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HIV Therapy—The State of ART

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The Future of HIV-1 Therapeutics

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 389))

Abstract

HIV Attachment. In this cross section, HIV is shown at the top and a target cell is shown at the bottom in blues. HIV envelope protein (A) has bound to the receptor CD4 (B) and then to coreceptor CCR5 (C), causing a change in conformation that inserts fusion peptides into the cellular membrane

Antiretroviral therapy changed the face of HIV/AIDS from that of soon and certain death to that of a chronic disease in the years following introduction of highly active antiretroviral therapy in 1995–1996 (initially termed HAART, but now most often abbreviated to ART since not all combinations of regimens are equally active). Since then, many new agents have been developed and introduced in response to problems of resistance, toxicity, and tolerability, and great advances have been achieved in accessibility of HIV drugs in resource-poor global regions. Potential challenges that providers of HIV therapy will face in the coming decade include continuing problems with resistance, especially where access to drugs is inconsistent, determining how best to combine new and existing agents, defining the role of preventive treatment (pre-exposure prophylaxis or PrEP), and evaluating the potential of strategies for cure in some populations.

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Abbreviations

HAART:

Highly active antiretroviral therapy

ART:

Antiretroviral therapy

HIV, HIV-1:

Human immunodeficiency virus, human immunodeficiency virus type 1

AIDS:

Acquired immune deficiency syndrome

PrEP:

Pre-exposure prophylaxis

AZT:

Zidovudine

ddI:

Didanosine

ddC:

Zalcitidine

d4T:

Stavudine

3TC:

Lamivudine

FTC:

Emtricitabine

ABC:

Abacavir

TDF:

Tenofovir disoproxil fumarate

RT:

Reverse transcriptase

DNA:

Deoxyribonucleic acid

RNA:

Ribonucleic acid

NVP:

Nevirapine

EFV:

Efavirenz

ETV:

Etravirine

DLV:

Delavirdine

RPV:

Rilpivirine

SQV:

Saquinavir

IDV:

Indinavir

NFV:

Nelfinavir

FPV:

Fosamprenavir

LPV:

Lopinavir

RTV/r:

Ritonavir

TPV:

Tipranavir

ATV:

Atazanavir

DRV:

Darunavir

T20:

Enfurvirtide

RAL:

Raltegravir

ETG:

Elvitegravir

DTG:

Dolutegravir

MVC:

Maraviroc

NRTI:

Nucleoside reverse transcriptase inhibitor

NNRTI:

Non-nucleoside reverse transcriptase inhibitor

TP:

Triphosphate

NS5A:

Non-structural protein 5A of hepatitis C virus

Kd:

Kilodalton

PI:

Protease inhibitor

INSTI:

Integrase strand transfer inhibitor

CSF:

Cerebrospinal fluid

CYP3A:

Cytochrome P450 isoform protein 3A

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

DHHS:

Department of health and human services

IC50:

Inhibitory concentration 50 %

PCR:

Polymerase chain reaction

SREBP-1:

Sterol regulator element-binding protein 1

PPAR-gamma:

Peroxisome proliferator-activated receptor gamma

OAT, OATP:

Organic anion transporter

gUGT:

Glucuronosyltransferase

CNS:

Central nervous system

MDR1:

Multidrug resistance transporter 1

HSCT:

Hematopoetic stem cell transplant

CCR5:

CC Chemokine receptor 5 gene

ANRS:

Agence Nationale de Recherche sur le Sida

VISCONTI:

Virological and immunological studies in controllers after treatment interruption

CD3:

Cluster of differentiation surface marker 3

CD4:

Cluster of differentiation surface marker 4

HDAC:

Histodeacytelase inhibitor

CRISPR:

Clustered regularly interspaced short palindromic repeat protein

Cas-9:

CRISPR-associated protein 9

Fem-PrEP:

Women’s preventative treatment study

VOICE:

Vaginal and oral interventions to control the epidemic

MSM:

Men who have sex with men

US:

United States

IVDU:

Intravenous drug users

CDC:

Centers for Disease Control

NIH:

National Institutes of Health

DAIDS:

Division of AIDS

NIAID:

National Institute of Allergy and Infectious Disease

NIMH:

National Institute of Mental Health

NIDA:

National Institute of Drug Abuse

NICHD:

National Institute of Child Health and Human Development

NHLBI:

National Heart Lung and Blood Institute

NIGMS:

National Institute of General Medical Sciences

NIDDK:

National Institute of Diabetes and Digestive and Kidney Diseases

NIA:

National Institute on Aging

PPI:

Proton pump inhibitor

ADH:

Alcohol dehydrogenase

OCT2:

Organic cation transporter 2

MATE1:

Multidrug and toxin extrusion protein 1

UGT1A:

Uracil diphosphate glucuronosyltransferase 1 protein family

CYPnLn, nLn:

Cytochrome protein isoforms of P-450, e.g., CYP1A2 or 1A2, CYP1A6, or 1A6.

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Acknowledgments:

The authors wish to thank the Veterans Administration and the VA San Diego Healthcare System for their continued support for excellence in clinical care of HIV-infected veterans. This work was also supported by the University of California, San Diego, Center for AIDS Research, NIH/DAIDS P30 AI036214, which is in turn supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, and NIDDK. Thanks for assistance, proofing, and comments from Douglas Richman, David Goodsell, Bruce Torbett, and Wei-Wei Chiu.

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  1. Infectious Disease 9-111F, VA San Diego Healthcare System, San Diego, CA, 92161, USA

    David Looney

  2. University of California San Diego, La Jolla, CA, 92093, USA

    David Looney & Scott Johns

  3. Pharmacy 119, VA San Diego Healthcare System, San Diego, CA, 92161, USA

    Ariel Ma & Scott Johns

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  1. David Looney
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  2. Ariel Ma
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Correspondence to David Looney .

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  1. Departments of Molecular and Experimental Medicine and Immunology and Microbial Science (MEM 131), The Scripps Research Institute, La Jolla, California, USA

    Bruce E. Torbett

  2. Department of Integrative Structural and Computational Biology, and RCSB Protein Data Bank, The Scripps Research Institute, La Jolla, California, USA

    David S. Goodsell

  3. Department of Pathology, University of California, San Diego, La Jolla, California, USA

    Douglas D. Richman

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Looney, D., Ma, A., Johns, S. (2015). HIV Therapy—The State of ART. In: Torbett, B., Goodsell, D., Richman, D. (eds) The Future of HIV-1 Therapeutics. Current Topics in Microbiology and Immunology, vol 389. Springer, Cham. https://doi.org/10.1007/82_2015_440

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