title: Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection.
abstract: The incidence and severity of infections in childhood is typically greater in males. The basis for these observed sex differences is not well understood, and potentially may facilitate novel approaches to reducing disease from a range of conditions. We here investigated sex differences in HIV-infected children in relation to antiretroviral therapy (ART) initiation and post-treatment outcome. In a South African cohort of 2,101 HIV-infected children, we observed that absolute CD4+ count and CD4% were significantly higher in ART-naïve female, compared to age-matched male, HIV-infected children. Absolute CD4 count and CD4% were also significantly higher in HIV-uninfected female versus male neonates. We next showed that significantly more male than female children were initiated on ART (47% female); and children not meeting criteria to start ART by >5 yrs were more frequently female (59%; p<0.001). Among ART-treated children, immune reconstitution of CD4 T-cells was more rapid and more complete in female children, even after adjustment for pre-ART absolute CD4 count or CD4% (p=0.011, p=0.030, respectively). However, while ART was initiated as a result of meeting CD4 criteria less often in females (45%), ART initiation as a result of clinical disease in children whose CD4 counts were above treatment thresholds occurred more often in females (57%, p<0.001). The main sex difference in morbidity observed in children initiating ART above CD4 thresholds, above that of TB disease, was as a result of wasting and stunting observed in females with above-threshold CD4 counts (p=0.002). These findings suggest the possibility that optimal treatment of HIV-infected children might incorporate differential CD4 treatment thresholds for ART initiation according to sex.
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
authors.forename: Emily
authors.initials: E
authors.lastname: Adland
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
authors.forename: Paolo
authors.initials: P
authors.lastname: Paioni
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
authors.forename: Alice
authors.initials: A
authors.lastname: Swordy
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
authors.forename: Luisa
authors.initials: L
authors.lastname: Mori
authors.affiliation: Kimberley Hospital, Kimberley, Durban, South Africa.
authors.forename: Leana
authors.initials: L
authors.lastname: Laker
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenchhoff
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
authors.forename: Philippa C
authors.initials: PC
authors.lastname: Matthews
authors.affiliation: Department of Paediatrics, Imperial College, London, United Kingdom.
authors.forename: Gareth
authors.initials: G
authors.lastname: Tudor-Williams
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
authors.forename: Nora
authors.initials: N
authors.lastname: Lavandier
authors.affiliation: Kimberley Hospital, Kimberley, Durban, South Africa.
authors.forename: Anriette
authors.initials: A
authors.lastname: van Zyl
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hurst
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, MA, United States of America; Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), University of KwaZulu-Natal, Durban, South Africa; Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.affiliation: Centre for Paediatrics, Blizard Institute, Queen Mary University of London, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Prendergast
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom; Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Philip
authors.initials: P
authors.lastname: Goulder
authors.affiliation: Kimberley Hospital, Kimberley, Durban, South Africa.
authors.forename: Pieter
authors.initials: P
authors.lastname: Jooste
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012720:Severity of Illness Index; D012737:Sex Factors; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D044966:Anti-Retroviral Agents