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Virologic Outcomes on Second Line Antiretroviral Therapy (ART) for HIV-infected Tanzanian Children with and without Clinical or Immunologic Failure at ART Switch Oral Abstract MOAB0203.

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  1. Virologic Outcomes on Second Line Antiretroviral Therapy (ART)for HIV-infected Tanzanian Children with and without Clinical or Immunologic Failure at ART Switch Oral Abstract MOAB0203 E. Reddy1, S. Emmett2,3, B. Mmbaga4, W. Schimana5, G. Kinabo4, J. Bartlett2,6, J. Crump1,6, M. Swai4, C. Cunningham2 1Duke University Medical Center and Kilimanjaro Christian Medical Centre, Moshi, Tanzania, United Republic of, 2Duke University Medical Center, Durham, United States, 3Howard Hughes Medical Institute, Bethesda, United States, 4Kilimanjaro Christian Medical Center, Moshi, Tanzania, United Republic of, 5Elizabeth Glaser Pediatric AIDS Foundation, Moshi, Tanzania, United Republic of, 6Duke Global Health Institute, Durham, United States

  2. Background • Most HIV-infected children receiving antiretroviral therapy (ART) in resource limited settings are monitored using clinical and/or immunologic criteria • These criteria can be insensitive in detecting virologic failure1 • Children changed to second line therapy may have accumulated extensive resistance mutations that place them at risk for virologic failure 1Emmett S. et al. JAIDS 54: 368-375.

  3. Predicting Pediatric Virologic Failure (VF) in Tanzania • Cross sectional study of HIV-infected children receiving ART for ≥ 180 days at the Kilimanjaro Christian Medical Centre Child Centred Family Care Clinic (CCFCC), a free clinic in northern Tanzania • Aged 12 mos. – 16 years, enrolled during routine clinic visits • HIV RNA, CD4+ lymphocyte measurement drawn at enrollment • Clinical and CD4+ lymphocyte history abstracted from chart • Determination of clinical/immune failure based on 2006 World Health Organization (WHO) Guidelines

  4. Predicting Pediatric VF in Tanzania cont. • Genotypic resistance testing performed on samples with HIV RNA ≥1000 copies/mL after reaching 75% target enrollment • Children with HIV RNA ≥400 copies/mL observed prospectively for 360 days after 2nd line start or a max. of 2 years (follow up ongoing) • ART decisions at discretion of clinicians, primarily following WHO 2006 Guidelines • 1st line ART = AZT/3TC or d4T/3TC + NVP or EFV • 2nd line ART = ABC/ddI/LPV/rtv • Repeat HIV RNA drawn (subject to test availability) after ≥70 days 2nd line ART

  5. Characteristics of 206 children with or without virologic failure (VF) at enrollment

  6. N

  7. HIV-1 genotype for 52 samples with HIV RNA ≥1000 copies/mL N HIV-1 subtypes

  8. Nucleos(t)ide Reverse Transcriptase (NRTI) Mutations • 40 (88.5%) of 45 samples had NRTI mutations • 22 (48.9%) had at least one TAM • 16 (35.5%) had ≥2 TAMs

  9. Non-nuceloside Reverse Transcriptase (NNRTI) and Total Mutations • 40 (88.5%) of 45 had NNTRI mutations • 35 (77.8%) had ≥ 3 total mutations (NRTI + NNRTI)

  10. N Time to ART start

  11. Immunologic & Virologic Outcomes after 2nd line ART • Laboratory data complete for 31 children after a mean (median) of 170 (173) days of 2nd line ART • 23 (74.2%) of 31 met virologic treatment goal: • At least 1log10 decline in HIV RNA after 70 days (N=3) OR • HIV RNA <400 by 180 days (N=20) • 27 (87.1%) of 31 children had CD4% above range of severe immune suppression

  12. Clinical Outcomes After 2nd Line ART • 53 (92.9%) of 57 children clinically well after 180 days • 1 (1.7%) had worsening chronic lung disease; lost to follow up 90 days into observation period (persistent VF) • 3 died: 2 with wasting syndrome, 1 nephropathy (all persistent VF) • 3 (4.3%) of 69 children with VF awaiting 2nd line at 180 days d/t lack of appropriate ART: 2 with TB and 1 requiring liquid protease inhibitor

  13. N p = 0.06 TAMs @ VF HIV RNA @ VF, log10 copies/mL Patient Characteristics

  14. Conclusions • The majority of children attained at least initial virologic suppression on 2nd line ART • Most with ≥ 2 TAMs suppressed on 2nd line • Clinical/immune failure at ART switch associated with subsequent virologic suppression • Adherence vs. earlier switch • Early VF of 1/4 concerning considering lifetime ART treatment goal • Larger numbers and longer follow up needed to determine true cost/benefit ratio of virologic monitoring in resource-limited pediatric ART programs

  15. Acknowledgements • CCFCC at Kilimanjaro Christian Medical Centre: Drs. Mark Swai, Grace Kinabo, BlandinaMmbaga; Sister Martha Mushi; additional staff HedwigaMrema, ElissianaNdossa, George Chambo and DoriceKiama • Duke University: Research Funds—Duke Center for AIDS Research (P30 AI 64518); Additional Investigator Support Dr. Reddy—AIDS Research and Training Grant (T32 AI007392-18; Drs. Crump and Bartlett—International Studies on AIDS Associated Coinfections award (ISAAC) (U01 AI-03-036); Dr. Crump—Fogarty International Center (D43 PA-03-018); Dr. Emmett—Howard Hughes Medical Institute; HIV Genotyping—Dr. FengGao • Elizabeth Glaser Pediatric AIDS Foundation: For support to CCFCC and support of follow up HIV RNA assays; investigator support to Dr. Werner Schimana

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