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Drug Interactions in HIV: Nucleoside, Nucleotide, and Nonnucleoside Reverse Transcriptase Inhibitors and Entry Inhibitors

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Drug Interactions in Infectious Diseases: Antimicrobial Drug Interactions

Part of the book series: Infectious Disease ((ID))

Abstract

Recommended antiretroviral regimens for the treatment of HIV infection are composed of a combination of at least three antiretroviral medications. Most commonly, two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are combined with a medication from another antiretroviral drug class. This chapter reviews the pharmacology and drug interactions related to NRTIs, nonnucleoside reverse transcriptase inhibitors (NNRTIs), and entry inhibitors, including fusion inhibitors and CCR5 antagonists. NRTIs and enfuvirtide, a fusion inhibitor, have the fewest drug-drug interactions, as most are not hepatically eliminated. NNRTIs are frequent perpetrators of drug-drug interactions due to cytochrome P450 enzyme modulation. Both NNRTIs and the CCR5 antagonist, maraviroc, may also be victims of drug-drug interactions related to cytochrome P450 metabolism. This chapter emphasizes the clinical significance and management of common drug interactions associated with these antiretroviral drug classes.

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Abbreviations

ART:

Antiretroviral therapy

AUC:

Area under the concentration-time curve

BCRP:

Breast cancer resistance protein

BMD:

Bone mineral density

CCB:

Calcium channel blockers

CCR5:

C-C motif co-receptor 5

CES1:

Hepatic carboxylesterase

Cmax:

Maximum concentration

COC:

Combined oral contraceptives

CrCl:

Creatinine clearance

CSF:

Cerebrospinal fluid

CYP:

Cytochrome P450

FDC:

Fixed dose combination

HMG-CoA:

3-Hydroxy-3-methylglutaryl-coenzyme A

INR:

International normalized ratio

MAC:

Mycobacterium avium complex

MRP4:

Multidrug resistance protein 4

NNRTI:

Nonnucleoside reverse transcriptase inhibitors

NRTI:

Nucleoside/nucleotide reverse transcriptase inhibitor

OAT:

Organic anion transporter

OATP:

Organic anion-transporting polypeptides

OCT:

Organic cation transporters

PBMCs:

Peripheral blood mononuclear cells

PDE-5:

Phosphodiesterase type-5

P-gp:

P-glycoprotein

PrEP:

Pre-exposure prophylaxis

SNP:

Single-nucleotide polymorphisms

TAF:

Tenofovir alafenamide fumarate

TDF:

Tenofovir disoproxil fumarate

TFV:

Tenofovir

UGT:

Uridine-5′-diphosphate glucuronosyltransferase

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Authors and Affiliations

  1. University of Nebraska Medical Center, College of Pharmacy, Department of Pharmacy Practice, Omaha, NE, USA

    Lauren R. Cirrincione & Kimberly K. Scarsi

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  1. Lauren R. Cirrincione
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  2. Kimberly K. Scarsi
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Correspondence to Kimberly K. Scarsi .

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Editors and Affiliations

  1. College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA

    Manjunath P. Pai

  2. Department of Pharmaceutical Sciences, Skagg School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA

    Jennifer J. Kiser

  3. Division of Pharmacy Practice and Administration, UMKC School of Pharmacy at MSU, Springfield, Missouri, USA

    Paul O. Gubbins

  4. College of Pharmacy and Medicine, University of Illinois at Chicago, Chicago, Illinois, USA

    Keith A. Rodvold

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Cirrincione, L.R., Scarsi, K.K. (2018). Drug Interactions in HIV: Nucleoside, Nucleotide, and Nonnucleoside Reverse Transcriptase Inhibitors and Entry Inhibitors. In: Pai, M., Kiser, J., Gubbins, P., Rodvold, K. (eds) Drug Interactions in Infectious Diseases: Antimicrobial Drug Interactions. Infectious Disease. Humana Press, Cham. https://doi.org/10.1007/978-3-319-72416-4_8

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  • DOI: https://doi.org/10.1007/978-3-319-72416-4_8

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