Friday, January 14, 2011

DHHS Updates Treatment Guidelines for HIV-Infected Adults, Teens

From Medscape Medical News

Laurie Barclay, MD

January 13, 2011 — The Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents has updated guidelines for the use of antiretroviral (ARV) agents for HIV-1-infection in this population. The guidelines were posted online January 10.

The DHHS panel, a working group of the Office of AIDS Research Advisory Council, aimed to provide recommendations for clinicians based on current evidence regarding ARV drugs used to treat adults and adolescents with HIV infection in the United States. The new guidelines, which update those issued December 1, 2009, highlight baseline evaluation; treatment goals; indications to begin ARV therapy (ART); choice of initial therapy in ART-naive patients; drugs or combinations that should be avoided; management of adverse effects, drug interactions, and treatment failure; and specific ART-related considerations applicable to various patient subgroups.

"...ART for the treatment of ...HIV infection has improved steadily since the advent of potent combination therapy in 1996," write panel co-chairs John G. Bartlett, MD, from Johns Hopkins University in Baltimore, Maryland, and H. Clifford Lane, MD, from National Institutes of Health in Bethesda, Maryland, and colleagues. "New drugs have been approved that offer new mechanisms of action, improvements in potency and activity even against multidrug-resistant viruses, dosing convenience, and tolerability."

Specific Updated Changes

Specific changes in these updated guidelines from the December 1, 2009, version of the guidelines include the following:

* The DHHS panel highlighted the importance of clinical research to answer remaining questions concerning the optimal safety and efficacy of ART, and it therefore encourages both protocol development and patient enrollment in well-designed, Institutional Review Board–approved clinical trials.
* For a patient receiving a suppressive ART regimen with a CD4 T-cell count well above the threshold for risk for opportunistic infection, clinicians seldom use changes in CD4 T-cell count to make decisions regarding ART changes. Therefore, the panel now recommends that the CD4 T-cell count may be monitored less often in such patients, such as every 6 to 12 months vs every 3 to 6 months, provided there are no clinical status changes, including the patient having new HIV-associated clinical symptoms or beginning treatment with interferon, corticosteroids, or antineoplastic agents.
* For some viral load assays, low-level positive viral load results (usually < 200 copies/mL) have been commonly reported. To eliminate most cases of viremia caused by isolated blips or test variability, the panel now defines virologic failure as a confirmed viral load of more than 200 copies/mL for the purpose of patient monitoring.

Recommendations on Drug-Resistance Testing

New recommendations regarding drug-resistance testing include the following:

* More specific recommendations are given regarding when to use genotypic testing to identify resistance to integrase strand transfer inhibitors (INSTIs).
* If transmitted INSTI resistance is suspected, it may be helpful to include genotypic testing for INSTI resistance because standard genotypic drug-resistance testing involves testing only for mutations in the reverse transcriptase and protease genes.
* For patients in whom an INSTI-based regimen fails, genotypic testing for INSTI resistance should be considered to help decide whether a drug from this class should be included in subsequent regimens.

Combination Regimens

Changes to the "What to Start" recommendations regarding initial combination regimens for the ARV-naive patient include the following:

* Maraviroc plus zidovudine/lamivudine is now considered to be an "Acceptable Regimen" after US Food and Drug Adminstration approval of maraviroc for use in ART-naive patients, based on findings from a randomized controlled trial using maraviroc plus zidovudine/lamivudine.
* Maraviroc plus tenofovir/emtricitabine and maraviroc plus abacavir/lamivudine are now considered to be regimens that may be acceptable, although additional definitive data are needed.
* Ritonavir-boosted saquinavir–based regimens are now designated as "Regimens that are Acceptable but Should be Used with Caution" vs "Alternative PI[Protease Inhibitor]-based Regimens." This change reflects a recent change in the Invirase (Roche Laboratories) product label because significant PR and QT interval prolongations were found in a healthy volunteer study.

Coinfection With Hepatitis B Virus

More specific recommendations are offered for treatment of patients with HIV coinfected with hepatitis B virus, including recommendations for patients with lamivudine/emtricitabine–resistant hepatitis B virus infection and for those unable to tolerate tenofovir-based regimens.

Coinfection With Tuberculosis

Updates to management of Mycobacterium tuberculosis/HIV coinfection reflect survival and clinical benefits of starting ART earlier in treatment-naive patients with active tuberculosis (TB) disease, based on findings from recent randomized controlled trials. The following recommendations address initiating ART in patients being treated for active TB but not yet on ART:

* ART should be given to all HIV-infected patients with diagnosed active TB.
* Patients with a CD4 T-cell count of less than 200 cells/mm3 should start ART within 2 to 4 weeks of starting TB treatment.
* Patients with a CD4 T-cell count of 200 to 500 cells/mm3 should start ART within 2 to 4 weeks, or at least by 8 weeks after starting TB treatment.
* Most panel members also recommend that patients with a CD4 T-cell count of more than 500 cells/mm3 start ART within 8 weeks of TB therapy.

New Table Formats

The most common and/or severe known ARV-associated adverse events, listed by ARV drug class, are displayed in a new table format.

Several sections and pertinent tables have also been updated, including those on coreceptor tropism assays, treatment goals, starting ART in treatment-naive patients, what drugs and regimens not to use, virologic and immunologic failure, regimen simplification, exposure-response relationship and therapeutic drug monitoring for ARV agents, acute HIV infection, HIV and illicit drug users, HIV-2 infection, drug interactions, and drug characteristics.

"The provider can make recommendations most likely to lead to positive outcomes only if the patient's own point of view and social context are well known," the panel concludes. "...The Panel anticipates continued progress in the simplicity of regimens, improved potency and barrier to resistance, and reduced toxicity. The Panel hopes the guidelines are useful and is committed to their continued adjustment and improvement."

Financial disclosures for members of the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents are available on the DHHS' AIDS Info site.

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. January 10, 2011.

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