The study & treatment groups
RESEARCH STUDY
OPTIMA is a research study to find the best way to treat people who have taken a wide range of anti-HIV drugs in several different combinations and who now have a viral load above 2,500 on their current combination.
Doctors have several ideas of what to do in this situation but it is not clear which approach is best. It is for this reason that a randomised study is needed. People will be randomised to a treatment group by chance, like tossing a coin. Randomisation reduces the possibility that doctors or patients influence the results by their personal opinions on a particular approach. The answers from a randomised study can be trusted.
The different approaches are detailed in the treatment groups section below. Anyone joining this study must be willing to follow the treatment group given to them at randomisation. Everyone entering the study will be carefully monitored and their health comes first. However where possible and safe, you will be encouraged to stay in the treatment group you were given at randomisation. If too many people swap and change the treatment group they were randomised to, it will not be possible to prove whether one idea is better than another.
Everyone on the study needs to take their medication as directed by their doctor. This can be difficult but necessary to see if there is a difference between the treatments. If you are not interested or happy with being in any of the treatment groups then it would be better not to join this study.
You may be included if
ü You are aged 18 years or more
ü You have HIV infection
ü You have had failure of at least two different multi-drug combinations, which included drugs of all three classes or are resistant to all three classes of anti-HIV drugs
ü You've been taking HIV drugs for at least three months continuously (unless you choose OPTION 2 in the UK substudy)
ü You have a CD4 count below 300
ü You have a viral load above 2,500
You may be excluded if
û You are pregnant, or intend to become pregnant
û In the opinion of your doctor, Mega-ART of five or more anti-HIV drugs is unsafe for you to take (unless you choose OPTION 3)
û You currently have a serious, uncontrolled opportunistic infection (OI)
û You have a serious non HIV related illness
The OPTIONS in OPTIMA Pilot
The OPTIONS in OPTIMA pilot give you 3 ways of joining this study they are:
OPTION 1 You will be randomised to both parts of the study. You will have a drug-free period of three months or no drug-free period and then receive either 'standard ART' or 'Mega-ART' treatment. For example you may get any one of the 4 Treatment Groups below.
OPTION 2 You can choose whether or not to have a drug free period and then be randomised for how many drugs you take. For example yo may get either Treatment Group 1 or 2 below.
OPTION 3 You can choose how many drugs you take and then be randomise to whether you will have a drug free period or not. For example you may get either Treatment Group 3 or 4 but you choose the number of drugs you take when you take anti HIV drugs for the first time in the trial.
Treatment group 1 (applies to OPTION 1 and OPTION 2)
Standard Care – up to 4 anti-HIV drugs
There is a belief that if minor changes are made to the drugs you take, the decline in the CD4 count and rise in viral load may be slowed. The changes to drug therapy would be made with the results of a resistance test to guide the choice.
While no dramatic changes are expected, there may be benefits as the regimen should be more stable and easier to follow than treatment groups two and four. There is some evidence that this approch may still have some benefit.
Some of the other treatment groups have high amounts of risk associated with them and increases in the number of drugs to take.
Pros and Cons
J Not much change.
J Less drugs to take (than some other treatment groups).
J Less risk of opportunistic infections if no HIV drug free period.
L Less chance of a dramatic positive change.
L Using up to four drugs may not be as potent as using five or more anti-HIV drugs.
L May continue to develop resistance to existing drugs.
Treatment group 2 (applies to OPTION 1 and OPTION 2)
Mega ART – 5 or more anti-HIV drugs
The resistance test that will be done when a person is screened for this study is likely to show resistance to many drugs. Where little or no resistance is shown to a drug this would be chosen. (Unless the person has been unable to tolerate it before and does not want to give it another try.)
The thinking behind this treatment group is that even if the virus is resistant, each drug is still doing something against HIV. So if you get several small bits of work from several drugs you get more effect and less virus. A doctor may suggest more that five drugs - some have tried up to 11 with favourable results in the reduction in HIV viral load.
Pros and Cons
J A fall in viral load has been seen in some smaller studies.
J Less risk of opportunistic infections with constant anti-HIV drugs.
J This approach is successful in other areas such as cancer treatment.
L More drugs can theoretically increase risk of side effects.
L Difficulty taking large combinations at conflicting times.
L It is unknown how long the effect will last for.
Treatment group 3 (applies to OPTION 1 and OPTION 3)
Stop anti-HIV drugs for 3 months then restart with up to 4 drugs
Another idea is to stop all drugs for up to 12 weeks then restart with up to four drugs. The choice of drugs for the new regimen will be guided by the results of the resistance test. The thinking behind this is that changes, which make the virus less resistant to drugs, have been seen in the virus when HIV drugs are not taken for around 12 weeks. The changes to the virus make the virus easier to kill by the anti-HIV drugs that had almost stopped working before. Twelve weeks is chosen because, in tests most of the changes in the virus happen around 10 weeks after stopping drugs.
People are carefully monitored during the drug free period to detect early any dangerous drop in CD4 counts or opportunistic infections, and if this occurs you will be able to restart treatment immediately.
Pros and Cons
J A harder hit to the virus when drugs are restarted.
J The HIV drug free period gives you and your body a rest from the toxic anti-HIV drugs.
J Gives a chance for the resistant virus to reduce.
L You may worry about not being treated when on the HIV drug free period.
L Your CD4 count may fall and may not come back to the same level when drugs are restarted.
L Viral load is expected to rise and may take time to (or may never) reduce once drugs have been restarted.
L Increased risk of opportunistic infections and the need to take drugs to prevent them.
L Unknown how long the hard hit (the effect of the drug free period) will last for and whether this makes a difference in the long run.
Treatment group 4 (applies to OPTION 1 and OPTION 3)
Stop anti-HIV drugs for 3 months then restart with 5 or more anti-HIV drugs
This idea combines the effects of the drug free period and the enlarged hitting power of Mega-ART (more than five anti-HIV drugs), it is thought that this approach might have the greatest chance of reducing the viral load and raising the CD4 count, however it could also have the most disadvantages.
Pros and Cons
J In small studies this idea has had better results.
J Harder hit to virus when drugs are restarted.
J The HIV drug free period gives you and your body a rest from the toxic anti-HIV drugs.
J Combination of many drugs may reduce the viral load.
J Gives a chance for the resistant virus to reduce.
L You may worry about not being treated when on the HIV drug free period.
L Your CD4 count may fall and may not come back to the same level when drugs are restarted.
L Viral Load is expected to rise and may take time to (or may never) reduce once drugs have been restarted.
L Increased risk of opportunistic infection and the need to take drugs to prevent them.
L Unknown how long the hard hit (the effect of the drug free period) will last for and whether this makes a difference in the long run.
L More drugs can theoretically increase risk of side effects.
L Difficulty taking large combinations at conflicting times.
For full details regarding the OPTIONS in OPTIMA substudy click here.
Participating clinics will be able to give you more detailed information and help if you decide if this study is right for you. You can also visit the full patient information sheet page on this site or contact the independent advisory groups details on the links page.