Important Drug-Drug Interactions in HIV-Infected Persons on Antiretroviral Therapy: An Update on New Interactions Between HIV and Non-HIV Drugs

Abstract

Advances in antiretroviral therapy have turned HIV into a chronic, manageable disease. Patients often require treatment for co-morbid conditions as well as HIV, and consequently, pharmacokinetic interactions between antiretrovirals (ARVs) and other drug classes are an increasing concern. Protease inhibitors and non-nucleoside reverse transcriptase inhibitors are involved in the CYP450 or other transporter systems, and may be associated with higher risk of clinically significant drug interactions. One reverse transcriptase inhibitor, abacavir, has demonstrated weak inhibition of CYP3A4, 2D6 and 2C9 in vitro, but is not associated with any clinically significant interactions involving the CYP450 system. The integrase inhibitor raltegravir is not involved in the CYP450 system, and may be a suitable option to use when trying to minimize interactions with other drug classes. This review summarizes recently published data on clinically significant drug interactions between ARVs and other drug classes including antineoplastics, immunosuppressant transplant drugs, directly acting antivirals for hepatitis C, antifungals, antimalarials, corticosteroids, psychotropics, hormonal contraceptives, anticoagulants, drugs for pulmonary hypertension, and herbal products. In situations of suspected or potential interactions, close monitoring is warranted, and dose adjustments or substitutions may be required.

A Review of Daclatasvir Drug–Drug Interactions

“…The complex nature of many HIV regimens in terms of their DDI profile and the preference not to switch well-tolerated regimens in virally suppressed patients implies that the ideal HCV partner regimen for the treatment of co-infection has a low probability of DDIs. The probability of a DDI between DCV and antiretroviral agents often reflects the degree of impact the antiretroviral regimen has on CYP3A4 [22]. …”

Drug–Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation: A Review

“…The management of cART and immunosuppressive therapy is extremely challenging, as witnessed by high allograft rejection rates observed in this immune system dysregulated population, 5 but also increased risk of infections, high rates of drug toxicity and the profound drug-drug interactions between cART and immunosuppressants. [6][7][8] As transplantation in the HIV population becomes increasingly common there is a need to optimize the pharmacologic management of this population. Specifically, there is a need for cART regimens that have less potential for drug-drug interactions and minimal overlapping toxicities when used in combination with common immutnosuppressive regimens.…”

Antiviral drug discovery: broad-spectrum drugs from nature

“…Most notable are the currently developed anti-HCV protease and polymerase inhibitors that in combination have a potential for curing close to all chronic HCV infections 29 . However, DAAs are still challenged with unsolved issues such as elevated costs, both for development and implementation 30 , emergence of pathogen resistance 31 , poor treatment responses in selected patient groups [32][33][34][35] or drug-drug interactions leading to toxicity [36][37][38][39][40] . These problems become even more relevant in co-infections as of HIV and HCV, for which combination treatment can be a clinical challenge 38,41,42 .…”