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Ryom L.,Copenhagen University | Mocroft A.,University College London | Kirk O.,Copenhagen University | Ross M.,Mount Sinai School of Medicine | And 8 more authors.
AIDS | Year: 2014

Objectives: Whilst several antiretroviral drugs have been associated with moderate chronic kidney disease (CKD), their contribution to advanced CKD and end-stage renal disease (ESRD) remain unknown. Design: D:A:D participants with at least three estimated glomerular filtration rates (eGFR) after February 2004 were followed until the first of advanced CKD (confirmed eGFR≤30 ml/min,≥3 months apart), ESRD (dialysis ≥3 months/transplantation), 6 months after last visit or February 2012. Methods: Poisson regression was used to assess risk factors for advanced CKD/ESRD including exposure to potential nephrotoxic antiretroviral drugs and antiretroviral drug discontinuation rates according to latest eGFR. Results: Among 35 192 persons contributing 200 119 person years of follow-up (PYFU), 135 (0.4%) developed advanced CKD (n=114)/ESRD (n=21); incidence rate=0.67 [95% confidence interval (CI), 0.56-0.79]/1000 PYFU. Tenofovir (TDF) was particularly frequently discontinued as eGFR declined. After adjustment, those previously exposed but currently off TDF had similar advanced CKD/ESRD rate ratios compared with those unexposed [1.00 (95% CI, 0.66-1.51)], while those currently on TDF had reduced rates [0.23 (95% CI, 0.13-0.41)]. No consistent associations with other antiretroviral drugs were seen. Results were robust after time-lagging antiretroviral drug exposure, stratifying by baseline eGFR, and allowing for competing risks. Other predictors were diabetes, hypertension, baseline eGFR, smoking and current CD4 + cell count. The incidence rate in nonsmokers with baseline eGFR60 and no diabetes or hypertension was 0.16 (95% CI 0.09-0.26)/1000 PYFU. Conclusion: Neither current nor recent antiretroviral drug use predicted advanced CKD/ESRD during 6 years median follow-up in a large, heterogenenous and primarily white cohort. TDF discontinuation rates increased with decreasing eGFR, leaving a selected group still on TDF at lower advanced CKD/ESRD risk. Traditional renal risk factors and current CD4+ cell count were the strongest advanced CKD/ESRD predictors. © 2014 Wolters Kluwer Health.

PubMed | Harvard University, Kirby institute, Roskilde University, Instituto Nacional Of Ciencias Medicas Y Nutricion and 19 more.
Type: Journal Article | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2016

Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes.We searched databases to identify randomized trials that compared NNRTI- vs PI/r-based initial therapy. A metaanalysis calculated risk ratios (RRs) or mean differences (MDs), as appropriate. Primary outcome was death or progression to AIDS. Secondary outcomes were death, progression to AIDS, and treatment discontinuation. We calculated RR of virologic suppression and MD for an increase in CD4 cells at week 48.We included 29 trials with 9047 participants. Death or progression to AIDS occurred in 226 participants in the NNRTI arm and in 221 in the PI/r arm (RR, 1.03; 95% confidence interval, .87-1.22; 12 trials; n = 3825), death in 205 participants in the NNRTI arm vs 198 in the PI/r arm (1.04; 0.86-1.25; 22 trials; n = 8311), and progression to AIDS in 140 participants in the NNRTI arm vs 144 in the PI/r arm (1.00; 0.80-1.25; 13 trials; n = 4740). Overall treatment discontinuation (1.12; 0.93-1.35; 24 trials; n = 8249) and from toxicity (1.21; 0.87-1.68; 21 trials; n = 6195) were comparable, but discontinuation due to virologic failure was more common with NNRTI (1.58; 0.91-2.74; 17 trials; n = 5371). At week 48, there was no difference between NNRTI and PI/r in virologic suppression (RR, 1.03; 0.98-1.09) or CD4(+) recovery (MD, -4.7 cells; -14.2 to 4.8).We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.

PubMed | Melbourne Sexual Health Center, Sexual Health and Blood Borne Virus Unit, Health Diagnostic Laboratory, Darwin Lab and 8 more.
Type: Journal Article | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2016

Antimicrobial resistance (AMR) by Neisseria gonorrhoeae is considered a serious global threat.In this nationwide study, we used MassARRAY iPLEX genotyping technology to examine the epidemiology of N. gonorrhoeae and associated AMR in the Australian population. All available N. gonorrhoeae isolates (n = 2452) received from Australian reference laboratories from January to June 2012 were included in the study. Genotypic data were combined with phenotypic AMR information to define strain types.A total of 270 distinct strain types were observed. The 40 most common strain types accounted for over 80% of isolates, and the 10 most common strain types accounted for almost half of all isolates. The high male to female ratios (>94% male) suggested that at least 22 of the top 40 strain types were primarily circulating within networks of men who have sex with men (MSM). Particular strain types were also concentrated among females: two strain types accounted for 37.5% of all isolates from females. Isolates harbouring the mosaic penicillin binding protein 2 (PBP2)-considered a key mechanism for cephalosporin resistance-comprised 8.9% of all N. gonorrhoeae isolates and were primarily observed in males (95%).This large scale epidemiological investigation demonstrated that N. gonorrhoeae infections are dominated by relatively few strain types. The commonest strain types were concentrated in MSM in urban areas and Indigenous heterosexuals in remote areas, and we were able to confirm a resurgent epidemic in heterosexual networks in urban areas. The prevalence of mosaic PBP2 harboring N. gonorrhoeae strains highlight the ability for new N. gonorrhoeae strains to spread and become established across populations.

Bradshaw D.,Kirby Institute | Matthews G.,Kirby Institute | Danta M.,University of New South Wales
Current Opinion in Infectious Diseases | Year: 2013

Purpose of Review: Increasing evidence has emerged for permucosal transmission of hepatitis C amongst HIV-infected MSM. Recent Findings: A rising incidence of acute hepatitis C virus (HCV) in HIV-infected MSM has been observed since 2000 in Europe, Australia, USA and Asia. Transmission appears to occur through the permucosal rather than the more usual parenteral route. Although often multifactorial, permucosal risk factors can be classified as behavioural (sexual practices and mucosally administered drugs) and biological (HIV and sexually transmitted infections). This review will describe the epidemiology of HCV infection in this cohort. Current and future treatment strategies will also be outlined in the context of novel, orally bioavailable, directly acting antiviral therapies. Summary: An improved understanding of HCV epidemiology will allow implementation of more effective public health interventions to limit onward transmission of HCV. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Small W.,British Columbia Center for Excellence in | Small W.,Simon Fraser University | Small W.,Kirby Institute | Maher L.,Kirby Institute | And 7 more authors.
International Journal of Drug Policy | Year: 2013

Background: Illicit drug markets are a key component of the risk environment surrounding injection drug use. However, relatively few studies have explored how injection drug users' (IDUs) involvement in drug dealing shapes their experiences of drug market-related harm. This exploratory qualitative study aims to understand IDUs' dealing activities and roles, as well as the perceived benefits and risks related to participation in illicit drug markets, including experiences of drug market violence. Methods: Ten IDUs with extensive involvement in drug dealing activities were recruited from the Vancouver Injection Drug User Study (VIDUS) and participated in semi-structured qualitative interviews, which elicited discussion of experiences dealing drugs, perceived benefits and hazards related to dealing, and understandings of drug market violence. Results: Participant's involvement in drug market activities included corporate sales, freelance or independent sales, and opportunistic sales termed "middling" as well as drug market-related hustles entailing selling bogus drugs and robbing dealers. Participants primarily dealt drugs to support their own illicit drug use, and we found that arrest and criminal justice involvement, hazards stemming from drug debts, and drug market-related violence were key risks related to dealing activities. Conclusion: The challenges of managing personal consumption while selling drugs exacerbates the hazards associated with drug dealing. Efforts to address drug dealing among IDUs should consider both drug dependency and the material conditions that propel drug users towards dealing activities. Interventions should explore the potential of combining enhanced drug treatment programs with low threshold employment and alternative income generation opportunities. © 2013 .

Zablotska I.B.,Kirby Institute | Prestage G.,Kirby Institute | Wit J.D.,University of New South Wales | Grulich A.E.,Kirby Institute | And 2 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2013

Background: We aimed to describe the current use of antiretrovirals (ARVs) before unprotected anal intercourse (UAI) among Australian gay men, which may represent informal HIV preexposure prophylaxis (PrEP). Methods: Using data from Australian Gay Community Periodic Surveys conducted in 2011, we assessed the preventive use of ARVs before UAI and its association with sociodemographic characteristics, sexual practices, and drug use in the preceding 6 months. Associations were assessed using multivariate logistic regression analysis. Results: Of 3677 sexually active non-HIV-positive men, 2.5% reported taking ARVs before UAI. The likelihood of ARV use before UAI was significantly higher if any of the following behaviors were also reported: > 1 sex partner; UAI with casual partners, irrespective of reporting UAI with regular partners [adjusted odds ratio (AOR) = 2.36; 95% confidence interval (CI): 1.24 to 4.48] or not (AOR = 2.71; 95% CI: 1.44 to 5.07); injecting drugs at least monthly (AOR = 2.56; 95% CI: 1.03 to 6.36); using "party" drugs, occasionally (AOR = 2.23; 95% CI: 1.33 to 3.73) or regularly (AOR = 5.34; 95% CI: 2.99 to 9.56); and group sex while using party drugs, occasionally (AOR = 2.42; 95% CI: 1.29 to 4.53) or regularly (AOR = 5.31; 95% CI: 2.62 to 10.76). Among non-HIVpositive men in regular relationships with HIV-positive partners or partners of unknown HIV status, 1.7% and 4.7%, respectively, reported preventive ARV use before UAI. Conclusions: Our findings illustrate sporadic use of ARVs before UAI among gay men in Australia, which was associated with high-risk casual sex and party drug use. These initial data contribute to a much needed understanding of the informal use of ARVs for HIV prevention. Copyright © 2012 by Lippincott Williams and Wilkins.

Martin L.,Sydney Sexual Health Center | Knight V.,Sydney Sexual Health Center | Read P.J.,Sydney Sexual Health Center | Read P.J.,Kirby Institute | And 2 more authors.
Sexually Transmitted Diseases | Year: 2013

BACKGROUND: Sydney Sexual Health Centre (SSHC) Xpress clinic has significantly reduced the length of stay and waiting time for clients at SSHC but is currently only available to clients who can read and understand a high level of English. This reduces access for culturally and linguistically diverse (CALD) clients. This study sought to determine the acceptability of 4 proposed components of an express clinic model among CALD clients: computer-assisted self-interview (CASI), self-collection of swabs/urine specimens, not having a physical examination, and consultation with a health promotion officer rather than with a clinician. Differences in acceptability based on language group, new or return client status, sex worker status, clinic visited status, and age were analyzed. METHODS: A cross-sectional, anonymous questionnaire was offered to all female Chinese, Thai, and Korean clients attending SSHC between March and November 2012. Multivariate regression and Pearson χ statistical analyses were conducted using STATA 12 software. RESULTS: A total of 366 questionnaires were returned from 149 Thai, 145 Chinese, and 72 Korean participants. After multivariate analysis, the only predictor of willingness to use an express model of service provision was language group: overall, 67% Thai (odds ratio, 3.74: confidence interval [CI], 2.03-6.89; P < 0.01) and 64% Korean (odds ratio, 3.58; CI, 1.77-7.25, P < 0.01) said that they would use it compared with 35% Chinese. Age, history of sex work, new or returning clients, and general or language clinic attendance did not impact on choices. Within the preference for individual components of the model, more Thai women were happy with using a health promotion officer (43.2%) than Chinese (14.1%) or Korean (8.5%) (P < 0.001); no groups were happy with forfeiting a physical examination; Thai (48.6%) and Korean (40.9%) were happier with self-swabbing than Chinese women (23.9%, P < 0.001); and more Thai were happy to use a CASI (44.2%) than Chinese (12%) or Korean (11.1%; P < 0.001). CONCLUSIONS: This research shows that the components of an express model used at SSHC are not favorable to our CALD client base. Despite a CALD express clinic having the potential to reduce waiting times, most clients did not favor reduced waiting time over being physically examined or using a CASI. Copyright © 2013 American Sexually Transmitted Diseases Association. All rights reserved.

Naidoo S.,Jan Medical | Wand H.,Kirby Institute
Sexually Transmitted Infections | Year: 2013

Background and objectives Trichomonas vaginalis is known to be the most common, curable, sexually transmitted infection among sexually active women and may be associated with the acquisition and transmission of HIV. The purpose of this analysis is to determine the prevalence and incidence of T vaginalis and assess risk factors associated with T vaginalis infection in a cohort of women participating in a clinical trial. Methods We analysed data from women participating in a phase III vaginal diaphragm trial conducted in two communities in Durban, South Africa from 2003 to 2006. A total of 3492 women were screened and 1485 women meeting the respective study eligibility criteria were enrolled. T vaginalis infection was determined at the initial screening visit and at quarterly visits among the enrolled women. Sexual behaviour and sociodemographic data were collected as per the study protocol. Combined data were analysed using STATA V.10.0. Results At baseline, prevalence of infection was 6.5%. The overall incident rate was estimated to be 8.6/100 women-years. Prevalent T vaginalis infection was associated with having a concurrent chlamydial infection and incident infections were associated with increased number of sex partners. Conclusions T vaginalis infection was found to be relatively high among this cohort of women. Given the association of this infection with HIV, there is an evident need for T vaginalis screening and treatment in populations at risk for both infections.

PubMed | QIMR Berghofer Medical Research Institute, Medicines for Malaria Venture and Kirby Institute
Type: Journal Article | Journal: The Journal of infectious diseases | Year: 2016

The emergence of drug-resistant malaria highlights the need for new agents. A desired characteristic of candidate antimalarials is rapid killing of parasites. This is typically measured by the rate of exponential clearance of parasitemia following treatment. However, this clearance rate excludes the highly variable lag phase, when the parasitemia level may increase, remain constant, or decrease. Understanding factors determining this lag phase is important for drug development.We assessed the kinetics of parasitemia in 112 volunteers infected with blood-stage Plasmodium falciparum and treated with 8 different antimalarials. The parasitemia level was measured by quantitative polymerase chain reaction. We analyzed the relationship between the timing of treatment in the parasite growth cycle, and whether the parasitemia level rose or fell in the first 12 or 24 hours after treatment.The timing of treatment in the parasite life cycle predicted whether subjects experienced rises or falls in parasitemia level after treatment. Antimalarials were unable to prevent rises in the parasitemia level in the first 12 hours. However, in the first 24 hours after treatment, fast-acting but not slow-acting drugs reduced the parasitemia level independent of when treatment was administered.The highly variable lag phase depends on the speed of action of an antimalarial and when in the periodic growth cycle it is administered.

Schaffer A.,Center for Epidemiology and Research | Muscatello D.,Center for Epidemiology and Research | Cretikos M.,Center for Epidemiology and Research | Gilmour R.,Center for Health Protection | And 2 more authors.
BMC Public Health | Year: 2012

Background: In Australia, the 2009 epidemic of influenza A(H1N1)pdm09 resulted in increased admissions to intensive care. The annual contribution of influenza to use of intensive care is difficult to estimate, as many people with influenza present without a classic influenza syndrome and laboratory testing may not be performed. We used a population-based approach to estimate and compare the impact of recent epidemics of seasonal and pandemic influenza. Methods. For 2007 to 2010, time series describing health outcomes in various population groups were prepared from a database of all intensive care unit (ICU) admissions in the state of New South Wales, Australia. The Serfling approach, a time series method, was used to estimate seasonal patterns in health outcomes in the absence of influenza epidemics. The contribution of influenza was estimated by subtracting expected seasonal use from observed use during each epidemic period. Results: The estimated excess rate of influenza-associated respiratory ICU admissions per 100,000 inhabitants was more than three times higher in 2007 (2.6/100,000, 95% CI 2.0 to 3.1) than the pandemic year, 2009 (0.76/100,000, 95% CI 0.04 to 1.48). In 2009, the highest excess respiratory ICU admission rate was in 17 to 64 year olds (2.9/100,000, 95% CI 2.2 to 3.6), while in 2007, the highest excess rate was in those aged 65 years or older (9.5/100,000, 95% CI 6.2 to 12.8). In 2009, the excess rate was 17/100,000 (95% CI 14 to 20) in Aboriginal people and 14/100,000 (95% CI 13 to 16) in pregnant women. Conclusion: While influenza was diagnosed more frequently and peak use of intensive care was higher during the epidemic of pandemic influenza in 2009, overall excess admissions to intensive care for respiratory illness was much greater during the influenza season in 2007. Thus, the impact of seasonal influenza on intensive care use may have previously been under-recognised. In 2009, high ICU use among young to middle aged adults was offset by relatively low use among older adults, and Aboriginal people and pregnant women were substantially over-represented in ICUs. Greater emphasis on prevention of serious illness in Aboriginal people and pregnant women should be a priority in pandemic planning. © 2012 Schaffer et al.; licensee BioMed Central Ltd.

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