2010, at the XVIII International AIDS Conference in Vienna, Austria, the Centre for the AIDS Programme of Research in South Africa (CAPRISA) reported the results of a clinical study evaluating a microbicide gel containing the antiretroviral drug Tenofovir as a way to protect women against HIV during sexual intercourse. Analysis of the data revealed that the gel significantly reduced the risk of infection by HIV (by 39%) and HSV-2 (by 51%). Below is the original press release of the organizations (CAPRISA/FHI/CONRAD/Technology Innovation Agency/USAID) involved in the study.


STUDY OF MICROBICIDE GEL SHOWS REDUCED RISK OF HIV & HERPES INFECTIONS IN WOMEN

VIENNA, AUSTRIA (July 19, 2010) — Researchers have achieved an important scientific breakthrough in the fight against HIV and genital herpes with a vaginal gel that significantly reduces a woman’s risk of being infected with these viruses.  The results of the ground-breaking safety and effectiveness study of an antiretroviral microbicide gel study were reported today by the Centre for the AIDS Programme of Research in South Africa (CAPRISA) at the XVIII International AIDS Conference in Vienna, Austria.

The microbicide containing 1% tenofovir—an antiretroviral drug widely used in the treatment of HIV—was found to be 39% effective in reducing a woman’s risk of becoming infected with HIV during sex and 51% effective in preventing genital herpes infections in the women participating in the trial. Should other studies of tenofovir gel confirm these results, widespread use of the gel, at this level of protection, could prevent over half a million new HIV infections in South Africa alone over the next decade.

“Tenofovir gel could fill an important HIV prevention gap by empowering women who are unable to successfully negotiate mutual faithfulness or condom use with their male partners,” said study co- principal investigator, Dr. Quarraisha Abdool Karim, Associate Director of CAPRISA and Associate Professor of Epidemiology at Columbia University. “This new technology has the potential to alter the course of the HIV epidemic, especially in southern Africa where young women bear the brunt of this devastating disease.”

Tenofovir works by preventing HIV from growing inside human cells. Taken in pill form, tenofovir is a common component of various three-drug cocktails that are used to treat HIV infections. The new results now indicate that tenofovir formulated as a topical gel and inserted into the female genital tract also has great promise for use in HIV and herpes simplex virus type-2 (HSV-2) prevention.

The CAPRISA 004 trial of tenofovir gel involved 889 women at high risk of HIV infection at an urban and a rural site in KwaZulu-Natal, South Africa. Overall, 98 women out of the 889 became HIV positive during the trial—with 38 in the tenofovir gel group and 60 in the placebo gel group.  Out of the 434 women who tested negative for herpes at the start of the trial, 29 became infected in the tenofovir group and 58 became infected in the placebo group. The reduced rates of HIV and herpes infections among the women who used the tenofovir gel are statistically significant. 

“Tenofovir gel has a potential dual effect in preventing HIV.  Since women with genital herpes are much more likely to become infected with HIV, the additional protection of tenofovir gel against herpes creates a second mechanism whereby the gel may have a bigger impact in preventing HIV,” said study co-principal investigator, Dr Salim S. Abdool Karim, Director of CAPRISA and Pro Vice-Chancellor (Research) of the University of KwaZulu-Natal, South Africa. “The trial results are a significant first step toward establishing the effectiveness of antiretroviral drugs for HIV and genital herpes prevention; confirmatory studies are now urgently needed.”

During monthly visits, all participants were provided with HIV risk-reduction counseling, condoms and treatment for sexually transmitted infections, and each was clinically examined for potential side effects and tested for HIV infection. The study was double-blinded and neither the researchers nor the participating women knew whether a woman in the study received tenofovir gel or placebo gel. Women in the study were advised to use the gel up to 12 hours before sex and soon after having sex for a maximum of two doses in 24 hours – a dosing strategy referred to as BAT24.  Participants used the gel for a minimum of one year and a maximum of two and a half years.  The trial team observed no substantive safety concerns from use of the gel.  Further, no increase in risky behavior was observed in the women. 

The CAPRISA researchers also found that the protective effect against HIV and genital herpes increased as use of the tenofovir gel increased. Women who used the gel in more than 80% of their sex acts had a 54% reduction in HIV infections, whereas those who used the gel in less than half of their sex acts had a 28% reduction in HIV infections.  Among those women who became infected, tenofovir gel had no effect on the amount of HIV in their bloodstream at the time of infection.  Also, none of the women who became infected with HIV showed resistance to tenofovir. 

All volunteers to the study who tested HIV positive were provided care including ARV treatment at the CAPRISA clinics and women who became infected during the study were enrolled into CAPRISA studies and/or the CAPRISA AIDS treatment program at their respective sites for ongoing care and support.  

This study was jointly funded by the Governments of South Africa and the United States, through the Technology Innovation Agency (TIA) and the US Agency for International Development (USAID), respectively. USAID provided $16.5M and TIA provided $1.1 for the study.  "USAID is proud to be the major donor of this first-ever proof of concept that a vaginal microbicide can effectively and safely reduce the risk of HIV transmission from men to vulnerable women.  The success of the CAPRISA 004 trial perfectly complements the Global Health Initiative and our focus on women's health, both in prevention and sustainable health delivery systems," stated USAID Administrator Raj Shah.

The promising findings of the CAPRISA 004 study is only a first step in determining if tenofovir gel is effective in preventing HIV and herpes infection; additional studies are urgently needed to confirm and extend the findings of the CAPRISA study.  Important information is expected from current studies such as the Microbicide Trials Network’s VOICE study, which is currently assessing daily tenofovir gel as well as daily tenofovir and Truvada tablets in women in several African countries.  Studies of daily Truvada tablets are underway in intravenous drug users, young high-risk women and men who have sex with men.

 “We are proud to have partnered with CAPRISA and CONRAD on this important study. We see it as a major victory in the field of HIV prevention research. This is the first evidence that an antiretroviral drug in a gel form – a microbicide – can reduce HIV and genital herpes infection in women,” said Ward Cates, President of FHI. “The next step is to see whether other studies underway confirm these exciting results.”

Only after drug regulatory authorities determine that tenofovir gel is safe and effective for HIV prevention, can the gel be made available to the public for HIV prevention. Since this process can take several years, TIA and U.S.-based CONRAD are working together to address the challenges to making the gel available first to women in South Africa. 

"CONRAD has given the rights to manufacture this gel to the government of South Africa to get this much needed product to women in South Africa as rapidly as possible," said Dr. Henry Gabelnick, Executive Director of CONRAD, who provided the gel for the study.  “The Technology Innovation Agency (TIA) is working closely with the South African government, CAPRISA and CONRAD to ensure that this important innovation makes an impact in preventing the spread of HIV/AIDS,” said Dr. Mamphela Ramphele, Chairperson of TIA. 

Ambassador Eric Goosby, U.S. Global AIDS Coordinator said, “The results of the CAPRISA trial provide new hope and direction for not only HIV prevention, but also broader efforts under the Global Health Initiative.  We recognize that microbicides will be a great asset to HIV prevention efforts, and the U.S. Government is pleased to support this important research."

Professor Malegapuru Makgoba, Vice-Chancellor of the University of KwaZulu-Natal stated, “This piece of research is a significant milestone for women in the thirty year history of the HIV/AIDs epidemic, microbicides and antiretroviral research. The research represents that which is best in science with
direct translation into prevention policy, bringing a message of hope and empowerment to women, policymakers and scientists.  These research findings will not only significantly alter the shape and form but also the future direction of this devastating epidemic.”

"The trial's findings create a new vision for the opportunity for prevention of HIV and re-define the public health approach to HIV control," added Dr Linda Fried, Dean of the Mailman School of Public Health of Columbia University, New York.

The trial was conducted by CAPRISA in partnership with the U.S.-based organizations FHI and CONRAD with funding from USAID. Gilead Sciences donated the active ingredient for the manufacture of the tenofovir gel.

End


CAPRISA (www.caprisa.org) is an AIDS research institute of the University of KwaZulu-Natal and Columbia University.  Its headquarters are at the Nelson R Mandela School of Medicine, University of KwaZulu-Natal in Durban, South Africa. CAPRISA is a designated UNAIDS Collaborating Centre for HIV Prevention Research. The main goal of CAPRISA is to undertake globally relevant and locally responsive research that contributes to understanding HIV pathogenesis, prevention and epidemiology, as well as the links between tuberculosis and AIDS care. CAPRISA comprises four research programmes: HIV pathogenesis & vaccines, HIV and TB treatment, Microbicides, and HIV prevention and epidemiology.
Contact: Dr. Leila Mansoor, mobile: +1 2783.786.3078, mansoor@ukzn.ac.za

FHI (www.fhi.org) is a global health and development organization whose rigorous, science-based approach builds programs that create lasting change. Founded in 1971, FHI maintains offices and staff worldwide, helping to forge strong local relationships that enable us to make measurable progress against disease, poverty, and inequity—improving lives for millions. FHI was the primary recipient of USAID funds for the project and provided scientific and operational expertise to the South African scientists in the CAPRISA 004 trial.
Contact: Beth Robinson, mobile: +1 919.768.2204, brobinson@fhi.org

CONRAD (www.conrad.org) was established in 1986 and is a Division of the Department of Obstetrics and Gynecology at Eastern Virginia Medical School (EVMS) in Norfolk, VA, where it has laboratories and a clinical research center. The main office is located in Arlington, VA with additional offices in West Chester, PA and collaborators around the world. CONRAD is committed to improving reproductive health by researching and developing new contraceptive options and products to prevent HIV and STI infections. Contact:  Annette Larkin, mobile: +1 703.772.6427, larkinannette@yahoo.com

Technology Innovation Agency, formerly known as LIFElab (www.tia.org.za) TIA was formed from a merger of several DST funded instruments, including LIFElab.  TIA is mandated to stimulate and intensify technological innovation in order to improve economic growth and the quality of life of all South Africans by developing and exploiting technological innovations. To this end, TIA is set up to be a world class innovation agency that supports and enables technological innovation to achieve socio-economic benefits for South Africa through leveraging strategic partnerships.
Contact: Kagiso Ntanga, mobile +27 82 808 9180, kagiso.ntanga@tia.za.org

USAID (www.usaid.gov) is an independent federal government agency that receives overall foreign policy guidance from the Secretary of State.  With headquarters in Washington, D.C., USAID’s strength is its field offices around the world.  We work in close partnership with private voluntary organizations, indigenous organizations, universities, American businesses, international agencies, other governments and other U.S. government agencies.  USAID has working relationships with more than 3,500 American companies and over 300 U.S.-based private voluntary organizations.
Contact:  Nicole Schiegg, nschiegg@usaid.gov

Potent HIV entry inhibitor identified in bananas

19 March 2010

A recent publication by a group of scientists from the University of Michigan Medical Center reports the characterization and antiviral activity of a lectin isolated from the fruit of bananas (Musa acuminata). This jacalin-related lectin, BanLec, binds to high mannose carbohydrate structures that are major components of the envelope of several viruses, including HIV's envelope. In vitro experiments performed by the group showed potent inhibition of HIV primary isolates and laboratory strains of various subtypes and co-receptor tropism with an EC50 in the low nanomolar to picomolar range. BanLec was shown to bind to viral envelope glycoprotein gp120 via carbohydrate structures recognized by monoclonal antibody 2G12. Binding of BanLec to viral gp120 inhibits HIV entry into host cells, presumably by interfering with viral attachment to the cellular receptor. BanLec's anti-HIV activity in vitro compared favorably to other lectins such as snowdrop lectin and Griffithsin, and to Fuzeon and Maraviroc, two commercially available HIV drugs acting as entry inhibitors. According to the scientists, BanLec could be eventually developed as a potential microbicide component.


Source: Swanson et al., J Biol Chem 285(12): 8646-8655, March 19, 2010

Influenza vaccine composition for 2010-2011 season

09 March 2010

On February 18, 2010, after reviewing global reports on viral activity, Influenza virus experts of the World Health Organization (WHO) announced their recommendations for the composition of the Influenza vaccines for use in the northern hemisphere during the forthcoming Influenza season. A similar meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) took place on February 22, 2010.

Both committees recommended the following Influenza virus strains to be included in the vaccines for the 2010-2011 season (November 2010 to April 2011):

  • an A/California/7/2009 (H1N1)-like virus
  • an A/Perth/16/2009 (H3N2)-like virus*
  • a B/Brisbane/60/2008-like virus


*A/Wisconsin/15/2009 is an A/Perth/16/2009 (H3N2)-like virus and is a 2010 southern hemisphere vaccine virus.

The A/California/7/2009 (H1N1)-like strain in the vaccine represents the so-called “swine” virus associated with the mild pandemic that occurred in 2009.


Sources: WHO press release, Feb. 18, 2010, and FDA press release, Feb. 22, 2010

World AIDS Day 2009 and status of the epidemic

01 December 2009

UNAIDS and the WHO have just released their annual AIDS epidemic update. According to the report, more than 33.4 million people worldwide were living with HIV in 2008, including 31.3 million adults and 2.1 million children less than 15 years of age. The total number of people living with the virus in 2008 represented an increase of 20% compared to the number in 2000, and the prevalence was roughly threefold higher than in 1990.

A total of 2.7 million people were newly infected with HIV in 2008 and there were 2.0 million AIDS-related deaths. As stated in the report, these data indicate that globally the spread of HIV has peaked in 1996, when more than 3.5 million new HIV infections occurred during the year.  

Sub-Saharan Africa remains the area of the globe that is the most affected by the disease, with more than 22.4 million people living with HIV in 2008 and accounting for 71% of all new HIV infections in 2008.

Other points discussed in the report:

  • Overall improvement in national HIV surveillance systems and estimation methodology
  • Apparent stabilization of the epidemic in most regions, although prevalence continues to increase in Eastern Europe and Central Asia and in other parts of Asia due to a high rate of new HIV infections
  • AIDS continues to be a major global health priority
  • There is geographic variability between and within countries and regions
  • The epidemic is evolving, with patterns changing over time
  • There is evidence of success in HIV prevention
  • Improved access to treatment is having an impact: antiretroviral therapy coverage rose from 7% in 2003 to 42% in 2008
  • There is increased evidence of risk among key populations

See details in the complete report freely available at      http://data.unaids.org/pub/Report/2009/2009_epidemic_update_en.pdf

A controversial HIV/AIDS vaccine combination shows modest efficacy

01 October 2009

The results of the Phase III clinical trial RV144 based on the administration of two HIV vaccines as a prime-boost combination to healthy volunteers were announced on September 24, 2009. The data released showed that the vaccine regimen was safe and reduced the risk of HIV infection by 31.2% compared to placebo, a modest but significant indication of protection. These results came as a surprise to many experts: the ALVAC vCP1521 vaccine component had never been tested alone for efficacy in HIV-uninfected people and had elicited a less than robust immune response in previous trials, while the AIDSVAX B/E vaccine component when tested alone had failed to prevent or affect the outcome of HIV-1 infection in previous Phase III trials done in the US and Thailand. A decision had been made in the past by the NIH not to proceed in the US with a Phase III trial of a similar vaccine series, ALVAC vCP1452 plus AIDSVAX B/B.
 
The RV144 trial, also called Thai Phase III HIV vaccine study, opened in October 2003 and enrolled 16,402 men and women ages 18 to 30 years old at various levels of risk for HIV infection.  The trial was sponsored by the U.S. Army in collaboration with NIAID, the Thai Ministry of Public Health, Sanofi Pasteur (producer of ALVAC) and Global Solutions for Infectious Diseases (GSID, producer of AIDSVAX), and was conducted in the Rayong and Chon Buri provinces of Thailand under the direction of Dr. Supachai Rerks-Ngarm, of the Thai Ministry of Public Health’s Department of Disease Control.

Half of the participants to the trial received a prime-boost regimen of two vaccines: ALVAC vCP1521 vaccine (primer), a recombinant Canarypox vector developed by Sanofi Pasteur and expressing the HIV gp120 glycoprotein of Thailand strain CRF01_AE (isolate 92TH023) linked to HIV gp41 glycoprotein amino acid sequences from LAI strain, along with HIV-1 Gag and protease proteins (strain LAI, subtype B), and AIDSVAX B/E vaccine (booster), a mixture of recombinant gp120 glycoproteins from viral strains MN (subtype B) and CRF01_AE (isolate A244) initially developed by VaxGen Inc., and now licensed to GSID. The vaccine regimen was designed to stimulate both the cellular and the antibody-producing arms of the immune system against two HIV subtypes present in Thailand. The other half of the participants received a placebo. Study participants received the ALVAC primer vaccine or placebo at enrolment and again after 1 month, 3 months and 6 months. The AIDSVAX B/E booster vaccine or placebo was given to participants at 3 and 6 months. Participants were tested for HIV infection every 6 months for 3 years. During each clinic visit, they were counselled on how to avoid becoming infected with HIV.

During the study, 74 of 8,198 placebo recipients became infected with HIV compared to 51 of 8,197 participants who received the vaccine regimen. This level of effectiveness in preventing HIV infection was found to be statistically significant (p=0.039) although the confidence intervals for the estimate in the reduction in risk were wide (95% confidence interval 1.1% - 51.1%). The vaccine regimen had no effect, however, on the amount of virus in the blood of volunteers who acquired HIV infection during the study. Individuals who became infected by HIV while participating in the Thai trial have been provided access to HIV care and treatment including HAART, based on the guidelines of the Thai Ministry of Public Health.

Additional details and results of this study are expected to be presented at the AIDS Vaccine 2009 conference, October 19 - 22 in Paris, France.

 

Sources: NIAID News Release, September 24, 2009; AIDSmap News, September 24, 2009 (www.aidsmap.com)

FDA approves 4 vaccines for A(H1N1) Influenza virus

26 September 2009

On September 15 2009, the FDA announced the approbation of four monovalent vaccines to protect against the so-called “swine” A(H1N1) Influenza virus that has reached pandemic level globally. The vaccine manufacturers are CSL, MedImmune, Novartis, and Sanofi Pasteur. They all produced the vaccines based on the traditional embryonated chicken egg manufacturing process, a relatively low yield but well-established procedure also used for seasonal Influenza vaccine preparation. The viral strain included in each of the vaccines was A/California/7/2009 (H1N1). While vaccines produced by CSL, Novartis and Sanofi Pasteur are administered by injection, MedImmune’s vaccine is given by intranasal (nasal spray) administration. In the coming weeks, the manufacturers will mass produce vaccine doses for distribution to health authorities.

Novartis and GlaxoSmithKline also announced on September 25 2009 that their respective pandemic A(H1N1) Influenza virus vaccines received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA).

The first A(H1N1) Influenza virus vaccine to receive official approval was PANFLU.1, made by Sinovac in China. The company announced on September 3 2009 that the State Food and Drug Administration (SFDA) had approved the registration application for the vaccine and issued a production license for it.

 

Sources: FDA Press release, September 15, 2009; respective Press releases of Novartis and GlaxoSmithKline, September 25, 2009; Sinovac Press release, September 3, 2009

Influenza virus A/H1N1 has reached pandemic level

11 June 2009

On June 11, 2009 the WHO raised the level of Influenza pandemic alert to Phase 6, the highest possible level. After reviewing the latest figures with Influenza experts, the agency declared that the ongoing outbreak of Influenza A/H1N1 (reported earlier as Swine Influenza virus A/H1N1) has now reached the stage of “sustained person-to-person transmission within multiple regions of the world”, and thus qualifies as full-blown pandemic.

As Dr. Margaret Chan, Director-General of WHO declared, “The world is now at the start of the 2009 Influenza pandemic”. The last Influenza pandemic goes back to 1968 and was associated with the Hong Kong strain.

So far, the vast majority of patients infected with the A/H1N1 strain experience mild symptoms and make a rapid and full recovery. The number of deaths seen globally remains limited. However, as stated by Dr. Chan, “although the pandemic appears to have moderate severity in comparatively well-off countries, it is prudent to anticipate a bleaker picture as the virus spreads to areas with limited resources, poor health care, and a high prevalence of underlying medical problems”.

This particular Influenza virus A/H1N1 infects preferentially young people under the age of 25 years. Most cases of severe and fatal infections have been in adults between the ages of 30 and 50 years. This pattern of infection differs from that seen during epidemics of seasonal influenza, when most deaths occur in frail elderly people.

 

Source: Press release by Dr. Chan (WHO Director-General), June 11, 2009

Influenza virus A H1N1 (Swine Influenza virus A/H1N1) : Current status

02 May 2009

According to WHO data, as of May 1, 2009 (23:30 GMT), 13 countries have reported 367 confirmed cases of Swine Influenza virus A /H1N1 infection. The virus is now called Influenza A (H1N1) to avoid confusion arising from its porcine origin, which made some people believe that they could become infected by consumption of pork products.

The United States Government has reported 141 laboratory confirmed human cases, including one death. Mexico has reported 156 confirmed human cases of infection, including nine deaths.

Other countries have reported laboratory confirmed cases with no deaths:  Austria (1), Canada (34), China, Hong Kong, Special Administrative Region (1), Denmark (1), Germany (4), Israel (2), Netherlands (1), New Zealand (4), Spain (13), Switzerland (1) and the United Kingdom (8).

Some Influenza experts now consider the currently circulating virus as relatively benign, based on the limited number of people needing hospital care and the small number of fatalities (at least in the USA). Also, there has been so far only limited transmission of the virus from infected people to relatives under the same roof. Some genetic traits appear to be lacking in this virus that were found in the Influenza virus that caused the Spanish flu pandemia of 1918 or in the Avian Influenza virus H5N1 which killed about 250 people mostly in Asia a few years ago.

Nevertheless, there is a real possibility that this Influenza A (H1N1) virus come back in the Fall with increased virulence, as happened in the case of the Spanish flu virus with devastating consequences.  The coming weeks and months could prove crucial as the virus is expected to infect people globally, potentially accumulating mutations along the way. One possible scenario is for the virus to recombine with an Avian Influenza virus in Asia, which could result in a new, more pathogenic Influenza virus.

Source: WHO Press Release, May 1, 2009 and WHO website

WHO raises the level of Influenza pandemic alert to Phase 5

30 April 2009

On April 29, WHO Director-General, Dr. Margaret Chan, announced that the decision was made by the organism to raise the level of Influenza pandemic alert from Phase 4 to Phase 5, following discussions with Influenza experts and evaluation of the current situation.

As of 18:00 GMT, 29 April 2009, WHO figures indicate that nine countries have officially reported 148 cases of swine influenza A/H1N1 (swine flu) infection. The United States Government has reported 91 laboratory confirmed human cases, with one death. Mexico has reported 26 confirmed human cases of infection including seven deaths.

The following countries have reported laboratory confirmed cases with no deaths - Austria (1), Canada (13), Germany (3), Israel (2), New Zealand (3), Spain (4) and the United Kingdom (5).

According to Dr. Chan, “All countries should immediately activate their pandemic preparedness plans. Countries should remain on high alert for unusual outbreaks of influenza-like illness and severe pneumonia. At this stage, effective and essential measures include heightened surveillance, early detection and treatment of cases, and infection control in all health facilities. This change to a higher phase of alert is a signal to governments, to ministries of health and other ministries, to the pharmaceutical industry and the business community that certain actions should now be undertaken with increased urgency, and at an accelerated pace.”

Phase 5 (out of 6) represents a stage when there is evidence of widespread human infection in two or more countries and of efficient human-to-human transmission of the virus. This is a strong signal that a full-blown pandemic (Phase 6) is imminent and that there is little time left for implementation of mitigation measures.

 

Source: WHO Press release and website, April 29, 2009

Swine Influenza virus in young adults in US and Mexico

26 April 2009

As of April 24, 2009 US health authorities have reported 7 human cases (5 in California and 2 in Texas) of Influenza-like illness associated with the confirmed detection of Swine Influenza A/H1N1, on top of 9 additional suspect cases. Only one of the 7 confirmed cases required hospitalization, and no deaths were reported.  On April 26, 8 cases of Swine Influenza virus infection were confirmed in students of a New York high school. Some of the students visited Mexico a few days earlier.

The Government of Mexico also reported detection of Influenza-like illness starting March 18 and rising steadily through April in the Federal District of Mexico. As of April 23, more than 854 cases of pneumonia have been reported in the capital, resulting in 59 deaths. In San Luis Potosi, central Mexico, 24 cases of Influenza-like illness led to 3 deaths. Another 4 cases with no fatalities were also reported in Mexical, near the US border. Of the Mexican cases, 18 were confirmed in a Canadian laboratory as being caused by Swine Influenza A/H1N1, with 12 of the isolates genetically identical to the strains identified in the California cases.

Most of the cases occurred in otherwise healthy young adults, while Influenza virus normally affects the very young and the very old. The Swine Influenza A/H1N1 viruses involved in this outbreak have not been previously detected in pigs or humans.  So far, these viral isolates have shown sensitivity to oseltamivir (Tamiflu®), but resistance to amantadine and rimantadine.

These events are of high concern to the WHO, with constant contact established with health authorities of the US, Mexico and Canada to follow the situation and evaluate the risk which these Influenza-like illness events pose to the international community. WHO’s partners in the Global Alert and Response Network have been alerted and are ready to assist as requested by the Member States.

 

Source: WHO Press Release, April 24, 2009 and Associated Press

Regulatory approval of Ixiaro, a second-generation vaccine for prevention of JEV infection

30 March 2009

A new vaccine designed to prevent infection by Japanese Encephalitis virus (JEV) has been approved by the regulatory authorities of two countries since the beginning of 2009. The vaccine, called Ixiaro, has been developed by Intercell AG over a period of 10 years and has already been tested successfully in more than 5000 individuals. Ixiaro was approved by the Therapeutic Goods Administration (TGA) in Australia on January 23, 2009 and by the Food and Drugs Administration (FDA) in the US on March 30, 2009. The vaccine consists in inactivated virus particles prepared using cell cultures, which represents an advance in vaccine production. Each year, more than 30,000 to 50,000 cases of JEV infection are reported mainly in Asia, where the virus is transmitted by mosquitoes. The infection is fatal in about 30% of those who show symptoms and leaves half of survivors with permanent brain damage.  There are no antiviral drugs available for treatment.

 

Source: Intercell’s Press release, March 30, 2009

CROI 2009 Reports

03 March 2009

16th Conference on Retroviruses and Opportunistic Infections (CROI), Montreal, February 8-11, 2009

 

This summary is based on the following sources: CME Newsletter for the 16th CROI, presented by The Johns Hopkins University School of Medicine (http://www.viraled.com/uploads/files/16th_CROI_Newsletter_ViralEd.pdf), and hivandhepatitis.com (http://www.hivandhepatitis.com/2009icr/croi/docs/021709_aa.html)

 
Timing for initiation of antiretroviral therapy
  • New data confirms clinical benefits associated with treating HIV-infected people having CD4+ cell counts between 350 and 500 cells/mm3, and shows survival benefit in patients treated with CD4+ counts > 500 cells/mm3
  • Data from ART-CC study shows significant increase in risk of AIDS and death when treatment is postponed until CD4+ cell count drops below 350 cells/mm3 (Sterne J. et al., Abstract 72LB).
  • New data from NA-ACCORD study comparing survival in HIV-infected people who initiated antiretroviral treatment within 18 months of presentation with CD4+ cell counts > 500 cells/mm3, or deferred treatment until 18 months following presentation: delaying ART is associated with a 36% increased risk of death (Kitahata M. et al., Abstract 71).
  • Both ART-CC and NA-ACCORD argue for earlier initiation of ART for asymptomatic patients than what is generally recommended.
 
Antiretroviral treatment in cases of acute HIV infection
  • New data from the Dutch Primo-SHM cohort presented at CROI2009 suggests that patients with acute HIV infection may benefit from a short course of therapy followed by treatment interruption: the majority of patients who were treated and then interrupted treatment were able to remain off therapy after more than 200 weeks of follow-up, while most of the patients who were untreated during primary HIV infection eventually started therapy (Steingrover R. et al., Abstract 70bLB).
 

Viral replication in patients with undetectable HIV RNA

  • New data supports the notion that low levels of HIV replication occur in patients with a plasma HIV RNA <50 copies/mL.
  • Hatano et al. (Abstract 425) used a highly sensitive assay (transcription-mediated amplification assay) that has a sensitivity to an HIV RNA level of <3 copies/mL with 180 “virologically suppressed” patients with an HIV RNA <50 copies/mL as determined by conventional assays. They found that 76% to 87% of these patients still had a quantifiable HIV RNA with their ultra-sensitive assay even after over 7 years of antiretroviral treatment. There is also substantial evidence for HIV replication in other viral reservoirs in patients with a plasma HIV RNA <50 copies/mL (Sheth P. et al., Abstract 50; Degray G. et al., Abstract 402).
  • Treatment intensification had no effect on low levels of HIV production (Jones J. et al., Abstract 423b; Gandhi R. et al., Abstract 424). This suggests that antiretroviral therapy alone will not be able to eliminate HIV, no matter how potent the regimen.
 

No long-term clinical benefit associated with IL-2 combined with HAART

  • In recent years, IL-2 combined with antiretroviral treatment has been shown to improve CD4+ counts, but no clinical benefits have been associated with this immunological improvement.
  • Two clinical studies, ESPRIT and SILCAAT, evaluated potential long-term benefits of IL-2-induced CD4+ cell count increase. In ESPRIT, CD4+ cell count increases were shown to be maintained over 7 years but no clinical benefits were observed (Losso M. et al., Abstract 90aLB). In fact, IL-2 administration was associated with an increase in grade 4 clinical events such as local reaction to injection and vascular reactions, primarily deep venous thrombosis. SILCAAT reached essentially the same conclusions, with no clinical benefits (Levy Y. et al., Abstract 90bLB).
 

BENCHMRK 96-week data: Raltegravir in heavily-experienced patients

  • BENCHMRK 1 and 2 are ongoing phase III, double blinded studies that enrolled triple-class resistant patients failing their current antiretroviral therapy. The 2 studies are usually combined into a single report.
  • At 96 weeks, Raltegravir (RAL) plus optimized background therapy (OBT) continued to show a potent, superior, and durable antiretroviral efficacy. At 96 weeks, 57% and 26% of the patients in the RAL and placebo arms, respectively, maintained an HIV RNA <50 copies /mL (p<0.001) (Steigbigel R. et al., Abstract 571b). The immunologic responses showed a mean CD4+ count gain in the RAL + OBT arm of 123 cells/mm3 vs. 49 cells/mm3 in the placebo + OBT arm.
  • RAL failures were generally associated with mutations of amino acids Q148, N155, or Y143, in combination with at least one other mutation.
  • Results at 96 weeks continue to demonstrate the superiority of RAL over placebo. The virologic responses and tolerability initially observed at 48 weeks are sustained.
 

Switching from Lopinavir/ritonavir (Kaletra) to Raltegravir (Isentress): SWITCHMRK study (Eron et al., Abstract 70aLB)

  • At 24 weeks, using a "non-completer = failure" analysis, raltegravir did not demonstrate non-inferiority compared with lopinavir/ritonavir based on the pre-defined margin of -12%.
  • Switching from Kaletra to Raltegravir leads to less potent HIV suppression, but better lipid profiles.
  • Most viral rebounds in the raltegravir group occurred within the first 4 weeks after switching. In the 2 SWITCHMRK studies combined, a majority of patients who experienced virological rebound after switching to raltegravir were treatment-experienced (84%) and had a history of prior virological failure (66%).
  • Changes in CD4 count were statistically similar in the Raltegravir and Kaletra arms in both studies.
  • At 12 weeks, raltegravir was associated with significantly more favorable mean percentage changes from baseline in blood lipid levels compared with Kaletra.
 

Pharmacoenhancer replacements for Ritonavir: GS-9350 and SPI-452

GS-9350 (Kearney B. et al., Abstract 40)

  • Potent inhibitor of CYP 3A, without any HIV activity;
  • In Phase I dose escalation study, the highest dose of GS-9350 (200 mg) showed inhibition of CYP 3A similar to 200 mg of RTV. All doses were well tolerated and there were no drug-related Grade 3/4 laboratory abnormalities. There were no changes or differences seen in lipids across all subjects for 14 days.
  • A Phase I pilot study to evaluate a fixed-dose tablet containing GS-9350, Elvitegravir (EVG) 150 mg, and Tenofovir (TDF) 300 mg and Emtricitabine (FTC) 200 mg was performed. Forty-four healthy volunteers were recruited and given EVG/TDF/ FTC plus either 100 mg or 150 mg of GS-9350 in a fixed dose tablet and the concentration gradients of EVG were measured compared to RTV boosted EVG. Both doses produced levels that were considered therapeutic, with the 150 mg dose maintaining levels that were 11 fold greater than IC50 for EVG, without any changes in levels of TDF or FTC. The treatments were well tolerated with two grade 3 adverse events, ALT elevation (GS9350 100 mg FTC), and one subject with appendicitis.

SPI-452 (Guttendorf R, et al. Abst. 41)

  • Study 0452-001 involved 67 subjects who took twodifferent PI agents, either ATV 300 mg or DRV 600 mg, as asingle dose to determine what boosted levels of these drugscould be achieved. They were followed for an additionalseven days to allow the drug to washout and then weregiven increasing dosages of once daily SPI-452 (20 mg, 50mg, or 200 mg or placebo) for fifteen days. The PI agents,Darunavir 600 mg and Atazanavir 300 mg were then alsogiven on the 15th day, as well as a placebo. On day 16,they received only the PI agents and the placebo without anyof the previously used booster.Results showed that SPI-452 was well absorbed and reacheda steady state level within 14 days. There was a pronouncedboosting effect on the peak concentration of both DRV (37-foldincrease) and ATV (13-fold). This boosting effect persistedthrough day 16, when SPI-452 had been discontinued theday prior. Headache, nausea/vomiting and diarrhea were themost common adverse events and there were no safety issues during this 15 day study. SPI-452 is currently formulated in a liquid form which can be an issue for development.

Scientists report that Vicriviroc’s anti-HIV activity is enhanced by Rapamycin

16 January 2009

A group of researchers at the Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, under the direction of R.C. Gallo reported in the December 23, 2008 issue of PNAS that the anti-HIV activity of Vicriviroc, a CCR5 co-receptor antagonist now in clinical Phase III for HIV/AIDS, correlated inversely with the density of the co-receptor on the surface of patients’ lymphocytes. The authors showed that Vicriviroc’s antiviral activity can be improved markedly by combining it with low doses of the transplantation drug Rapamycin, which reduces CCR5 co-receptor density.  The drug combination had synergistic effect against HIV in vitro. Antiviral activity was observed against drug-sensitive and Vicriviroc- or Maraviroc-resistant viral strains.

 

Source: www.hivandhepatitis.com and Heredia et al., PNAS 105(51): 20476-81, 2008

Nobel Prize 2008 awarded for discovery and characterization of important human viruses

12 October 2008

On October 6, the Nobel Foundation announced its decision to award the Nobel Prize in Physiology or Medicine 2008  to Professor Harald zur Hausen from Germany (half of the prize), and to Professor Françoise Barré-Sinoussi and Professor Luc Montagnier from France (sharing half of the prize), for their pioneer work on “two viruses causing severe human diseases”.

Prof. zur Hausen went against current dogma in the 1970s to hypothesize and demonstrate that some human Papillomaviruses (HPV) could integrate their genomic DNA into the genome of human cells and transform them into tumor cells. He was eventually able to demonstrate that cervical cancer in women was caused by HPV, with viral subtypes 16 and 18 most commonly involved in the process. His work was instrumental in understanding HPV biology and diversity, and paved the way to the development of vaccines to prevent HPV infection.

Prof. Barré-Sinoussi worked with Prof. Montagnier in the early 1980s to identify the cause of a new syndrome initially seen more frequently in homosexual patients, characterized by profound immunodeficiency and unusual types of opportunistic infections. They isolated and identified a new retrovirus from lymph nodes and lymphocytes of patients, which became known as human immunodeficiency virus or HIV. Other major groups contributed to the characterization of HIV but the French scientists are generally credited for HIV discovery.

 

Source: Press release from Nobel Assembly at Karolinska Institutet, Oct. 6, 2008

The FDA approves 2008-2009 seasonal Influenza vaccines for distribution in the US

02 September 2008

On August 5, 2008, the Food and Drugs Administration (FDA) announced the approbation of the six Influenza vaccines that will be available in the US for the 2008-2009 flu season. The vaccines are manufactured by CSL Ltd. (Afluria), GlaxoSmithKline (Fluarix), ID Biomedical Corp. (FluLaval), MedImmune (FluMist), Novartis Vaccines (Fluvirin), and Sanofi Pasteur (Fluzone).

Each vaccine contains the same three viral strains, all of which were recommended by the FDA and the World Health Organization (WHO) earlier this year:  A/Brisbane/59/2007 (H1N1)-like virus, A/Brisbane/10/2007 (H3N2)-like virus, and B/Florida/4/2006-like virus.

 
 

Source: FDA News, August 5, 2008

Roche drops all research programs on therapies for HIV/AIDS

22 August 2008

Roche announced in early July 2008 to AIDS specialists and activists that it will abandon its current research programs on therapeutic drugs for HIV/AIDS. The Switzerland-based company had been active since the early days of the HIV epidemic and successfully brought to market innovative anti-HIV drugs, including the first protease inhibitor (Saquinavir, Invirase) and the first entry inhibitor (Enfuvirtide, Fuzeon).

The decision was made following disappointing results in recent clinical trials with novel compounds designed to interfere with HIV protease or viral entry into target cells. Sales of antiretroviral drugs by the company have also been very low last year, leading to a reduced market share.

 
 

Source : Financial Times.com. July 11, 2008

European authorities approve Prepandrix™, a pre-pandemic vaccine for Avian Influenza virus

01 June 2008

On May 19, 2008 GlaxoSmithKline announced that the European Medicines Agency (EMEA) has granted a marketing authorization in all 27 Europe member states for Prepandrix™, a pre-pandemic vaccine against Avian Influenza virus H5N1.

A pre-pandemic Avian Influenza virus vaccine consists in a vaccine that is prepared in advance using viral strains in circulation in areas of the world where sporadic cases of human infection are reported. It is intended to be used immediately after a pandemic is officially declared to provide some protection to the population. During this period, a pandemic vaccine developed specifically for the viral strain identified as the source of the pandemic can be manufactured, a process that takes several months.

Prepandrix™ is a pre-pandemic vaccine based on Avian Influenza virus H5N1 A/Vietnam/1194/04, a viral strain recommended by the World Health Organization (WHO) for this type of vaccine. In clinical trials, the vaccine elicited at least a 4-fold increase in serum neutralizing antibodies in 77% to 85% of subjects against three distinct H5N1 strain variants, A/Indonesia/5/05, A/Anhui/1/05 and A/turkey/Turkey/1/05 respectively.

The vaccine will be stockpiled by European governments in the event of an Avian Influenza virus pandemic and will be administered to people 18-60 years old following immunization plans adopted by member states.

 

Source: GlaxoSmithKline press release, May 19, 2008

Composition of Influenza vaccine for 2008-2009 season

27 February 2008
On February 14, 2008, after reviewing global reports on viral activity, Influenza virus experts of the World Health Organization (WHO) announced their recommendations regarding the composition of the Influenza vaccine for use in the northern hemisphere during the forthcoming Influenza season. A similar meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) took place on February 21, 2008.
 
Both committees recommended the following Influenza virus strains to be included in the vaccines for the 2008-2009 season (November 2008 to April 2009):
  • an A/Brisbane/59/2007 (H1N1)-like virus
  • an A/Brisbane/10/2007 (H3N2)-like virus
  • a B/Florida/4/2006-like virus
 
A recommendation will be made by the WHO in September 2008 regarding the composition of vaccines for the southern hemisphere for the next Influenza season (May to October 2009).
 
 

Sources: WHO press release, Feb. 14, 2008, and FDA press release, Feb. 25, 2008

 

Influenza virus strains recommended by WHO for inclusion in vaccines in recent years

Season Hemisphere Subtype A Subtype B
2007-08     Northern
  • A/Solomon Islands/3/2006(H1N1)-like virus
  • A/Wisconsin/67/2005 (H3N2)-like virus
  • B/Malaysia/2506/2004-like virus
2007 Southern
  • A/New Caledonia/ 20/99 (H1N1)-like virus
  • A/Wisconsin/67/2005 (H3N2)-like virus
  • B/Malaysia/2506/2004-like virus
2006-07 Northern
  • A/New Caledonia/20/99 (H1N1)-like virus
  • A/Wisconsin/67/2005 (H3N2)-like virus
  • B/Malaysia/2506/2004-like virus
2006 Southern
  • A/New Caledonia/20/99 (H1N1)-like virus
  • A/California/7/2004 (H3N2)-like virus
  • B/Malaysia/2506/2004-like virus
2005-06 Northern
  • A/New Caledonia/20/99 (H1N1)-like virus
  • A/California/7/2004 (H3N2)-like virus
  • B/Shanghai/361/2002-like virus
2005 Southern
  • A/New Caledonia/20/99 (H1N1)-like virus
  • A/Wellington/1/2004 (H3N2)-like virus
  • B/Shanghai/361/2002-like virus

Carraguard® is safe as microbicide but does not prevent HIV transmission

18 February 2008
On February 18, 2008 the nonprofit research organization Population Council announced the results of a clinical Phase III trial completed in South Africa with the candidate microbicide Carraguard®. According to the sponsor, Carraguard® proved to be safe for vaginal use in women. Unfortunately, the product showed no efficacy at preventing male-to-female HIV transmission during vaginal intercourse.
 
The clinical trial was initiated in March 2004 and ended in March 2007. It enrolled more than 6,202 seronegative women at three sites in South Africa. The women received either Carraguard® and condoms or a placebo gel and condoms, along with HIV education, risk-reduction and safer-sex counseling. During the trial, there were 134 new cases of HIV infection in the Carraguard® group (an incidence of 3.3 infections per 100 woman-years), and 151 new cases of HIV infection in the placebo group (an incidence of 3.7 infections per 100 woman-years). There was no statistically significant difference between the two groups.
 
Carraguard® is made of carrageenan, a seaweed derivative classified by the FDA as “Generally recognized as safe”. The product had showed efficacy at preventing HIV infection of cells in culture. In addition, it protected mice from infection by other sexually transmitted pathogens. Extensive safety studies had also been completed with success in earlier clinical trials with humans. 
 
The Phase III trial was funded by USAID and the Bill & Melinda Gates Foundation. The Population Council is now developing next-generation microbicides using Carraguard® gel combined with other antiviral compounds.
 
 

Source: Population Council news release, February 18, 2008

FDA grants accelerated approval to Etravirine, a novel non-nucleoside reverse transcriptase inhibitor for HIV/AIDS

18 January 2008
On January 18, 2008 the FDA officially announced the accelerated approval of Tibotec’s experimental drug Etravirine (Intelence, TMC125) as a new drug to treat patients with HIV/AIDS.
 
Etravirine represents a new compound added to the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), which interfere with the activity of HIV reverse transcriptase by binding outside the active site of the enzyme. It is the first NNRTI to be approved since Bristol-Myers Squibb’s Sustiva in 1998.
 
One of the main assets of the new drug is its activity against HIV strains resistant to other antiviral agents including NNRTIs already on the market. FDA’s approval was based mainly on the results of two Phase III clinical trials, DUET-1 and DUET-2. Etravirine will be used in combination with other antiretroviral drugs in treatment-experienced patients who have evidence of viral replication and HIV-1 strains resistant to a NNRTI and other drugs. Like previous NNRTI drugs, Etravirine’s side effects include rash. The new drug also shows significant interactions with other compounds used to treat HIV-infected patients.
 
 

Source: FDA press release, January 18, 2008

FDA announces approval of rapid detection test for 4 respiratory viruses

18 January 2008
On January 18, 2008, the FDA announced the approval for market of ProFlu+, a new test manufactured by Prodesse Inc. of Milwaukee. The test is based on real-time multiplex PCR amplification of viral genetic material potentially present in secretions taken from the back of the throat in patients. It is specifically designed to detect Influenza virus type A, Influenza virus type B, Respiratory Syncytial virus subtype A and Respiratory Syncytial virus subtype B. These four viruses are commonly associated with respiratory illnesses such as Influenza, bronchiolitis and pneumonia and are leading causes of lower respiratory tract infections.
 
ProFlu+ is designed as a complement to other diagnostic tools and has the advantage of delivering results in about 3 hours only. The test has already been released on the European market in October 2007.
 
Prodesse Inc. is currently developing other similar tests such as Pro hMPV+ for detection of Human Metapneumoviruses and ProParaflu+ for differentiation of Parainfluenza viruses.
 
 

Sources: FDA press release, January 18, 2008, and Prodesse press release, January 4, 2008

FDA approves new test to detect and identify 12 respiratory viruses from a single sample

03 January 2008
On January 3, 2008, the FDA announced the approval for market of a new test called xTAG Respiratory Viral Panel, which is manufactured by Luminex Molecular Diagnostics of Toronto, Canada. The test allows the specific detection and identification of a series of 12 human viruses causing respiratory illnesses: Influenza A virus (no specific subtypes), Influenza A virus subtypes H1 and H3, Influenza B virus, Respiratory Syncytial virus subtypes A and B, Human Metapneumovirus, Parainfluenza virus 1, 2 and 3, Rhinovirus, and Adenovirus.
 
The xTAG panel is the first FDA-cleared test for infectious respiratory disease viruses that uses a multiplex platform, allowing several tests to be processed using the same sample. It is designed as a PCR-based nucleic acid amplification of specific viral sequences present in secretions taken from the back of the throat in patients with possible respiratory tract infections. In the test, specific color-coded microspheres (beads) bind to the amplified viral genetic material and are read by lasers so that the specific virus can be identified.
 
 

Sources: FDA press release, January 3, 2008, and Luminex Molecular Diagnostics website

Antiviral InteliStrat Inc. reaches a new milestone

05 October 2007
Antiviral InteliStrat Inc. proudly announces that its proprietary Database now contains strategic information on more than 1800 compounds and vaccines for viral diseases, compared to about 1700 a few months ago. This represents the largest collection of data of its kind exclusively dedicated to products for the prevention and treatment of infections in humans caused by viruses from one of more than 21 viral families.
 

The Database regroups product files for over 690 inhibitor compounds, 860 vaccines, 140 immunomodulator agents, and 90 antibody products among others. The files detail the nature and properties of the products, mechanism of action, viral resistance, some preclinical and clinical information currently available, along with sponsors and development status. The products included in the database represent all stages of development, from basic research to market status. Several of the products are still in development, while others have been dropped from clinical trials, making the Database a real testimony to the efforts deployed globally by mankind in its fight against viral diseases.

Antiviral InteliStrat Inc. launches its "Ultimate Database" on antiviral drugs and vaccines

15 May 2007
Antiviral InteliStrat Inc announced today that it has launched a unique database that has no equivalent worldwide. The company has assembled the most complete and detailed database ever made on drugs and vaccines for viral infections in humans. It contains over 1,700 files describing compounds and vaccines developed exclusively for viral diseases by more than 450 sponsors, all accessible on a single web site.
 
Exclusively dedicated to antiviral drugs and vaccines, the database is designed primarily to provide the most up-to-date information to analysts, scientists and decision makers in the pharmaceutical and biotech industry or in the academia who are involved at any level in the discovery and development of preventive and therapeutic treatments for viral diseases.
In addition to drugs and vaccines currently available on the market, the database also contains several hundreds of products that are either filed for approbation by regulatory authorities, still being evaluated in clinical trials, or at earlier stages of development. The database even includes several products that failed at one point during development and were abandoned, products that can still provide valuable information.
 
About Antiviral InteliStrat Inc.
 
Antiviral InteliStrat Inc is a Laval-based society founded by expert virologists, aimed at offering the most recent information to specialists in the domain in order to speed up the discovery and development of novel products for prevention and treatment of viral diseases in humans. The society’s mission is to become the reference for information regarding new antiviral compounds and vaccines. To learn more about the society, visit www.antiviralintelistrat.com.  
 
For more information: Jocelyn Yelle, Ph.D., President, Antiviral InteliStrat Inc., (450) 688-7101, cell phone : (514) 816-8856   jyelle@antiviralintelistrat.com.

The Web site and online database have been realized by K3 Media.

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