Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Utilidade das seqüências ITS do nrDNA para o estudo de poliplóides em Passiflora misera

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Utilidade das seqüências ITS do nrDNA para o estudo de poliplóides em Passiflora misera

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Estudo molecular dos genes de defesa codificadores de proteínas BETV 1 homólogas em espécies brasileiras de Passiflora

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Estudo molecular dos genes de defesa codificadores de proteínas BETV 1 homólogas em espécies brasileiras de Passiflora

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Increased glutamate receptor and transporter expression in the cerebral cortex and striatum of gcdh-/- mice: possible implications for the neuropathology of glutaric acidemia type I.

We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits), AMPA (GluR2 subunit) and kainate (GluR6 subunit), as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT) and glutaryl-CoA dehydrogenase deficient (Gchh-/-) mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh-/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh-/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh-/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh-/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh-/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh-/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh-/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I

Glutamate receptor mRNA expression levels in cerebral cortex and striatum from wild type (WT) and <i>Gcdh^-/-</i> mice at 7 (A), 30 (B) and 60 (C) days of life.

<p>Results are expressed as mean ± standard deviation for five independent experiments (animals) per group. *p≤0.05, **p≤0.01, ***p≤0.001 compared to WT (Student's t test for unpaired samples).</p

NMDA and non-NMDA receptor mRNA expression in cerebral cortex of 30-day-old wild type (WT) and <i>Gcdh^-/-</i> mice submitted to a normal (0.9% lysine) or high lysine (4.7%) diet.

<p>NR1 (A), NR2A (B), NR2B (C), GluR2 (D) and GluR6 (E). Results are expressed as mean ± standard deviation for five independent experiments (animals) per group. *p≤0.05 compared to WT; **p≤0.01, ***p≤0.001 compared to WT; ^#p≤0.01 compared to <i>Gcdh^-/-</i> mice submitted to a normal diet (Student's t test for unpaired samples).</p

NR2A, NR2B, GLT1 and GLAST protein levels striatum of 60-day-old wild type (WT) and <i>Gcdh</i>^-/- mice.

<p>β-actin was used as the endogenous control. Results are expressed as mean ± standard deviation for four independent experiments (animals) per group. *p≤0.05 compared to WT (Student's t test for unpaired samples).</p