Volunteers are now being sought for the clinical trialA clinical trial is a research study to answer specific questions about vaccines or new therapies or new ways of using known treatments. Clinical trials are used to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people. Trials are in four phases: Phase I tests a new drug or treatment in a small group; Phase II expands the study to a larger group of people; Phase III expands the study to an even larger group of people; and Phase IV takes place after the drug or treatment has been licensed and marketed. of an experimental(Of a drug) Not licensed for use in humans, or as a treatment for a particular condition. Experimental drugs are studied in clinical trials to determine their safety and efficacy, and are sometimes made available via Special Access Schemes prior to their approval. preventive HIV vaccine. People at high risk of contracting HIV, aged between 18 and 45, who live in Sydney are eligible for the trial.
HIV-negative partners of people with HIV, both men and women, are considered ‘high risk’ from the perspective of the researchers and will be eligible to participate if they meet age and health criteria.
‘High risk’ is defined using current Australian epidemiological data. In addition to the regular partners of people already diagnosed with HIV, it includes men and women who have accessed post-exposure prophylaxis (PEP), men who have had unprotected anal sex in the last six months and men who have been diagnosed with an STI[Sexually Transmissible (or Transmitted) Infection] Infections spread by the transfer of organisms from person to person during sexual contact. Also called venereal disease (VD) (an older public health term) or sexually transmitted diseases (STDs). that might have been transmitted through anal sex in the last twelve months.
About 100 people are being sought from the Sydney site, and 3000 are expected to enrol in the study overall, which includes sites in the US, Canada and the Caribbean.
Why high risk?
The trial is aiming to get some data on whether the experimental vaccine shows any efficacy(Of a drug or treatment). The maximum ability of a drug or treatment to produce a result regardless of dosage. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed. In the standard procedure, Phase II clinical trials gauge efficacy, and Phase III trials confirm it. in either preventing HIV acquisition or reducing viral loadA measurement of the quantity of HIV RNA in the blood. Viral load blood test results are expressed as the number of copies (of HIV) per milliliter of blood plasma. in vaccinated people who are subsequently exposed to HIV. To do this, people whose behaviour places them at significant risk of HIV are enrolled. All participants are then provided with information and support to reduce their risk, but given the human factor, some HIV risk behaviour – and potentially some seroconversions – will occur.
Risks and benefits
The decision about whether or not to participate a trial like this is a very personal one. There are no obvious benefits for participants, as it is unknown whether the experimental vaccine will be effective, and there is the inconvenience of having to attend the clinicalPertaining to or founded on observation and treatment of participants, as distinguished from theoretical or basic science. site, St Vincent’s Hospital, for injections and follow-up.
Volunteers will receive materials and counselling aimed at supporting safe sex practice. This might help individuals to modify their behaviour.
The trial is randomisedA method based on chance by which study participants are assigned to a treatment group. Randomization minimizes the differences among groups by equally distributing people with particular characteristics among all the trial arms. The researchers do not know which treatment is better. From what is known at the time, any one of the treatments chosen could be of benefit to the participant and placebo-controlledA method of investigation of drugs in which an inactive substance (the placebo) is given to one group of participants, while the drug being tested is given to another group. The results obtained in the two groups are then compared to see if the investigational treatment is more effective in treating the condition., so half of all participants will be randomly selected to receive an inactive substance while the other half will receive the experimental vaccine. It is double-blindedA clinical trial design in which neither the participating individuals nor the study staff knows which participants are receiving the experimental drug and which are receiving a placebo (or another therapy). Double-blind trials are thought to produce objective results, since the expectations of the doctor and the participant about the experimental drug do not affect the outcome; also called double-masked study., so neither the participants nor the trial doctors will know who is getting the experimental product and who is getting the placeboA dummy medical treatment, designed to have no pharmacological effect, administered to the control group of a clinical trial..
There is a risk from taking any experimental product, which potential participants need to consider. This risk is reduced in this vaccine trial though as the product has already been used in more than 250 people in earlier safety trials, with no serious adverse events. An individual still may have an unforseen reaction, however.
Perhaps the most significant factor that potential participants need to consider is the likelihood of becoming ‘vaccine antibody positive’, if they participate in the trial. ‘Vaccine antibody positivity’ is the term used to describe the situation where volunteers in vaccine trials may test positive on some HIV tests (such as the screening ELISA test used in Australia) even if they are not HIV infected. This occurs because the body’s immune system makes a response to the presence of the vaccine which some of the cruder HIV tests read as an antibody response to HIV. It is readily distinguishable from a true HIV positive antibody response with further testing.
Up to 80% of people who receive the active vaccine in this study are expected to get a ‘vaccine antibody positivity’ reaction and this response persists for several years at least – possibly for life. This vaccine reaction may be problematic for an individual intending to live or work in certain countries overseas where HIV testing facilities may be limited.
Is it likely to work?
No-one knows whether the experimental vaccine will work – whether it will prevent HIV acquisition or whether it will reduce viral load if vaccinated people subsequently seroconvert. Researchers certainly do not expect it to be 100 percent effective in preventing HIV acquisition.
The vaccine is made from fragments of HIV genesThe most basic unit of genetic information. ‘stitched’ into a weakened form of a common cold virusA small infective organism which is incapable of reproducing outside a host cell., called adenovirus 5. The vaccine is intended to stimulate a CTL – “killer T-Cell” – response to augment the body’s response to HIV if exposure occurs. Because of the way the CTL response works, some researchers hypothesise that the vaccine may be more likely to suppress viral replication to low levels rather than prevent infection, if indeed it has any effect at all. However this is still considered a ‘preventive’ vaccine trial rather than a therapeutic trial, as it is enrollingThe act of signing up participants into a study. Generally this process involves evaluating a participant with respect to the eligibility criteria of the study and going through the informed consent process. HIV negative people.
The experimental vaccine has been developed by Merck Research laboratories. In Australia the trial is being run through the National Centre in HIV EpidemiologyThe branch of medical science that deals with the study of incidence and distribution and control of a disease in a population. and Clinical Research, with its clinical site at St Vincent’s Hospital Darlinghurst.
- For more information call Dr Rebekah Puls on (02) 9385 0872