Drug resistance prevalence and HIV-1 variant characterization in the naive and pretreated HIV-1-infected paediatric population in Madrid, Spain

Madrid cohort of HIV-infected children; Miguel de Mulder; Gonzalo Yebra; Leticia Martín; Luís Prieto; María José Mellado; Pablo Rojo; María Ángeles Muñoz-Fernández; Santiago Jiménez de Ory; José Tomas Ramos; Africa Holguín

doi:10.1093/jac/dkr305

Drug resistance prevalence and HIV-1 variant characterization in the naive and pretreated HIV-1-infected paediatric population in Madrid, Spain

Madrid cohort of HIV-infected children, Miguel de Mulder, Gonzalo Yebra, Leticia Martín, Luís Prieto, María José Mellado, Pablo Rojo, María Ángeles Muñoz-Fernández, Santiago Jiménez de Ory, José Tomas Ramos, Africa Holguín

Royal (Dick) School of Veterinary Studies

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Drug resistance mutations affect antiretroviral therapy (ART) effectiveness in HIV-1-infected children, compromising long-term therapy. HIV-1 variants and drug resistance mutations were identified in HIV-infected children from Madrid, Spain.

METHODS: Patients from the Madrid cohort of HIV-infected children (1993-2009) with available pol sequences or infected samples stored at the Spanish HIV-1 BioBank were selected. Specimens were used to perform new pol sequences when not available. HIV-1 variants were characterized by phylogenetic analysis. Resistance mutations were identified according to the International AIDS Society-USA list (2009).

RESULTS: In 198 patients, pol sequences were recovered from routine resistance testing (n = 98) or newly performed using stored plasma, lymphocytes or DNA (n = 100). Patients were mostly Europeans (90%), with moderate to severe AIDS symptoms (65%), on ART (85%) when the specimen was sequenced and infected by subtype B (90%). Among the 19 HIV-1 non-B variants found, 58% were recombinants (8CRF02_AG, 1CRF08_BC, 1CRF12_BF and 1CRF13_cpx) and the rest were 'pure' non-B subtypes (1A2, 2C, 2D, 1F1, 1G and 1H). Transmitted drug resistance (TDR) mutations were detected in 13% of naive children; 4%, 7% and 10% for protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), respectively. Global resistance prevalence was higher (66%) among ART-exposed children; 37% for PIs, 54% for NRTIs and 35% for NNRTIs.

CONCLUSIONS: HIV-1 non-B variants infected 10% of the cohort during 1993-2009. Resistant viruses were present in 26.5% and 66% of naive and pretreated children, respectively. Our data suggest that TDR prevalence in children could be higher than that reported in adults in Spain. The provided data will help to improve clinical management of HIV-infected children in Spain.

Original language	English
Pages (from-to)	2362-71
Number of pages	10
Journal	Journal of Antimicrobial Chemotherapy
Volume	66
Issue number	10
Early online date	2 Aug 2011
DOIs	https://doi.org/10.1093/jac/dkr305
Publication status	Published - Oct 2011

Keywords

Acquired Immunodeficiency Syndrome
Adolescent
Anti-HIV Agents
Antiretroviral Therapy, Highly Active
Base Sequence
Child
Child, Preschool
Cohort Studies
Drug Resistance, Viral
Female
HIV Infections
HIV-1
Humans
Infant
Male
Molecular Sequence Data
Mutation
Phylogeny
Protease Inhibitors
Reverse Transcriptase Inhibitors
Sequence Analysis, DNA
Spain
pol Gene Products, Human Immunodeficiency Virus
Journal Article
Research Support, Non-U.S. Gov't

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10.1093/jac/dkr305

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Madrid cohort of HIV-infected children, de Mulder, M., Yebra, G., Martín, L., Prieto, L., Mellado, M. J., Rojo, P., Muñoz-Fernández, M. Á., Jiménez de Ory, S., Ramos, J. T., & Holguín, A. (2011). Drug resistance prevalence and HIV-1 variant characterization in the naive and pretreated HIV-1-infected paediatric population in Madrid, Spain. Journal of Antimicrobial Chemotherapy, 66(10), 2362-71. https://doi.org/10.1093/jac/dkr305

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title = "Drug resistance prevalence and HIV-1 variant characterization in the naive and pretreated HIV-1-infected paediatric population in Madrid, Spain",

abstract = "BACKGROUND: Drug resistance mutations affect antiretroviral therapy (ART) effectiveness in HIV-1-infected children, compromising long-term therapy. HIV-1 variants and drug resistance mutations were identified in HIV-infected children from Madrid, Spain.METHODS: Patients from the Madrid cohort of HIV-infected children (1993-2009) with available pol sequences or infected samples stored at the Spanish HIV-1 BioBank were selected. Specimens were used to perform new pol sequences when not available. HIV-1 variants were characterized by phylogenetic analysis. Resistance mutations were identified according to the International AIDS Society-USA list (2009).RESULTS: In 198 patients, pol sequences were recovered from routine resistance testing (n = 98) or newly performed using stored plasma, lymphocytes or DNA (n = 100). Patients were mostly Europeans (90%), with moderate to severe AIDS symptoms (65%), on ART (85%) when the specimen was sequenced and infected by subtype B (90%). Among the 19 HIV-1 non-B variants found, 58% were recombinants (8CRF02_AG, 1CRF08_BC, 1CRF12_BF and 1CRF13_cpx) and the rest were 'pure' non-B subtypes (1A2, 2C, 2D, 1F1, 1G and 1H). Transmitted drug resistance (TDR) mutations were detected in 13% of naive children; 4%, 7% and 10% for protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), respectively. Global resistance prevalence was higher (66%) among ART-exposed children; 37% for PIs, 54% for NRTIs and 35% for NNRTIs.CONCLUSIONS: HIV-1 non-B variants infected 10% of the cohort during 1993-2009. Resistant viruses were present in 26.5% and 66% of naive and pretreated children, respectively. Our data suggest that TDR prevalence in children could be higher than that reported in adults in Spain. The provided data will help to improve clinical management of HIV-infected children in Spain.",

keywords = "Acquired Immunodeficiency Syndrome, Adolescent, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Base Sequence, Child, Child, Preschool, Cohort Studies, Drug Resistance, Viral, Female, HIV Infections, HIV-1, Humans, Infant, Male, Molecular Sequence Data, Mutation, Phylogeny, Protease Inhibitors, Reverse Transcriptase Inhibitors, Sequence Analysis, DNA, Spain, pol Gene Products, Human Immunodeficiency Virus, Journal Article, Research Support, Non-U.S. Gov't",

author = "{Madrid cohort of HIV-infected children} and {de Mulder}, Miguel and Gonzalo Yebra and Leticia Mart{\'i}n and Lu{\'i}s Prieto and Mellado, {Mar{\'i}a Jos{\'e}} and Pablo Rojo and Mu{\~n}oz-Fern{\'a}ndez, {Mar{\'i}a {\'A}ngeles} and {Jim{\'e}nez de Ory}, Santiago and Ramos, {Jos{\'e} Tomas} and Africa Holgu{\'i}n",

year = "2011",

month = oct,

doi = "10.1093/jac/dkr305",

language = "English",

volume = "66",

pages = "2362--71",

journal = "Journal of Antimicrobial Chemotherapy",

issn = "0305-7453",

publisher = "Oxford University Press",

number = "10",

}

Madrid cohort of HIV-infected children, de Mulder, M, Yebra, G, Martín, L, Prieto, L, Mellado, MJ, Rojo, P, Muñoz-Fernández, MÁ, Jiménez de Ory, S, Ramos, JT & Holguín, A 2011, 'Drug resistance prevalence and HIV-1 variant characterization in the naive and pretreated HIV-1-infected paediatric population in Madrid, Spain', Journal of Antimicrobial Chemotherapy, vol. 66, no. 10, pp. 2362-71. https://doi.org/10.1093/jac/dkr305

Drug resistance prevalence and HIV-1 variant characterization in the naive and pretreated HIV-1-infected paediatric population in Madrid, Spain. / Madrid cohort of HIV-infected children; de Mulder, Miguel; Yebra, Gonzalo et al.

In: Journal of Antimicrobial Chemotherapy, Vol. 66, No. 10, 10.2011, p. 2362-71.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Drug resistance prevalence and HIV-1 variant characterization in the naive and pretreated HIV-1-infected paediatric population in Madrid, Spain

AU - Madrid cohort of HIV-infected children

AU - de Mulder, Miguel

AU - Yebra, Gonzalo

AU - Martín, Leticia

AU - Prieto, Luís

AU - Mellado, María José

AU - Rojo, Pablo

AU - Muñoz-Fernández, María Ángeles

AU - Jiménez de Ory, Santiago

AU - Ramos, José Tomas

AU - Holguín, Africa

PY - 2011/10

Y1 - 2011/10

N2 - BACKGROUND: Drug resistance mutations affect antiretroviral therapy (ART) effectiveness in HIV-1-infected children, compromising long-term therapy. HIV-1 variants and drug resistance mutations were identified in HIV-infected children from Madrid, Spain.METHODS: Patients from the Madrid cohort of HIV-infected children (1993-2009) with available pol sequences or infected samples stored at the Spanish HIV-1 BioBank were selected. Specimens were used to perform new pol sequences when not available. HIV-1 variants were characterized by phylogenetic analysis. Resistance mutations were identified according to the International AIDS Society-USA list (2009).RESULTS: In 198 patients, pol sequences were recovered from routine resistance testing (n = 98) or newly performed using stored plasma, lymphocytes or DNA (n = 100). Patients were mostly Europeans (90%), with moderate to severe AIDS symptoms (65%), on ART (85%) when the specimen was sequenced and infected by subtype B (90%). Among the 19 HIV-1 non-B variants found, 58% were recombinants (8CRF02_AG, 1CRF08_BC, 1CRF12_BF and 1CRF13_cpx) and the rest were 'pure' non-B subtypes (1A2, 2C, 2D, 1F1, 1G and 1H). Transmitted drug resistance (TDR) mutations were detected in 13% of naive children; 4%, 7% and 10% for protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), respectively. Global resistance prevalence was higher (66%) among ART-exposed children; 37% for PIs, 54% for NRTIs and 35% for NNRTIs.CONCLUSIONS: HIV-1 non-B variants infected 10% of the cohort during 1993-2009. Resistant viruses were present in 26.5% and 66% of naive and pretreated children, respectively. Our data suggest that TDR prevalence in children could be higher than that reported in adults in Spain. The provided data will help to improve clinical management of HIV-infected children in Spain.

AB - BACKGROUND: Drug resistance mutations affect antiretroviral therapy (ART) effectiveness in HIV-1-infected children, compromising long-term therapy. HIV-1 variants and drug resistance mutations were identified in HIV-infected children from Madrid, Spain.METHODS: Patients from the Madrid cohort of HIV-infected children (1993-2009) with available pol sequences or infected samples stored at the Spanish HIV-1 BioBank were selected. Specimens were used to perform new pol sequences when not available. HIV-1 variants were characterized by phylogenetic analysis. Resistance mutations were identified according to the International AIDS Society-USA list (2009).RESULTS: In 198 patients, pol sequences were recovered from routine resistance testing (n = 98) or newly performed using stored plasma, lymphocytes or DNA (n = 100). Patients were mostly Europeans (90%), with moderate to severe AIDS symptoms (65%), on ART (85%) when the specimen was sequenced and infected by subtype B (90%). Among the 19 HIV-1 non-B variants found, 58% were recombinants (8CRF02_AG, 1CRF08_BC, 1CRF12_BF and 1CRF13_cpx) and the rest were 'pure' non-B subtypes (1A2, 2C, 2D, 1F1, 1G and 1H). Transmitted drug resistance (TDR) mutations were detected in 13% of naive children; 4%, 7% and 10% for protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), respectively. Global resistance prevalence was higher (66%) among ART-exposed children; 37% for PIs, 54% for NRTIs and 35% for NNRTIs.CONCLUSIONS: HIV-1 non-B variants infected 10% of the cohort during 1993-2009. Resistant viruses were present in 26.5% and 66% of naive and pretreated children, respectively. Our data suggest that TDR prevalence in children could be higher than that reported in adults in Spain. The provided data will help to improve clinical management of HIV-infected children in Spain.

KW - Acquired Immunodeficiency Syndrome

KW - Adolescent

KW - Anti-HIV Agents

KW - Antiretroviral Therapy, Highly Active

KW - Base Sequence

KW - Child

KW - Child, Preschool

KW - Cohort Studies

KW - Drug Resistance, Viral

KW - Female

KW - HIV Infections

KW - HIV-1

KW - Humans

KW - Infant

KW - Male

KW - Molecular Sequence Data

KW - Mutation

KW - Phylogeny

KW - Protease Inhibitors

KW - Reverse Transcriptase Inhibitors

KW - Sequence Analysis, DNA

KW - Spain

KW - pol Gene Products, Human Immunodeficiency Virus

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/jac/dkr305

DO - 10.1093/jac/dkr305

M3 - Article

C2 - 21810838

VL - 66

SP - 2362

EP - 2371

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 10

ER -

Drug resistance prevalence and HIV-1 variant characterization in the naive and pretreated HIV-1-infected paediatric population in Madrid, Spain

Abstract

Keywords

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