Browsing by Author "Meredith, Sandra"

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    Open Access
    Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment
    (2014-02-12) Shiau, Stephanie; Kuhn, Louise; Strehlau, Renate; Martens, Leigh; McIlleron, Helen; Meredith, Sandra; Wiesner, Lubbe; Coovadia, Ashraf; Abrams, Elaine J; Arpadi, Stephen M
    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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    The spread of Tomato yellow leaf curl virus from the Middle East to the world
    (Public Library of Science, 2010) Lefeuvre, Pierre; Martin, Darren P; Harkins, Gordon; Lemey, Philippe; Gray, Alistair J A; Meredith, Sandra; Lakay, Francisco; Monjane, Adérito; Lett, Jean-Michel; Varsani, Arvind
    Author Summary Tomato yellow leaf curl virus (TYLCV) poses a serious threat to tomato production throughout the temperate regions of the world. Our analysis, using a suite of bioinformatic tools applied to all publically available TYLCV genome sequences, suggests that the virus probably arose somewhere in the Middle East between the 1930s and 1950s and that its global spread only began in the 1980s after the emergence of two strains - TYLCV-Mld and -IL. In agreement with others, we also find that the highly invasive TYLCV-IL strain has jumped at least twice to the Americas - once from the Mediterranean basin in the early 1990s and once from Asia in the early 2000s. Although our results corroborate historical accounts of TYLCV-like symptoms in tomato crops in the Jordan Valley in the late 1920s, they indicate that the region around Iran is both the current center of TYLCV diversity and is the site where the most intensive ongoing TYLCV evolution is taking place. However, our analysis indicates that this region is epidemiologically isolated suggesting that novel TYLCV variants found there are probably not direct global threats. Moreover, we identify the Mediterranean basin as the main launch-pad of global TYLCV movements.