Natur- und kulturräumlicher Überblick über den Staat; Ausgliederung einzelner durch Viehzucht, Landwirtschaft, Bergbau bzw. Industrie bestimmter Räume, die überwiegend in engem Zusammenhang mit den natürlichen Ressourcen stehen; Stand verschiedener landwirtschaftlicher Projekte. (DÜI-Kse)
IntroductionDespite normalization of total CD4 counts, ongoing immune dysfunction is noted amongst those on antiretroviral therapy (ART). Low CD4/CD8 ratio is associated with a high risk of AIDS and non‐AIDS events and may act as a marker of immune senescence [1]. This ratio is improved by ART although normalization is uncommon (~7%) [2]. The probability of normalization of CD4 count is improved with immediate ART initiation in primary HIV infection (PHI) [3]. We examined whether CD4/CD8 ratio similarly normalized in immediate vs. deferred ART at PHI.Material and MethodsUsing data from the SPARTAC trial and the UK Register of HIV Seroconverters, we examined the effect of ART with time (continuous) from HIV seroconversion (SC) on CD4/CD8 ratio (≥1) adjusted for sex, risk group, ethnicity, enrolment from an African site and both CD4 count and age at ART initiation. We also examined that effect by dichotomizing HIV duration at ART initiation (ART started within six months of SC: early ART; ART initiated>six months after SC: deferred). We also considered time to CD4 count normalization (≥900 cells/mm3).ResultsIn total, 353 initiated ART with median (IQR) 97.9 (60.5, 384.5) days from estimated seroconversion; 253/353 early ART, 100 deferred ART. At one year after starting ART, 114/253 (45%) early ART had normalized CD4/8 ratio, compared with 11/99 (11%) in the deferred group, whilst 83/253 (33%) of early ART had normalized CD4 counts, compared with 3/99 (3%) in the deferred group. Individuals initiating within six months of PHI were significantly more likely to reach normal ratio than those initiating later (HR, 95% CI 2.96, 1.75 – 5.01, p<0.001). The longer after SC ART was initiated, the reduced likelihood of achieving normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.96 – 0.99 for each 30‐day increase). CD4 count at ART initiation was also associated with normalization, as expected (HR 1.002, 95% CI 1.001 – 1.002, p<0.001). There was an association between normal CD4/CD8 ratio and being virally suppressed (<400 copies HIV RNA/ml) p<0.001. CD4 count normalization was also significantly more likely for those initiating early (HR 5.00, 95% CI 1.52 – 16.41, p=0.008).ConclusionsThe likelihood of achieving normalization of CD4/CD8 ratios was increased if ART was initiated within six months of PHI. Higher CD4/CD8 ratio may reflect a more "normal" immune phenotype conferring enhanced prognosis and predict post‐treatment control.
AbstractIntroductionEarly antiretroviral therapy (ART) has improved neurodevelopmental outcomes of HIV‐infected (HIV‐positive) children; however, little is known about the longer term outcomes in infants commencing early ART or whether temporary ART interruption might have long‐term consequences. In the children with HIV early antiretroviral treatment (CHER) trial, HIV‐infected infants ≤12 weeks of age with CD4 ≥25% were randomized to deferred ART (ART‐Def); immediate time‐limited ART for 40 weeks (ART‐40W) or 96 weeks (ART‐96W). ART was restarted in the time‐limited arms for immunologic/clinical progression. Our objective was to compare the neurodevelopmental profiles in all three arms of Cape Town CHER participants.MethodsA prospective, longitudinal observational study was used. The Griffiths mental development scales (GMDS), which includes six subscales and a global score, were performed at 11, 20, 30, 42 and 60 months, and the Beery‐Buktenica developmental tests for visual motor integration at 60 months. HIV‐exposed uninfected (HEU) and HIV‐unexposed (HU) children were enrolled for comparison. Mixed model repeated measures were used to compare groups over time, using quotients derived from standardized British norms.ResultsIn this study, 28 ART‐Def, 35 ART‐40W, 33 ART‐96W CHER children, and 34 HEU and 39 HU controls were enrolled. GMDS scores over five years were similar between the five groups in all subscales except locomotor and general Griffiths (interaction p < 0.001 and p = 0.02 respectively), driven by early lower scores in the ART‐Def arm. At 60 months, scores for all groups were similar in each GMDS scale. However, Beery visual perception scores were significantly lower in HIV‐infected children (mean standard scores: 75.8 ART‐Def, 79.8 ART‐40W, 75.9 ART‐96W) versus 84.4 in HEU and 90.5 in HU (p < 0.01)).ConclusionsEarly locomotor delay in the ART‐Def arm resolved by five years. Neurodevelopmental outcomes at five years in HIV‐infected children on early time‐limited ART were similar to uninfected controls, apart from visual perception where HIV‐infected children scored lower. Poorer visual perception performance warrants further investigation.
Background Comparison of changes in body composition, adipokines and inflammatory markers after initial therapy with a nucleos(t)ide reverse transcriptase inhibitor (N(t)RTI)- sparing or containing regimen are scarce. Design Randomised Clinical Trial. Methods This is the body composition substudy of NEAT 001/ANRS 143, a randomised trial comparing darunavir/ritonavir (DRV/r) plus either raltegravir (RAL) or tenofovir disoproxil fumarate/ emtricitabine (TDF/FTC) in 805 ART naïve HIV-infected adults. The primary endpoint was percentage change in limb fat at week 96. Secondary endpoints were associations among these changes and metabolic markers (IL-6, insulin, leptin, adiponectin, FGF-23). Results 126 subjects (61 DRV/r + RAL and 65 DRV/r + TDF/FTC) were included. The rate of change in BMI between groups for RAL versus TDF/FTC at week 96 was 1.5% per 48-week period (p = 0.015). The rate of change in limb fat mass, trunk fat mass, total body fat and total lean mass was for RAL versus TDF/FTC at week 96 was 2.5% (p = 0.38), 7.3% ((p = 0.021), 4.9% (p = 0.061) and 1.3% (p = 0.12) respectively. Baseline insulin and leptin levels were correlated with baseline limb fat and trunk fat mass [r = 0.31 (p = 0.0043)/r = 0.28 (p = 0.0011) for limb fat, and r = 0.63 (p<0.0001)/r = 0.50(p<0.0001) for trunk fat]. After adjustment, a 10% faster increase in leptin between baseline and week 48 was associated with a more rapid increase in limb fat at week 48 (0.5% per 48 weeks, p<0.001), total body fat mass (0.6% per 48 weeks, p<0.001), and trunk fat mass (0.3% per 48 weeks, p = 0.0026). Conclusions After week 96 a N(t)RTI sparing regimen of DRV/r + RAL produced a numerically greater percentage increase in body composition variables with only change in trunk fat mass and BMI being significant ; NEAT is a project funded to the Instituto Superiori di Sanita´-Rome, by the European Union under the Sixth Framework Programme, project number LSHP-CT-2006-037570. This analysis was also partially funded by a grant from the Ministerio de Sanidad y Asuntos Sociales de España (2009/TRA-054). The trial was also supported by Gilead Sciences, Janssen Pharmaceuticals, and Merck Laboratories, and the French National Institute for Health and Medical Research-France Recherche Nord&Sud SIDA-HIV He´patites (Inserm-ANRS) is the sponsor and a funder of the trial
