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Articles by John Kaldor
Total Records ( 3 ) for John Kaldor
  Handan Wand , Donna Spiegelman , Matthew Law , Bin Jalaludin , John Kaldor and Lisa Maher
  ObjectiveTo determine risk factors and estimate their population-level contribution to hepatitis C virus (HCV) burden. MethodsEstablished and potentially modifiable risk factors were estimated using partial population attributable risk (PARp) in a cohort of new injecting drug users (IDUs) in Sydney, Australia. ResultsA total of 204 hepatitis C seronegative IDUs were recruited through street-based outreach, methadone clinics and needle and syringe programmes (NSPs) and followed-up at 3-6-monthly intervals. A total of 61 HCV seroconversions were observed during the follow-up [overall incidence rate of 45.8 per 100 person-years (95% confidence interval: 35.6-58.8)]. Overall, five potentially modifiable risk factors (sharing needles/syringes, sharing other injecting equipment, assisted injecting, frequency of injection and not being in drug treatment) accounted for approximately 50% of HCV cases observed. ConclusionWhile sharing needles/syringes or other injecting equipment were associated most strongly with increased risk of HCV infection, the PARp associated with these behaviours was relatively modest (12%) because they are relatively low-prevalence behaviours. Our analyses suggest that more HCV infection could be avoided by changing more common, but less strongly associated behaviours such as assisted injecting or daily injecting. Results suggest that to have a very substantial effect on HCV, a range of risk factors need modifying. The most efficient use of scarce resources in reducing HCV infections will require complex balancing between the PAR for a given risk factor(s), the efficacy of interventions to actually modify the risk factor, and the cost of these interventions.
  Allison M. Salmon , Ingrid van Beek , Janaki Amin , John Kaldor and Lisa Maher
  Aims  Supervised injecting facilities (SIFs) are effective in reducing the harms associated with injecting drug use among their clientele, but do SIFs ease the burden on ambulance services of attending to overdoses in the community? This study addresses this question, which is yet to be answered, in the growing body of international evidence supporting SIFs efficacy. Design  Ecological study of patterns in ambulance attendances at opioid-related overdoses, before and after the opening of a SIF in Sydney, Australia. Setting  A SIF opened as a pilot in Sydney’s ’red light’ district with the aim of accommodating a high throughput of injecting drug users (IDUs) for supervised injecting episodes, recovery and the management of overdoses. Measurements  A total of 20 409 ambulance attendances at opioid-related overdoses before and after the opening of the Sydney SIF. Average monthly ambulance attendances at suspected opioid-related overdoses, before (36 months) and after (60 months) the opening of the Sydney Medically Supervised Injecting Centre (MSIC), in the vicinity of the centre and in the rest of New South Wales (NSW). Results  The burden on ambulance services of attending to opioid-related overdoses declined significantly in the vicinity of the Sydney SIF after it opened, compared to the rest of NSW. This effect was greatest during operating hours and in the immediate MSIC area, suggesting that SIFs may be most effective in reducing the impact of opioid-related overdose in their immediate vicinity. Conclusions  By providing environments in which IDUs receive supervised injection and overdose management and education SIF can reduce the demand for ambulance services, thereby freeing them to attend other medical emergencies within the community.
  Zabrina L. Brumme , Chanson J. Brumme , Jonathan Carlson , Hendrik Streeck , Mina John , Quentin Eichbaum , Brian L. Block , Brett Baker , Carl Kadie , Martin Markowitz , Heiko Jessen , Anthony D. Kelleher , Eric Rosenberg , John Kaldor , Yuko Yuki , Mary Carrington , Todd M. Allen , Simon Mallal , Marcus Altfeld , David Heckerman and Bruce D. Walker
  During acute human immunodeficiency virus type 1 (HIV-1) infection, early host cellular immune responses drive viral evolution. The rates and extent of these mutations, however, remain incompletely characterized. In a cohort of 98 individuals newly infected with HIV-1 subtype B, we longitudinally characterized the rates and extent of HLA-mediated escape and reversion in Gag, Pol, and Nef using a rational definition of HLA-attributable mutation based on the analysis of a large independent subtype B data set. We demonstrate rapid and dramatic HIV evolution in response to immune pressures that in general reflect established cytotoxic T-lymphocyte (CTL) response hierarchies in early infection. On a population level, HLA-driven evolution was observed in ~80% of published CTL epitopes. Five of the 10 most rapidly evolving epitopes were restricted by protective HLA alleles (HLA-B*13/B*51/B*57/B*5801; P = 0.01), supporting the importance of a strong early CTL response in HIV control. Consistent with known fitness costs of escape, B*57-associated mutations in Gag were among the most rapidly reverting positions upon transmission to non-B*57-expressing individuals, whereas many other HLA-associated polymorphisms displayed slow or negligible reversion. Overall, an estimated minimum of 30% of observed substitutions in Gag/Pol and 60% in Nef were attributable to HLA-associated escape and reversion events. Results underscore the dominant role of immune pressures in driving early within-host HIV evolution. Dramatic differences in escape and reversion rates across codons, genes, and HLA restrictions are observed, highlighting the complexity of viral adaptation to the host immune response.
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