US adult treatment guidelines updated (December 2007)
An update of the US Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents were release on 1 December 2007.
These guidelines very usefully highlight changes from the last edition with a yellow background for easy comparison.
- Adding the recommendation for resistance testing for all patients either on diagnosis or 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 B
- Preferred first line dual nukes: tenofovir/FTC or AZT/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 still a preferred first line choice. Abacavir/3TC is only an alternative option, despite being the backbone nucleosides in the trials used to recommend fosamprenavir.
- Preferred NNRTI is efavirenz; alternative is nevirapine.
- Preferred boosted PIs for first-line therapy are atazanavir/r, fosamprenavir/r, lopinavir/r. Alternative PI-regimens are unboosted atazanavir (but not with tenofovir), 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 two, or preferably three, active drugs and includes recently developed drugs (maraviroc, raltegravir, etravirine). They also recognise 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 200350 cells/mm3) and 85% (starting with CD4 >350 cells/mm3) increases in CD4 T-cell counts in treatment-naive patients with initial antiretroviral regimens are approximately 150 cells/mm3 over the first year. A CD4 T-cell count plateau may occur after 46 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.
The guidelines are available online and in PDF format: