CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

(1) they were “responders”( HIV-RNA <400 copies/ml and no severe immunosuppression after ≥ 1 yr on ART [time 0]) AND (2) ≥ 1 HIV-RNA and CD4 measurement within 15 mos of time 0. Outcome was CD4 decline to belowWHO-defined thresholds for severe immunosuppression (CD4<20%/750 cells/mm 3 if age 12-35 mos, CD4 <15%/350 cells/mm 3 if age 36-59 mos, CD4 <15%/200 cells/mm 3 if age ≥ 5 yrs). We determined the probability of the outcome during the 3 yrs after time 0 if viral suppression was maintained, censoring follow-up at the first of (1) day before first HIV-RNA measurement >400 copies/ml (2) day before a >15 mo gap in testing or (3) end of follow-up due to death, loss to follow-up (LTFU), transfer out or database closure. Associations between characteristics at time 0 and CD4 decline were examined using Cox-proportional hazards models. Results: 5984 children met the inclusion criteria; most were ≥ 2 years old at time 0 with no/mild immunosuppression and on ART for <18 mos. The probability of a CD4 decline to severe immunosuppression was <3% (Table). Risk of CD4 decline was higher in children age <2 yrs (Adjusted Hazard Ratio [aHR]:3.40 [95%CI: 2.52-4.57]), those with moderate vs no/mild immunosuppression (aHR:3.29 [2.57-4.21]) and duration on ART ≥ 18 mos (aHR:1.68 [1.28-2.21]). A subsequent CD4 measurement was available in 169 of 270 (62%) children with after initial CD4 decline. The decline was transient in 86%, with recovery at next measurement. Among 270 children with a CD4 decline, outcomes in the following yr were: 85.2% in care, 1.1% died, 1.9% LTFU and 11.9% transferred out.

Table: Characteristics at time 0 and probability (95% CI) of CD4 decline within 3 yrs. No/mild immunosuppression defined as CD4 ≥ 25%/1000 cells/mm 3 (age <5 yrs) or ≥ 20%/500 cells/mm3 (age ≥ 5 yrs). Conclusions: These results suggest that CD4 monitoring could be reduced or stopped in children >2 yrs with viral suppression who attain CD4 indicating no/mild immunosuppression within 18 mos of starting ART.

TUESDAY, FEBRUARY 24, 2015 Session P-U5 Poster Session

Poster Hall

2:30 pm– 4:00 pm Determinants of Disease Progression in Children 921 Impact of Sex Differences on Disease Outcome in Pediatric HIV in South Africa Masahiko Mori 1 ; Emily Adland 1 ; Alice Swordy 1 ; Maximilian Muenchhoff 1 ; Nora Lavandier 1 ; Jacob Hurst 1 ;Thumbi Ndung’u 2 ; Andy Prendergast 3 ; Philip J. Goulder 1 ; Pieter Jooste 4

1 University of Oxford, Oxford, United Kingdom; 2 University of KwaZulu-Natal, Durban, South Africa; 3 Queen Mary University of London, London, United Kingdom; 4 Kimberley Hospital, Durban, South Africa Background: To identify sex differences in CD4 count and viral load in antiretroviral therapy (ART)-naïve children, and in ART initiation and post-treatment outcome among ART- treated HIV-infected children. Methods: We studied 2168 South African HIV-infected children, of whom 1819 initiated ART. Statistical analyses were performed to identify sex differences in HIV disease outcome measures, including pre-ART CD4 and viral load; ART initiation; and post-ART immune reconstitution and mortality. Results: Absolute CD4+ count and CD4%were higher in ART-naïve female compared to age-matched male HIV-infected children. CD4 count and CD4%were also significantly higher in female versus male HIV-uninfected neonates. Compared with children in whom ART was initiated (47% female), children who did not meet criteria to start ART by >5yrs were more frequently females (59%; p<0.0001). Among ART-treated children, there was no significant sex difference in mortality post-ART. However, immune reconstitution of CD4 T-cells to the levels of age-matched uninfected controls was more rapid and more complete in female children (Figure). Whereas ART was initiated as a result of meeting CD4 criteria less often in females (45%), ART initiation above CD4 thresholds, due to meeting clinical criteria, occurred more often in females (58%, p=0.0005).

Poster Abstracts

Figure. Sex differences Immune reconstitution amongst the patients who started treatment under the pre-2013 WHO guidelines. Sex differences by log rank test are shown as follows: A. CD4+ T cell percentage recovery (>35%) rate among the children who started ART aged 1-4 years old with CD4+ T cell <25%. B. Absolute CD4+ T cell count recovery (>750/ul) among children initiating ART aged ≥ 5 years old with CD4+ T cell counts <350/ul. Conclusions: Significant sex differences are evident in disease outcome in HIV-infected children. These data suggest that, in females, CD4 counts are intrinsically higher from birth, resulting in delayed ART initiation and increased morbidity. These findings are of relevance in considering optimal ART use in HIV-infected children.

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CROI 2015