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Randomized Controlled Trial
. 2014 Feb 12:14:39.
doi: 10.1186/1471-2431-14-39.

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

Stephanie Shiau, Louise Kuhn, Renate Strehlau, Leigh Martens, Helen McIlleron, Sandra Meredith, Lubbe Wiesner, Ashraf Coovadia, Elaine J Abrams, Stephen M Arpadi  1
Affiliations
Randomized Controlled Trial

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

Stephanie Shiau et al. BMC Pediatr. .

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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Figures

Figure 1
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.
Figure 2
Figure 2
Immunologic and anthropometric outcomes over time. Mean CD4 percent (A) and CD4 count (B), weight-for-age z-score (WAZ) (C) and height-for-age z-score (HAZ) (D) before treatment, at randomization, and at scheduled visits with measurements through 148 weeks after randomization in Neverest 2 by sex and randomization group; Abbreviations: WAZ, weight-for-age z-score; HAZ, height-for-age z-score; LPV/r, lopinavir-boosted ritonavir; NVP, nevirapine.
See this image and copyright information in PMC

References

    1. Sterling TR, Vlahov D, Astemborski J, Hoover DR, Margolick JB, Quinn TC. Initial plasma HIV-1 RNA levels and progression to AIDS in women and men. N Engl J Med. 2001;344(10):720–725. doi: 10.1056/NEJM200103083441003. - DOI - PubMed
    1. Farzadegan H, Hoover DR, Astemborski J, Lyles CM, Margolick JB, Markham RB, Quinn TC, Vlahov D. Sex differences in HIV-1 viral load and progression to AIDS. Lancet. 1998;352(9139):1510–1514. doi: 10.1016/S0140-6736(98)02372-1. - DOI - PubMed
    1. Soon GG, Min M, Struble KA, Chan-Tack KM, Hammerstrom T, Qi K, Zhou S, Bhore R, Murray JS, Birnkrant DB. Meta-analysis of gender differences in efficacy outcomes for HIV-positive subjects in randomized controlled clinical trials of antiretroviral therapy (2000–2008) AIDS Patient Care STDS. 2012;26(8):444–453. doi: 10.1089/apc.2011.0278. - DOI - PubMed
    1. Moore AL, Kirk O, Johnson AM, Katlama C, Blaxhult A, Dietrich M, Colebunders R, Chiesi A, Lungren JD, Phillips AN. Virologic, immunologic, and clinical response to highly active antiretroviral therapy: the gender issue revisited. J Acquir Immune Defic Syndr. 2003;32(4):452–461. doi: 10.1097/00126334-200304010-00017. - DOI - PubMed
    1. Ofotokun I, Pomeroy C. Sex differences in adverse reactions to antiretroviral drugs. Top HIV Med. 2003;11(2):55–59. - PubMed

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