Pharmexa-Epimmune and Bavarian Nordic Begin AIDS Vaccine Trial
The biotechnology companies Pharmexa-Epimmune and Bavarian Nordic initiated a Phase I AIDS vaccine trial, funded by the US National Institutes of Health (NIH), at the end of April to evaluate the safety and immunogenicity of two vaccine candidates administered in a prime-boost combination. The first candidate, EP1233, is an epitope-based DNA vaccine candidate developed at Pharmexa-Epimmune with funding from the US National Institute of Allergy and Infectious Diseases (NIAID). The second candidate uses a modified vaccinia Ankara (MVA) viral vector to deliver HIV proteins matching those in the DNA candidate.
This trial is being conducted by the HIV Vaccine Trials Network (HVTN) and is known as HVTN 067. Investigators plan to enroll 108 volunteers at sites in three US cities—Nashville, Rochester, and San Francisco—and preliminary results are expected by the end of the year.
Guidelines for Male Circumcision Issued
The World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recently issued recommendations on the practice of male circumcision for HIV prevention (New Data on Male Circumcision and HIV Prevention: Policy and Programme Implications). They suggest the procedure should be recognized internationally as an important intervention to reduce the transmission of HIV and advised countries with high HIV prevalence and low rates of male circumcision to consider rapidly and dramatically increasing access to this surgical procedure for men at risk of heterosexual transmission of HIV. The guidelines also recommended that circumcision be included broadly as part of a comprehensive strategy to prevent HIV transmission, along with the use of condoms, voluntary counseling and testing services, and the treatment of other sexually transmitted diseases.
The release of these guidelines follows an international consultation with various governments, researchers, human rights advocates, funding agencies, and civil society members that was held from March 6-8 in Geneva, Switzerland. Many individual countries are also in the process of establishing national guidelines on the introduction of male circumcision programs.
UNAIDS chose to issue these recommendations after the results from three randomized, controlled clinical trials showing the procedure can reduce the risk of heterosexual transmission of HIV infection in men by as much as 60%. These trials were conducted in Kisumu, Kenya; Rakai District, Uganda; and Orange Farm, South Africa. Studies to predict the impact of different prevention technologies on the course of the epidemic suggest that implementation of circumcision programs in sub-Saharan Africa could prevent 5.7 million new HIV infections over the next 20 years.
The WHO/UNAIDS guidelines recommend more research on how male circumcision will affect HIV transmission to women, as well as the risks and benefits of performing circumcision in men who are already HIV infected. An ongoing study sponsored by the Bill & Melinda Gates Foundation is looking at how male circumcision affects HIV transmission to female partners. Unpublished data from an already conducted study in Uganda, which was presented at an Institute of Medicine Meeting on HIV prevention trials (see Optimizing prevention research), suggests that HIV transmission between recently circumcised HIV-infected men and their female partners may be increased if they engage in sexual activity before their surgical wound is completely healed, and this process may take longer in HIV-infected men.
Another concern for developing countries is ensuring access to safe services, which requires training providers to conduct the procedure under sterile conditions and then monitoring compliance. The recommendations also suggest that men seeking circumcision be offered counseling services to help prevent behavioral disinhibition. Researchers are planning to establish a limited number of sites to serve as centers of excellence for adult male circumcision. The site in Rakai, Uganda where the US NIH-sponsored trial was conducted has now received funding from PEPFAR to serve as a center of excellence in the region.
Institute of Medicine Releases Report on US AIDS Plan
The prestigious US-based Institute of Medicine (IOM), a division of the National Academy of Sciences, recently released a report on the US President's Emergency Plan for AIDS Relief (PEPFAR), satisfying a requirement set by Congress for a three-year review of the initiative. PEPFAR is a five-year, US$15 billion program and represents the largest commitment made by any nation to fighting HIV/AIDS. It currently provides HIV education, treatment, and prevention services in 15 countries, including Botswana, Cote d'Ivoire, Ethiopia, Guyana, Haiti, Kenya, Mozambique, Namibia, Nigeria, Rwanda, South Africa, Tanzania, Uganda, Vietnam, and Zambia. After conducting a comprehensive evaluation of PEPFAR's progress, including visits to many of the countries targeted by the initiative, the IOM praised the program's efforts to provide medical care to millions of people, particularly in severely resource-strained settings. Since its inception in 2003, PEPFAR has provided antiretroviral therapy to more than 800,000 individuals, voluntary counseling and testing services for HIV to almost 19 million people, and services to prevent mother-to-child transmission of HIV to more than 6 million pregnant women.
The report also made several recommendations on how PEPFAR could improve their approach, including removing provisions that set aside $3 billion—far more than is spent on condom distribution or preventing mother-to-child transmission—to focus on abstinence-only education, which has been one of the most controversial aspects of the program. Critics say this restriction has taken funding away from evidence-based strategies and pushed abstinence instead of the more comprehensive ABC approach (abstinence, be faithful, use condoms). Jaime Sepulveda of the University of California, San Francisco who chaired the IOM committee said a one-size-fits all approach to HIV prevention is not helping and that PEPFAR should promote evidence-based prevention strategies, including promotion of clean needle and syringe exchange programs in countries where the epidemic is fueled primarily by injection-drug users (Lancet 369, 1155, 2007).
The IOM also recommended that PEPFAR no longer require all generically produced versions of antiretrovirals (ARVs) be licensed by the US Food and Drug Administration before they can be purchased and used in PEPFAR's programs. Instead the independent panel recommended that PEPFAR support the already-established generic drug approval system at the World Health Organization. The advantage of using these so-called generic ARVs is that they can be purchased at much lower costs than those produced by the pharmaceutical companies that brought them to market.
Other recommendations included transitioning from an emergency-based approach to a longer-term strategic plan, addressing the long-standing issues that contribute to the spread of HIV in each of the target countries, and expanding and improving care and treatment services for orphans.
The goals of PEPFAR are to provide ARVs to 2 million HIV-infected people, prevent 7 million new HIV infections, and provide care services to 10 million individuals either infected with or affected by HIV/AIDS, including orphans. The legislation supporting this initiative must be reauthorized by Congress this fall before entering its final two years. Sepulveda said in the report that the lessons from PEPFAR should be used to motivate other nations to make even larger investments in HIV/AIDS programs in the countries hardest hit by the pandemic.
South Africa Launches New AIDS Plan
At the end of April the South African government released a new national AIDS plan, outlining the country's strategy to combat the epidemic. At the end of last year, there were 5.5 million South Africans living with HIV/AIDS, according to estimates from UNAIDS, and the number of HIV-infected people continues to rise. In response to these grim statistics, the 160-page plan includes a proposal for halving the number of new HIV infections by 2011. It also proposes improving diagnosis of HIV/AIDS, providing life-saving antiretroviral treatment to 80% of the estimated one million South Africans that are in need, and reducing the rate of mother-to-child transmission of HIV to below 5% over the next five years. Implementation of the report's proposals will cost an estimated $6 billion.
The "HIV and AIDS and STI Strategic Plan for South Africa, 2007-2011" was prepared after consultation with government officials, UNAIDS, research institutions in the country, and several representatives of civil society. The release of this comprehensive plan was lauded by many organizations, including the Treatment Action Campaign and AIDS Law Project, and civil society representatives who have been critical of the government's sluggish response to the AIDS epidemic. It was also endorsed by the recently restructured South African National AIDS Council (SANAC).
Vaccine Briefs written by Kristen Jill Kresge.