Antiviral InteliStrat Inc.

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.