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Analysis of Nevirapine Resistance in HIVNET 012 Susan H. Eshleman, MD/PhD HPTN Central Laboratory

Analysis of Nevirapine Resistance in HIVNET 012 Susan H. Eshleman, MD/PhD HPTN Central Laboratory 2/21/02. Selection and Fading of Resistance Mutations in Women and Infants Receiving Nevirapine to Prevent HIV-1 Vertical Transmission (HIVNET-012) AIDS (2001) 15:1951-1957

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Analysis of Nevirapine Resistance in HIVNET 012 Susan H. Eshleman, MD/PhD HPTN Central Laboratory

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  1. Analysis of Nevirapine Resistance in HIVNET 012 Susan H. Eshleman, MD/PhD HPTN Central Laboratory 2/21/02

  2. Selection and Fading of Resistance Mutations in Women and Infants Receiving Nevirapine to Prevent HIV-1 Vertical Transmission (HIVNET-012) AIDS (2001) 15:1951-1957 SH Eshleman, M Mracna, LA Guay, M Deseyve, S Cunningham, M Mirochnick, P Musoke, T Fleming, MG Fowler, LM Mofenson, F Mmiro, and JB Jackson

  3. Applied Biosystems ViroSeqTM HIV-1 Genotyping System Primary NVPR mutations K103N and Y181C Secondary NVPR mutations A98G, L100I, V106A, V108I, Y188C, G190A

  4. Performance of the Applied Biosystems ViroSeq HIV-1 Genotyping System for Sequence-Based Analysis of Non-subtype B HIV-1 from Uganda J Clin Microbiology (2001) 39: 4323-4327 M Mracna, G Becker-Pergola, J Dileanis, LA Guay, S Cunningham, JB Jackson, and SH Eshleman

  5. NVPR in women in HIVNET 012 NVPR mutations were detected in 21 (19%) of 111 women 6-8 weeks after single dose NVP The rate of NVPR was similar among women whose infants were or were not infected NVPR mutations faded from detection by 12-24 months in all evaluable women

  6. Detection of NVPR in women at 6-8 wks was associated with a high baseline VL and low baseline CD4 cell count It was not possible to evaluate the relationship between NVPR and maternal death

  7. NVPR in infants in HIVNET 012 NVPR mutations were detected in 11 (46%) of 24 infants 6-8 wks after single dose NVP The number of infants analyzed was too small to determine whether NVPR was associated with HIV-1 infection at birth or infant death NVPR mutations faded from detection by 12 months in all evaluable infants

  8. Comparison of NVPR mutations in 10 mother-infant pairs Mother WT WTWT WT WT WT K103N K103N K103N K103N+V106A+Y181C Infant Y181C Y181C Y181C Y181C Y181C+G190A Y181C+Y188C Y181C+Y188C Y181C Y181C+K103N K103N

  9. Analysis of late infected infants 11 infants had HIV-1 infection diagnosed after age 6-8 wks (median 10 mo, range 77-550 days) Samples were available from 9/11 infants (2-9 mo after diagnosis) 8/9 lacked NVPR mutations, including 2 whose mothers had NVPR mutations at 6-8 wks 1 infant diagnosed at 12 mo had K103N and Y181C at 15 and 18 mo. The mother had the same mutations at 6 wks.

  10. Conclusions HIV-1 variants with NVPR mutations can be selected in women and infants after single dose NVP NVPR mutations are detected more frequently in infants than women at 6-8 wks Different patterns of NVPR mutations are detected in infants vs. women

  11. Conclusions NVPR mutations were infrequently detected in infants with late HIV-1 infection NVPR mutations appear to fade from detection in women and infants over time

  12. Impact of HIV-1 subtype on women receiving single-dose NVP prophylaxis in HIVNET 012 J Infect Dis (2001) 184:914-917 SH Eshleman, G Becker-Pergola, M Deseyve, LA Guay, M Mracna, T Fleming, S Cunningham, P Musoke, F Mmiro, and JB Jackson

  13. We examined the relationship between HIV-1 subtype, MTCT and the development of NVPR in women in HIVNET 012 32 women whose infants were HIV-1 infected by 6-8 weeks of age 70 women whose infants were uninfected Subtypes identified (pol region) 50 A, 35 D, 4 C, and 13 recombinant

  14. The rate of NVPR was higher among women with subtype D than A D=10/35 (29%) A=6/50 (12%) Baseline viral loads and CD4 cell counts were similar among women with subtype A vs. D Adjusted OR = 4.94, 95%CI = 1.21-20.22 There was no apparent difference in MTCT among women with subtype A vs. D Additional studies are needed to further define the relationship between HIV-1 subtype and NVPR among women receiving NVP prophylaxis

  15. Acknowledgements HIVNET 012 study team Lab personnel at Johns Hopkins Univ. and Makerere Univ. PROJECT SUPPORT The Elizabeth Glaser Pediatric AIDS Foundation HIV Prevention Trials Network (HPTN) HIV Network for Prevention Trials ( HIVNET) AIDS Clinical Trials Groups (ACTG) Applied Biosystems

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