By Kristen Jill Kresge
Two preventive AIDS vaccine trials begin
GeoVax, a US-based biotechnology company, recently began enrolling volunteers for a Phase I trial to evaluate the safety and immunogenicity of the company's AIDS vaccine candidates at four US sites in conjunction with the HIV Vaccine Trials Network (HVTN).
The vaccine utilizes a prime-boost immunization strategy to first deliver two doses of a DNA plasmid vaccine comprised of gag, pro, RT, env, tat, rev, and vpu genes from clade B HIV. This will be followed by two booster immunizations with a modified vaccinia Ankara (MVA) vector carrying clade B gag, pol, and env genes. These candidates were developed by Harriet Robinson at Emory University's Yerkes National Primate Research Center in Atlanta, who is also a co-founder of GeoVax, in collaboration with researchers at the US National Institutes of Health (NIH) and the US Centers for Disease Control and Prevention (CDC). The DNA candidate was tested in a previous safety trial in three US cities.
The trial will be conducted in multiple phases in order to determine the optimal dose and schedule for delivery of the prime-boost vaccinations, beginning with a dose-escalation study in only 12 volunteers. Once safety and immunogenicity data for this group are reviewed, a higher dose of the two candidates will be administered to 36 volunteers. Subsequently a larger group of 72 volunteers will then receive the higher dose in a study intended to optimize the dosing schedule.
A second trial also began recently in Zambia to evaluate the safety and immunogenicity of tgAAC09, an AIDS vaccine candidate that uses an adeno-associated virus (AAV) vector carrying genes for clades A and C HIV. This Phase II trial is the first AIDS vaccine trial to take place in the country and is being conducted by IAVI in collaboration with the Zambia Emory HIV Research Project.
The vaccine candidate was developed by US-based biotechnology company Targeted Genetics in collaboration with IAVI and the Children's Hospital in Columbus, Ohio. Safety and immunogenicity data from a series of Phase I trials using a lower dose of tgAAC09 in Belgium, Germany, and India should be available later this year. This Phase II study is a multi-center trial and volunteers are also being enrolled at sites in South Africa and Uganda.
Vaccine against human papilloma-virus receives US approval
The first vaccine capable of preventing cervical cancer recently received approval and licensure by the US Food and Drug Administration (FDA) for use in females ages 9-26. Gardasil, the quadrivalent vaccine manufactured by Merck, also prevents the development of precancerous genital lesions and genital warts caused by four types of the human papillomavirus (HPV), which is the most common sexually-transmitted infection in the US according to the CDC and is responsible for 3700 deaths each year (see Cervical cancer vaccines, IAVI Report 9, 5, 2005).
The efficacy of the vaccine, administered through 3 immunizations over a period of 6 months, was illustrated in 4 Phase III trials conducted in 21,000 women in several countries. At the end of June the CDC's Advisory Committee on Immunization Practices will consider recommending vaccination with Gardasil. This recommendation greatly influences whether or not the vaccine is routinely used and will open the possibility that the high cost of vaccination will be covered by national health insurance programs in the US.
However, the greatest need for the vaccine lies in developing countries, where the majority of the 250,000 deaths from cervical cancer occur each year. On June 5, the Bill & Melinda Gates Foundation awarded the Seattle-based not-for-profit organization Program for Appropriate Technology in Health (PATH) a US$27.8 million grant to conduct a five-year effort to ensure that this vaccine is made available to women and girls in developing countries. PATH is collaborating with Merck and GlaxoSmithKline, which also manufactures a cervical cancer vaccine, as well as officials in Peru, India, Uganda, and Vietnam to establish mechanisms for financing purchase of these vaccines and to ease introduction efforts.
World AIDS Vaccine Day commemorated
On May 18 communities around the world held events to commemorate an annual day dedicated to the development of a safe and effective AIDS vaccine. Activities in Uganda were organized by several of the organizations conducting vaccine trials or preparatory work in the country, including IAVI, the Uganda Virus Research Institute, Makerere University, Walter Reed Army Institute of Research, and US-based Johns Hopkins University. Several local AIDS groups and non-governmental organizations held a march through the city and the AIDS Information Center provided free voluntary counseling and testing for HIV. It is estimated that 6000 people attended these events.
In collaboration with the Vaccine Support Networks and the Ministry of Health's National sub-committee on AIDS vaccines, IAVI sponsored several events in five provinces throughout Kenya. The US National Institutes of Health also sponsored several community events throughout the US. Other activities were held in India, as well as many other countries around the world, to raise awareness and highlight advances in the field.
This day was chosen as a reminder of the urgent need for an AIDS vaccine after US President Bill Clinton called for a renewed commitment toward the development of a vaccine by saying "only a truly effective, preventive HIV vaccine can limit and eventually eliminate the threat of AIDS."
United Nations convenes annual meeting on AIDS to adopt an updated political declaration
Just days before researchers and activists around the world marked the 25th year of battling the HIV epidemic, the United Nations General Assembly Special Session (UNGASS) on HIV/AIDS convened in New York City to revise the "declaration of commitment" on AIDS, which was created at the first meeting of this kind held five years ago. This high-level event, held from May 31 to June 2, was attended by more than 10 heads of state and leaders from more than 140 UN member states, as well as over 1000 representatives from activist groups and other civil society organizations.
Although few of the goals laid out in the 2001 declaration adopted by the General Assembly were achieved, the total expenditure on AIDS in developing countries, which reached $8.3 billion last year, did fall within the target range of $7-10 billion set in the initial document. This money has in part provided treatment for the 1.3 million people now receiving antiretrovirals (ARVs), up from just 240,000 in 2001, and helped to quadruple the number of people accessing voluntary HIV counseling and testing services.
But now the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that $20-23 billion will be needed each year until 2010 to control the spread of AIDS and provide ARV treatment, care, and prevention services. The record number of civil society groups involved in the meeting pushed for the assembly to endorse a new target of providing ARVs to 80% of HIV-infected individuals in need and to an equal number of HIV-infected pregnant women to prevent them from transmitting the virus to their infants. However after extensive negotiations many of the organizations involved, including the International AIDS Society and the International Council of AIDS Service Organizations, were disappointed with the final declaration.
Many said that it failed to set concrete goals for the future by which progress could be measured. Instead much of the wrangling during the three-day meeting was centered on language as several countries and organizations became embroiled in the use of terms like "vulnerable groups" to describe men who have sex with men, transactional sex workers, or injection drug users, who are at increased risk of HIV infection.
Prior to the meeting IAVI and its partners worked to ensure that the UN leaders recognized how research into new prevention technologies, like vaccines and microbicides, could play an important role in combating the epidemic in the future and in the final declaration AIDS vaccines were acknowledged as crucial to global public health.
Just before UNGASS took place, UNAIDS released the 2006 Report on the global AIDS epidemic. This report highlighted the accomplishments of the last five years, while also pointing out that few of the countries fulfilled their commitments based on the 2001 declaration. The report cited a slowdown in the global epidemic for the first time, highlighted by a decline in HIV prevalence in Kenya, Zimbabwe, Burkina Faso, Haiti, and other countries in the Caribbean. But even as infection rates are dropping in some areas, the overall number of people dying from AIDS or AIDS-related illnesses continues to rise. Increasing HIV prevalence was reported in several countries, including China, Indonesia, Papua New Guinea, and Vietnam, and there is evidence of possible "HIV outbreaks" in Bangladesh and Pakistan, according to UNAIDS.
This report also declared India as the nation with the highest number of HIV-infected individuals at 5.7 million, surpassing South Africa, which still has the greatest prevalence owing to its much smaller population. While HIV prevalence is declining in four Indian states where efforts have been focused on improving access to prevention services, the epidemic in South Africa shows no evidence of decline.