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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

Sex differences in CD4+ T cell count, CD4% and viral load, amongst 2,101 ART-naïve South African children.A. Absolute CD4 counts changes with age. B. CD4% changes with age. C. Viral load changes with age. In each panel, the solid lines are Loess-smoothed regression lines for female children and the dotted lines are Loess-smoothed regression lines for male children. A multivariable linear regression model, with both sex and age as covariates, shows significantly lower absolute CD4 counts in males (p = 0.005); significantly lower CD4% in males (p = 3.7x10-7); and no significant difference in viral load between the sexes.
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pone.0131591.g003: Sex differences in CD4+ T cell count, CD4% and viral load, amongst 2,101 ART-naïve South African children.A. Absolute CD4 counts changes with age. B. CD4% changes with age. C. Viral load changes with age. In each panel, the solid lines are Loess-smoothed regression lines for female children and the dotted lines are Loess-smoothed regression lines for male children. A multivariable linear regression model, with both sex and age as covariates, shows significantly lower absolute CD4 counts in males (p = 0.005); significantly lower CD4% in males (p = 3.7x10-7); and no significant difference in viral load between the sexes.

Mentions: Initial analyses were undertaken of all 2,101 HIV-infected children enrolled, using the immediate pre-ART timepoint in those (n = 1819) who received ART, and the enrollment timepoint for the slow progressor children (n = 282) who never received ART. Among these ART-naïve, HIV-infected children studied, absolute CD4 counts and CD4% were significantly higher in females (median 481/ul vs 444/ul, p = 0.013; 17% vs 14%, p<0.001, Table 1, Fig 3). CD4 counts were a mean of 88/ul higher and CD4% a mean of 3% higher in females compared to males aged 0–13yrs. Although there was no sex difference in viral load in the cohort overall pre-ART, males aged ≥12yr showed a marginally higher viral load compared to females (4.7 vs 4.5 log c/ml, p<0.001, Mann-Whitney U-test).


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)

Sex differences in CD4+ T cell count, CD4% and viral load, amongst 2,101 ART-naïve South African children.A. Absolute CD4 counts changes with age. B. CD4% changes with age. C. Viral load changes with age. In each panel, the solid lines are Loess-smoothed regression lines for female children and the dotted lines are Loess-smoothed regression lines for male children. A multivariable linear regression model, with both sex and age as covariates, shows significantly lower absolute CD4 counts in males (p = 0.005); significantly lower CD4% in males (p = 3.7x10-7); and no significant difference in viral load between the sexes.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131591.g003: Sex differences in CD4+ T cell count, CD4% and viral load, amongst 2,101 ART-naïve South African children.A. Absolute CD4 counts changes with age. B. CD4% changes with age. C. Viral load changes with age. In each panel, the solid lines are Loess-smoothed regression lines for female children and the dotted lines are Loess-smoothed regression lines for male children. A multivariable linear regression model, with both sex and age as covariates, shows significantly lower absolute CD4 counts in males (p = 0.005); significantly lower CD4% in males (p = 3.7x10-7); and no significant difference in viral load between the sexes.
Mentions: Initial analyses were undertaken of all 2,101 HIV-infected children enrolled, using the immediate pre-ART timepoint in those (n = 1819) who received ART, and the enrollment timepoint for the slow progressor children (n = 282) who never received ART. Among these ART-naïve, HIV-infected children studied, absolute CD4 counts and CD4% were significantly higher in females (median 481/ul vs 444/ul, p = 0.013; 17% vs 14%, p<0.001, Table 1, Fig 3). CD4 counts were a mean of 88/ul higher and CD4% a mean of 3% higher in females compared to males aged 0–13yrs. Although there was no sex difference in viral load in the cohort overall pre-ART, males aged ≥12yr showed a marginally higher viral load compared to females (4.7 vs 4.5 log c/ml, p<0.001, Mann-Whitney U-test).

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