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The pharmacotherapy of HIV infection is a rapidly moving field. Three-drug combinations are the current minimum standard of care for this infection, so available agents and formulations constitute several thousand possible regimens. Knowing the essential features of the pathophysiology of this disease and how chemotherapeutic agents affect the virus and the host is critical in developing a rational approach to therapy. Unique features of this drug class include the need for lifelong administration to control virus replication and the possibility of rapid emergence of permanent drug resistance if these agents are not used properly.



ABC: abacavir

ADME: absorption, distribution, metabolism, excretion

AIDS: acquired immunodeficiency syndrome

5′-AMP: adenosine 5′-monophosphate

AUC: area under plasma concentration-time curve

cDNA: complementary DNA

CLCr: creatinine clearance

CMP: cytidine monophosphate

CNS: central nervous system

CSF: cerebrospinal fluid

CYP: cytochrome P450

dCMP: deoxycytidine monophosphate

ddC: dideoxycytidine

ddI: didanosine

DF: disoproxil fumarate

DRESS: drug reaction with eosinophilia and systemic symptoms

d4T: stavudine

eCLCr: estimated creatinine clearance

env: envelope protein gp160

FDA: Food and Drug Administration

FTC: emtricitabine

GI: gastrointestinal

HBV: hepatitis B virus

HIV: human immunodeficiency virus

HTLV: human T-cell lymphotrophic virus

IMP: inosine 5′-monophosphate

InSTI: integrase strand transfer inhibitor

IRIS: immune reconstitution inflammatory syndrome

LTR: long terminal repeat

NDP: nucleoside diphosphate

NNRTI: nonnucleoside reverse transcriptase inhibitor

NRTI: nucleos(t)ide reverse transcriptase inhibitor

OATP: organic anion-transporting polypeptide

PI: protease inhibitor

PK: pharmacokinetic

PRPP: phosphoribosyl pyrophosphate

QTc: corrected cardiac QT interval

RNase H: ribonuclease H

RT: reverse transcriptase

SIV: simian immunodeficiency virus

t1/2: half-life of elimination

TAF: tenofovir alafenamide

TAM: thymidine analogue mutation

3TC: lamivudine

TDF: tenofovir disoproxil fumarate

vRNA: viral RNA

ZDV: zidovudine


Human immunodeficiency viruses are lentiviruses, a family of retroviruses evolved to establish chronic persistent infection with gradual onset of clinical symptoms. Replication is constant following infection, and although some infected cells may harbor nonreplicating virus for years, in the absence of treatment there generally is no true period of viral latency following infection (Deeks et al., 2015). Humans and nonhuman primates are the only natural hosts for these viruses.

There are two major families of HIV. Most of the epidemic involves HIV-1; HIV-2 is more closely related to SIV and is concentrated in western Africa. HIV-1 is genetically diverse, with at least five distinct subfamilies or clades. HIV-1 and HIV-2 have similar sensitivity to most antiretroviral drugs, although the NNRTIs are HIV-1 specific and have no activity against HIV-2.

Virus Structure

HIV is a typical retrovirus with a small RNA genome of 9300 base pairs. Two copies of the genome are contained in a nucleocapsid core surrounded by a lipid bilayer, or envelope that is derived from the host cell plasma membrane (Figure 64–1). The viral genome encodes three major open ...

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