Singapore, Jan 13, 2010: It has been known for many years that Human Immunodeficiency Virus is an extremely difficult virus to render inactive, and no cure presently exists. Research for a viable HIV vaccine is one of the several strategies to fight AIDS, with other approaches based upon antiviral treatments such as highly active antiretroviral therapy (HAART).
There is an evidence that a vaccine may be possible. Work with monoclonal antibodies (MAb) has proven that the human body can defend itself against HIV. More recently in 2009, the number of potential candidates for antibodies and early stage results from clinical trials have been announced by various teams.
However, these are all early results, and have not been developed to the point of human testing. The HIV/AIDS virus mutates rapidly, which makes it extremely skillful at developing resistance to drugs. To minimize this risk, people with HIV are generally treated with a combination of HAART, that attack the virus on several fronts at once. The introduction of HAARTs in 1996 transformed the treatment of HIV, improving the quality and prolonging the lives of many infected people. Nevertheless, they are not a cure.
Although the price of HAART has fallen significantly in recent years, their cost remains an obstacle to access in the developing world. Moreover, the health infrastructure required to deliver antiretroviral therapy is lacking in many places.
The urgency of the search for a vaccine against HIV stems from the AIDS-related death toll of over 60 million people since 1981. Despite the intense international response to the HIV/AIDS pandemic, HIV continues to spread, causing more than 14,000 new infections every day, and 95 percent of these are in the
developing world.
Therefore, an HIV vaccine is generally considered as the most likely, and perhaps the only way by which the AIDS pandemic can be halted. However, after over 25 years of research, HIV-1 remains a difficult target for a vaccine. Status of development
Status of Development
In February 2003, the AIDSVAX vaccine from Vaxgen, CA, US, was declared a failure in North America as there was not a statistically significant reduction of HIV infection within the study population. In November 2003, it also failed clinical trials in Thailand for the same reason. These vaccines both targeted gp120 and were specific for the geographical regions.
In September 2007, it was announced that the trial for V520 (funded by National Institute of Allergy and Infectious Diseases (NIAID), which is a division of the National Institutes of Health (NIH), and the pharmaceutical company Merck) would be discontinued after it determined that the vaccination was ineffective. Additionally, it was also concluded that V520 may have made some recipients more receptive to infection by HIV-1. Merck developed the experimental vaccine called V520 to stimulate HIV-specific cellular immunity, which prompts the body to produce T cells that kill HIV-infected cells. In the previous smaller trials, this vaccine was found to be safe, because of the lack of adverse effects on the patients. The vaccine showed induced cellular immune responses against HIV in more than half of the volunteers. The HVTN expected to finish the study in 2009, but ceased further treatment administration and declared that the vaccine was ineffective at preventing HIV-infection
In September 2007. The results of the V520 trial caused other companies and institutions engaged in HIV vaccine research to call for a re-examination of their vaccine development strategies. It was only in November 2009, the world witnessed the first successful HIV vaccine trial in history. The study results representing a significant scientific advance, was the first demonstration that a vaccine can prevent HIV infection in adult population, and are of great importance.
The trial named as RV144 HIV vaccine study results, revealed a 31.2 percent vaccine efficacy in preventing HIV infections. These results have instilled new hope in the HIV vaccine research field and promise that a safe and highly effective HIV vaccine may become available in the world. No vaccine safety issues were observed in the trial
.
The phase III trial, involving 16,395 adult male and female volunteers in Thailand, was a test-of-concept of a novel HIV vaccine regimen with two different candidate vaccines developed by Sanofi-Pasteur and the non-profit organization Global Solutions for Infectious Diseases. The trial was performed by the Thai Ministry of Public Health, and sponsored by the United States Army Surgeon General. It received funding from the United States National Institute for Allergy and Infectious Diseases and the United States Army Medical Research.
The most recent development in this direction is the Indian HIV/AIDS vaccine entering the final stage this month with scientists from the Tuberculosis Research Center (TRC), Chennai, and the National AIDS Research Institute (NARI), Pune, giving the last round of shots to 32 candidates enrolled in trials. The trial, one among the approximately 150 trials currently underway worldwide, combines a DNA and vector-based vaccine for the dreaded disease. The investigational vaccine candidate, TBC-M4, is designed to protect people who are not infected with HIV from contracting HIV/AIDS. The vaccine candidate consists of a recombinant Modified Vaccinia Ankara (MVA) targeting HIV-1 subtype C, the most predominant HIV subtype in India
In August 2008, when TRC reported the first significant progress in the clinical trials of the vaccine, it was only a vector-based vaccine and scientists said the results could be improved substantially. TRC, an Indian Council of Medical Research (ICMR) institute, had done the trials along with National AIDS Control Organization (NACO) and the International AIDS Vaccine Initiative (IAVI).
The results so far showed that it was safe and have shown some stimulating immune response. For the second round of trials, TRC and NARI have recruited 16 healthy volunteers. Of these, six have already received two shots of the DNA vaccine at the beginning of the trial and subsequently after a month, followed by the MVA vaccine in the third month; six received two doses of the MVA vaccine. All of them will receive the last shot of MVA this month. Four other volunteers would receive placebos.
Early this year, the South African AIDS Vaccine Initiative also announced the start of a trial to study a vaccine candidate developed by local South African scientists. These developments show the HIV vaccine research and development is continuing to move forward.
Asia scenario
Asia has been the base for some extremely successful large-scale HIV prevention programs. The choice of Thailand as the latest venue for the RV 144 Clinical Trial has made it the world’s most popular region, into the spotlight regarding the HIV/AIDS pandemic and the global response to it.
While the majority of the world’s approximately 40 million HIV-infected individuals live in sub-Saharan Africa, the Asia-Pacific region now accounts for about one in four of new infections occurring across the globe each year.
Among millions of HIV infected individuals in Asia, few receive the antiretroviral treatment and there are very few institutes involved in HIV vaccine research. A major barrier to the treatment access in Asia is the high cost of antiretroviral drugs, as both first and second line drugs are still unaffordable to many governments and the barrier to vaccine research is fund.
Cheaper generic anti HIV drugs are now produced by a number of pharmaceutical manufacturers in Asia. At least 25 to 30 Asian companies are manufacturing anti-HIV drugs that are becoming increasingly available in the region and elsewhere. Yet even where drugs are available, the poor state of healthcare in many Asian countries is hindering governments’ abilities to organize life-long treatment programs for millions of people living with HIV. Moresoever, there are very few institutes actively engaged in HIV vaccine research.
Funding scenario
Public agencies and institutions dominate R&D funding for HIV vaccines followed by the philantropic funders like the Bill & Melinda Gates Foundation and the Wellcome Trust and the commercial sector. Interest in HIV prevention research from public, private and philanthropic funders over the last decade has supported key R&D priorities, moved the field forward and brought it closer to new HIV prevention options.
A new report released by UNAIDS, estimates that an investment of $25 billion will be required for the global AIDS response in 2010 for low and middle-income countries—$11.3 billion more than is available today.
The investment needs is based on the country-defined targets to reach universal access to HIV prevention, treatment care and support by 2010. The HIV Vaccines and Microbicides Resource Tracking Working Group report identified investments of almost $1.2 billion in HIV prevention research in 2008, of which $868 million supported vaccine R&D, and $244 million supported microbicide R&D, while other HIV prevention R&D received much lower levels of funding. AIDS vaccine research declined for the first time since 2000, falling by 10 percent from 2007 levels.
At the same time, funding for both microbicides and pre-exposure prophylaxis (PrEP) increased by eight and 13 percent, respectively. “Research to develop new HIV prevention tools and strategies is essential to prevent new infections, and an HIV vaccine still holds the greatest hope to ending the epidemic. It is vitally important that investments into research for HIV prevention be sustained and increased for as long as it takes to reach those goals,” states Michel Sidibe, Executive Director of UNAIDS in the report. Funding in HIV vaccine research has seen key shifts in the last two years. The halting of the STEP and Phambili vaccine trials in late 2007, which were testing a candidate vaccine developed by Merck, ended the only pharmaceutical company partnerships for HIV vaccine research.
This resulted in a decline in not only the industry funding levels but also among the public groups in 2008. However post RV144 trial, the funding situation seemed to recover. Levels were even lower across other HIV prevention research priorities. The private groups have continued to provide ARV compounds for development as potential microbicides, and as oral PrEP.
The Working Group also reports that there is an increased investment in microbicide R&D which reflects increased interest in research on antiretroviral (ARV)- based candidates over vaccine. Increased funding for microbicide R&D over the past decade has fostered a major expansion for the field; clinical trials of microbicide candidates have been conducted in 27 countries around the world. And although there have been few failures, the recent developments show that the search for a viable vaccine against HIV is continuing to move forward.
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