Publications (3)9.54 Total impact

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    ABSTRACT: Patients starting highly active antiretroviral therapy (HAART) may have a suboptimal CD4 increase despite rapid virological suppression. The frequency and the significance for patient care of this discordant response are uncertain. This study was designed to determine the incidence of a discordant response at two time-points, soon after 6 months and at 12 months, and to determine the relationship with clinical outcomes. Data obtained in the UK Collaborative HIV Cohort Study were analysed. A total of 2584 treatment-naïve patients starting HAART with HIV viral load (VL) > 1000 HIV-1 RNA copies/mL at baseline and < 50 copies/mL within 6 months were included in the analysis. Patients were classified at either 6-10 (midpoint 8) months or 10-14 (midpoint 12) months as having a discordant (CD4 count increase < 100 cells/microL from baseline) or concordant response (CD4 count increase >or= 100 cells/microL). Discordant responses occurred in 32.1% of patients at 8 months and in 24.2% at 12 months; 35% of those discordant at 8 months were concordant at 12 months. A discordant response was associated with older age, lower baseline VL, and (at 12 months) higher baseline CD4 cell count. In a multivariate analysis it was associated with an increased risk of death, more strongly at 12 months [incidence rate ratio (IRR) 3.35, 95% confidence interval (CI) 1.73-6.47, P < 0.001] than at 8 months (IRR 2.08, 95% CI 1.19-3.64, P = 0.010), but not with new AIDS events. Discordant responders have a worse outcome, but assessment at 12 months may be preferred, given the number of 'slow' responders. Management strategies to improve outcomes for discordant responders need to be investigated.
    Full-text · Article · Oct 2009 · HIV Medicine
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    ABSTRACT: Background: Little is known about the long term risk of development of HIV-1 drug resistance for patients starting antiretroviral therapy (ART) with three or four drug regimens in routine clinical practice. Methods: We analysed a large cohort study of patients seen in one of six large HIV clinics in and around London, UK. The focus of this analysis was on patients who started ART with two nucleosides plus either a single protease inhibitor (PI), a PI with ritonavir, abacavir or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Results: 4306 patients were followed; 1436 (33%) started with a single PI, 279 (6%) with a PI plus ritonavir, 156 (4%) with triple nucleosides and 2435 (57%) with an NNRTI. The overall cumulative risk of viral load failure was 38% by 6 years. Risk of >= 1 major IAS-USA mutation was 27% by 6 years; risk of mutations from at least two of the three main drug classes was 20% over the same period. These are lower limit estimates as test results were not available for many with viral load failure. Risk of PI mutations being detected in people who started ART with regimens containing a PI with ritonavir was significantly lower than the risk of NNRTI mutations being detected in those starting with NNRTI-containing regimens (relative hazard, 0.31; 95% CI, 0.15-0.61; p = 0.0008). Conclusion: In routine practice, rates of viral load failure and of resistance detection in patients who started ART with three or four drugs are appreciable. (c) 2005 Lippincott Williams C Wilkins.
    No preview · Article · Mar 2005 · AIDS
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    A Rider · I Williams · E Shum · L Mirabella
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    ABSTRACT: Bonded composite repair of metallic structure has become a useful aircraft structural life extension solution over the last two decades. Repairs have been applied to aircraft worldwide and in the last decade, the United States Air Force (USAF) has used bonded repair technology to solve some difficult flight safety and fleet readiness problems. In Australia, the Royal Australian Air Force (RAAF) has been using bonded technology in niche applications for over 20 years. One of the initial applications involved repair to the Mirage III fleet, whilst repairs to F-111 have been ongoing. DSTO and the RAAF also applied a patch to the F-111 lower wing skin in a region that contained a critical crack for the limit load condition. The most extensive use of bonded composite repairs to metallic structure in the USAF was for the wing-cracking problem in the Lockheed C-141. Over one thousand patches were applied to cracked fuel weepholes in the aging Starlifter. For the C-141, the repair option was the most practical solution to ensure the flight safety of the fleet, whilst maintaining operational readiness. Although part replacement would have served to restore structural integrity to an original condition, the wing planks in question were complex, 33-foot-long, integrally stiffened, highly priced items. As such, no stockpile of parts existed, and Lockheed was incapable of producing the components in the volume and time required to prevent a significant impact on fleet availability. Whilst there are obvious advantages in using bonded repairs, the technology does have disadvantages, which have limited the widespread application on aircraft fleets throughout the world. Bonded repairs typically are not preferred in applications where bolted repairs or component replacement are feasible. Commercial airline maintenance organisations rarely use bonded repairs due to risks and complications perceived by many practising engineers. The reliability of bonded repairs relies heavily on the skills of the technicians applying the repairs and the quality of the engineering systems the practitioners adhere to. Due to a limited number of isolated incidents in which bonded structure on aircraft have catastrophically failed, the technology is not yet considered to be mature. In contrast to the perceptions of commercial airline maintenance engineers, defence based applications of the technology have been very reliable. The implementation of quality management systems by the RAAF have produced durable and reliable repairs on a range of aircraft for a number of years. Additionally, the long-term environmental durability of adhesively bonded structure cannot be easily predicted without supporting field evidence. Typically, certification can only be provided in initial construction, where quality control of the bonding procedures can be guaranteed within the confines of a factory environment. It is more difficult for bonded repairs carried out on aircraft structure in the field to be performed with similar environmental control and repairs, as such, are not given structural credit. Clearly, the ability to certify the environmental durability of bonded repairs will expand their application and will offer substantial cost benefits to aircraft maintenance. Research and development needs to focus on methods to improve and guarantee the reliability of the technology and, therefore, facilitate certification and consequent widespread usage. An agreement between DSTO and the US Air Force Research Laboratory (AFRL) was established as a part of a larger Aging Aircraft Project Agreement (PA). As a part of this agreement a large experimental program was organised to examine the long-term durability of bonded composite repairs to metallic aircraft structure. An important aspect of the program was to examine the reliability and performance of current or recently developed surface treatments for metallic surfaces being repaired in field situations. The program involved the production of over 100 metal skinned honeycomb beam samples that were each patched with boron composite doublers. The beam samples are now being cyclically loaded in four point bending rigs at the DSTO tropical test facility in Innisfail, northern Queensland. It was anticipated that cyclic loading of the beams would result in adhesive disbonding for samples where the surface treatments were known to be inferior on the basis of accelerated laboratory testing. The overall results were hoped to enable the durability of metal to adhesive bonds present in boron composite repairs to be assessed for conditions similar to those expected in aircraft operating environments. An additional outcome of the research was hoped to be the ability to correlate accelerated durability testing conducted in the laboratory with more realistic ageing conditions expected in aircraft service. The current report details the beam construction and patch lay-up, together with the details of the surface pretreatments applied to the metallic adherend and the loading conditions employed, as well as initial results from testing. An agreement between DSTO and the US Air Force Research Laboratory (AFRL) was established as a part of a larger Aging Aircraft Project Agreement (PA). As a part of this agreement a large experimental program was organised to examine the long-term environmental durability of bonded composite repairs to metallic aircraft structure. An important aspect of the program was to examine the reliability and performance of current or recently developed surface treatments for metallic surfaces being repaired in field situations. The program involved the production of over 100 metal skinned honeycomb beam samples that were each patched with boron composite doublers. The beam samples are now being cyclically loaded in four point bending rigs at the DSTO tropical test facility in Innisfail, northern Queensland. It was anticipated that cyclic loading of the beams would result in adhesive disbonding for samples where the surface treatments were known to be inferior on the basis of accelerated laboratory testing. The overall results were hoped to enable the durability of metal to adhesive bonds present in boron composite repairs to be assessed for conditions similar to those expected in aircraft operating environments. An additional outcome of the research was hoped to be the ability to correlate accelerated durability testing conducted in the laboratory with more realistic aging conditions expected in aircraft service DGTA
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