Abstract
ABSTRACTBackgroundThe introduction of human immunodeficiency virus (HIV) protease inhibitors (PIs) has led to a dramatic decline in the morbidity and mortality associated with HIV infection. However, the concomitant use of PIs and other antiretrovirals (ARVs) can be complicated by drug-drug interactions (DDIs), adversely affecting levels of PIs.MethodA quantitative, retrospective drug utilisation study was performed using data obtained from the medicine claims database of a pharmacy benefit management company during 2004, 2005 and 2006. The possible DDIs found among ARVS themselves were identified using the classification by Tatro.ResultsThe percentage of ARV prescriptions claimed of the total number of medicine items increased from 1.68% (n = 43 482) during 2004 to 3.18% (n = 51 613) during 2005, then to 4.74% (n = 47 085) during 2006. A total of 1 326, 1 863 and 960 possible DDIs were identified among ARVs themselves for 2004, 2005 and 2006 respectively. Of these, ritonavir (unboosted or boosted) presented with the most possible DDIs, accounting for 74.28% (n = 985) for 2004; 67.90% (n = 1 265) for 2005; and 27.50% (n = 264) for 2006. The highest prevalence of DDIs identified was between ritonavir (unboosted) and saquinavir (n = 974, 5) for 2005 and 2006; followed by indinavir (n = 490, 129, 155) for 2004 to 2006; and efavirenz (n = 274) for only 2004; then ritonavir (boosted), co-formulated as lopinavir/ritonavir, and efavirenz (n = 118, 88, 34) for 2004 to 2006; nevirapine (n = 49, 37) for 2004 and 2005; indinavir (n = 9) for 2004; and saquinavir (n = 22) for 2006.ConclusionThese findings indicate that concomitant use of PIs such as ritonavir, a potent cytochrome P450(CYP)3A4 enzyme inhibitor, and other ARVs is complicated by possible DDIs and therefore further studies need to be done on the ARV combinations and management of these DDIs.
Highlights
In managing human immunodefiency virus (HIV)-1 infection, the current best available route is to achieve both sustained suppression and altered natural history of viral replication in all cellular and body compartments, using highly active antiretroviral therapy (HAART).[1,2]The HAART regimens currently recommended as first-line treatment are protease inhibitor (PI) based or non-nucleoside reverse transcriptase inhibitor (NNRTI) based[3]; triple nucleoside reverse transcriptase inhibitor (NRTI)-based regimens are an alternative when protease inhibitors (PIs)- or NNRTI-based regimens are unsuitable.[4]
The highest prevalence of drug-drug interactions (DDIs) identified was between ritonavir and saquinavir (n = 974, 5) for 2005 and 2006; followed by indinavir (n = 490, 129, 155) for 2004 to 2006; and efavirenz (n = 274) for only 2004; ritonavir, co-formulated as lopinavir/ritonavir, and efavirenz (n = 118, 88, 34) for 2004 to 2006; nevirapine (n = 49, 37) for 2004 and 2005; indinavir (n = 9) for 2004; and saquinavir (n = 22) for 2006
These findings indicate that concomitant use of PIs such as ritonavir, a potent cytochrome P450(CYP)3A4 enzyme inhibitor, and other ARVs is complicated by possible DDIs and further studies need to be done on the ARV combinations and management of these DDIs
Summary
In managing human immunodefiency virus (HIV)-1 infection, the current best available route is to achieve both sustained suppression and altered natural history of viral replication in all cellular and body compartments, using highly active antiretroviral therapy (HAART).[1,2]The HAART regimens currently recommended as first-line treatment are protease inhibitor (PI) based or non-nucleoside reverse transcriptase inhibitor (NNRTI) based[3]; triple nucleoside reverse transcriptase inhibitor (NRTI)-based regimens are an alternative when PI- or NNRTI-based regimens are unsuitable.[4]. The introduction of HIV-1 PIs has been associated with a dramatic reduction in AIDS-related morbidity and mortality because there are potent ARV agents that, either alone or co-administered with NRTIs, have demonstrated substantial virological and immunological responses sustained over long periods of followup.[6] Ritonavir is one of the four potent synthetic HIV PIs that have revolutionised HIV therapy. Among the PIs, ritonavir (a so-called booster) is the most employed in combination with other ARVs to enhance plasma drug concentration and, increase antiretroviral activity.[7] It is the most potent inhibitor of CYP3A4, is the most likely PI medication to cause DDIs.[6]. The introduction of human immunodeficiency virus (HIV) protease inhibitors (PIs) has led to a dramatic decline in the morbidity and mortality associated with HIV infection. The concomitant use of PIs and other antiretrovirals (ARVs) can be complicated by drug-drug interactions (DDIs), adversely affecting levels of PIs
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