Analysis of primary resistance mutations to HIV-1 entry inhibitors in therapy naive subtype C HIV-1 infected mother-infant pairs from Zambia

Hongyan Guo, Chang Liu, Bin Liu, Charles Wood, Xiaohong Kong

Research output: Contribution to journalArticle

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Abstract

Background: Small molecular CCR5 inhibitors represent a new class of drugs for treating HIV-1 infection. The evaluation of the primary resistance mutations associated with entry inhibitors during HIV-1 perinatal transmission is required because they may have a profound impact on the clinical management in MTCT. Objectives: To evaluate the primary resistance mutations to maraviroc and vicriviroc during perinatal transmission and analyze the sensitivity of Env derived from mother-infant pairs to maraviroc. Study design: Nine MIPs infected by subtype C HIV-1 were recruited to analyze the prevalence and transmission of primary resistance mutations to maraviroc and vicriviroc. Moreover, Env derived from six MIPs were employed to construct provirus clones and to analyze the sensitivity to maraviroc. Results: Mutations A316T, conferring partial resistance to maraviroc, T307I and R315Q, both conferring partial resistance to vicriviroc are prevalent in mother and infant cohorts, indicating the transmission of primary resistance mutations during HIV-1 perinatal transmission. However, the mutations of acutely infected mothers seem to directly transmit to their corresponding infants, while some mutations at low frequency of chronically infected mothers would be lost during transmission. Moreover, provirus clones derived from acutely infected MIPs are less susceptible to maraviroc than those from chronically infected MIPs. Conclusions: Our study suggests that the transmission mode of primary resistance mutations and the sensitivity to maraviroc are dependent on infection status of MIPs either acutely or chronically infected. These results may indicate that higher dose of maraviroc could be needed for treatment of acutely infected MIPs compared to chronically infected MIPs.

Original languageEnglish (US)
Pages (from-to)233-239
Number of pages7
JournalJournal of Clinical Virology
Volume58
Issue number1
DOIs
StatePublished - Sep 1 2013

Fingerprint

HIV Fusion Inhibitors
Zambia
HIV-1
Mothers
Mutation
Proviruses
Therapeutics
Clone Cells
maraviroc
HIV Infections

Keywords

  • MTCT HIV-1 Subtype C Primary resistance Maraviroc Vicriviroc

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Analysis of primary resistance mutations to HIV-1 entry inhibitors in therapy naive subtype C HIV-1 infected mother-infant pairs from Zambia. / Guo, Hongyan; Liu, Chang; Liu, Bin; Wood, Charles; Kong, Xiaohong.

In: Journal of Clinical Virology, Vol. 58, No. 1, 01.09.2013, p. 233-239.

Research output: Contribution to journalArticle

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AB - Background: Small molecular CCR5 inhibitors represent a new class of drugs for treating HIV-1 infection. The evaluation of the primary resistance mutations associated with entry inhibitors during HIV-1 perinatal transmission is required because they may have a profound impact on the clinical management in MTCT. Objectives: To evaluate the primary resistance mutations to maraviroc and vicriviroc during perinatal transmission and analyze the sensitivity of Env derived from mother-infant pairs to maraviroc. Study design: Nine MIPs infected by subtype C HIV-1 were recruited to analyze the prevalence and transmission of primary resistance mutations to maraviroc and vicriviroc. Moreover, Env derived from six MIPs were employed to construct provirus clones and to analyze the sensitivity to maraviroc. Results: Mutations A316T, conferring partial resistance to maraviroc, T307I and R315Q, both conferring partial resistance to vicriviroc are prevalent in mother and infant cohorts, indicating the transmission of primary resistance mutations during HIV-1 perinatal transmission. However, the mutations of acutely infected mothers seem to directly transmit to their corresponding infants, while some mutations at low frequency of chronically infected mothers would be lost during transmission. Moreover, provirus clones derived from acutely infected MIPs are less susceptible to maraviroc than those from chronically infected MIPs. Conclusions: Our study suggests that the transmission mode of primary resistance mutations and the sensitivity to maraviroc are dependent on infection status of MIPs either acutely or chronically infected. These results may indicate that higher dose of maraviroc could be needed for treatment of acutely infected MIPs compared to chronically infected MIPs.

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