A Closer Look at the New U.S. DHHS HIV Treatment Guidelines for Adults and Adolescents (Part 1)

An Interview With Joel Gallant, M.D., M.P.H.

December 10, 2007

This is part 1 of an update of the U.S. DHHS HIV Treatment Guidelines for Adults and Adolescents. For part 2, please click here.

Listen to full interview (13 min., 5.5MB MP3)
HIV medicine is an incredibly dynamic field, with the treatment landscape changing dramatically every few years. There are several reference tools that are meant to help clinicians keep up. One of the most critical is a document that is periodically updated by the U.S. Department of Health and Human Services, or DHHS.

Entitled "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents," the document is put together by a panel of 35 people. The members are mostly clinicians and researchers from universities throughout the United States, but also include a number of advocates and HIV-infected patients. The guidelines produced by the panel provide an invaluable summary of the current state-of-the-art in antiretroviral therapy.

The panel released its latest update to the guidelines on Dec. 1, 2007, and we've asked my guest today, Dr. Joel Gallant, a member of that DHHS panel, to provide a summary of the update. Dr. Gallant is a widely respected HIV clinician and researcher. He's also a professor of medicine and epidemiology at the Johns Hopkins University School of Medicine in Baltimore.

Joel Gallant, M.D., M.P.H.

For many years, the guidelines were a step behind what the savviest HIV specialists were doing. Do you think the guidelines have caught up to practice?

I think they are pretty responsive. But they will always be potentially a step behind really expert clinicians, just because they really depend on data that are reasonably mature -- preferably published data, although, certainly they do look at presented data, as well. There will always be clinicians who are kind of aware of these changes, aware of very early data that are too early to be considered by the guidelines panel, and are acting on those data. Those clinicians would probably say that the guidelines are a step behind.

On the other hand, there are examples of situations where physicians, acting on very early data, have turned out to be wrong. So I think the guidelines sort of wait until the data are pretty clear before they'll make a recommendation. It just depends on whether the savvy clinician turns out to be right in his or her interpretation of the data, or turns out to be wrong.

Can you walk us through what's new in the document?

Sure. I think the most important thing that's new is the issue of when to start. The previous set of guidelines recommended treatment for people with CD4 counts below 200, and recommended that therapy be considered in people with CD4 counts between 200 and 350.1 The new guidelines just come out and say that we should be treating patients at CD4s below 350. This is based on a variety of considerations, most importantly some data from observational cohort studies, as well as just the changing risk/benefit ratio, with better, safer, more effective and better tolerated therapies, and increasing evidence of benefit, with higher CD4 counts.

The other thing that the panel does now is that they no longer define a group of people who should not be treated. In the past, they basically said that if your CD4 was about 350 and your viral load was below 100,000, you should defer therapy.

The current guidelines say that there are some people who should be treated at higher CD4 counts. They specifically note: pregnant women, but that's not a new recommendation; people with HIV-associated nephropathy, or HIVAN; people who are coinfected with hepatitis B and who need treatment for their hepatitis B. The reason for that is because it's a lot easier to treat both infections than to try to treat hepatitis B with drugs that don't have HIV activity.

The panel also points out that there may be patients with higher CD4 counts, for whom therapy is appropriate, just based on the potential risks and benefits and the patients' readiness and willingness to adhere to therapy.

Examples might be: somebody in a discordant couple with fears of transmission; people with high CD4 counts, but CD4 counts that are declining rapidly; or people with very high viral loads. The panel doesn't get specific there, but it points out that 350 is not an absolutel cutoff, and that you might choose to treat earlier.

That's what I consider to be the most important set of changes. But some other ones involve laboratory testing. The guidelines have been recommending baseline resistance testing with genotype tests prior to therapy in treatment-naive patients. But they now come out and say that resistance tests should be performed at the time the patient enters into clinical care, regardless of whether the plan is to initiate therapy. The reason for that is because these tests are the most accurate shortly after infection, and with greater time they begin to miss the presence of the resistant virus that's there and archived in the reservoir, or present at low levels. So, the sooner you can do the test, the better.

The important thing is for clinicians to do the test, and then to make sure and save the resistance test results. It may be years before the patient starts therapy, and you'll want to have access to those results when you do start.

The recent approval of maraviroc [Selzentry, Celsentri] has led to a recommendation that tropism testing be done prior to the initiation of this drug. We know that if you have dual/mixed or X4-tropic virus, you're not going to respond virologically to maraviroc. The other risk to using maraviroc, in that case, is that you'd only be treating a portion of the viral population with the drug. Therefore, you wouldn't be protecting the other drug in the combination against resistance. So it's very important to make sure you're using the tropism assay and to only use maraviroc in people with R5-tropic virus, keeping in mind that the tropism assay can occasionally miss low level dual/mixed or X4 virus. So even having that test isn't complete assurance.

The guidelines also point out that you might consider doing a tropism assay, again, if the patient failed maraviroc. It's unclear what you would do with that information at that moment. But it would be to know whether they failed maraviroc because they selected out dual/mixed or X4 virus, or whether they failed due to resistance. The reason for that is because if, in the future, we have additional CCR5 inhibitors, those who failed with selection of X4 or dual/mixed virus would not be candidates for any of them.

Then, finally, they now recommend HLA-B*5701 testing prior to any initiation of abacavir [Ziagen] therapy. We have seen great data with PREDICT-1 and SHAPE,2,3 showing that this is a great test to reduce the risk of HSR [hypersensitivity reaction]. If it's a positive test, the patient is very likely to develop HSR, and should not take abacavir. In fact, the guidelines recommend that abacavir allergy be listed in the patient's medical record, just based on that test.

If the test is negative, then it's okay to go ahead and initiate abacavir, but there have been occasional reports of HSR in people with a negative test. So you still need to counsel the patient about HSR. But the likelihood is much reduced with this test.

The only other changes are just the mention of some of the new drugs for treatment-experienced patients: raltegravir [MK-0518, Isentress], the new integrase inhibitor maraviroc, which we already talked about; and then, coming soon we hope, etravirine, or TMC125, the new second-generation NNRTI [non-nucleoside reverse transcriptase inhibitor]. So the guidelines talk about the use of these drugs. They emphasize how important it is to use these drugs in combinations that are likely to be effective to avoid resistance, and again, reiterate what they have said in previous versions, that the goal of therapy now is an undetectable viral load for all patients, not just treatment-naive patients. The reason for that is because it's achievable, using the right combination of these new agents.

So those are the changes. What we're still waiting on are the new guidelines for what to start with, the initial regimen, which we hope to see within the next month or two. The DHHS sometimes comes out with sections of the guidelines as they become available, since these are online guidelines, rather than published. We'll be waiting for that piece to come out very soon.

Could you comment on the new section about immunologic failure? It defined immunologic failure as a failure to achieve an adequate CD4 count, despite virologic suppression, and discussed patients with persistently low CD4 counts.

That's always been the case; there's not much you can do about it. Again, I'll just speak from personal opinion here. I'm not familiar with that section as well as I should be, so I won't talk about it, per se. But there are some considerations that you might think about if somebody doesn't have a good CD4 response. One would be: Are they on a drug that suppresses their bone marrow, like AZT [zidovudine, Retrovir]? By getting them off AZT and on to a different drug you might see an improvement in the lymphocyte count which would, in turn, increase the CD4 count.

Then there's this data from ACTG 5142,4 and some other studies, suggesting that the boosted protease inhibitors, specifically lopinavir/ritonavir [Kaletra], might give you a better CD4 response than efavirenz [Sustiva, Stocrin], even though in that study efavirenz was better from a virologic standpoint.

So what we don't know is, if somebody's on efavirenz and not having a desirable CD4 response, will you get a better response by switching them to, say, lopinavir/ritonavir? We don't have those data to know. But it's interesting to just kind of speculate.

But, for the most part, if you have suppressed the viral load, you have done what you can do. There are not a lot of other things that you can do. Usually, in most cases, it is not an indication to change the regimen, with the possible exceptions of the things I mentioned.

How often do you think these guidelines are used by the typical practitioner? It's not read as often as it should be, I understand.

I think one of the problems is that the guidelines document is quite long and it's quite detailed. It's really an excellent document for finding out all the latest information on HIV therapy. Unfortunately, what happens is, people think of the guidelines as just a bunch of tables and they know what's in the tables about when to start and what to start with. But not enough people actually read the document in its entirety.

Even if you already are way ahead of things -- you are an expert clinician, you are practicing ahead of the guidelines, you have already been treating people below 350, all those kinds of things -- I think you can still learn a lot from actually reading the document. When I have to go to someplace to get references, or to make sure I'm thinking of the right studies, I'll often use this as a tool because it's such a comprehensive discussion of the issue.

Do you keep this on your PDA?

I don't have it on my PDA, but I have it on all my computers, including a PDF version of the latest guidelines. Of course, you can just go online and read it. It is lengthy, like I said, but well worth the trouble.

Well, thank you, Dr. Gallant, for taking the time to talk with us.

My pleasure.

To view a PDF of the guidelines, click here. To download a PDA version, click here.


  1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Washington, DC: US Dept of Health and Human Services; December 1, 2007.
  2. Mallal S, Phillips E, Carosi G, et al. PREDICT-1: a novel randomised prospective study to determine the clinical utility of HLA-B*5701 screening to reduce abacavir hypersensitivity in HIV-1 infected subjects (study CNA106030). In: Program and abstracts of the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007; Sydney, Australia. Abstract WESS101.
  3. Saag M, Balu R, Brachman P, et al. High sensitivity of HLA-B*5701 in whites and blacks in immunologically-confirmed cases of abacavir hypersensitivity (ABC HSR). In: Program and abstracts of the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007; Sydney, Australia. Abstract WEAB305.
  4. Riddler SA, Haubrich R, DiRienzo G, et al, for the AIDS Clinical Trials Group 5142 Study Team. A prospective, randomized, phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection -- ACTG 5142. In: Program and abstracts of the XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada. Abstract THLB0204.

This is part 1 of an update of the U.S. DHHS HIV Treatment Guidelines for Adults and Adolescents. For part 2, please click here.

This article was provided by TheBodyPRO.
See Also
Read the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents (PDF)


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