STEP Study
Encyclopedia
The STEP Study or Phambili Trial was a clinical trial
which tested the efficacy of an HIV vaccine
. Vaccination in the study ended suddenly and before it was scheduled to finish when pre-determined endpoints happened and indicated that the vaccine being tested certainly was not an effective tool for preventing infection with HIV.
The branch of the study which was conducted in Africa was called the "Phambili Trial" or "HVTN 503".
and the HIV Vaccine Trials Network
(HVTN) were the study organizers. The study was co-sponsored by Merck, NIAID, and the HVTN. There was also a "STEP Study Oversight Committee" which was a group with representatives from the above three organizations.
In South Africa the trial was overseen by the South African AIDS Vaccine Initiative
.
The study involved giving participants three vaccinations of adenovirus
synthetically modified to contain gag, pol, and nef proteins from HIV. The replication-deficient adenovirus vector carried these HIV-1 genes into the cell. It was hoped that this delivery system would induce a cell-mediated immune response to the modified adenovirus which would both decrease infection and viral set point. Since researchers created synthetic portions of the HIV genome to be ligated into the adenovirus vector, there was no risk of contracting HIV from the vaccine.
49 of the 914 men in the vaccine group and 33 men of 922 in the placebo group
had tested HIV-positive. The protocol expected that the group which had received the vaccine would have a lower or equal infection rate
as compared to the control group, but this was not seen. In fact, certain groups of the vaccine recipients were seen to have higher risk of HIV infection as compared to the placebo group. Merck closed the study because the vaccine was ineffective but clear evidence that the vaccine was detrimental has not been found. By November 2007 all participants were unblinded when researchers informed them whether they had received the vaccine or placebo.
While almost everyone enrolled in the STEP study had received the full course of the vaccine when the vaccination cessation was announced, no one in this African trial had been entirely vaccinated.
of Seattle Biomed stated that "the experimental inoculation... actually increased the chances that some people would later acquire HIV."
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
which tested the efficacy of an HIV vaccine
HIV vaccine
An HIV vaccine that protects vaccinated individuals from HIV infection is the goal of many HIV research programmes. Currently, there is no effective vaccine against HIV, the virus that causes AIDS...
. Vaccination in the study ended suddenly and before it was scheduled to finish when pre-determined endpoints happened and indicated that the vaccine being tested certainly was not an effective tool for preventing infection with HIV.
Other names
STEP was also known as "HVTN 502", "Merck V520 Protocol 023", "Merck V520-023", and the "MRK Ad5 gag/pol/nef vaccine". STEP is not an acronym.The branch of the study which was conducted in Africa was called the "Phambili Trial" or "HVTN 503".
Study organizers
Merck & Co.Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
and the HIV Vaccine Trials Network
HIV Vaccine Trials Network
The HIV Vaccine Trials Network is a non-profit organization which connects physicians and scientists with activists and community educators for the purpose of conducting clinical trials seeking a safe and effective HIV vaccine. Collaboratively, research professionals and laypeople review...
(HVTN) were the study organizers. The study was co-sponsored by Merck, NIAID, and the HVTN. There was also a "STEP Study Oversight Committee" which was a group with representatives from the above three organizations.
In South Africa the trial was overseen by the South African AIDS Vaccine Initiative
South African AIDS Vaccine Initiative
The South African AIDS Vaccine Initiative or SAAVI is a South African organization with the mission of coordinating the research and development of HIV vaccines in and for South Africa.-History:...
.
Study design
Candidates for enrollment into the study were men and women identified as high risk candidates for HIV infection but who were currently HIV-negative. It began in 2005 and halted the enrollment of new participants in September 2007 because of potential study-related risk to participants.The study involved giving participants three vaccinations of adenovirus
Adenoviridae
Adenoviruses are medium-sized , nonenveloped icosahedral viruses composed of a nucleocapsid and a double-stranded linear DNA genome...
synthetically modified to contain gag, pol, and nef proteins from HIV. The replication-deficient adenovirus vector carried these HIV-1 genes into the cell. It was hoped that this delivery system would induce a cell-mediated immune response to the modified adenovirus which would both decrease infection and viral set point. Since researchers created synthetic portions of the HIV genome to be ligated into the adenovirus vector, there was no risk of contracting HIV from the vaccine.
Study cessation
On September 21, 2007 sponsors of the STEP study announced that further vaccination would cease and that vaccination in the Phambili Trial would be paused pending review. On October 23, 2007 the sponsors announced that the Phambili Trial would stop further immunizations.49 of the 914 men in the vaccine group and 33 men of 922 in the placebo group
Placebo-controlled studies
A Placebo-controlled study is a way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate control group receives a sham "placebo" treatment which is specifically designed to have no real effect...
had tested HIV-positive. The protocol expected that the group which had received the vaccine would have a lower or equal infection rate
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
as compared to the control group, but this was not seen. In fact, certain groups of the vaccine recipients were seen to have higher risk of HIV infection as compared to the placebo group. Merck closed the study because the vaccine was ineffective but clear evidence that the vaccine was detrimental has not been found. By November 2007 all participants were unblinded when researchers informed them whether they had received the vaccine or placebo.
While almost everyone enrolled in the STEP study had received the full course of the vaccine when the vaccination cessation was announced, no one in this African trial had been entirely vaccinated.
Response
Alan AderemAlan Aderem
Alan Aderem is a biologist, specializing in immunology and cell biology. Dr. Aderem's particular focus is the innate immune system, the part of the immune system that responds generically to pathogens....
of Seattle Biomed stated that "the experimental inoculation... actually increased the chances that some people would later acquire HIV."