Updated DHHS Antiretroviral Therapy Guidelines Reclassify Some First-Line Drugs

On October 14, 2011, the U.S. Department of Health and Human Services (DHHS) issued updated guidelines for the use of antiretroviral therapy (ART) in adults and adolescents. The European AIDS Clinical Society (EACS) also released revised guidelines at the 13th European AIDS Conference last week in Belgrade.

The full revised DHHS guidelines are available online. Changes are summarized in an introductory section, "What's New in the Guidelines?"

The key changes in this version focus on which drugs to start in a first-line regimen for treatment-naive patients.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs):

• Efavirenz (Sustiva) plus tenofovir/emtricitabine (the drugs in the Truvada coformulation) remains the sole "preferred" first-line regimen, except for women during the first trimester of pregnancy.
• Regimens containing nevirapine (Viramune) are now classified as "acceptable" for appropriate patients, including women with pre-treatment CD4 T-cell counts below 250 cells/mm³ and men below 400 cells/mm³ (people with higher counts are at greater risk for hypersensitivity reactions).
• The recently approved rilpivirine (Edurant) was added as an "alternative" component of initial therapy, given accumulated data supporting its safety and efficacy.
• In contrast, the new EACS guidelines rate efavirenz and nevirapine equally as recommended options, but do not include rilpivirine.

Protease Inhibitors:

• Once-daily ritonavir-boosted atazanavir (Reyataz) and boosted darunavir (Prezista) plus tenofovir/emtricitabine are the "preferred" options.
• Darunavir plus abacavir/lamivudine (the drugs in the Epzicom coformulation) was reclassified as an "alternative" due to additional data.
• Unboosted fosamprenavir (Lexiva) was removed due to inferior potency and risk of drug resistance in patients who experience virological failure.
• The preferred regimen for pregnant women is lopinavir/ritonavir (Kaletra) plus zidovudine/lamivudine (the drugs in Combivir).
• The new EACS guidelines are more flexible, recommending boosted atazanavir, boosted darunavir, or lopinavir/ritonavir, combined with either tenofovir/emtricitabine or abacavir/lamivudine

Integrase Inhibitors:

• Raltegravir (Isentress) -- the sole approved integrase inhibitor -- plus tenofovir/emtricitabine remains the "preferred" regimen.
• Raltegravir plus abacavir/lamivudine was upgraded to "alternative" due to accumulation of favorable data.
• The new EACS guidelines recommend raltegravir only with tenofovir/emtricitabine.

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs):

• Tenofovir/emtricitabine remains the sole "preferred" option, except for pregnant women.
• Abacavir/lamivudine remains an "alternative"; DHHS demoted abacavir/lamivudine from"preferred" to "alternative" status in 2008 due to concerns that abacavir may increase the risk of cardiovascular problems and may not be as effective for people with high pre-treatment viral load.
• The revised guidelines include more discussion of the comparative risks and benefits of abacavir/lamivudine and tenofovir/emtricitabine, given that numerous observational and randomized studies since 2008 have produced conflicting data.
• DHHS concludes that abacavir/lamivudine "remains a good alternative dual-NRTI option for some ART-naive patients."
• Zidovudine/lamivudine was reclassified from "alternative" to "acceptable" overall, but remains the preferred NRTI combination for pregnant women receiving antiretroviral drugs to prevent perinatal HIV transmission.
• Didanosine/lamivudine was removed as a dual-NRTI option for initial therapy due to lack of clinical trial experience and greater toxicity than other available options.
• The new EACS guidelines recommend tenofovir/emtricitabine and abacavir/lamivudine equally.

When to Start ART

As for when to initiate HIV treatment -- a subject of ongoing controversy -- the DHHS guidelines continue to advise starting when a person's CD4 cell count falls below 500 cells/mm³. Above that level, the panel was evenly split on whether to start or defer therapy.

The new EACS guidelines are more conservative, recommending treatment initiation at a threshold of 350 cells/mm³. However, ART is advised below 500 cells/mm³ --  or even sooner -- for several patient populations including pregnant women and people with co-existing conditions such as HIV-associated kidney disease, neurocognitive impairment, human papillomavirus (HPV)-associated cancers (e.g., anal or cervical cancer), and hepatitis B or C coinfection.

10/18/11

References

U.S. Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. October 14, 2011.

R Klein and K Struble. U.S. Food and Drug Administration (FDA). Revised Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. HIV/AIDS Update. October 15, 2011.

European AIDS Clinical Society (EACS). Guidelines. Version 6.0. October 2011.