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Summary : Adherence to highly-active antiretroviral therapy (HAART) is important for successful viral suppression. However, HAART is difficult to take on a long-term basis. Factors that influence adherence include the complexity of the regimen, the number of daily doses, the number of pills, and dietary restrictions. Different formulations and combinations have led to simplified regimens that provide significant advantages in terms of acceptability and adaptability to specialized situations, such as directly observed therapy.
The number of daily doses:
The pharmacokinetics of some NRTIs (ddI, d4T, 3TC) and NNRTI's (efavirenz, nevirapine) make once daily dosing of these agents feasible. Ritonavir boosting, which takes advantage of pharmacokinetic interactions between PIs, has opened the way to simplified twice or even once daily dosing of PIs. Antiviral efficacy has been shown for regimens including indinavir/ritonavir (800/100 mg) bid, Fortovase/ritonavir (1600/100 mg) once-daily, and lopinavir/ritonavir bid. Trials comparing the antiviral efficacy of boosted-PI regimens head-to-head are underway. Combinations of NNRTIs and PIs also take advantage of pharmacokinetic interactions. Newer antiretrovirals, such as tenofovir, a nucleotide-reverse-transcriptase inhibitor, which is dosed once-daily (300 mg), add to therapy simplification.
The number of pills:
Newer formulations have reduced the daily number of pills. Trizivir, a combination pill of AZT, 3TC, and Abacavir, is administered as a single pill twice daily, and has established antiviral efficacy in treatment-naīve patients. Newer formulations of antiretrovirals include enteric-coated ddI which is better tolerated and can be administered once daily.
Dietary restrictions:
Dietary restrictions have been lessened by certain pharmacokinetic interactions, such as ritonavir boosting. However, components of once-daily regimens may still need to be taken at separate times during the day if ddI is part of the regimen. Treatment simplification should be part of a comprehensive approach to enhance adherence to antiretroviral therapy. Other aspects of this approach include limiting drug-related toxicity, improving tolerability, and providing ongoing psychosocial support for HIV-infected individuals.
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