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Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection.

Mori M, Adland E, Paioni P, Swordy A, Mori L, Laker L, Muenchhoff M, Matthews PC, Tudor-Williams G, Lavandier N, van Zyl A, Hurst J, Walker BD, Ndung'u T, Prendergast A, Goulder P, Jooste P - PLoS ONE (2015)

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus

Study cohorts of HIV-infected South African children analyzed.
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pone.0131591.g001: Study cohorts of HIV-infected South African children analyzed.

Mentions: The Kimberley study cohorts are represented in Fig 1. Of 2,101 HIV-infected children in total attending the Kimberley hospital outpatient clinic, ART was initiated in 1,819; of these, post-ART CD4 data were unavailable in 188 subjects (52% female), either because of care being transferred to other clinics or loss to follow up. Of the remaining 1,631 subjects, CD4 data were incomplete in 56 cases; in 222 cases ART was initiated because of meeting clinical criteria, as opposed to CD4 criteria. Post-treatment follow up data (all of CD4+ T cell count, CD4%, viral load, and survival) were available for 1,244 of the 1,353 children in whom ART was initiated. The proportion of children who were female in the subgroups described is shown in Fig 2.


Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection.

Mori M, Adland E, Paioni P, Swordy A, Mori L, Laker L, Muenchhoff M, Matthews PC, Tudor-Williams G, Lavandier N, van Zyl A, Hurst J, Walker BD, Ndung'u T, Prendergast A, Goulder P, Jooste P - PLoS ONE (2015)

Study cohorts of HIV-infected South African children analyzed.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494714&req=5

pone.0131591.g001: Study cohorts of HIV-infected South African children analyzed.
Mentions: The Kimberley study cohorts are represented in Fig 1. Of 2,101 HIV-infected children in total attending the Kimberley hospital outpatient clinic, ART was initiated in 1,819; of these, post-ART CD4 data were unavailable in 188 subjects (52% female), either because of care being transferred to other clinics or loss to follow up. Of the remaining 1,631 subjects, CD4 data were incomplete in 56 cases; in 222 cases ART was initiated because of meeting clinical criteria, as opposed to CD4 criteria. Post-treatment follow up data (all of CD4+ T cell count, CD4%, viral load, and survival) were available for 1,244 of the 1,353 children in whom ART was initiated. The proportion of children who were female in the subgroups described is shown in Fig 2.

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus