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Search Results: 1 - 10 of 199825 matches for " Matthew G Law "
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Trends in detectable viral load by calendar year in the Australian HIV observational database
Law Matthew G,Woolley Ian,Templeton David J,Roth Norm
Journal of the International AIDS Society , 2011, DOI: 10.1186/1758-2652-14-10
Abstract: Background Recent papers have suggested that expanded combination antiretroviral treatment (cART) through lower viral load may be a strategy to reduce HIV transmission at a population level. We assessed calendar trends in detectable viral load in patients recruited to the Australian HIV Observational Database who were receiving cART. Methods Patients were included in analyses if they had started cART (defined as three or more antiretrovirals) and had at least one viral load assessment after 1 January 1997. We analyzed detectable viral load (>400 copies/ml) in the first and second six months of each calendar year while receiving cART. Repeated measures logistic regression methods were used to account for within and between patient variability. Rates of detectable viral load were predicted allowing for patients lost to follow up. Results Analyses were based on 2439 patients and 31,339 viral load assessments between 1 January 1997 and 31 March 2009. Observed detectable viral load in patients receiving cART declined to 5.3% in the first half of 2009. Predicted detectable viral load based on multivariate models, allowing for patient loss to follow up, also declined over time, but at higher levels, to 13.8% in 2009. Conclusions Predicted detectable viral load in Australian HIV Observational Database patients receiving cART declined over calendar time, albeit at higher levels than observed. However, over this period, HIV diagnoses and estimated HIV incidence increased in Australia.
Trends in all cause and viral liver disease-related hospitalizations in people with hepatitis B or C: a population-based linkage study
Heather F Gidding, Gregory J Dore, Janaki Amin, Matthew G Law
BMC Public Health , 2011, DOI: 10.1186/1471-2458-11-52
Abstract: HBV and HCV notifications were linked to their hospital (July 2000-June 2006), HIV and death records. Standardized hospitalization ratios (SHRs) were calculated using rates for the NSW population. Random effects Poisson regression was used to examine temporal trends.The SHR for all causes and non alcoholic liver disease was two-fold higher in the HCV cohort compared with the HBV cohort (SHRs 1.4 (95%CI: 1.4-1.4) v 0.6 (95%CI: 0.6-0.6) and 14.0 (95%CI: 12.7-15.4) v 5.4 (95%CI: 4.5-6.4), respectively), whilst the opposite was seen for primary liver cancer (SHRs 16.2 (95%CI: 13.8-19.1) v 29.1 (95%CI: 24.7-34.2)). HIV co-infection doubled the SHR except for primary liver cancer in the HCV/HIV cohort. In HBV and HCV mono-infected cohorts, all cause hospitalization rates declined and primary liver cancer rates increased, whilst rates for non alcoholic liver disease increased by 9% in the HCV cohort but decreased by 14% in the HBV cohort (P < 0.001).Hospital-related morbidity overall and for non alcoholic liver disease was considerably higher for HCV than HBV. Improved treatment of advanced HBV-related liver disease may explain why HBV liver-related morbidity declined. In contrast, HCV liver-related morbidity increased and improved treatments, especially for advanced liver disease, and higher levels of treatment uptake are required to reverse this trend.Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is associated with increased morbidity and mortality. Several data linkage studies have reported an excess burden of hepatocellular carcinoma (HCC) and mortality, particularly from advanced liver disease [1-5]. They also highlight an increased disease burden associated with HBV/HIV, HCV/HIV and HBV/HCV co-infection [2-4,6]. These population-based studies outline the relative incidence of cancer and mortality, but there are limited data comparing the impact of HBV and HCV infection on hospitalization rates. The one published study compared the average
Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the Treat Asia HIV observational database
Lim Poh-Lian,Zhou Jialun,Ditangco Rossana A,Law Matthew G
Journal of the International AIDS Society , 2012, DOI: 10.1186/1758-2652-15-1
Abstract: Background Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality. Methods TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models. Results There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years. Conclusions Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits.
Hidden Drug Resistant HIV to Emerge in the Era of Universal Treatment Access in Southeast Asia
Alexander Hoare,Stephen J. Kerr,Kiat Ruxrungtham,Jintanat Ananworanich,Matthew G. Law,David A. Cooper,Praphan Phanuphak,David P. Wilson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010981
Abstract: Universal access to first-line antiretroviral therapy (ART) for HIV infection is becoming more of a reality in most low and middle income countries in Asia. However, second-line therapies are relatively scarce.
Testing Commercial Sex Workers for Sexually Transmitted Infections in Victoria, Australia: An Evaluation of the Impact of Reducing the Frequency of Testing
Eric P. F. Chow, Glenda Fehler, Marcus Y. Chen, Catriona S. Bradshaw, Ian Denham, Matthew G. Law, Christopher K. Fairley
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0103081
Abstract: Background The frequency of testing sex workers for sexually transmitted infections (STIs) in Victoria, Australia, was changed from monthly to quarterly on 6 October 2012. Our aim was to determine the impact of this change to the clients seen at the Melbourne Sexual Health Centre (MHSC). Methods Computerised medical records of all clients attending at MHSC from 7 October 2011 to 7 October 2013 were analysed. Results Comparing between the monthly and quarterly testing periods, the number of consultations at MSHC with female sex workers (FSW) halved from 6146 to 3453 (p<0.001) and the consultation time spent on FSW reduced by 40.6% (1942 h to 1153 h). More heterosexual men (p<0.001), and women (p<0.001) were seen in the quarterly testing period. The number of STIs diagnosed in the clinic increased from 2243 to 2589 from the monthly to quarterly period, respectively [15.4% increase (p<0.001)]. Up to AU$247,000 was saved on FSW testing after the shift to quarterly testing. Conclusions The change to STIs screening frequency for sex workers from monthly to quarterly resulted in a 15% increase in STI diagnoses in the clinic and approximate a quarter of a million dollars was diverted from FSW testing to other clients. Overall the change in frequency is likely to have had a beneficial effect on STI control in Victoria.
Moving Away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE) - Agents That Concern Prescribers and Patients: A Feasibility Study and Call for a Trial
Amit C. Achhra, Mark A. Boyd, Matthew G. Law, Gail V. Matthews, Anthony D. Kelleher, David A. Cooper
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099530
Abstract: Objectives Regimens sparing RATE (ritonavir, abacavir, tenofovir, efavirienz) agents might have better long-term safety. We conducted a feasibility exercise to assess the potential for a randomised trial evaluating RATE-sparing regimens. Design Observational. Methods We first calculated RATE-sparing options available to an average patient receiving RATE agents. We reviewed treatment history and all resistance assays from patients attending the St. Vincent’s Hospital (Sydney) clinic and receiving ≥2 RATE agents (n = 120). A viable RATE-sparing regimen with 2 or 3 fully-active agents was constructed from the following six ‘safer’ agents: rilpivirine or etravirine; atazanavir; raltegravir; maraviroc; and lamivudine. Activity for each drug was predicted as 1 (full-activity), 0.5 or 0 (no activity) using the Stanford mutation database. The utility of maraviroc was calculated assuming both maraviroc activity and inactivity where unknown. The analysis was restricted to regimens for which supporting evidence was identified in the literature or conference proceedings. Finally, we calculated the proportion of patients in the nationally representative Australian HIV Observational Database (AHOD) cohort receiving ≥2 RATE agents (n = 1473) to measure the potential population-level uptake of RATE-sparing agents. Results Assuming full maraviroc activity, 117(97.5%) and 107(89.2%) individuals had at least one option with 2 or 3 active RATE-sparing agents, respectively. Assuming no maraviroc activity this decreased to 113(94.2%) and 104(86.7%), respectively. In AHOD, 837(56.8%) patients were receiving ≥2 RATE agents. Conclusion Feasible treatment switch options sparing RATE agents exist for the majority of patients. Understanding the pros and cons of switching stable patients onto new RATE-sparing regimens requires evidence derived from randomised controlled trials.
Long-Term Survival in HIV Positive Patients with up to 15 Years of Antiretroviral Therapy
Hamish McManus,Catherine C. O'Connor,Mark Boyd,Jennifer Broom,Darren Russell,Kerrie Watson,Norman Roth,Phillip J. Read,Kathy Petoumenos,Matthew G. Law
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048839
Abstract: Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models.
High Viral Fitness during Acute HIV-1 Infection
Alicia Arnott,Darren Jardine,Kim Wilson,Paul R. Gorry,Kate Merlin,Patricia Grey,Matthew G. Law,Elizabeth M. Dax,Anthony D. Kelleher,Don E. Smith,Dale A. McPhee
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012631
Abstract: Several clinical studies have shown that, relative to disease progression, HIV-1 isolates that are less fit are also less pathogenic. The aim of the present study was to investigate the relationship between viral fitness and control of viral load (VL) in acute and early HIV-1 infection. Samples were obtained from subjects participating in two clinical studies. In the PULSE study, antiretroviral therapy (ART) was initiated before, or no later than six months following seroconversion. Subjects then underwent multiple structured treatment interruptions (STIs). The PHAEDRA study enrolled and monitored a cohort of individuals with documented evidence of primary infection. The subset chosen were individuals identified no later than 12 months following seroconversion to HIV-1, who were not receiving ART. The relative fitness of primary isolates obtained from study participants was investigated ex vivo. Viral DNA production was quantified using a novel real time PCR assay. Following intermittent ART, the fitness of isolates obtained from 5 of 6 PULSE subjects decreased over time. In contrast, in the absence of ART the fitness of paired isolates obtained from 7 of 9 PHAEDRA subjects increased over time. However, viral fitness did not correlate with plasma VL. Most unexpected was the high relative fitness of isolates obtained at Baseline from PULSE subjects, before initiating ART. It is widely thought that the fitness of strains present during the acute phase is low relative to strains present during chronic HIV-1 infection, due to the bottleneck imposed upon transmission. The results of this study provide evidence that the relative fitness of strains present during acute HIV-1 infection may be higher than previously thought. Furthermore, that viral fitness may represent an important clinical parameter to be considered when deciding whether to initiate ART during early HIV-1 infection.
A Randomised Trial Comparing Genotypic and Virtual Phenotypic Interpretation of HIV Drug Resistance: The CREST Study
Gillian Hales, Chris Birch, Suzanne Crowe, Cassy Workman, Jennifer F Hoy, Matthew G Law, Anthony D Kelleher, Douglas Lincoln, Sean Emery
PLOS ONE , 2006, DOI: 10.1371/journal.pctr.0010018
Abstract: Objectives The aim of this study was to compare the efficacy of different HIV drug resistance test reports (genotype and virtual phenotype) in patients who were changing their antiretroviral therapy (ART). Design Randomised, open-label trial with 48-week followup. Setting The study was conducted in a network of primary healthcare sites in Australia and New Zealand. Participants Patients failing current ART with plasma HIV RNA > 2000 copies/mL who wished to change their current ART were eligible. Subjects were required to be > 18 years of age, previously treated with ART, have no intercurrent illnesses requiring active therapy, and to have provided written informed consent. Interventions Eligible subjects were randomly assigned to receive a genotype (group A) or genotype plus virtual phenotype (group B) prior to selection of their new antiretroviral regimen. Outcome Measures Patient groups were compared for patterns of ART selection and surrogate outcomes (plasma viral load and CD4 counts) on an intention-to-treat basis over a 48-week period. Results Three hundred and twenty seven patients completing > one month of followup were included in these analyses. Resistance tests were the primary means by which ART regimens were selected (group A: 64%, group B: 62%; p = 0.32). At 48 weeks, there were no significant differences between the groups for mean change from baseline plasma HIV RNA (group A: 0.68 log copies/mL, group B: 0.58 log copies/mL; p = 0.23) and mean change from baseline CD4+ cell count (group A: 37 cells/mm3, group B: 50 cells/mm3; p = 0.28). Conclusions In the absence of clear demonstrated benefits arising from the use of the virtual phenotype interpretation, this study suggests resistance testing using genotyping linked to a reliable interpretive algorithm is adequate for the management of HIV infection. Trial Registration ACTR.org.au ACTRN012605000781640
Control of Viremia and Prevention of AIDS following Immunotherapy of SIV-Infected Macaques with Peptide-Pulsed Blood
Robert De Rose,Caroline S. Fernandez,Miranda Z. Smith,C. Jane Batten,Sheilajen Alcantara,Vivienne Peut,Erik Rollman,Liyen Loh,Rosemarie D. Mason,Kim Wilson,Matthew G. Law,Amanda J. Handley,Stephen J. Kent
PLOS Pathogens , 2008, DOI: 10.1371/journal.ppat.1000055
Abstract: Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIVmac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably ~10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans.
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