US adult and adolecent HIV treatment guidelines updated twice – on 1 December 2007 and 29 January 2008:

http://www.hivatis.org

PDF:

http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf 1.7 MB

Taken together, the updates included the following changes

• Resistance testing on diagnosis and before starting treatment
• Starting treatment when CD4 count is <350 cells/mm3
• Use of HLA B*5701 testing prior to using abacavir
• Starting HIV treatment for people coinfected with HBV who need to treat their hepatitis
• Preferred first line dual nukes: tenofovir/FTC or abacavir/3TC; this is the first time that the guidelines have even mentioned lipoatrophy, and although they recognise it occurred more frequently with AZT compared to tenofovir, AZT is no longer a preferred first line choice.
• Preferred NNRTI is efavirenz; aternative is nevirapine
• Preferred boosted PIs for first-line therapy are atazanavir/r, fosamprenavir/r, lopinaivr/r, Alternative PI-regimens are unboosted atazanavir (but not with tenofovir), saquinavir/r, fosamprenavir twice daily, boosted fosamprenavir once-daily and lopinavir/r once-daily. Lowest recommendations are for nelfinavir, and boosted saquinavir.
• Nelfinavir is now contraindicated in pregnancy because of the unknown risk of small amounts of a byproduct (ethyl methanesulfonate or EMS)
• Changes to management of treatment experienced patients stress for the need for at least two or preferably three active drugs and includes recently developed drugs (maraviroc, raltegravir, etravirine), but also recognises that there is no consensus on the optimal time to switch a failing regimen
• A new discussion on immunological failure that quantifies chances of reaching over 500 cells/mm3.

“The proportion of patients experiencing immunologic failure depends on how failure is defined, the observation period, and the CD4 T-cell count when treatment was started. In the longest study conducted to date, the percentage of patients with suppressed viremia who reached a CD4 T-cell count >500 cells/mm3 through 6 years of treatment was 42% (starting treatment with a CD4 <200 cells/mm3), 66% (starting with CD4 200–350 cells/mm3) and 85% (starting with CD4 >350 cells/mm3) increases in CD4 T-cell counts in treatment-naïve patients with initial antiretroviral regimens are approximately 150 cells/mm3 over the first year. A CD4 T-cell count plateau may occur after 4–6 years of treatment with suppressed viremia.

A persistently low CD4 T-cell count while on suppressive antiretroviral therapy is associated with a small, but appreciable, risk of AIDS- and non– AIDS-related morbidity and mortality. For example, in the FIRST study, a low CD4 T-cell count on therapy was associated with an increased risk for AIDS-related complications (adjusted hazard ratio of 0.57 for CD4 T-cell count 100 cells/mm3 higher). Similarly, a low CD4 T-cell count was associated with an increased risk for non-AIDS events, including cardiovascular, hepatic, renal and cancer events. Other studies support these associations.”

Unlike French guidelines, use of IL-2 to boost CD4 counts to above 200 cells/mm3 in immunological non-responders is only recommended within a clinical trial setting.