More

detailed recommendations for the use of TDM are available in the BHIVA guidelines for the routine investigation and monitoring of adult HIV-1-infected individuals 2011 [10]. As for all other investigations, it is essential that TDM is undertaken correctly, especially with regard to timing (undertaken when steady state has been achieved). A consensus has been achieved for defining targets [11] for many ARVs. With many newer agents, evidence for a defined minimum target for efficacy is either weak or lacking, and evidence for an upper toxicity cut-off for most ARVs is lacking. We recommend patients stopping ART containing BKM120 supplier an NNRTI in combination with an NRTI backbone replace all drugs with a PI (LPV/r) for 4 weeks (1C). We recommend patients stopping a PI-containing regimen stop all drugs Ku-0059436 molecular weight simultaneously and no replacement is required (1C). Proportion of patients with an undetectable VL on ART who, on stopping a regimen containing an NNRTI in combination with a NRTI backbone, are switched to

PI/r for 4 weeks. In general, treatment interruptions are not recommended for most patients. Whatever the reason for stopping ART (e.g. drug toxicity, intercurrent illness, after pregnancy or patient choice), pharmacological issues must be considered for a clinician to give guidance. The half-life of each drug included in the regimen is critical. There is the potential for monotherapy or dual therapy if ARV drugs with different half-lives are stopped simultaneously. NNRTI and NRTI resistance mutations have been detected following discontinuation of previously suppressive regimens [12] and may have the potential to affect the likelihood of

viral re-suppression on restarting an NNRTI-based ART regimen. There are limited data on which to base recommendations for how to protect against development of resistance in the period immediately following treatment cessation. Rucaparib supplier Several discontinuation strategies have been proposed [13], and choice is influenced by clinical considerations, patient wishes and pharmacological principles. Options include: (i) simultaneously stopping all drugs in a regimen containing drugs with similar half-lives; (ii) a staggered stop, discontinuing the drug with the longest half-life first in a regimen containing drugs with short and long half-lives; or (iii) replacing all drugs with a drug with a short half-life and high genetic barrier to resistance (i.e. a PI). There is no randomized comparison of these three strategies. However, in one study a lower number of emergent resistance mutations were seen in patients switching to a PI compared with those undertaking a simultaneous or staggered stop [12].