August 24, 2009
QUESTIONS AND ANSWERS
The HVTN 505 HIV Vaccine Regimen Study
HVTN 505 is a Phase II exploratory clinical study examining a combination of two investigational vaccines. Specifically, the study will (1) test whether the vaccine regimen can reduce viral load (the amount of HIV in the blood) of vaccinated people who later become infected with HIV and (2) provide additional information about the existing good safety record of the vaccine regimen.
The study is not intended to lead to the licensure of the vaccine regimen being tested. However, it is designed to answer important scientific questions that could lead to the discovery and development of new and improved HIV vaccines in the future.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, is sponsoring the HVTN 505 study. The NIAID-supported HIV Vaccine Trials Network (HVTN) is conducting the clinical trial.
NIAID’s Dale and Betty Bumpers Vaccine Research Center (VRC) developed the two investigational vaccines that are being studied.
HVTN 505 is evaluating two different vaccines in a prime-boost strategy where one vaccine is used to prime the immune system and another vaccine is used to boost the immune response. This type of strategy generally induces different types of immune system responses compared with vaccine regimens in which only one type of vaccine is administered.
The HVTN 505 vaccine regimen consists of a series of three immunizations with a recombinant DNA-based vaccine (the priming vaccine) over the course of eight weeks followed by a single immunization in week 24 with a recombinant vaccine (the boosting vaccine) that uses a weakened adenovirus type 5 (Ad5) to carry the vaccine contents and stimulate the immune system. Adenoviruses are common viruses that normally cause colds, but the Ad5 virus used in the study’s vaccine regimen has been disabled so that it cannot cause a cold or other respiratory illness.
Neither the DNA-based vaccine nor the Ad5 vaccine can infect study participants with HIV. Both vaccines have been given to hundreds of people in previous clinical trials. No one acquired HIV infection through immunizations with either vaccine because they both lack many of the pieces of the virus that are required to cause infection. Unlike other vaccines, such as those designed to combat influenza, these investigational HIV vaccines are not made from live, killed or attenuated (weakened) HIV, therefore, it is impossible to acquire HIV infection or develop AIDS from the vaccines.
HVTN 505 will enroll 1,350 HIV-negative men who have sex with men ages 18 to 45 in the United States. Further, the male study volunteers must be circumcised and at time of screening Ad5-seronegative (meaning they do not have antibodies resulting from previous exposure to the Ad5 virus).
Pending final site approvals, the study will be conducted in the following U.S. cities:
HVTN 505 is a Phase II, randomized, placebo-controlled, double-blind clinical trial. This means that neither the study participants nor the study clinical staff will know who receives injections of the vaccine regimen and who receives the placebo injections. Of the 1,350 participants, 675 participants will receive the investigational vaccine regimen; 675 participants will receive the placebo injections.
The well-being and safety of study participants is always our top priority. Before its commencement, the HVTN 505 study protocol was independently reviewed by NIAID, the U.S. Food and Drug Administration, a centralized institutional review board (IRBs), and additional reviews by IRBs at individual sites where HVTN 505 will be conducted. These evaluations were conducted to ensure that the study is scientifically, ethically, and clinically appropriate and that it adheres to accepted standards for protecting human clinical research participants.
Additionally, an independent data and safety monitoring board (DSMB) composed of clinical research experts, statisticians, ethicists and community representatives, will conduct regularly scheduled interim analyses of HVTN 505’s clinical data. Real-time monitoring of new HIV infections as they are diagnosed will also be conducted to keep the closest possible watch on the safety of the study participants.
Each HVTN 505 study participant will receive the best available HIV prevention services, including risk-reduction assessments, counseling on how to avoid HIV exposure, free condoms, and guidance on how to access HIV prevention services in their local communities.
HVTN 505’s enrollment criteria are also designed to protect the study participants because the Ad5 vaccine is similar but distinct from the Ad5 vaccine evaluated in an HIV vaccine study known as Step (Statement: Immunizations Are Discontinued in Two HIV Vaccine Trials). Specifically, the study is limited to men who have sex with men in the United States who are circumcised and who do not have Ad5 antibodies at enrollment. This requirement is in place because there were more HIV infections among male vaccine recipients in the Step study who were not circumcised and who had Ad5 antibodies at enrollment than among those participants with the same characteristics who received the placebo injection. Conversely, Step vaccine recipients who were circumcised and without Ad5 antibodies at enrollment had similar rates of HIV infection to those who received the placebo vaccine.
Based on what is known about the Step study findings, there were no signs of increased susceptibility to HIV infection among male vaccine recipients who were circumcised and did not have antibody responses to Ad5 at enrollment. That is why the HVTN 505 study has been designed to include only those male volunteers who have these characteristics.
Although all clinical trials carry some risks and it is not known exactly how the investigational vaccine regimen that is being studied in HVTN 505 will perform, there is no existing information to suggest that the study’s two-part vaccine strategy presents a safety risk in this population.
Further, there are distinct differences between the vaccine regimen developed by the VRC and the vaccine tested in the Step study. For example, HVTN 505 features a DNA-based priming immunization while the Step study tested an Ad5-based vaccine as a single product. Additionally, the Ad5-based vaccines evaluated in both studies differ in their HIV gene makeup, construction, dosing schedule, number of doses, and the types of immune responses they induce.
A vaccine that reduces viral load in people infected with HIV would be a significant scientific breakthrough. Reducing viral load is important because typically people infected with HIV who have lower viral loads take longer to become sick and develop symptoms of AIDS. People with reduced levels of virus may also have a diminished ability to transmit the virus to others. Therefore, an HIV vaccine that reduces viral load may benefit a vaccinated individual who later becomes infected with HIV by delaying the onset of illness and the lifetime need for antiretroviral medicines. It may also benefit the public health by reducing HIV transmission to uninfected people.
The study teams at each site in the 12 cities where HVTN 505 is being conducted are prepared to ensure that participants who acquire HIV infection during the study have access to the highest quality of medical care and HIV treatment available in their local communities.
Please see the HVTN’s Web site at www.Hopetakesaction.org or at the study listing on ClinicalTrials.gov.
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Last Updated August 24, 2009