Tim R H Read

Monash University (Australia), Melbourne, Victoria, Australia

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Publications (69)355.86 Total impact

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    ABSTRACT: Background: In response to increasing HIV and other sexually transmissible infection (HIV/STI) notifications in Australia, a social marketing campaign Drama Downunder (DDU) was launched in 2008 to promote HIV/STI testing among men who have sex with men (MSM). We analyzed prospective data from (1) an online cohort of MSM and (2) clinic-level HIV/STI testing to evaluate the impact of DDU on HIV, syphilis, gonorrhea, and chlamydia testing. Materials and methods: (1) Cohort participants who completed 3 surveys (2010-2014) contributed to a Poisson regression model examining predictors of recent HIV testing.(2) HIV, syphilis, gonorrhea, and chlamydia tests among MSM attending high caseload primary care clinics (2007-2013) were included in an interrupted time series analysis. Results: (1) Although campaign awareness was high among 242 MSM completing 726 prospective surveys, campaign recall was not associated with self-reported HIV testing. Reporting previous regular HIV testing (adjusted incidence rate ratio, 2.4; 95% confidence interval, 1.3-4.4) and more than 10 partners in the previous 6 months (adjusted incidence rate ratio, 1.2; 95% confidence interval, 1.1-1.4) was associated with recent HIV testing. (2) Analysis of 257,023 tests showed increasing monthly HIV, syphilis, gonorrhea, and chlamydia tests pre-DDU. Post-DDU, gonorrhea test rates increased significantly among HIV-negative MSM, with modest and nonsignificant increasing rates of HIV, syphilis, and chlamydia testing. Among HIV-positive MSM, no change in gonorrhea or chlamydia testing occurred and syphilis testing declined significantly. Conclusions: Increasing HIV/STI testing trends among MSM occurred pre- and post-DDU, coinciding with other plausible drivers of testing. Modest changes in HIV testing post-DDU suggest that structural changes to improve testing access may need to occur alongside health promotion to increase testing frequency.
    No preview · Article · Dec 2015 · Sexually transmitted diseases
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    ABSTRACT: Objective: Cytological screening for anal cancer precursors is not always possible. We investigated digital ano-rectal examination (DARE) as a means of early anal cancer detection in HIV-positive men who have sex with men (MSM). Methods: We recruited 327 HIV-positive MSM aged 35 and over from clinics with HIV physicians in Melbourne, Australia, to receive an annual DARE. We analyzed baseline data from patient questionnaires regarding general, anal and sexual health, adverse effects from the anal examination, cancer worry, and quality of life. Results: The majority of men (82%, 95% CI:78-87) felt relaxed during the DARE, 1% (95% CI:0-3) complained of pain, and 1% (95% CI:0-4) reported bleeding after the examination. Nearly all men (99%, 95% CI:96-100) were willing to continue with an annual DARE. Quality of life was unaffected with utility scores of 0.76 before examination vs. 0.77 two weeks after examination, (p = 0.41). An anal abnormality was detected in 86 men (27%, 95% CI:22-31), with one anal cancer identified. The specialist referral rate following DARE was 5% (95% CI:3-8). Recruitment rates were significantly associated with the clinic setting (sexual health centre 78%, general practice 13%, hospital 14%, p = 0.002) and specialty (sexual health physician 67%, general practitioner 20%, infectious disease physician 14%, p = 0.031). Conclusion: Annual DARE to detect anal cancer in HIV-positive MSM was acceptable for patients, with minimal side effects. Strategies to increase HIV physician's patient recruitment would be needed if DARE were to be implemented in anal cancer screening.
    Full-text · Article · Oct 2015 · Journal of Medical Screening
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    ABSTRACT: Background: There has been limited research on the lived experience of taking antiretrovirals as HIV pre-exposure prophylaxis (PrEP). We explored men’s experiences as participants in Australia’s first PrEP demonstration project. Methods: After attending clinic visits, participants completed a self-report online survey on behaviour, attitudes and experiences. This paper analyses responses to the first (i.e. 3-month) survey on: 1) pill taking (including adherence and interruptions); 2) sex since starting PrEP; and 3) disclosing PrEP use. Responses to items on experiences of PrEP were measured on a 5-point scale (1=strongly disagree, 5=strongly agree). Results: At 31 March 2015, 76 participants had completed a 3-month survey; all gay/bisexual men (mean age 37.7 years). Forty-one men (53.9%) reported missing any PrEP doses. The median number of doses missed was 1 (mean 2.04). Missing doses was most commonly attributed to forgetting. Six men reported interrupting PrEP for 2 days or more. Side-effects (usually mild) were reported by 34 men (44.7%). Participants strongly agreed that PrEP had reduced their worries about HIV acquisition (mean 4.53; SD 0.77); they agreed that they were open with sexual partners about PrEP (mean 4.20; SD 1.2), and agreed that PrEP made them feel more confident about sex (mean 4.17; SD 0.98). Participants moderately agreed that they were careful to whom they disclosed (mean 3.36; SD = 1.4). However they disagreed that they had experienced negative reactions (mean 1.99; SD 1.14), and disagreed that potential sex partners would avoid them (mean 2.03; SD 1.01). Conclusion: These findings are notable because they support the results of recent qualitative research on the role of PrEP in decreasing anxiety around HIV. Caution around disclosure (including to sexual partners) suggests concern about negative reactions (despite few actual occurrences) and underscores the current novelty of PrEP as a prevention strategy.
    No preview · Conference Paper · Sep 2015
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    ABSTRACT: Introduction: Pre-exposure prophylaxis (PrEP) substantially decreases HIV risk among uninfected people, but risk compensation reduces prevention benefits. PrEP trials and extensions found no decrease in condom use, but included extensive risk reduction education. We investigated changes in condom use in the VicPrEP study, the first study assessing implementation of PrEP as routine practice in Australia. Methods: Enrollment commenced in June 2014, with capacity for 115 at risk HIV negative gay/bisexual men and heterosexual serodiscordant couples seeking to conceive. Participants are recruited from three GP clinics, one sexual health clinic, and one hospital clinic in Melbourne. Participants consent to using daily Truvada for at least one year, and complete baseline and three-monthly clinical examinations and self-report behavioural surveys. Results: At 15 March 2015, 92 participants completed baseline surveys, and 76 completed three-month follow-up; all gay/bisexual men (mean age 37.7 years; 67.4% university educated; 75.0% Australian born). In the past three months half had regular partners (Baseline: 48.9%, Follow-up: 55.8%; ns); nearly all had casual partners (Baseline: 90.2%, Follow-up: 88.2%; ns). Mean frequency of intercourse in the past three months remained stable for regular partners (Baseline: 19.0, Follow-up: 18.9; ns), and decreased for casual partners (Baseline: 19.1, Follow-up: 16.0; p=.056). Condom use was assessed on a 5-point scale (1=never, 5=always), and decreased with regular partners (Baseline: mean 2.0 [SD 1.6], Follow-up: mean 1.7 [SD 1.3]), and casual partners (Baseline: mean 3.0 [SD 1.3], Follow-up: mean 2.5 [SD 1.4]; p=.002). Serosorting, viral load sorting, strategic positioning and withdrawal remained unchanged with regular and casual partners. Conclusion: This is a first study internationally documenting decreasing condom use amongst HIV-negative gay/bisexual using PrEP. Findings highlight the potential for the benefits of PrEP to be reduced when implemented in routine practice because of risk compensation. This underscores the continued importance of promoting sexual risk reduction practices, including consistent condom use.
    No preview · Conference Paper · Sep 2015
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    ABSTRACT: Background: Increasing the frequency of HIV testing in men who have sex with men (MSM) will reduce the incidence of HIV. Trends in HIV testing among MSM in Melbourne, Australia over the last 11 years have been investigated. Methods: A retrospective study was conducted using electronic medical records of the first presentation of MSM who attended the Melbourne Sexual Health Centre between 2003 and 2013. Factors associated with HIV testing (year, demographic characteristics and sexual practices) were examined in multivariable logistic regression analyses. Jonckheere-Terpstra tests were used to examine the significance of trends in the mean time since the last HIV test. Results: Of 17 578 MSM seen; 13 489 attended for the first time during the study period. The proportion of first attendances who had previously tested and reported a HIV test in the last 12 months increased from 43.6% in 2003 to 56.9% in 2013 (adjusted ptrend = 0.030), with a corresponding decrease in median time since the last HIV test from 19 months [interquartile range (IQR) 6-42] in 2003 to 10 months (IQR4-24) in 2013 (ptrend <0.001). The proportion of high-risk MSM (who reported unprotected anal intercourse and/or >20 partners in 12 months) who reported an HIV test in the last 12 months was unchanged (ptrend = 0.242). Conclusions: Despite HIV testing becoming more frequent, the magnitude of change over the last decade is insufficient to substantially reduce HIV incidence. A paradigm shift is required to remove barriers to testing through strategies such as point-of-care rapid testing or access to testing without seeing a clinician.
    No preview · Article · Jul 2015 · Sexual Health
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    ABSTRACT: The rapid rise in syphilis cases has prompted a number of public health campaigns to assist men who have sex with men (MSM) recognize and present early with symptoms. This study aimed to investigate the temporal trend of the duration of self-report symptoms and titre of rapid plasma reagin (RPR) in MSM with infectious syphilis. Seven hundred and sixty-one syphilis cases in MSM diagnosed at the Melbourne Sexual Health Centre (MSHC) from 2007-2013 were reviewed. Median duration of symptoms and RPR titres in each year were calculated. The median durations of symptoms with primary and secondary syphilis were 9 [interquartile range (IQR) 6-14] days and 14 (IQR 7-30) days, respectively. The overall median titre of RPR in secondary syphilis (median 128, IQR 64-256) was higher than in primary syphilis (median 4, IQR 1-32) and in early latent syphilis (median 32, IQR 4-64). The median duration of symptoms for primary syphilis, secondary syphilis and titre of RPR level did not change over time. Public health campaigns were not associated with a significant shorter time from onset of symptoms to treatment. Alternative strategies such as more frequent testing of MSM should be promoted to control the syphilis epidemic in Australia.
    No preview · Article · Jun 2015 · Epidemiology and Infection
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    ABSTRACT: There is little known regarding the transmissibility of human papillomavirus (HPV) between different sites in men who have sex with men (MSM) and heterosexual individuals. We conducted a retrospective analysis investigating all new patients attending the Melbourne Sexual Health Centre in Australia between 2002 and 2013. We describe the prevalence and ratio of the first episode of anogenital warts in MSM and heterosexual males and females. The proportion of new MSM clients with anal and penile warts was 4·0% (362/8978) and 1·6% (141/8978), respectively; which gave an anal-to-penile wart ratio of 1:2·6. About 13·7% (1656/12112) of heterosexual males had penile warts and 10·0% (1121/11166) of females had vulval warts, which yielded a penile-to-vulval wart ratio of 1:0·7. Penile–anal transmission has a higher ratio than penile–vulval transmission, suggesting that the anal epithelium may be more susceptible to HPV infection than the vulval epithelium in females; these ratios are important in modelling the control of HPV in MSM.
    No preview · Article · May 2015 · Epidemiology and Infection
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    ABSTRACT: Background Australia has provided free quadrivalent human papillomavirus (HPV) vaccines to school girls since mid-2007 and a catch-up programme in the community to women aged up to 26 years in 2007–2009. We describe the temporal trend of genital warts in different populations in Melbourne. Methods We analysed the proportion diagnosed with genital warts for all new patients attending Melbourne Sexual Health Centre from July 2004 to June 2014, stratified by different risk groups and age. Adjusted ORs were calculated to compare the annual trend in the proportion of patients with genital warts in different risk groups in the prevaccination period (before June 2007) and the vaccination period (after July 2007). Results The proportion with genital warts decreased in women aged <21 years, from 18.4% in 2004/2005 to 1.1% in 2013/2014 (p<0.001), but increased in women aged >32 years, from 4.0% to 8.5% (p=0.037). The odds per year for diagnosis of genital warts adjusted for number of sexual partners in the vaccination period were 0.55 (95% CI 0.47 to 0.65) and 0.63 (95% CI 0.54 to 0.74) in women and heterosexual men aged <21 years, respectively. There was no change in adjusted odds of genital warts in both women and men aged >32 years. A small annual decline in genital warts was observed in men who have sex with men (aOR=0.92; 95% CI 0.88 to 0.97). Conclusions Genital warts have now become rare in young Australian women and heterosexual men 7 years after the launch of the national HPV vaccination programme but in stark contrast, remain common in men who have sex with men.
    No preview · Article · May 2015 · Sexually Transmitted Infections
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    ABSTRACT: To examine whether the rapid increase of gonorrhoea notifications in Victoria, Australia, identified by nucleic acid amplification test (NAAT) is supported by similar changes in diagnoses by culture, which has higher specificity, and to determine the proportion of tests positive among women tested. Retrospective analysis of Medicare reporting of dual NAATs in Victoria, Victorian Department of Health gonorrhoea notifications, and gonorrhoea culture data at the Melbourne Sexual Health Centre (MSHC), among women, 2008 to 2013. Gonorrhoea notifications and testing methods. Gonorrhoea cases identified by NAAT increased from 98 to 343 cases over the study period. Notifications by culture alone decreased from 19 to five cases. The proportion of NAATs positive for gonorrhoea in Victoria was low (0.2%-0.3%) and did not change over time (P for trend, 0.66). Similarly, the proportion of women tested at the MSHC for gonorrhoea who tested positive (0.4%-0.6%) did not change over time (P for trend, 0.70). Of untreated women who had a positive NAAT result for gonorrhoea and were referred to the MSHC, 10/25 were confirmed by culture. The positivity of gonorrhoea in women identified by culture remains stable over time. Using NAAT for gonorrhoea screening in low-prevalence populations will result in many false positives. Positive NAAT results among low-risk women should be regarded as doubtful, and confirmatory cultures should be performed.
    Full-text · Article · Apr 2015 · The Medical journal of Australia
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    ABSTRACT: Objectives In Australia, CD4 cell count is monitored approximately every 6 months in HIV-infected patients during antiretroviral therapy (ART). The aim of this study was to determine if routine CD4 monitoring contributed to decisions on changes to ART, and to estimate how reduced CD4 monitoring could contribute to cost savings in Australia. Methods We conducted a retrospective cohort analysis investigating all HIV-infected patients who attended the Melbourne Sexual Health Centre (MSHC) in Australia from 1 April 2011 to 1 October 2013. We reviewed the electronic medical records of all patients who changed or stopped antiretroviral regimens during this time period to determine whether CD4 cell count could have contributed to this clinical decision. Results Among 1004 patients with HIV infection on ART, none [95% confidence interval (CI) 0–2.3%] of the 162 clinical decisions to change or stop treatment were influenced by CD4 cell counts. Reducing the current biannual CD4 monitoring strategy to annually could potentially save ∼AU$ 1.5 million (US$ 1.4 million) each year in Australia [i.e. ∼AU$ 74 700 (US$ 67 700) could be saved per 1000 HIV-infected patients during ART]. Conclusions Routine CD4 monitoring in HIV-infected patients during ART could be reduced from biannually to annually, as it rarely influences clinical decisions in patients' management. Not only could this avoid patients being unnecessarily anxious about normal fluctuations in their CD4 counts but it would also result in cost savings.
    No preview · Article · Mar 2015 · HIV Medicine
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    ABSTRACT: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.
    Full-text · Article · Mar 2015 · PLoS Medicine
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    ABSTRACT: To determine the risk-adjusted temporal trend of gonorrhea and chlamydia positivity and associated risk behaviors among men who have sex with men (MSM) attending a sexual health clinic in Melbourne in Australia. Gonorrhea and chlamydia positivity by anatomical site adjusted for year of test, age, number of sexual partners, and condom use among MSM attending Melbourne Sexual Health Centre from 2007 to 2013 were calculated using generalized estimating equation regression models. A total of 12,873 MSM were included with a median age of 30.0 years. The proportion with pharyngeal, urethral, and anal gonorrhea was 1.7%, 2.3%, and 2.9%, respectively. The adjusted odds of gonorrhea positivity increased by 9% (95% confidence interval [CI], 3%-15%), 11% (95% CI, 6%-17%), and 12% (95% CI, 7%-17%) per year, respectively. The proportion of MSM who were infected with anal chlamydia was 5.6%, with an average increase of 6% (95% CI, 3%-10%) per year; however, no significant change was observed in urethral chlamydia positivity (adjusted odds ratio, 1.02; 95% CI, 0.98-1.06). Increases in gonorrhea and chlamydia positivity were primarily restricted to MSM who reported more than 10 partners in 12 months. The number of partners in the last 12 months fell from 16.6 to 10.5, whereas consistent condom use with casual partners decreased from 64.6% to 58.9% over the study period. Gonorrhea and chlamydia have increased among MSM despite the decrease in the number of sexual partners and are occurring primarily in MSM with high numbers of partners and persist after adjusting for known risk factors, suggesting that unmeasured factors (e.g., more assortative mixing patterns) may explain the observed changes.
    No preview · Article · Feb 2015 · Sex Transm Dis
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    ABSTRACT: Background: Loss to follow-up (LTFU) in HIV-positive cohorts is an important surrogate for interrupted clinical care which can potentially influence the assessment of HIV disease status and outcomes. After preliminary evaluation of LTFU rates and patient characteristics, we evaluated the risk of mortality by LTFU status in a high resource setting. Methods: Rates of LTFU were measured in the Australian HIV Observational Database for a range of patient characteristics. Multivariate repeated measures regression methods were used to identify determinants of LTFU. Mortality by LTFU status was ascertained using linkage to the National Death Index. Survival following combination antiretroviral therapy initiation was investigated using the Kaplan-Meier (KM) method and Cox proportional hazards models. Results: Of 3,413 patients included in this analysis, 1,632 (47.8%) had at least one episode of LTFU after enrolment. Multivariate predictors of LTFU included viral load (VL)>10,000 copies/ml (Rate ratio (RR) 1.63 (95% confidence interval (CI):1.45-1.84) (ref ≤400)), time under follow-up (per year) (RR 1.03 (95% CI: 1.02-1.04)) and prior LTFU (per episode) (RR 1.15 (95% CI: 1.06-1.24)). KM curves for survival were similar by LTFU status (p=0.484). LTFU was not associated with mortality in Cox proportional hazards models (univariate hazard ratio (HR) 0.93 (95% CI: 0.69-1.26) and multivariate HR 1.04 (95% CI: 0.77-1.43)). Conclusions: Increased risk of LTFU was identified amongst patients with potentially higher infectiousness. We did not find significant mortality risk associated with LTFU. This is consistent with timely re-engagement with treatment, possibly via high levels of unreported linkage to other health care providers.
    No preview · Article · Nov 2014 · Antiviral therapy
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    ABSTRACT: Background Human papillomavirus (HPV) is a causative agent in oropharyngeal squamous cell carcinoma. The natural history of oral HPV in HIV-positive men who have sex with men (MSM) is unclear. Methods Detection of oral human papillomavirus in 173 HIV-positive MSM using oral rinse samples 3 years apart was investigated. HPV DNA was detected by polymerase chain reaction, and genotyped by Roche Linear Array. Results Of 173 men tested in 2010, 30 had at least one HPV genotype (17%, 95% CI: 12–23), 15 at least one hr-HPV (9%, 95% CI: 5–14) and 8 had HPV 16 (5%, 95% CI: 2–9) detected. In 2013, 33 had at least one HPV genotype (19%, 95% CI: 14–26), 20 had at least one hr-HPV (12%, 95% CI: 7–17) and 7 had HPV 16 (4%, 95% CI: 2–8) detected. Of 30 men at baseline (2010) with any HPV detected, 14 (47%, 95% CI: 28–66) had at least one persistent genotype. Of the 15 men in 2010 with high risk (hr-) HPV, 6 men (40%, 95% CI: 16–68) had at least one persistent hr-HPV genotype. The incidence rate of detection of at least one new HPV genotype was 4.8 per 100 person years (95% CI: 3.1–7.0), of at least one hr-HPV genotype was 3.2 per 100 person years (95% CI: 1.8–5.1) and of HPV 16 was 0.8 per 100 person years (95% CI: 0.2–2.0). The clearance rate was 14.9 per 100 person years (95% CI: 8.2–24.2) for any HPV, 18.2 per 100 person years (95% CI: 8.2–32.7) for hr-HPV and 17.4 per 100 person years (95% CI: 5.0–38.8) for HPV-16. Persistent HPV detection was associated with duration of HIV (OR 1.13 (per additional year), 95% CI: 1.00–1.26) and tonsillectomy (OR 8.17, 95% CI: 1.30–51.40). Conclusion The same oral HPV genotype was detected again after 3 years in nearly half of HIV-positive men who have sex with men.
    Full-text · Article · Jul 2014 · PLoS ONE
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    ABSTRACT: Nongonococcal urethritis (NGU) is a common clinical syndrome, but no etiological agent is identified in a significant proportion of cases. Whether the spectrum of pathogens differs between heterosexual men (MSW) and men who have sex with men (MSM) is largely unstudied but of considerable clinical relevance. A retrospective review was done using the electronic medical record database of Melbourne Sexual Health Centre, Australia. Cases were first presentations of symptomatic acute NGU with >= 5 polymorphonuclear leukocytes (PMNL)/high-powered field (HPF) on urethral Gram stain between January 2006 and December 2011. First-stream urine was tested for Chlamydia trachomatis and Mycoplasma genitalium by PCR. Demographic, laboratory, and behavioral characteristics of cases were examined by univariate and multivariable analyses. Of 1,295 first presentations of acute NGU, 401 (32%; 95% confidence interval [CI] of 29 to 34%) had C. trachomatis and 134 (11%; 95% CI of 9 to 13%) had M. genitalium detected. MSM with acute NGU were less likely to have C. trachomatis (adjusted odds ratio [AOR] = 0.4; 95% CI of 0.3 to 0.6) or M. genitalium (AOR = 0.5; 95% CI of 0.3 to 0.8) and more likely to have idiopathic NGU (AOR = 2.4; 95% CI of 1.8 to 3.3), to report 100% condom use for anal/vaginal sex (AOR = 3.6; 95% CI of 2.7 to 5.0), or to have engaged in sexual activities other than anal/vaginal sex (AOR = 8.0; 95% CI of 3.6 to 17.8). Even when C. trachomatis or M. genitalium was detected, MSM were more likely than MSW to report consistent condom use (OR = 4.7; 95% CI of 2.6 to 8.3). MSM with acute NGU are less likely to have the established bacterial sexually transmitted infections (STIs) and more likely to report protected anal sex or sexual activity other than anal sex prior to symptom onset than MSW. These data suggest that the etiologic spectrum of pathogens differs between MSM and MSW in acute NGU and that relatively low-risk practices are capable of inducing acute NGU.
    Preview · Article · Jun 2014 · Journal of Clinical Microbiology

  • No preview · Conference Paper · Jun 2014
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    ABSTRACT: Pre- and postabrasion oral rinse samples (ORS) and a toothbrush sample detected human papillomavirus (HPV) DNA in at least one sample among 45 (26%) of 173 HIV-positive men who have sex with men. There was moderate agreement for HPV genotype detection between the preabrasion and postabrasion ORS (κ = 0.49; 95% confidence interval [CI], 0.37 to 0.61). There was good agreement between postabrasion ORS and toothbrushes (κ = 0.70; 95% CI, 0.60 to 0.80). The sensitivities for HPV genotypes detected were 80% (95% CI, 69 to 88) for preabrasion ORS, 65% (95% CI, 54 to 76) for postabrasion ORS, and 75% (95% CI, 63 to 84) for toothbrushes.
    Full-text · Article · Apr 2014 · Journal of clinical microbiology
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    ABSTRACT: Published online February 10, 2014 http://dx.doi.org/10.1016/S0140-6736(13)62187-X 1 Effi cacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial ENCORE1 Study Group* Summary Background The optimum dose of key antiretroviral drugs is often overlooked during product development. The ENCORE1 study compared the effi cacy and safety of reduced dose efavirenz with standard dose efavirenz in combination with tenofovir and emtricitabine as fi rst-line treatment for HIV infection. An eff ective and safe reduced dose could yield meaningful costsavings. Methods ENCORE1 is a continuing non-inferiority trial in HIV-1-infected antiretroviral-naive adults in 38 clinical sites in 13 countries. Participants (plasma HIV-RNA >1000 log 10 copies per mL, CD4 T-cell count 50–500 cells per μL) were randomly assigned by a computer-generated sequence with a blocking factor of four (stratifi ed by clinical site and by screening viral load) to receive tenofovir plus emtricitabine with either a reduced daily dose (400 mg) or a standard dose (600 mg) of efavirenz. Participants, physicians, and all other trial staff were masked to treatment group. The primary endpoint was the diff erence in proportions of participants with plasma HIV-RNA of less than 200 copies per mL at 48 weeks. Treatment groups were regarded as non-inferior if the lower limit of the 95% CI for the diff erence in viral load was less than –10% by modifi ed intention-to-treat analysis. Adverse events were summarised by treatment. This trial is registered with ClinicalTrials.gov, number NCT01011413. Findings The modifi ed intention-to-treat analysis consisted of 630 patients (efavirenz 400=321; efavirenz 600=309). 32% were women; 37% were African, 33% were Asian, and 30% were white. The mean baseline CD4 cell count was 273 cells per μL (SD 99) and median plasma HIV-RNA was 4·75 log 10 copies per mL (IQR 0·88). The proportion of participants with a viral load below 200 copies per mL at week 48 was 94·1% for efavirenz 400 mg and 92·2% for 600 mg (diff erence 1·85%, 95% CI −2·1 to 5·79). CD4 T-cell counts at week 48 were signifi cantly higher for the 400 mg group than for the 600 mg group (mean diff erence 25 cells per μL, 95% CI 6–44; p=0·01). We recorded no diff erence in grade or number of patients reporting adverse events (efavirenz 400=89·1%, efavirenz 600=88·4%; diff erence 0·75%, 95% CI −4·19 to 5·69; p=0·77). Study drug-related adverse events were signifi cantly more frequent in the 600 mg group than in the 400 mg group (146% [47] vs 118 [37]), diff erence −10·5%, 95% CI −18·2 to −2·8; p=0·01) and signifi cantly fewer patients with these events stopped treatment (400 mg=6 [2%], 600 mg=18 [6%], diff erence −3·96%, 95% CI −6·96 to −0·95; p=0·01). Interpretation Our fi ndings suggest that a reduced dose of 400 mg efavirenz is non-inferior to the standard dose of 600 mg, when combined with tenofovir and emtricitabine during 48 weeks in ART-naive adults with HIV-1 infection. Adverse events related to the study drug were more frequent with 600 mg efavirenz than with 400 mg. Lower dose efavirenz should be recommended as part of routine care.
    Full-text · Article · Feb 2014 · The Lancet
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    ABSTRACT: The aim of the study was to assess the significance of low-level viraemia (LLV) and the timing of treatment change in low/middle-income country (L/MIC) compared with high-income country (HIC) settings. Patients with virological control following commencement of combination antiretroviral therapy (cART) were included in the study. LLV was defined as undetectable viral load (<50 HIV-1 RNA copies/mL) followed by confirmed detectable viral load < 1000 copies/mL. Virological failure was defined as viral load > 1000 copies/mL. Kaplan-Meier plots of time to virological failure by prior LLV and income category were generated. Regimen changes in the setting of LLV were compared between sites. Sensitivity analysis of rates of LLV and virological failure by person-years and number of tests was conducted for differing definitions of LLV and virological failure. A total of 1748 patients from HICs and 823 patients from L/MICs were included in the study. One hundred and ninety-six (11.2%) HIC participants and 36 (4.4%) L/MIC participants experienced at least one episode of LLV. Of the patients who underwent regimen switch in HIC settings, the majority changed from a nucleoside reverse transcriptase inhibitor (NRTI)/protease inhibitor (PI) regimen to an NRTI/nonnucleoside reverse transcriptase inhibitor (NNRTI) regimen (26.8%). Very few switches were made in L/MIC settings. Rates of LLV were significantly higher for HICs compared with L/MICs per 1000 person-years (28.6 and 9.9 per 1000 person-years, respectively), but not in terms of the number of tests (9.4 and 7.2 per 1000 tests, respectively). Rates of virological failure per test were significantly higher for L/MICs compared with HICs (30.7 vs. 19.6 per 1000 tests, respectively; P < 0.001). LLV was a significant predictor of virological failure at 2 years in L/MICs [0.25; 95% confidence interval (CI) 0.11-0.50; P = 0.043] but not in HICs (0.13; 95% CI 0.08-0.22; P = 0.523). LLV is weakly predictive of virological failure at 2 years in L/MICs but not in HICs. This suggests that interventions targeted at subjects with LLV in L/MICs would help to improve treatment outcomes.
    No preview · Article · Jan 2014 · HIV Medicine
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    ABSTRACT: Abstract Both antiretroviral treatment interruption (TI) and cessation have been strongly discouraged since 2006. We describe the incidence, duration, and risk factors for TI and loss-to-follow-up (LTFU) rates across 13 countries. All 4689 adults (76% men) in two large HIV cohorts in Australia and Asia commencing combination antiretroviral therapy (ART) to March 2010 were included. TI was defined by ART cessation >30 days, then recommencement, and loss to follow-up (LTFU) by no visit since 31 March 2009 and no record of death. Survival analysis and Poisson regression methods were used. With median follow-up of 4.4 years [interquartile range (IQR):2.1-6.5], TI incidence was 6.7 per 100 person years (PY) (95% CI:6.1-7.3) pre-2006, falling to 2.0 (95% CI:1.7-2.2) from 2006 (p<0.01). LTFU incidence was 3.5 per 100 PY (95% CI:3.1-3.9) pre-2006, and 4.1 (95% CI:3.5-4.9) from 2006 (p=0.22). TIs accounted for 6.4% of potential time on ART pre-2006 and 1.2% from 2006 (p<0.01), and LTFU 4.7% of potential time on ART pre-2006 and 6.6% from 2006 (p<0.01). Median TI duration was 163 (IQR: 75-391) days pre-2006 and 118 (IQR: 67-270) days from 2006 (p<0.01). Independent risk factors for the first TI were: Australia HIV Observational Database participation; ART initiation pre-2006; ART regimens including stavudine and didanosine; three nucleoside analogue reverse transcriptase inhibitors; ≥7 pills per day; and ART with food restrictions (fasting or with food). In conclusion, since 2006, 7.8% of patients had significant time off treatment, which has the potential to compromise any 'test and treat' policy as during the interruption viral load will rebound and increase the risk of transmission.
    No preview · Article · Dec 2013 · AIDS patient care and STDs

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Institutions

  • 2015
    • Monash University (Australia)
      • Central Clinical School
      Melbourne, Victoria, Australia
  • 2014-2015
    • University of Vic
      Vic, Catalonia, Spain
  • 2010-2015
    • University of Melbourne
      • Population Mental Health Group
      Melbourne, Victoria, Australia
  • 2007-2013
    • Alfred Hospital
      • Melbourne Sexual Health Centre
      Melbourne, Victoria, Australia
  • 2003-2013
    • Melbourne Health
      Melbourne, Victoria, Australia
  • 2009
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia