Research - A Randomized Trial of HAART in Acute/Early HIV Infection Version 3.0

[minus_25]

Has anybody heard or participated in this study?  It's being conducted by the Johns Hopkins University , Bloomberg School of Public Health as part of the Acute Infection and Early Disease Research Project (AIEDRP).

The following are parts of the consent form.  It's a long read, I know, but I would really appreciate everyone's opinion:

------------------------------------------------------------------------
Introduction:

This consent form explains the research study you are being asked to join.  Please review this form carefully and ask any questions about the study before you agree to join.  You may  ask questions at any time after joining the study.  

Purpose of Research Project:

You are being asked to take part in this study because you have been infected with HIV, possibly within the past year.  HIV is the virus that causes AIDS.  We now know a lot about how to treat HIV in people who have had the virus for a long time. There are many medicines approved to treat HIV.  People usually take a combination of 3 – 4 medicines. Once these medicines are started, they are usually taken for many years. This is known as HAART (Highly Active Antiretroviral Therapy). However, we still do not know the best way to treat people who have been infected within the past year. We think that if we give HAART for 12 months during the first year of HIV infection, and then stop the treatment, we might be able to keep your immune system working better and increase the number of years that you can go before you need to take HAART again. We do not know this for sure; and this is what we hope to learn through this study. We are also going to study the side effects that the people taking HAART develop. We want to see if taking HAART early and only for one year leads to fewer side effects.

In order to study these questions, we will give treatment to half the people who are in this study, and half will not receive treatment.  Who will receive treatment will be decided by chance.  The treatment will last one year.  We will then follow both the people who received treatment and those who did not.  We want to see if giving treatment right away is more helpful than waiting to start treatment.  

According to the current guidelines for the treatment of HIV infection, the benefits of treating people with acute or early disease are based on theory, and have not been proven in studies.  We hope to answer this question through this study.

This study will be done at six centers throughout Canada and the United States. We plan to enroll 180 people into this study. Your participation in the study will last for 3 years. It is possible that we may extend the length of this study. If that happens you will be asked to sign another consent form to allow us to follow you for an additional period of time.

Procedures:

   The Screening Visit:

Before you can enter this study, you will have a screening visit to find out if you can be in this study.  You will have standard tests used in the care of patients with HIV.

At the screening visit we will:
•   Ask you questions about your medical history
•   Ask how you think you were exposed to HIV
•   Ask you about any medications that you are taking
•   Talk about high-risk behaviors (like using drugs or having sex without a condom)
•   Draw blood for routine laboratory tests.  The total blood drawn at this visit will be about 6 tablespoons and will look at your red and white blood cells (hematology), your liver and kidney (chemistry) and the amount of fats in your blood (lipids).
•   Measure your T-cell count, which tells us how well your immune system is working.
•   Measure the amount of HIV in your blood, or viral load.
•   Test for HIV antibodies (tests which tell us you are HIV positive).
•   Test your HIV drug sensitivity (genotype).  This means we will find out which drugs are likely to work against your HIV infection.
•   Test for Hepatitis B and Hepatitis C (diseases which can affect your liver) and syphilis.
•   If you are a woman who can have a child, you will have a pregnancy test.

If these tests tell us that you were exposed to HIV infection more than 12 months ago, you will not be able to take part in this study.  In that case, we will help you find a doctor who can treat your HIV infection.  

If you meet certain eligibility criteria (page 11), you will be invited to come back to join the study.


   The Randomization Visit:

If you want to take part in this study, you will come back for your next study visit within fourteen days.  At this visit you will have a complete physical exam. Then the decision will be made as to whether you will receive Highly Active Antiretroviral Therapy (HAART) right away or you will not be treated unless it is clinically needed. This decision will be made randomly, like flipping a coin. To make this decision, we will make a telephone call to a computerized randomization center while you are with the study coordinator. You will find out then if you will be getting treatment.

If you are going to receive treatment, a study doctor will review your HIV sensitivity test. This doctor will recommend medicines that should work well for you. This will be based on what we know about treating HIV in people who have been infected for more than one year.  

We will talk about these drugs with you and ask you questions about your lifestyle. We will ask you about the kinds of foods you eat and how early you get up in the morning. We want to be sure that we have chosen a combination of drugs that you will be able to take. We will tell you about the side effects of each drug, how often you will need to take it, and how it should be taken.

There are many medicines available to treat HIV.  If you cannot take a particular drug, we can switch you to another one that may be easier for you to take.  It is very important that you take your medicines the way that they are prescribed. It is important that you tell the study staff if you are having problems with your medicines (like side effects or missing doses). If you are on treatment and miss three monthly study visits in a row your treatment will be stopped to avoid development of resistant virus unless it is clinically indicated for it to continue. If you are in jail or prison your study treatment will be stopped. However, we will ask you to continue in the study.

We will draw blood at this visit, for hematology, chemistry, t-cells and viral load tests. We may repeat an HIV test.  We will draw blood to store for future testing. The total blood drawn at the randomization visit will not be more than about 6 tablespoons.

If you are a woman who can have a baby and are randomized to begin treatment, you will have a pregnancy test each time before we give you any study medications.

   Additional Study Visits:

Additional study visits will take place after 1 and 2 weeks.  Then you will come back once a month for 1 year. At each of these visits, we will ask you questions about your health, any medications that you are taking (and any side effects you may be having), and high-risk behaviors.  If you are taking medicines to treat HIV we will ask you to complete a questionnaire about how you are doing with them.  Blood will be drawn and a physical exam will be done according to the schedule below.

Weeks 1, 2
•   Blood for hematology and chemistry (about 2 tablespoons)
•   Blood to test for HIV antibodies (only if your test was not positive at the last visit)
•   Physical exam (only if you are having any symptoms)

Months 1, 2, 4, 8, 10, 11
•   Blood for hematology and chemistry and viral load (about 3 tablespoons)
•   Blood to test for HIV antibodies (only if your test was not positive at the last visit)
•   Physical exam (only if you are having any symptoms)

Months 3, 6, 9 and every three months until the end of the study
•   Blood for hematology and chemistry, viral load, T-cells and storage for future testing (about 6 tablespoons)
•   Physical exam (only if you are having any symptoms)

Month 12 and every twelve months until the end of the study

•   Blood for hematology and chemistry, viral load, T-cells, lipids and storage for future testing (about 6 tablespoons)
•   Physical exam

After month twelve, study medicine will be stopped in all people who have been getting treatment. Some people may have one of their medicines changed for the last month before all therapy is stopped. This will be done to prevent resistance to the medication Sustiva. Before you begin HAART we will review the medications we would like you to take. If they include Sustiva  we will explain when and why we will replace them with a protease inhibitor. Treatment will not be stopped if there are medical reasons why treatment should be continued. Those medical reasons include pregnancy, low T-cells or chronic hepatitis B infection.  If you have been getting treatment you will come in for visits 1, 2 and 4 weeks after stopping treatment.  We will draw blood for viral load and storage for future testing at these visits.

Everyone taking part in this study will come in every 3 months until the end of the study (month 36).  At each visit we will ask you about how you are doing and blood will be drawn.

Each study visit should take about 30 minutes. The first two visits may take up to 1 hour. The total amount of blood drawn at each visit will be different, but will not be more than 6 tablespoons.

During the follow-up period we will watch your T-cells and your viral load closely. If at any time the study doctors think that you need treatment with antiretroviral medication, therapy will be offered.

Everyone in the study should have a primary care physician.  Your primary care physician will take care of any medical problems that you have that are not related to this study. With your permission, the study staff will keep your primary care physician up-to-date on your progress in the study. If you do not have a primary care physician, we can refer you to one.

The results of all lab tests performed during the study will be shared with you, and (with your permission) with your primary care provider.

Benefits:

The knowledge that we will gain from this study is very important.  Your participation will help us to understand how to treat people with acute or early HIV infection.  If you are randomized to receive treatment for your HIV infection, it is possible that you may benefit from this treatment.  It is also possible that you will not benefit.  Any treatment given to you will be tailored to your virus. This will be based on the results of the sensitivity test (genotype) that is done at your first study visit.

You may benefit from having very close follow-up of your HIV infection and frequent monitoring of your blood work. This follow-up and all study related lab tests will be provided at no cost to you.

Costs to You:

We have asked the companies that make anti-HIV medications to donate drugs to our study participants. Some drugs may be available free of charge. However, it is possible that the results of your sensitivity test may show that you would respond better to a medicine that we do not have access to.  In that case, we will ask that you use your health insurance to purchase that medicine. The study will reimburse you for any “co-pays” that you may have so that you will have no “out-of-pocket” expense.  If you do not have health insurance, we will put you in contact with a social worker that can find out what services you qualify for.

Leaving the Study Early:

You can agree to be in the study now and change your mind later. If you wish to stop, please tell us right away. Leaving this study early will not stop you from getting regular medical care at Johns Hopkins. If you leave the study early, we may use your health information that we already have if  it is needed for this study or any follow-up activities. If you leave the study early and give us permission, we will call you a month after your last visit to see how you are doing. If you were taking HAART at the time that you leave the study we will call you a second time (2 months after your last visit).

You may be taken out of the study if:

•   Staying in the study would be harmful to you.
•   You need treatment not allowed in this study.
•   You fail to follow instructions.
•   The study is cancelled.
•   You show bad behavior towards study or clinic staff.
•   You are under the influence of drugs or alcohol during a study visit.
•   There may be other reasons that we don’t know at this time to take you out of the study.

-----------------------------------------------------------------------------------

What do you all think?  Should I participate?  I realize you are not doctors, but do you think that the earlier one starts HAART treatment, the better off they will be in the long run?

I have some questions prepared and I am meeting with the project director on Friday afternoon to discuss everything in greater depth.

[lydgate]

As you said, most of us here are not doctors; and I don't even qualify as much of a lay expert on much of this stuff. That having been said, some non-expert thoughts (apologies if I'm just repeating what you know or getting something wrong):

The early (1997) thinking on HAART was "Hit Hard, Hit Early." In other words, treat HIV infection aggressively with a triple-cocktail, as early as possible after seroconversion. Then the pendulum swung back -- it wasn't clear that the benefits outweighed risks (including heavy side-effect burden, hepato-renal toxicities, adherence issues, emergence of lipo as a problem, among other things). And the discovery that even viral suppression below 400 or 50 copies, didn't mean viral elimination; discovery of latent viral reservoirs.

So treatment recommendations went to the now-standard guidelines based on whether T-cells are below 200, in the 200-350 range, in the 350-500 range, or above 500.

The pendulum seems to be swinging, a little, the other way back -- with more and more doctors recommending starting HAART when CD4s are above 350. (Others can perhaps provide links to studies indicating the benefits of this.)

Question: You were infected within the last year. What have your lab results been like?

Most unscientific remark: I've been positive for about 18 months now, and I was asked, about a year ago, if I wanted to participate in a study such as this one. My immediate, "gut," reaction was No! My CD4s were in the 700 to 900 range, 38 to 40%, VL very low. A reasonably "healthy" immune system (given the circumstances). If I had participated in the study, there was nevertheless a 50% chance that I would be put on meds -- with all the implications that has in terms of making lifestyle changes, adherence, dealing with potential side-effects. My feeling then was -- and still is -- I'm not potentially putting such strong chemicals in my body unless there is compelling evidence that tells me to do so.

And of course, this study is designed to see just whether that compelling evidence (for starting treatment early) exists. While I'd love to help the cause of science in as many ways as I can -- I'm about to enroll in a different as MGH -- my personal feeling in this case is that I'd rather wait for the evidence than be a part of it.

Again, this feeling is personal: other people most definitely feel differently. Starting treatment early, for some, makes them feel more in control of their infection, more "proactive." Others, whose initial T-cell numbers are lower than what they'd hoped, might enroll in this study in the hope that they get randomized to the treatment arm. So I'm DEFINITELY not telling you to enroll or not enroll. Simply articulating my few thoughts on the subject.

Hope others who have enrolled in studies respond. Keep us informed of your decision and progress.

Jay

[minus_25]

Thanks for the response Jay.  Sorry it took me so long to reply.  My counts are CD4 554 (28%), VL 35,164.

I'm still on the fence about joining this study.  I met with the project director and she assured me that there is absolutely no risk and that I'll be fine.  The doctor's involved have been dealing with HIV since the 80's.  They are not going to let me get sick.  With this study, I could fall into 1 of 2 groups.

I could be in one of two groups:

1.) If I'm in the group that does not receive the treatment - If my counts were to arrive at a level where treatment should start, I will be given treatment.

2.)  If I'm in the group that starts treatment - Part of me doesn't want to put toxic drugs into my body if they are not necessary.  But the other part of me feels that the earlier I start treatment, the quicker my viral load will drop and also my T-Cells will not decrease as rapidly.  I would actually be doing something (besides diet and exercise). I would feel more in control, like you said.

I also met with my infectious disease doctor to get his take on the study.  He did not give me any indication whether I should join it or not.  He just gave me a lot to think about.

He told me how he would proceed.  He would have me get the VL and CD4 tests again to see if they are consistent, and then 2 months later, get the tests done again, so he could see the rate of change and make a decision.  He said with my current results, he would not recommend treatment at this time.  He told me that he has had patients that wanted to start treatment as early as possible though.  He also had patients who did not want to start treatment after he recommended they should start.  Of course he pointed out that the reason for this this study is to determine when to start treatment and his opinion on how to proceed could change 2 years from now.  I can assure you that this doctor is very knowledgeable in HIV and the meds.  He's been dealing with it since the early 80's.

So ultimately, there is a 50/50 chance that I could be put in the correct group.  But isn't it this way right now with everyone, including yourself?  You said you don't want to put toxic drugs into your body unless necessary, but maybe that's the wrong group (or the correct group).  Right now, doctor's are not sure if that is beneficial in the long run.

Ok, my head hurts, so I'm going to stop typing for now.  I hope people comment.

[minus_25]

I have decided to do the study.  I'm in the "Do not start HAART treatment" group.  Of course, they assured me that they are not going to let me get sick, and if the doctors feel I should start treatment due to lab results, then I will start treatment.