Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission

Deborah Persaud, Abubaker Bedri, Carrie Ziemniak, Anitha Moorthy, Berhanu Gudetta, Aida Abashawl, Yohannes Mengistu, Saad B. Omer, Abdulhamid Isehak, Solomon Kumbi, Rahel Adamu, Sileshi Lulseged, Roxann Ashworth, Elham Hassen, Andrea Ruff

Research output: Contribution to journalArticle

Abstract

Nevirapine resistance mutations arise commonly following single or extended-dose nevirapine (ED-NVP) prophylaxis to prevent mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV), but decay within 6-12 months of single-dose exposure. Use of ED-NVP prophylaxis in infants is expected to rise, but data on decay of nevirapine resistance mutations in infants in whom ED-NVP failed remain limited. We assessed, in Ethiopian infants participating in the Six-Week Extended Nevirapine (SWEN) Trial, the prevalence and persistence of nevirapine resistance mutations at 6 and 12 months following single-dose or up to 6 weeks of ED-NVP, and correlated their presence with the timing of infection and the type of resistance mutations. Standard population genotyping followed by high-throughput cloning were done on dried blood spot samples collected during the trial. More infants who received ED-NVP had nevirapine resistance detected by standard population genotyping (high frequencies) at age 6 months compared with those who received single-dose nevirapine (SD-NVP) (58% of 24 vs. 26% of 19, respectively; p = 0.06). Moreover, 56% of ED-NVP-exposed infants with nevirapine resistance at age 6 months still had nevirapine resistance mutations present at high frequencies at age 1 year. Infants infected before 6 weeks of age who received either SD- or ED-NVP were more likely to have Y181C or K103N; these mutations were also more likely to persist at high frequencies through 1 year of age. HIV-infected infants in whom ED-NVP prophylaxis fails are likely to experience delayed clearance of nevirapine-resistant virus in the first year of life, which in turn places them at risk for early selection of multidrug-resistant HIV after initial therapy with nonnucleoside reverse transcriptase inhibitor-based regimens.

LanguageEnglish (US)
Pages823-829
Number of pages7
JournalAIDS Research and Human Retroviruses
Volume27
Issue number8
DOIs
StatePublished - Aug 1 2011

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Nevirapine
Mothers
HIV
Viruses
Mutation
Reverse Transcriptase Inhibitors

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission. / Persaud, Deborah; Bedri, Abubaker; Ziemniak, Carrie; Moorthy, Anitha; Gudetta, Berhanu; Abashawl, Aida; Mengistu, Yohannes; Omer, Saad B.; Isehak, Abdulhamid; Kumbi, Solomon; Adamu, Rahel; Lulseged, Sileshi; Ashworth, Roxann; Hassen, Elham; Ruff, Andrea.

In: AIDS Research and Human Retroviruses, Vol. 27, No. 8, 01.08.2011, p. 823-829.

Research output: Contribution to journalArticle

Persaud, D, Bedri, A, Ziemniak, C, Moorthy, A, Gudetta, B, Abashawl, A, Mengistu, Y, Omer, SB, Isehak, A, Kumbi, S, Adamu, R, Lulseged, S, Ashworth, R, Hassen, E & Ruff, A 2011, 'Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission' AIDS Research and Human Retroviruses, vol. 27, no. 8, pp. 823-829. DOI: 10.1089/aid.2010.0346
Persaud, Deborah ; Bedri, Abubaker ; Ziemniak, Carrie ; Moorthy, Anitha ; Gudetta, Berhanu ; Abashawl, Aida ; Mengistu, Yohannes ; Omer, Saad B. ; Isehak, Abdulhamid ; Kumbi, Solomon ; Adamu, Rahel ; Lulseged, Sileshi ; Ashworth, Roxann ; Hassen, Elham ; Ruff, Andrea. / Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission. In: AIDS Research and Human Retroviruses. 2011 ; Vol. 27, No. 8. pp. 823-829
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