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Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment.

Shiau S, Kuhn L, Strehlau R, Martens L, McIlleron H, Meredith S, Wiesner L, Coovadia A, Abrams EJ, Arpadi SM - BMC Pediatr (2014)

Bottom Line: ART outcomes in HIV-infected boys and girls in Johannesburg, South Africa from 2005-2010 were compared.Outcomes were compared between sexes within treatment strata.Sex differences are noted in treated HIV-infected children even at a young age, and appear to depend on treatment regimen.

View Article: PubMed Central - HTML - PubMed

Affiliation: Gertrude H, Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY USA. sma2@columbia.edu.

ABSTRACT

Background: While studies of HIV-infected adults on antiretroviral treatment (ART) report no sex differences in immune recovery and virologic response but more ART-associated complications in women, sex differences in disease progression and response to ART among children have not been well assessed. The objective of this study was to evaluate for sex differences in response to ART in South African HIV-infected children who were randomized to continue ritonavir-boosted lopinavir (LPV/r)-based ART or switch to nevirapine-based ART.

Methods: ART outcomes in HIV-infected boys and girls in Johannesburg, South Africa from 2005-2010 were compared. Children initiated ritonavir-boosted lopinavir (LPV/r)-based ART before 24 months of age and were randomized to remain on LPV/r or switch to nevirapine-based ART after achieving viral suppression. Children were followed for 76 weeks post-randomization and then long-term follow up continued for a minimum of 99 weeks and maximum of 245 weeks after randomization. Viral load, CD4 count, lipids, anthropometrics, drug concentrations, and adherence were measured at regular intervals. Outcomes were compared between sexes within treatment strata.

Results: A total of 323 children (median age 8.8 months, IQR 5.1-13.5), including 168 boys and 155 girls, initiated LPV/r-based ART and 195 children were randomized. No sex differences in risk of virological failure (confirmed viral load >1000 copies/mL) by 156 weeks post-randomization were observed within either treatment group. Girls switched to nevirapine had more robust CD4 count improvement relative to boys in this group through 112 weeks post-randomization. In addition, girls remaining on LPV/r had higher plasma concentrations of ritonavir than boys during post-randomization visits. After a mean of 3.4 years post-randomization, girls remaining on LPV/r also had a higher total cholesterol:HDL ratio and lower mean HDL than boys on LPV/r.

Conclusions: Sex differences are noted in treated HIV-infected children even at a young age, and appear to depend on treatment regimen. Future studies are warranted to determine biological mechanisms and clinical significance of these differences.

Trial registration: ClinicalTrials.gov Identifier: NCT00117728.

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Related in: MedlinePlus

Flow diagram of study participants in Neverest 2. Flow diagram of study participants in Neverest 2; Abbreviations: LPV/r, lopinavir-boosted ritonavir; NVP, nevirapine; ART, antiretroviral therapy; LTFU, lost to follow up; B, boys; G, girls.
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Figure 1: Flow diagram of study participants in Neverest 2. Flow diagram of study participants in Neverest 2; Abbreviations: LPV/r, lopinavir-boosted ritonavir; NVP, nevirapine; ART, antiretroviral therapy; LTFU, lost to follow up; B, boys; G, girls.

Mentions: The flow of participants is shown in Figure 1. A total of 323 HIV-infected children, including 168 (52%) boys, were enrolled in the study and initiated LPV/r-based ART. In the period between initiating LPV/r-based treatment and randomization to either remain on LPV/r or switch to nevirapine (pre-randomization phase), 38 (11.8%) died, 40 (12.4%) did not remain in follow up, and 50 (15.5%) did not meet criteria for randomization. Of the 195 children randomized in the study, 99 remained on LPV/r, including 50 (50.5%) boys, and 96 were switched to nevirapine, including 54 (56.3%) boys. Children were followed for 76 weeks post-randomization during which time four (2.1%) children died and 15 (7.7%) children were lost to follow up. Long-term follow up continued for a minimum of 99 weeks and maximum of 245 weeks after randomization. At study completion in June 2010, six (3.1%) children died, 28 (14.4%) were lost to follow-up, and five (2.6%) transferred out. 156 (80%) completed the final study visit.


Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment.

Shiau S, Kuhn L, Strehlau R, Martens L, McIlleron H, Meredith S, Wiesner L, Coovadia A, Abrams EJ, Arpadi SM - BMC Pediatr (2014)

Flow diagram of study participants in Neverest 2. Flow diagram of study participants in Neverest 2; Abbreviations: LPV/r, lopinavir-boosted ritonavir; NVP, nevirapine; ART, antiretroviral therapy; LTFU, lost to follow up; B, boys; G, girls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3927631&req=5

Figure 1: Flow diagram of study participants in Neverest 2. Flow diagram of study participants in Neverest 2; Abbreviations: LPV/r, lopinavir-boosted ritonavir; NVP, nevirapine; ART, antiretroviral therapy; LTFU, lost to follow up; B, boys; G, girls.
Mentions: The flow of participants is shown in Figure 1. A total of 323 HIV-infected children, including 168 (52%) boys, were enrolled in the study and initiated LPV/r-based ART. In the period between initiating LPV/r-based treatment and randomization to either remain on LPV/r or switch to nevirapine (pre-randomization phase), 38 (11.8%) died, 40 (12.4%) did not remain in follow up, and 50 (15.5%) did not meet criteria for randomization. Of the 195 children randomized in the study, 99 remained on LPV/r, including 50 (50.5%) boys, and 96 were switched to nevirapine, including 54 (56.3%) boys. Children were followed for 76 weeks post-randomization during which time four (2.1%) children died and 15 (7.7%) children were lost to follow up. Long-term follow up continued for a minimum of 99 weeks and maximum of 245 weeks after randomization. At study completion in June 2010, six (3.1%) children died, 28 (14.4%) were lost to follow-up, and five (2.6%) transferred out. 156 (80%) completed the final study visit.

Bottom Line: ART outcomes in HIV-infected boys and girls in Johannesburg, South Africa from 2005-2010 were compared.Outcomes were compared between sexes within treatment strata.Sex differences are noted in treated HIV-infected children even at a young age, and appear to depend on treatment regimen.

View Article: PubMed Central - HTML - PubMed

Affiliation: Gertrude H, Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY USA. sma2@columbia.edu.

ABSTRACT

Background: While studies of HIV-infected adults on antiretroviral treatment (ART) report no sex differences in immune recovery and virologic response but more ART-associated complications in women, sex differences in disease progression and response to ART among children have not been well assessed. The objective of this study was to evaluate for sex differences in response to ART in South African HIV-infected children who were randomized to continue ritonavir-boosted lopinavir (LPV/r)-based ART or switch to nevirapine-based ART.

Methods: ART outcomes in HIV-infected boys and girls in Johannesburg, South Africa from 2005-2010 were compared. Children initiated ritonavir-boosted lopinavir (LPV/r)-based ART before 24 months of age and were randomized to remain on LPV/r or switch to nevirapine-based ART after achieving viral suppression. Children were followed for 76 weeks post-randomization and then long-term follow up continued for a minimum of 99 weeks and maximum of 245 weeks after randomization. Viral load, CD4 count, lipids, anthropometrics, drug concentrations, and adherence were measured at regular intervals. Outcomes were compared between sexes within treatment strata.

Results: A total of 323 children (median age 8.8 months, IQR 5.1-13.5), including 168 boys and 155 girls, initiated LPV/r-based ART and 195 children were randomized. No sex differences in risk of virological failure (confirmed viral load >1000 copies/mL) by 156 weeks post-randomization were observed within either treatment group. Girls switched to nevirapine had more robust CD4 count improvement relative to boys in this group through 112 weeks post-randomization. In addition, girls remaining on LPV/r had higher plasma concentrations of ritonavir than boys during post-randomization visits. After a mean of 3.4 years post-randomization, girls remaining on LPV/r also had a higher total cholesterol:HDL ratio and lower mean HDL than boys on LPV/r.

Conclusions: Sex differences are noted in treated HIV-infected children even at a young age, and appear to depend on treatment regimen. Future studies are warranted to determine biological mechanisms and clinical significance of these differences.

Trial registration: ClinicalTrials.gov Identifier: NCT00117728.

Show MeSH
Related in: MedlinePlus