First Clinical Trial With a Novel Adenovirus Vector Begins
The Vaccine Research Center (VRC) at the US National Institute of Allergy and Infectious Diseases (NIAID) in partnership with GenVec recently began a Phase I clinical trial to evaluate the safety and immunogenicity of a novel adenovirus serotype 35 (Ad35)-based AIDS vaccine candidate in 15 volunteers. Vaccine candidates based on the more commonly circulating serotype Ad5 are now being tested in two large Phase IIb trials by the US-based company Merck in North and South America, the Caribbean, Australia, and South Africa and in a series of Phase II trials by the VRC. The VRC is also preparing to begin a Phase IIb trial with their DNA and Ad5 candidates in a prime-boost strategy through the Partnership for AIDS Vaccine Evaluation (PAVE).
One possible drawback to using Ad5 as a vector is the high prevalence of the naturally-circulating virus, especially in developing countries. People previously infected with Ad5 may have pre-existing immunity to the viral vector that could hinder their immune responses to the AIDS vaccine candidate. Ad35 has a much lower prevalence globally. Using a different serotype also opens up the possibility of using two different adenovirus vectors in a prime-boost strategy (see One-two combination). Previous studies have shown that immune responses are often blunted when non-human primates are given multiple immunizations with candidates that used Ad5 vectors.
The VRC's two-part trial will evaluate the safety of an intramuscular injection of the vaccine candidate at three different doses. Once the safety data is reviewed researchers will evaluate the safety and immunogenicity of the candidate when administered in combination with the VRC's Ad5 candidate.
Other groups, including IAVI and Dan Barouch of Beth Israel Deaconess Medical Center in Boston, are also investigating alternate serotypes of adenovirus for use as AIDS vaccine vectors. Barouch and colleagues expect to begin Phase I clinical trials later this year with two candidates—one using an Ad26 vector, which appeared more immunogenic than Ad35 in their non-human primate studies, and another with an Ad5/Ad48 chimeric vaccine vector. -Kristen Jill Kresge
UN Secretary General Appoints New AIDS Envoy for Africa
Elizabeth Mataka, formerly the executive director of the Zambia National AIDS Network and the vice-chair of the board for the Global Fund to Fight AIDS, Tuberculosis, and Malaria, was recently appointed to the position of Special Envoy for AIDS in Africa by Ban Ki-moon, the Secretary General of the United Nations (UN). Mataka is a native of Botswana and has been involved in HIV/AIDS prevention, treatment, and care for the past 16 years. She succeeds Stephen Lewis, who left the post after five years when previous Secretary General Kofi Annan retired at the end of 2006.
During his time as Special Envoy Lewis spoke passionately about the devastation that HIV/AIDS is causing in Africa and he became one of the most outspoken and well-known advocates for the rights of women on the continent (see An Interview with Stephen Lewis, IAVI Report 9, 3, 2005). The appointment of Mataka fulfills Lewis's request that his replacement be an African woman. She is the first African to hold the position of Special Envoy at the UN and as she assumes the post, the situation facing African women has never been more dire. As HIV continues to spread in sub-Saharan Africa, women are increasingly becoming infected. It is estimated that 4.6% of young women in sub-Saharan Africa are currently living with HIV, compared to 1.7% of young men. The most recent incidence study conducted in South Africa found the highest rates of new infections were occurring in young women between the ages of 20 and 29 (see Moving targets). -Kristen Jill Kresge
Female Contraceptive Diaphragm Shows No HIV Prevention Benefit
The recently completed study of the female contraceptive diaphragm indicates that the cervical barrier does not provide any additional benefit over already available prevention strategies in reducing HIV transmission in women. This first randomized controlled trial of the latex diaphragm was conducted by researchers at the University of California, San Francisco (UCSF) Women's Global Health Imperative and involved nearly 5000 female volunteers in Durban and Johannesburg, South Africa and Harare, Zimbabwe. Results of the trial showed that HIV incidence rates among women in the control group who only received condoms and counseling were nearly identical—at around 4%—to those seen in women who also received a diaphragm and lubricating gel. During the 18-month study, 158 new HIV infections occurred in the group of women who received the diaphragm, with 151 occurring in the control group (Lancet 370, 251, 2007).
Nancy Padian, principal investigator of the trial, says these results do not support adding the diaphragm to the current list of HIV prevention strategies. She promoted the idea of testing the diaphragm, which shields the cervix during sex, as a way to prevent HIV transmission after research initially conducted at UCSF suggested that the cervix may be a potential hot-spot for HIV infection (see Capping infection, IAVI Report 10, 4, 2006). The cervix is considered more vulnerable because it has a thinner cellular lining than the vaginal tract and has a high density of lymphocytes, one of the virus' primary targets.
Padian advocated testing the diaphragm as an HIV prevention strategy for many years before finally receiving US$37 million from the Bill & Melinda Gates Foundation. Prior to starting the efficacy trial, Padian conducted several acceptability studies to determine if African women were willing to use a diaphragm; as with many HIV prevention methods, excluding vaccines, compliance is crucial to the success of the intervention. In this study, women who received diaphragms reported using them during only 70% of their sexual acts. These women reported that condoms were used 54% of the time, while women in the control group who were not using the diaphragm reported that their partners used condoms 85% of the time.
Since condom use was lower in the diaphragm group yet the number of new infections was equivalent, it is possible that the diaphragm contributed to protection. However because the trial was not designed to compare the protective effects of the diaphragm to condoms, researchers are unable to draw any firm conclusions. The authors of the Lancet article did suggest the "observation that lower condom use in women provided with diaphragms did not result in increased infection merits further research."
This is the second HIV prevention trial this year to end with disappointing results. In January a study of the microbicidal gel cellulose sulfate showed that the product may have possibly increased women's risk of contracting HIV. A final study analysis was presented at the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Sydney. -Kristen Jill Kresge
India Revises Their HIV/AIDS Prevalence Estimates
The National AIDS Control Organization (NACO) in India recently revised their national HIV prevalence estimates, drastically reducing them from 0.9% to 0.36% in a country with a population of 1.1 billion. This puts the estimated number of HIV-infected people in the country at 2.5 million (with a range of 2.0-3.1 million), less than half of the figure previously projected by the Joint United Nations Programme on HIV/AIDS (UNAIDS). Since 2005 India was thought to have even more HIV-infected individuals than South Africa, based on previous surveillance data collected from antenatal clinics and from mainly high-risk individuals, but the new figures suggest this is not the case.
The new prevalence data in India reflects the country's efforts to expand their national HIV/AIDS surveillance system. Last year alone the government added 400 new HIV/AIDS testing sites and also conducted a population-based survey that tested 102,000 individuals for HIV infection. This, along with enhanced methodology, provided a much different estimate of the HIV prevalence within the general population. These new figures are endorsed by both UNAIDS and the World Health Organization (WHO) and were calculated with the help of the UN and the United States Agency for International Development (USAID).
The additional surveillance shows that in some of the southern states, including Tamil Nadu, the HIV prevalence has started to either stabilize or decline. This is promising news since HIV prevention has been a focus in these regions for several years. But Indian officials warn against assuming the country's HIV epidemic is sharply declining. Surveillance data from 2006 suggests that HIV infection rates among groups at high-risk of HIV infection, including injection-drug users and men who have sex with men, are actually increasing, especially in urban centers.
India's Health Minister, Anbumani Ramadoss, also announced a US$2.8 billion national program to provide free antiretroviral treatment to already infected individuals and to improve existing HIV prevention programs. -Kristen Jill Kresge