Two New AIDS Vaccine Trials Initiated in Africa
By Kristen Jill Kresge
In December researchers at the Karolinska Institute (KI) in Stockholm, Sweden, the US Military HIV Research Program (USMHRP), and the Muhimbili University College of Health Sciences, Tanzania, began a second vaccine trial to evaluate the safety and immunogenicity of administering immunizations of a DNA candidate and a modified vaccine Ankara (MVA) vaccine candidate in a prime/boost regimen. This Phase I/II trial will enroll 60 volunteers in Dar es Salaam, Tanzania.
The multiclade, seven plasmid DNA vaccine candidate comprised of several env, rev, gag, and RT genes was developed at the Swedish Institute for Infectious Disease Control and is based on HIV strains circulating in Tanzania. The MVA candidate, known as MVA-CMDR, was developed by National Institute of Allergy and Infectious Diseases (NIAID) and is manufactured by the Walter Reed Army Institute of Research (WRAIR). In this trial the candidates are being administered sequentially in a prime/boost regimen; meanwhile KI is also conducting another Phase I trial in Sweden evaluating just the MVA-CMDR candidate in 38 volunteers.
Last year at the annual AIDS Vaccine Meeting in Amsterdam, Eric Sandström of KI presented preliminary results of another placebo-controlled, Phase I trial in Sweden where volunteers received the DNA and MVA candidates in a prime-boost manner. This combination seemed to have promising immunogenicity, with 33 of 36 having positive responses—greater than 55 spot forming cells/million PBMCs—as measured by interferon-g ELISPOT assay.
More recently the South African AIDS Vaccine Initiative (SAAVI) and the HIV Vaccine Trials Network (HVTN), which is part of the US National Institutes of Health (NIH), initiated a second Phase IIb, test-of-concept trial in collaboration with Merck to evaluate the company's adenovirus-based vaccine candidate (MRKAd5). The trial is being called Phambili, which means 'going forward' in Xhosa, and will recruit 3000 volunteers in four South African provinces, including trial sites in Soweto, Cape Town, Klerksdorp, Medunsa, and Durban.
Another test-of-concept trial, known as the Step study, with the MRKAd5 candidate is currently ongoing at HVTN sites in the US, Canada, Peru, Dominican Republic, Haiti, Puerto Rico, Australia, Brazil, and Jamaica.
South Africa is currently hosting other AIDS vaccine trials as well as other HIV prevention trials, but the Phambili trial is the country's largest AIDS vaccine trial to date. It also marks the first time Merck's leading vaccine candidate is being evaluated in a population where the predominately circulating strain of HIV is not genetically matched with the antigens in the vaccine candidate. The epidemic in South Africa is primarily clade C HIV and the candidate is based on clade B. For more information about these or other ongoing preventive AIDS vaccine trials, visit the IAVI Report clinical trials database and the January 2007 Special Issue of VAX, 2006 Year in Review.
UNAIDS and WHO Release New Report on Global Epidemic
In advance of World AIDS Day, which was observed on December 1, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) released a report detailing updated global and regional estimates of the number of people newly infected with HIV in 2006. Twenty-five years after the first cases of AIDS were reported the epidemic is still spreading relentlessly around the globe. In 2006 alone, 4.3 million people were infected with HIV, the majority in sub-Saharan Africa (2.8 million). This brings the total number of people living with HIV/AIDS to approximately 40 million worldwide.
Since 2004 the number of people infected with HIV increased in every region of the world. Last year there were 270,000 individuals newly infected in Eastern Europe and Central Asia and 860,000 in South and Southeast Asia. In many regions these new infections are disproportionately occurring in young people. In the Russian Federation, 80% of HIV-infected individuals are younger than 30 years old. The primary route of transmission in the countries of Eastern Europe and Central Asia is still injection drug use and 67% of HIV infections in 2005 were a result of people injecting drugs with contaminated needles and syringes.
However, in eight African countries where sufficient data was available, HIV prevalence has declined among young people since 2000/2001. This trend is attributed to the success of HIV prevention messages targeting this age group that encourage young people to avoid behaviors that place them at risk of HIV infection. Throughout the world women are also continuing to bear the brunt of the HIV epidemic. In sub-Saharan Africa, 59% of the people living with HIV/AIDS are now women.
Despite promising advancements in the availability of HIV treatment in developing countries, 2.9 million people died from AIDS in 2006-the highest number ever reported for a single year. The vast majority of these deaths (72%) occurred in sub—Saharan Africa where the epidemic is still having the greatest impact, but worldwide AIDS is now the leading cause of death in people between the ages of 15 and 59.
The theme of this year's World AIDS Day was accountability and Kofi Annan, secretary-general of the United Nations, said in a USA Today editorial that, "as the number of infections continues unabated, we need to mobilize political will as never before." He called on every prime minister, president, parliamentarian, and politician to strengthen protections for vulnerable groups, including people living with HIV, young people, commercial sex workers, injection drug users, and men who have sex with men. Both UNAIDS and WHO emphasize the need to increase and improve prevention efforts that target people who are at greatest risk of HIV infection.
Mounting Data on Benefits of Male Circumcision
Results from two randomized, controlled clinical trials in Africa show that circumcision of male adults reduced their risk of acquiring HIV by approximately 50%. These results were released in December after the Data Safety Monitoring Board (DSMB)—an independent committee of clinical research experts, statisticians, ethicists, and community representatives—reviewed the interim data collected in these trials. Based on the substantial benefit offered by circumcision, male volunteers in the control group will now also be offered the surgical procedure. Researchers will continue to monitor the HIV infection rates among all volunteers and will also study how the procedure affects their risk behaviors.
Both of these trials—which took place in Rakai, Uganda, and in Kisumu, Kenya—were sponsored by NIAID, part of the NIH. The trial data confirmed the results of a previous circumcision study conducted in South Africa, which was the first to show that removal of the foreskin offered some protection against HIV infection (see Cutting HIV transmission and Brazil's model approach, IAVI Report 9, 3, 2005). Based on the mounting evidence that male circumcision offers protection from HIV infection, organizations like UNAIDS and WHO are currently working on recommendations for the implementation of adult male circumcision in countries where sexual transmission of HIV predominates. According to NIAID, studies in Africa have found that circumcision is an accepted practice, with 50-86% of those surveyed saying they would either have the procedure or want their partner to undergo circumcision if it was known to be safe, affordable, and have minimal side effects.
Another study sponsored by US-based Johns Hopkins University is still ongoing to determine if male circumcision reduces HIV transmission from men to women. However, public health experts agree that any intervention that reduces HIV rates in men by 50% will also result in fewer new HIV infections in women.