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INTRODUCTION

Safe and effective pharmacotherapy to treat and prevent human immunodeficiency virus (HIV) is one of the greatest achievements of science and public health in the past century. Infected individuals who maintain a daily oral regimen now have a normal or near-normal life expectancy. More than 30 approved drugs and dozens of formulations have produced thousands of possible drug combinations, but most patients receive one of a handful of well-tolerated and rigorously tested regimens. Unique features of antiretroviral therapy include the need for lifelong treatment to control virus replication and the possibility of rapid emergence of permanent drug resistance if these agents are not used properly. Although three-drug and two-drug combination oral regimens have radically altered the course of this epidemic, future options will include long-acting injectable and implantable formulations.

ABBREVIATIONS

Abbreviations

ABC: abacavir

ADME: absorption, distribution, metabolism, excretion

AIDS: acquired immunodeficiency syndrome

5-AMP: adenosine 5′-monophosphate

AUC: area under plasma concentration-time curve

CBT: cabotegravir

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

HCV: hepatitis C 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

LA: long-acting

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

RPV: rilpivirine

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

PATHOGENESIS OF HIV-RELATED DISEASE

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 is generally no true period of 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 simian immunodeficiency virus (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 nonnucleoside reverse transcriptase inhibitors (NNRTIs) are HIV-1 specific and have no activity against HIV-2.

Virus Structure

HIV is ...

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