Analysis of possible drug-drug interactions between ritonavir and other antiretrovirals in a section of the private health care sector in South Africa

BACKGROUND: 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. However, the concomitant use of PIs and other antiretrovirals (ARVs) can be complicated by drug-drug interactions (DDIs), adversely affecting levels of PIs. METHOD: A 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. RESULTS: The 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. CONCLUSION: 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 therefore further studies need to be done on the ARV combinations and management of these DDIs.