Antiviral InteliStrat Inc.

Link to Editorial published in STAT News, August 27, 2018, by Ruth Faden, Ruth Karron, and Carleigh Krubiner:

https://www.statnews.com/2018/08/27/ebola-vaccine-pregnant-lactating-women/

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

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

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

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

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.

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

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)

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

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.

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

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

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

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

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)

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

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.