By Kristen Jill Kresge
Study of Early HIV Infection Begins Enrollment
Active recruitment and enrollment of volunteers has now started at research sites in Lusaka, Zambia; Masaka, Uganda; Kigali, Rwanda; and Kangemi, Kenya for a multi-centre, epidemiological study of newly HIV-infected individuals being conducted by IAVI. Recently infected individuals for this research study are identified through participation in incidence studies where they are counseled on risk-reduction practices and tested for HIV at least four times a year.
This new study will track these HIV-infected individuals for up to five years to follow the natural course of HIV infection in these cohorts. All volunteers will receive counseling and care and will be referred to a program offering antiretroviral (ARV) treatment when needed. Investigators will also analyze samples of the newly-transmitted virus.
Data from this study could provide researchers with information about the virus that is transmitted and the early immunological events that take place during acute stages of HIV infection. This may offer several clues to help inform preventive vaccine design since ultimately this is the virus challenge that a vaccine would need to protect against.
The IAVI research study will also begin recruiting recently HIV-infected volunteers at other sites in Entebbe, Uganda; Cape Town, South Africa; and Kilifi, Kenya. Other groups, including the recently established Center for HIV/AIDS Vaccine Immunology (CHAVI) are studying individuals during the earliest stages of acute HIV infection (see An Interview with Barton Haynes). Links between these efforts and the IAVI-led research studies have already been established. Myron Cohen and others at the University of North Carolina are now also creating collaborations with several research sites in South Africa, Malawi, Uganda, Tanzania, the UK, and the US to identify individuals as soon as possible after the establishment of HIV infection.
African Union Launches Prevention Campaign
The African Union in partnership with the Joint United Nations Programme on HIV/AIDS (UNAIDS) initiated a unified call from many African leaders to increase and improve HIV prevention services on the continent. On April 11 leaders from several countries kicked off this initiative. Among these was Meles Zenawi, the Primer Minister of Ethiopia, who emphasized how the scale up of prevention services can have profound effects in dealing with the epidemic.
Elements of this comprehensive prevention plan include addressing the root causes of HIV transmission, increasing access to HIV testing and counseling services to increase knowledge about the virus and prevent transmission, and developing strategies specifically targeting women and youth with important messages on HIV prevention and behavior. At the launch, First Lady Jeannette Kagame of Rwanda spoke about the disproportionate number of women in Africa who are HIV infected. Other components of the effort include the need to strengthen and expand existing healthcare systems and programs on mother-to-child transmission of HIV.
Of the 5 million new HIV infections in 2003, 3.2 million occurred in sub-Saharan Africa, according to the latest UNAIDS statistics. And although access to HIV prevention and care has increased in recent years, the huge number of new infections can cause a significant burden on existing programs.
The World Health Organization (WHO) and UNAIDS predict that implementation of broad prevention programs such as these could help avert 63% of new HIV infections that are expected to occur in the next six years. This initiative was launched in advance of a Special Summit on HIV/AIDS, tuberculosis, and malaria that will convene next month in Abuja, Nigeria involving African Union heads of state.
Trial Sites in Kenya and Rwanda Expand Recruitment
The projected number of individuals participating in a Phase I AIDS vaccine trial in Kenya and Rwanda, conducted by IAVI in partnership with the Vaccine Research Center (VRC), will be increased based on early successes in recruitment. Project San Francisco began enrolling volunteers at the site in Kigali, Rwanda late last year—marking the start of the first AIDS vaccine trial in the country—and the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi began recruitment in January. Total enrollment for both sites was initially set at 64 volunteers but will now be increased to 104.
This trial is one of three closely coordinated trials testing the safety and immunogenicity of a "prime-boost" vaccination regimen with the VRC's DNA plasmid and adenovirus serotype 5 (Ad5) vaccine candidates (see On trials). Two sites affiliated with the Walter Reed Army Institute of Research and its partners began recruitment recently in Kampala, Uganda and Kericho, Kenya for a trial with the same candidates.
Sabina Wakasiaka, a nurse counselor from KAVI, credits the successful enrollment rates to outreach programs conducted in the last few years, which have helped to increase the vaccine literacy among many community organizations. The staff is also targeting more women for recruitment in this trial.
Other developments in Kenya include the opening of two new community clinics in Kilifi by the Kenya Medical Research Institute (KEMRI), with support from IAVI. One of these clinics, the Comprehensive Care and Research Clinic, will offer HIV testing and counseling services that can help facilitate future AIDS vaccine trials in the country, as well as house a clinical trials laboratory. Part of this building has also been reserved for provision of HIV treatment and care through the District Hospital, including a program for the prevention of mother-to-child transmission that tests over 4000 pregnant women each year.
The other newly-established clinic will focus mainly on couples voluntary counseling and testing, which can help identify individuals in serodiscordant relationships and who are therefore at high risk for HIV infection within their marriage or partnership. Couples counseling is an established practice at sites in Rwanda and Zambia that partner with IAVI, but this clinic is one of only a few to utilize this approach in Kenya. KEMRI also opened a new drop-in center and clinic for high-risk, HIV-uninfected individuals in Mtwapa. More than 300 uninfected volunteers have already been enrolled in a study to help promote an understanding among individuals at high risk of HIV infection of ways to lower this risk. Collaborators from the University of Washington will treat volunteers for sexually-transmitted diseases, including offering treatment to those who are incidentally infected with HIV during the course of the study.
WHO/UNAIDS Convene Meeting on Vaccine Clinical Trial Design
The World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recently sponsored a technical consultation with several experts in the AIDS vaccine field to discuss the design and implementation of Phase IIb "test of concept" trials, also referred to as "proof of concept" trials, in evaluating AIDS vaccine candidates and their implications for future approval and licensure.
This meeting, hosted by IAVI, was held in New York City and brought together representatives from a diverse range of organizations to consider how to design test of concept trials and the role they may play in the development of vaccines. Attendees included representatives from the Botswana Harvard AIDS Institute Partnership, Medical Research Council of South Africa, Chinese Center for Disease Control and Prevention, Project San Francisco in Rwanda, HIV Vaccine Trials Network (HVTN), US National Institutes of Health (NIH), US Centers for Disease Control and Prevention, US Food and Drug Administration, IAVI, Johns Hopkins University, as well as other representatives from India, Thailand, and Zambia.
The results of a single Phase IIb trial would not be expected to provide sufficient evidence of safety or efficacy for licensure. However experts at this meeting considered the pressure that could arise, particularly in regions hardest hit by AIDS, if a Phase IIb trial showed impressive efficacy. The group largely agreed that full Phase III trials would still be necessary to ensure the vaccine was safe and effective, but emphasized that governments and organizations conducting trials should consider these issues now.
Merck was the first company to begin a Phase IIb trial, in collaboration with the HVTN, for their lead AIDS vaccine candidate and they recently announced plans to begin another "proof of concept" trial with the same candidate in South Africa (see On trials). Other organizations, including the VRC at the US National Institutes of Health (NIH), are also considering using these trials to evaluate preliminary efficacy of their candidates.
The recommendations of this group will be presented to the WHO/UNAIDS Vaccine Advisory Committee and the resulting position paper will help these organizations evaluate the utility of Phase IIb test of concept trials for AIDS vaccines.