At 11.22am, as the needle drew back from 19-year-old Thabo’s arm in a room in Soweto, applause rang out. South Africa’s largest anti-HIV vaccine trial had begun.
Researchers hope the MRKAd5 multivalent HIV vaccine will prevent at least 30% of new infections, and may slow the progression of HIV to Aids.
Six hundred people will be vaccinated by Perinatal HIV Research Unit researchers at Chris Hani Baragwanath Hospital, from a sample of 3 000 who will participate in the trial at six sites countrywide. Called ‘Phambili†(Forward), the $35-million study is being conducted under the aegis of the South African Aids Vaccine Initiative and the Medical Research Council.
Thabo was followed by four more volunteers who gazed nervously at the cooler box where their injections lay on a bag of ice. Each syringe was labelled with a code matching the volunteers’ green trial identification cards. Only the pharmacist who filled the syringes knows whether the clear liquid inside is the vaccine or a placebo.
Trial principal investigator Professor Glenda Gray hopes that at least 60% of the sexually active 18- to 35-year-old participants will be female, because most previous trials have been on men.
Male and female immune systems differ subtly, meaning the vaccine could have a slightly different effect.
All of the first five volunteers have seen friends or relatives living and dying with the virus, and all have discussed their participation in the trial with relatives and partners.
Ranging in age from 19 to 25, they include a chef, an air hostess and a builder — but all are currently jobless.
They say they want to help combat Aids. Remarked Thabo: ‘For once I want to do something that will benefit other people. I’m God’s work.â€
Volunteers will receive three injections 28 days apart and undergo ongoing monitoring and HIV testing. The researchers estimate about 120 will become HIV-positive during the trial — a number calculated by halving the incidence in the volunteer group to account for the effect of safer sex counselling.
An interim analysis will be done on the immune responses of the first 600 participants. If the results are good, the trial will continue enrolling volunteers until researchers detect 120 new HIV infections among participants, at which point the trial will end.
If the immune response of participants to the vaccine is inadequate, the trial will be halted.
The trial will also determine whether the progress of any infections are affected. The hope is that the vaccine will lower the set point level of latent HIV, which would delay progression to Aids and reduce the hyper-infectiousness of newly infected individuals.
The MRKAd5 multivalent HIV vaccine consists of three HIV genes melded with an adenovirus vector, which transports its load around the body and hopefully triggers a strong immune response.
Its owner, Merck Sharpe & Dohme, has signed over the licence for the compound to the United States government’s National Institutes of Health, which is funding the trial.
Gray does not think this, or any vaccine currently being trialed, is likely to be 100% protective. Instead, she sees vaccines as part of a broad defence armoury — also including circumcision — which will cut the risk of infection by about 90%.
She says: ‘It is another armament. Ultimately it’s female controlled; no one knows you’ve got it. It protects you before sex, like adding airbags to a car for safety on top of seat belts.â€
One important result will be whether the vaccine triggers as strong a response in South Africans — who tend to have the clade C virus strain — as did previous tests in areas where clade B dominates. The ideal is a global vaccine that counters all strains.
Phambili may confirm that this is possible, even if MRKAd5 does not prove effective.
South Africans have very high levels of adenovirus infections, and one question to be tested by the trial is whether this decreases the vaccine’s impact.
The concern is that people already exposed to the vector virus will have a swift immune response to it — which could wipe out the vaccine before the HIV gene payload triggers its own responses.
Phambili is a Phase IIb ‘proof of concept†trial, meaning that it has passed Phase I safety tests and has shown statistical significance in stage II safety and efficacy trials. The trial sponsors are not sufficiently confident to move to expensive stage III trials involving thousands of people.
If successful, Phambili could be developed into a Phase III trial, essential for drugs to be registered for use in humans.