Recent changes to the US DHHS adult
and adolescent HIV treatment guidelines

On March 12, 2008, Project Inform held an Update Town Meeting in San Francisco on updates to the Federal Guidelines for treating HIV disease. Below is a synopsis of the information covered at the event.

 

Background

In early 2007, the DHHS Guidelines panel met and agreed to a complete review and update of the guidelines. Members of the panel, which include treating physicians, researchers, government officials and community members, were assigned to various subcommittees to review the document and recommend changes to the full panel. Two sets of updates have been issued, one in December 2007 and one in January 2008. Below is a brief overview of the changes thus far.

WHEN TO START

• ARV treatment should be started in anyone with a history of an AIDS-defining illness or before CD4 count falls below 350.
• ARV treatment is recommended regardless of CD4 count for:
• Pregnant women
• People with HIV Associated Nephropathy (HIVAN)
• People co-infected with Hepatitis B Virus (HBV) for whom treatment of HBV is warranted

In addition to these recommendations, a discussion was added about the potential benefits and risks of starting HIV treatment at CD4 counts above 350. The main points were:

• The risk of death or serious illness in people with CD4 counts above 350 is low, so any benefit from starting treatment at high CD4 counts is likely to be small.
• There are data — for example the ATHENA cohort — that show that people who start HIV treatment with CD4 counts above 350 are more likely to achieve and maintain CD4 counts above 800.
• Similarly, in the Johns Hopkins Cohort people who started treatment with CD4s below 350 were less likely to achieve and maintain CD4 counts above 500.
• Early HIV treatment has the potential to reduce HIV transmission rates.

Factors weighing against early treatment would be:

• the necessity of life-long treatment,
• the lack of long-term data on most (all?) HIV drugs,
• the potential for developing drug resistance, and
• the interference with quality of life.

The main issue here is the lack of randomized, prospective studies on when to start. Designing and implementing such a trial is challenging. Such studies would need to be large and long-term to gain useful information. This begs the question of the applicability of the information once the study is done. For example: if a ‘when to start’ trial had been done in the late 1990s, final data would just now be reportable. We would have a lot of information on Crixivan and Viracept based regimens. How helpful would that be?

WHAT TO START

The list of drugs appropriate for first line use was changed significantly. The fixed-dose combination pill Combivir was downgraded from ‘preferred’ to ‘alternative’ based largely on lipoatrophy data. Epzicom was upgraded from ‘alternative’ to ‘preferred’ based largely on the availability of HLA testing reducing the fear of abacavir hypersensitivity reactions. Several protease inhibitors changed position as well. Below is a summary table. Note that this is only for first line use.
 

CLASS	PREFERRED	ALTERNATIVE	NOT RECOMMENDED
NRTIs	Truvada Epzicom	Combivir ddI + 3TC or FTC	d4T
NNRTI	Sustiva	Viramune	Rescriptor Intelence
Protease Inhibitor	Reyataz—boosted Lexiva—boosted (2x/day) Kaletra (2x/day)	Reyataz—unboosted Lexiva—unboosted Lexiva—boosted, 1x/day Kaletra 1x/day Invirase—boosted	Invirase—unboosted Viracept Aptivus Prezista—boosted

 

The other classes of HIV drugs, including Entry Inhibitors (CCR5 and Fusion Inhibitors) and Integrase Inhibitors are not recommended at this time for first line therapy. In some cases this is due to safety concerns. In others it is simply a lack of supportive data.

Treatment Experienced
There were four important changes here. The first is a discussion of the data on the newly approved drugs, like Prezista, Isentress, Intelence, and Selzentry. All of these have been extensively studied in treatment experienced people. The second change was subtle but significant — strengthening the ‘treatment goals’ section to include language on undetectability and avoidance of functional monotherapy. Third, more discussion was added about the risks of treatment interruptions, flowing from the SMART, DART, PART and TRIVICAN studies. Last, new language was added on the potential for ‘simplification’, or reducing the number of drugs a treatment experienced person is taking when they are on a suppressive regimen.

Other changes
There were significant changes made in the TB section, including recommending rifabutin over rifamycin, a discussion of IRIS (Immune Reconstitution Inflammatory Syndrome).

Discussion
The Guidelines are meant to help HIV treating physicians better manage the care and treatment decision. The document is under constant review, by a dedicated volunteer group. The panel strives to incorporate the best evidence in an ongoing fashion. The stronger the evidence, the stronger the recommendations. Sometimes changes in the guidelines can appear to lag behind the cutting edge. This is sometimes due to simple time constraints. Other times, it has to do with strength of evidence. Currently, four community members are included in the panel to ensure that the user’s perspective is always part of the discussions.

The entire document can be found at http://aidsinfo.nih.gov.