Drug-Drug Interactions and HIV Therapy: What Should Pharmacists Know?

Abstract

Drug-interaction issues continue to present a major dilemma for the clinician caring for complex patients such as those infected with HIV. The inherent possibility of a drug interaction is magnified by the multitude of drugs being administered in highly-active antiretroviral therapy (HAART). In addition, other classes of medications are used to alleviate side effects, reduce toxicities associated with HAART, or treat concomitant diseases. The modification of one drug by another substance or drug-drug interaction is the main focus of this article. Drug-drug interactions may result in toxicity, treatment failure, or loss of effectiveness and can significantly affect a patient’s clinical outcome. An understanding of the fundamental mechanisms of HIV drug-drug interactions may allow for the early detection or avoidance of troublesome regimens and prudent management if they develop. Although HIV drug interactions are usually thought of as detrimental, resulting in a loss of therapeutic effect or toxicity, some drug interactions such as ritonavir boosted protease inhibitor–based antiretroviral treatments are beneficial and are commonly used in clinical practice. Therefore, pharmacists need to understand drug interaction mechanisms, remember key drug interactions, and vigilantly monitor patients for potential complications.

Prevalence of possible drugdrug interactions between antiretroviral agents in different age groups in a section of the private health care sector setting in South Africa

“…Although HIV drug interactions are usually thought of as detrimental, resulting in a loss of therapeutic effect or toxicity, some drug interactions such as RTV boosted PI‐based ARTs are beneficial and are commonly used in clinical practice (23). Therefore, pharmacists need to understand drug interaction mechanisms, remember key drug interactions, and vigilantly monitor patients for potential complications.…”

Fangjiomics: In Search of Effective and Safe Combination Therapies

“…On the other hand, drug‐drug interactions may result in toxicity, treatment failure, or loss of effectiveness and can significantly affect a patient's clinical outcome 71 . Interaction between drugs is also a significant cause of adverse drug reactions 72 .…”

Clinical Relevance of Drug Interactions in HIV-Infected Patients Receiving Antiretroviral Therapy

“…Table 2. General interactions due to enzyme inhibition by protease inhibitors Busti et al, 2004;DeSilva et al, 2001;DHHS, 2011;Krikorian & Rudorf, 2005;Piscitelli & Gallicano, 2001;Kashuba, 2005a;Robertson et al, 2005a;Tran et al, 2001;Winston & Boffito, 2005;Wire et al, 2006) of several drugs, increase their plasma levels, and may cause adverse drug reactions, which could cause grave health problems in patients. Thus, according to their clinical relevance, most could be classified in level 1 or 2.…”

“…Table 4. Clinical relevant bidirectional drug interactions mediated by PIs enzyme inhibition with other known drugs (Brophy et al, 2000;DHHS, 2011;Kashuba, 2005aKashuba, , 2005bKrikorian & Rudorf, 2005;Robertson et al, 2005b;Young, 2005) Young, 2005) lopinavir steady state concentration. (Dailly et al, 2005;Solas et al, 2004) The use of another low-dose PI as a pharmacokinetic extension agent (boosted), for instance ritonavir, is a strategy to counter this problem.…”

“…Table 6. Clinical relevant drug interactions due to enzyme induction mediated by NNRTIs (DeJesus et al, 2006;DHHS, 2011;Krikorian & Rudorf, 2005;Young, 2005) Methadone and efavirenz (nevirapine). Efavirenz and nevirapine may reduce methadone area under curve (AUC) by 57% and 46%, respectively.…”