By Kristen Jill Kresge and Roberto Fernandez-Larsson, Ph.D.
US Reverses Restriction on Global Fund Grant Recipients
The US government recently reversed its decision to force all international recipients of funding from the Global Fund to Fight AIDS, Tuberculosis, and Malaria to publicly condemn commercial sex work. Countries that receive money directly from the US government will still be required to comply with this restriction, which is part of the administration’s global AIDS initiative. But Randall Tobias, director of the President’s Emergency Plan for AIDS Relief (PEPFAR), rejected extending the plan to the 128 countries that currently receive Global Fund grants.
The announcement from Tobias came just weeks after Brazil made headlines for refusing millions of dollars in grants from the US Agency for International Development (USAID). Brazil rejected the grants because accepting the funding required the country to sign a pledge denouncing commercial sex work. A Brazilian national commission of scientists, cabinet members, and activists made the decision to decline the US grants because the country’s AIDS outreach and education programs work closely with marginalized, and often stigmatized, groups like sex workers, injection drug users, and other at-risk groups. The Brazilian commission decided that denouncing commercial sex work, which is legal in the country, would jeopardize this work.
“Many NGOs in Brazil are supporting the Ministry of Health position to refuse money from USAID. I believe the most important thing is to have a clear understanding about institutional interests, independently of who is the sponsor,” says Octavio Valente of Grupo Pela Vidda, a non-governmental organization based in Rio de Janeiro.
Brazil was the first country to refuse grant money based on a restriction imposed by the US. Human Rights Watch recently criticized Uganda, a major beneficiary of PEPFAR grants, for altering its HIV prevention programs to emphasize abstinence due to pressure from the US.
Although grants directly from the US government will still require countries to publicly express disapproval of sex work, more than 33,000 other organizations would have been affected if this policy were broadened to include countries receiving donations from the Global Fund. The US contributed a third of the money currently available through the Global Fund, which has thus far committed US$3 billion to public service organizations throughout the world. Multilateral organizations like the Global Fund had the right to refuse restrictions from donor countries until the US Justice Department revised its policy last year.
Several grass-roots organizations protested extending the limitation to the Global Fund by arguing that there is no advantage to forcing AIDS service organizations to stigmatize commercial sex workers. Tobias rescinded the requirement as he prepared to travel to Africa to meet with grant recipients. —KJK
New Arm of HVTN Trial Opens in Botswana
The HIV Vaccine Trials Network opened another arm of its HVTN 059 trial at a site in Gaborone, Botswana. Trial sponsors in Botswana plan to enroll 24 HIV-uninfected volunteers at low risk for HIV into this Phase I trial. All volunteers will receive three injections of the vaccine candidate, AVX101.
The Botswana arm of the trial is being run in cooperation with the Botswana Harvard AIDS Institute Partnership and the Ministry of Health. Several other sites in the US and South Africa are already participating in this trial. The National Institutes of Allergies and Infectious Diseases (NIAID) is conducting the US arm of the study along with AlphaVax, the manufacturer of the vaccine.
The Phase I study in Botswana will primarily evaluate the safety of the vaccine candidate. Immunogenicity will also be monitored as a secondary outcome of the trial. The vaccine candidate utilizes a replication defective alphavirus replicon vector derived from an attenuated strain of the Venezuelan Equine Encephalitis (VEE) virus, developed by the US-based company AlphaVax. Removal of the capsid gene and insertion of two mutations into the virus’s glycoprotein gene render it replication defective and therefore safe for testing in humans. The vector expresses the gag gene from HIV subtype C, which is predominant in sub-Saharan Africa. This trial will evaluate four possible doses of AVX101.
The start of this trial in Botswana was met with optimism. The country has one of the most serious HIV epidemics in the world with an adult prevalence estimated at 37% in 2003. Although Botswana has a nationally-sponsored treatment program for HIV-infected individuals, the uptake has been slow. The US Centers for Disease Control and Prevention estimates that only 10,000 people of the 110,000 in need are receiving treatment. —KJK
World AIDS Vaccine Day Commemorated
The annual World AIDS Vaccine Day took place on May 18th, eight years after US President Bill Clinton delivered an historic speech calling for new commitment worldwide toward the development of an AIDS vaccine. Clinton said, “Only a truly effective, preventive HIV vaccine can limit and eventually eliminate the threat of AIDS.”
This year was marked by several international community events. Five different regions of Kenya sponsored activities including advocacy walks and rallies featuring speeches by many organizations active in the search for an AIDS vaccine. The community activities emphasized the importance of partnerships between the potential trial volunteers, the scientific and research community, and the political leaders. Many AIDS organizations also used the day to emphasize the urgent need for an effective vaccine. The International AIDS Vaccine Initiative (IAVI) issued a statement detailing some of the challenges and promises of vaccine research. The AIDS Vaccine Advocacy Coalition also released their updated handbook on AIDS vaccines on the eve of World AIDS Vaccine Day. To view the IAVI statement or for more information on the AVAC handbook, visit www.iavi.org orwww.avac.org. —KJK
San Francisco Prepares for AIDS Vaccine Trial by Targeting Potential Volunteers
On the eve of hosting a large-scale AIDS vaccine trial, the San Francisco Department of Public Health (SFDPH) launched a new educational campaign to address public fears and misconceptions about participation in vaccine trials. The SFDPH created the website SFisReady.org to educate San Franciscans on AIDS vaccines and to encourage people to enroll in vaccine trials. This project was done in partnership with ISIS Inc, a nonprofit sexual health information agency and was announced on May 18th, World AIDS Vaccine Day.
The website provides concise information on AIDS vaccines, the eligibility requirements for participation in the trial, and the commitment required from potential volunteers. But all volunteers will still undergo a rigorous informed consent process detailing all of the benefits and potential risks of trial participation if they are interested in volunteering.
One common misconception about vaccine trials is that they put volunteers at risk for HIV infection. “Our goal is simple,” said Tom Kennedy, Director of Health Communications at ISIS in a statement. “We want to end the myth once and for all. You can’t get HIV from doorknobs and you can’t get it from vaccine trials.”
San Francisco is one of many US cities participating in a large-scale Phase IIb vaccine trial with the Merck vaccine candidate, an adenovirus serotype 5 (Ad5) vector containing the HIV genes gag, pol, and nef. The trial will enroll 1,500 people in 28 cities worldwide. This trial is a ‘proof-of-concept’ study and will evaluate the candidate’s ability to prevent HIV infection or slow disease progression in those who become HIV infected. A Phase III trial involving several thousand volunteers will be necessary if this study generates promising results and more ambitious public education campaigns may be required at this stage. For more information on this vaccine candidate or the trial, see the IAVI Database of AIDS Vaccines in Human Trials at /trialsdb/. —RFL
Merck Presents Protection Data on Rotavirus Vaccine
New data on the safety and efficacy of a live reassortant human-bovine rotavirus vaccine developed by Merck and Co., known as ROTATEQ, was recently presented at the annual meeting of the European Society for Paediatric Infectious Diseases in Valencia, Spain, on May 18-20. The company submitted a Biologics License Application for this vaccine to the US Food and Drug Administration (FDA) in April. Rotavirus is the most common cause of severe diarrhea among children and kills, due to severe dehydration, 1 in every 300 infants in developing countries, resulting in the death of more than 500,000 children annually worldwide.
In 1998 the FDA approved for use in children a live reassortant rhesus macaque-human rotavirus vaccine called Rotashield, developed by Wyeth. Subsequently the Advisory Committee on Immunization Practices (ACIP) decided that the vaccine should no longer be recommended for infants in the US because of a few rare cases of bowel obstruction (intussusception) among some infants during the first 1-2 weeks after vaccination. The risk of intussusception following Rotashield immunization was estimated to be 1:10,000 to 1:32,000 vaccinees.
The most recent study with the pentavalent ROTATEQ vaccine candidate (against serotypes G1, G2, G3, G4, and P1A) was tested for the incidence of intussusception in a group of 70,000 healthy 6- to 12-week old vaccinated infants. They found no statistical difference in the incidence of intussusception in vaccinated infants in the post-vaccination period or through three years of follow-up compared with the placebo group.
The vaccine was evaluated for efficacy against rotavirus dehydrating acute gastroenteritis in a double blind, placebo-controlled study conducted from 2001 to 2004 in 5,700 healthy 6- to 12-week old infants in the US (including the Navajo and White Mountain Apache Nations) and Finland. Infants were randomized to receive either 3 doses of the oral vaccine or placebo at 4- to 10-week intervals. Efficacy of the vaccine against rotavirus acute gastroenteritis of any severity caused by all vaccine serotypes was 74%, but the efficacy against severe rotavirus dehydrating acute gastroenteritis was 98%, the type associated with death by rapid dehydration.
Merck's vaccine is not the only rotavirus vaccine that could soon come to market. GlaxoSmithKline (GSK) has an attenuated human rotavirus candidate vaccine called Rotarix that is also in advanced safety trials.
In February the Global Alliance for Vaccines and Immunizations awarded the Program for Appropriate Health Technologies a US$30 million grant over 3 years to promote the use of rotavirus vaccines once they are licensed.—RFL