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Impaired CD4+ cell recovery during antiretroviral therapy in patients with HIV resistance mutations

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Abstract

Antiretroviral therapy is limited by the development of human immunodeficiency virus (HIV) resistance mutations. Although resistance testing is recommended during therapy failure, little is known about the optimal time points for testing or its impact on treatment. In this study, we investigated HIV polymorphisms and mutations and assessed their influence on the outcome of highly active antiretroviral therapy (HAART). We focused on viral load and CD4+ cell counts as the most important parameters for therapy response. Resistance mutations were present in 19% of all patients prior to antiretroviral treatment. Mutations causing direct antiretroviral drug resistance were observed in 10%. Analyzing therapy response, we found a significant correlation between resistance mutations and impaired CD4+ cell recovery six months after the initiation of antiretroviral treatment. Lower CD4+  cell counts were also observed in a subgroup of patients infected with a virus presenting mutations that directly lowered drug susceptibility.

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Abbreviations

ABC:

Abacavir, Ziagen

AIDS:

Acquired immunodeficiency syndrome

APV:

Amprenavir, agenerase

ART:

Antiretroviral therapy

ATV:

Atazanavir, Reyataz

AZT:

Zidovudine, Retrovir

CDC:

Centers for disease control

CCR:

Chemokine co-receptor

CD:

Cluster of differentiation

d4T:

Stavudine, Zerit

ddC:

Zalcitabine, Hivid

ddl:

Didanosine, Videx

DLV:

Delavirdine, rescriptor

EFV:

Efavirenz, Sustiva

FACS:

Fluorescence-activated cell sorter

FTC:

Emtricitabine, Emtriva

HAART:

Highly active antiretroviral therapy

HIV:

Human immunodeficiency virus

HT:

Heterozygote

IDV:

Indinavir, Crixivan

LPV:

Lopinavir+Ritonavir, Kaletra

NFV:

Nelfinavir, Viracept

NVP:

Nevirapine, Viramune

NRTI:

Nucleoside reverse transcriptase inhibitor

NNRTI:

Non-nucleoside reverse transcriptase inhibitor

PCR:

Polymerase chain reaction

PE:

Phycoerytrin

PI:

Protease inhibitor

SOC:

Standard of care

T20:

Enfuvirtide, Fuzeon

TDF:

Tenofovir disoproxil fumarate, Viread

RT:

Reverse transcriptase

RTV:

Ritonavir, Norvir

SQV:

Saquinavir, Fortovase

WHO:

World Health Organisation

WT:

Wild type

3TC:

Lamivudine; Epivir

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Authors and Affiliations

  1. Department of Neurology, Saarland University Hospital, Kirrbergerstrasse, Building 90, 66421, Homburg/Saar, Germany

    Kurt-Wolfram Sühs & R. Diem

  2. Department of Neuro-oncology, University Clinic Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    R. Diem

  3. Clinic for Immunology and Rheumatology, Hannover Medical School (MHH), 30625, Hannover, Germany

    Kurt-Wolfram Sühs, M. Stoll & R. E. Schmidt

  4. Outpatient Clinic for Internal Medicine and Immunology, Georgstraße 46, 30159, Hannover, Germany

    H. Heiken

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  1. Kurt-Wolfram Sühs
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Sühs, KW., Stoll, M., Diem, R. et al. Impaired CD4+ cell recovery during antiretroviral therapy in patients with HIV resistance mutations. Arch Virol 157, 433–440 (2012). https://doi.org/10.1007/s00705-011-1191-9

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