Important Clinical Updates

Important Updates: For HIV Chapter

As a result of a recent randomized controlled trial which showed that ART reduces the likelihood of spreading HIV the 2010 Guidelines on HIV treatment by the International Antiviral Society have been updated to state that all patients with HIV, regardless of CD4 count, may benefit from ART and should be offered treatment. It is noted that although there is no CD4 count threshold at which starting therapy is contraindicated, the evidence supporting treatment initiation increases as the CD4 cell count decreases.

Source: Melanie A. Thompson, MD; Judith A. Aberg, MD; Jennifer F. Hoy, MBBS, FRACP; et al. Antiretroviral Treatment of Adult HIV Infection 2012 Recommendations of the International Antiviral Society–USA Panel

JAMA. 2012;308(4):387-402. doi:10.1001/jama.2012.7961

Update as of August 2011:

New clinical guideline issued on diagnosis, management of stable COPD August, 2011.

Several collaborating medical societies, including the American College of Physicians (ACP), released new guidelines this on the diagnosis and management of stable chronic obstructive pulmonary disease (COPD).

The guideline, which updates and expands on a 2007 ACP guideline on this topic, was developed by a panel with members from ACP, the American College of Chest Physicians, the American Thoracic Society, and the European Respiratory Society, and represents an official, joint guideline from all four organizations.

This guideline addresses the value of history and physical examination for predicting airflow obstruction; the value of spirometry for screening or diagnosis of COPD; and COPD management strategies, specifically evaluation of various inhaled therapies (anticholinergics, long-acting â-agonists, and corticosteroids), pulmonary rehabilitation programs, and supplemental oxygen therapy.

The guideline was published in the Aug. 2 Annals of Internal Medicine.

Update as of February 2012:

Update to Diabetes Volume 6 of Edition 7 Chapter 3 Diabetes Management

A physician from University of Pennsylvania wrote the editors to note that, "…it would be important to include findings from the 2008 NEJM Holman article which reports the 10 yr follow-up to the original 10-yr 1998 UKPDS study (which was referenced in the case write-up). These findings show that there is a mortality benefit to early tight control in this group of patients, not only a preserved reduction in macrovascular disease and mortality in the metformin arm, but also a post-trial risk reduction in diabetes-related death and MI in the SU-insulin arm. It is just another way to emphasize to learners that being aggressive early, e.g. in newly diagnosed patients, does lead to benefit down the road in a "legacy effect" manner, and that this is a different group of patient than what ACCORD, ADVANCE, and VADT were studying."

Our chapter author responds, "I agree that "being aggressive early, e.g. in newly diagnosed patients, does lead to benefit down the road in a "legacy effect" manner" is an intriguing hypothesis, and could well turn out to be the case.

UKPDS studied newly-diagnosed diabetics in the 1970s thru early 1990s. These patients were not treated to current blood pressure or LDL goals. They were randomized to intensive versus conventional treatment (initiate treatment when the fasting glucose was above 108 mg/dL or 270 mg/dL). Patients were followed for 10 years, and about a 1-point separation in A1c was achieved (on average 7.0 versus 7.9, but with steady increase over time such that at 10 years median A1c was high 7s versus high 8s). The larger study, in which a sulfonurea-insulin based regimen was used, microvascular complications (but not mortality or macrovascular disease) were reduced. After completion of the trial (median 10 years), the surviving cohort was followed – for a median period of 8.5 years; standardized data collection was performed only for the first 5 post-trial years. Differences in A1c were lost by 1 year post-trial. Post-hoc analyses found that post-trial risk reductions emerged in the sulfonylurea–insulin group for myocardial infarction (15%, P=0.01), and death from any cause (13%, P=0.007). This is not RCT data – it is follow-up of a cohort that was in an RCT and for whom data is no longer being collected in a standardized manner and post-hoc analyses are being pursued.

It is not clear why RCT data has been heterogeneous, with ACCORD showing increased mortality from intensive control (at only 3.5 years), and other trials not showing this effect. Many think that it relates to whether patients were enrolled at diagnosis or later in the disease, but this is currently a hypothesis. UKPDS occurred in an era where lipids and HTN were not managed to current standards and DM diagnosis required a greater degree of hyperglycemia than in the current era.

Management of insulin in type 2 DM is a very broad topic, and I chose to focus on the relevant RCT data (UKPDS, VADT, ACCORD, and ADVANCE). The post-trial analysis of the UKPDS cohort certainly generates enthusiasm for the hypothesis that there is a "legacy effect" (i.e. mortality benefit of glucose control over the very long term), but I do not feel these findings have the same weight as RCT data, especially now that we have an RCT showing increased early mortality. If I re-wrote the chapter, I would certainly include the findings of the 2008 post-trial report."

The Editors of the Yale Office-based Medicine Curriculum welcome feedback on our chapters to improve the content and quality of the discussion, especially where the discussions are so rich.