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

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dc.contributor.authorShiau, Stephanie
dc.contributor.authorKuhn, Louise
dc.contributor.authorStrehlau, Renate
dc.contributor.authorMartens, Leigh
dc.contributor.authorMcIlleron, Helen
dc.contributor.authorMeredith, Sandra
dc.contributor.authorWiesner, Lubbe
dc.contributor.authorCoovadia, Ashraf
dc.contributor.authorAbrams, Elaine J
dc.contributor.authorArpadi, Stephen M
dc.date.accessioned2015-07-30T03:51:41Z
dc.date.available2015-07-30T03:51:41Z
dc.date.issued2014-02-12
dc.date.updated2015-01-15T17:57:31Z
dc.description.abstractAbstract 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
dc.identifier.apacitationShiau, S., Kuhn, L., Strehlau, R., Martens, L., McIlleron, H., Meredith, S., ... Arpadi, S. M. (2014). Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment. <i>BMC Pediatrics</i>, http://hdl.handle.net/11427/13580en_ZA
dc.identifier.chicagocitationShiau, Stephanie, Louise Kuhn, Renate Strehlau, Leigh Martens, Helen McIlleron, Sandra Meredith, Lubbe Wiesner, Ashraf Coovadia, Elaine J Abrams, and Stephen M Arpadi "Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment." <i>BMC Pediatrics</i> (2014) http://hdl.handle.net/11427/13580en_ZA
dc.identifier.citationShiau, S., Kuhn, L., Strehlau, R., Martens, L., McIlleron, H., Meredith, S., ... & Arpadi, S. M. (2014). Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir-and nevirapine-based treatment. BMC pediatrics, 14(1), 39.
dc.identifier.ris TY - Journal Article AU - Shiau, Stephanie AU - Kuhn, Louise AU - Strehlau, Renate AU - Martens, Leigh AU - McIlleron, Helen AU - Meredith, Sandra AU - Wiesner, Lubbe AU - Coovadia, Ashraf AU - Abrams, Elaine J AU - Arpadi, Stephen M AB - 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 DA - 2014-02-12 DB - OpenUCT DO - 10.1186/1471-2431-14-39 DP - University of Cape Town J1 - BMC Pediatrics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment TI - Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment UR - http://hdl.handle.net/11427/13580 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/13580
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2431-14-39
dc.identifier.vancouvercitationShiau S, Kuhn L, Strehlau R, Martens L, McIlleron H, Meredith S, et al. Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment. BMC Pediatrics. 2014; http://hdl.handle.net/11427/13580.en_ZA
dc.language.rfc3066en
dc.publisher.departmentDivision of Clinical Pharmacologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License*
dc.rights.holderShiau et al.; licensee BioMed Central Ltd.
dc.rights.urihttp://creativecommons.org/licenses/by/2.0*
dc.sourceBMC Pediatricsen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcpediatr/
dc.subject.otherHIVen_ZA
dc.subject.otherChildrenen_ZA
dc.subject.otherSex differencesen_ZA
dc.subject.otherAntiretroviral treatment outcomesen_ZA
dc.subject.otherPharmacokineticsen_ZA
dc.titleSex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment
dc.typeJournal Articleen_ZA
uct.type.filetype
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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