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Time to DNA-PCR Positivity in Non-Breastfed HIV-Infected Infants (Primarily Non-B HIV Subtype)

Time to DNA-PCR Positivity in Non-Breastfed HIV-Infected Infants (Primarily Non-B HIV Subtype). A Collaborative Analysis of Data from Cohorts in Thailand, South Africa, Botswana, and the United Kingdom International Collaborative Study of Pediatric Diagnostic Tests JuLy 19, 2011. Background.

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Time to DNA-PCR Positivity in Non-Breastfed HIV-Infected Infants (Primarily Non-B HIV Subtype)

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  1. Time to DNA-PCR Positivity in Non-Breastfed HIV-Infected Infants (Primarily Non-B HIV Subtype) A Collaborative Analysis of Data from Cohorts in Thailand, South Africa, Botswana, and the United Kingdom International Collaborative Study of Pediatric Diagnostic Tests JuLy 19, 2011

  2. Background • Accurate diagnostic tests to detect HIV infection in infants are critical to ensure early treatment • HIV DNA-PCR has imperfect sensitivity in the first two weeks of life • Previous studies found that time to HIV DNA-PCR positivity increase by about 15% with ZDV prophylaxis compared with no antiretrovirals (ARV) • Impact of combination ARV prophylaxis is not well characterized; no single cohort can adequately address this question

  3. Goals • Combine data from several cohorts of non-breastfeeding HIV-infected mother-infant pairs • Initial phase: cohorts with primarily non-B HIV subtype • Estimate the time to DNA-PCR positivity in non-breastfed HIV-infected infants • Assess differences in time to DNA-PCR positivity according to maternal/infant ARV regimen

  4. Inclusion/Exclusion Criteria • Inclusion criteria: • Infant HIV-infected and has at least one DNA-PCR result before age 3 months • Maternal HIV diagnosis before or within 1 month after birth • Excluded diagnostic tests with missing result or missing age at time of blood draw • Excluded one infant whose mother’s ARV exposure was unknown

  5. Statistical Methods • Used methods for interval-censored data • Timing of HIV infection uncertain; in interval between last negative and first positive DNA-PCR test • Estimated the cumulative probability of DNA-PCR positivity according to age and ARV • Non-parametric methods; Turnbull algorithm, Wilcoxon test • Exploratory regression modeling to adjust for potential confounders • Parametric methods; assumed Weibull distributions with proportional hazards; likelihood ratio test

  6. Participating Cohorts

  7. Infants Grouped by Most Complex Maternal/Infant ARV Infant ARV Prophylaxis Maternal ARV during Trimester of Delivery No ARV = Mother and infant did not receive ARV at any time (n=125) Single NRTI = Mother or infant received single NRTI (n=159) sdNVP (+/- ZDV) = Mother or infant received sdNVP +/- ZDV (n=105) >3 ARVS = Mother or infant received >3 ARVs (n=43)

  8. Demographics

  9. Characteristics (median [25th-75th percentile])

  10. Cumulative Probability of Positive DNA-PCR by Age (Non-Parametric) P value (Wilcoxon) =0.0002

  11. Cumulative Probability of Positive DNA-PCR by Age (Subset: 143 infants negative at birth or day 1) P value (Wilcoxon) =0.0007

  12. Cumulative Probability of Positive DNA-PCR by Age (Parametric - separate Weibull models, unadjusted)

  13. Adjustment for Confounders: Infants who Received ARV(Parametric, Proportional Hazards; HR >1 Means Earlier Positivity) *P value for CD4 = 0.80, viral load =0.89, gestational age=0.44, delivery type =0.91

  14. Summary and Conclusions • Lower DNA-PCR positivity at birth and greater increase in positivity by 14 days of age in HIV-infected, non-breastfed infants who had no ARV vs. those who had maternal or infant ARV • Suggests ARV prevents a large proportion of intrapartum transmission • Nonparametric estimates of the probability of DNA-PCR positivity by age differed significantly according to ARV group • Time to DNA-PCR positivity was later with receipt of >3 ARVs than with single NRTI or sd-NVP (+/- ZDV)

  15. Summary and Conclusions (2) • In preliminary parametric regression modeling, the association between ARV group and time to positivity did not remain statistically significant • However, adjustment did not change the hazard ratios and the confidence intervals were mostly above 1.0 • The small number of infants exposed to > 3 ARVs limited the statistical power to detect a difference; further study is needed • Our results may have implications for scheduling final HIV PCR diagnostic testing, particularly when resources are limited.

  16. International Collaborative Study of Pediatric Diagnostic Tests – Collaborators • R. Balasubramanian • D.E. Shapiro • M.G. Fowler • K. Dominguez • P. Tookey • J. Masters • J. Tosswill • M. Lallemant • N. Ngo-Giang Huang • M. McConnell • P. Mock • G. Sherman • S. Lockman • V. Novitsky • P. Palumbo • S. Nesheim • B. Bohannon • K. Rich • M. Hughes • We gratefully acknowledge the study participants

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