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Open Access Research article

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

Stephanie Shiau12, Louise Kuhn12, Renate Strehlau3, Leigh Martens3, Helen McIlleron45, Sandra Meredith4, Lubbe Wiesner4, Ashraf Coovadia3, Elaine J Abrams267 and Stephen M Arpadi1267*

Author Affiliations

1 Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY USA

2 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY USA

3 Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa

4 Department of Medicine, Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa

5 Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

6 ICAP, Mailman School of Public Health, Columbia University, New York, NY USA

7 Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY USA

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BMC Pediatrics 2014, 14:39  doi:10.1186/1471-2431-14-39

Published: 12 February 2014

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

Keywords:
HIV; Children; Sex differences; Antiretroviral treatment outcomes; Pharmacokinetics