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Background: Bacterial vaginosis (BV) is estimated to affect 1 in 3 women globally and is associated with obstetric and gynaecological sequelae. Current recommended therapies have good short-term efficacy but 1 in 2 women experience BV recurrence within 6 months of treatment. Evidence of male carriage of BV-organisms suggests that male partners may be reinfecting women with BV-associated bacteria (henceforth referred to as BV-organisms) and impacting on the efficacy of treatment approaches solely directed to women. This trial aims to determine the effect of concurrent male partner treatment for preventing BV recurrence compared to current standard of care. Methods: StepUp is an open-label, multicentre, parallel group randomised controlled trial for women diagnosed with BV and their male partner. Women with clinical-BV defined using current gold standard diagnosis methods (≥3 Amsel criteria and Nugent score (NS) = 4–10) and with a regular male partner will be assessed for eligibility, and couples will then be consented. All women will be prescribed oral metronidazole 400 mg twice daily (BID) for 7 days, or if contraindicated, a 7-day regimen of topical vaginal 2% clindamycin. Couples will be randomised 1:1 to either current standard of care (female treatment only), or female treatment and concurrent male partner treatment (7 days of combined antibiotics - oral metronidazole tablets 400 mg BID and 2% clindamycin cream applied topically to the glans penis and upper shaft [under the foreskin if uncircumcised] BID). Couples will be followed for up to 12 weeks to assess BV status in women, and assess the adherence, tolerability and acceptability of male partner treatment. The primary outcome is BV recurrence defined as ≥3 Amsel criteria and NS = 4–10 within 12 weeks of enrolment. The estimated sample size is 342 couples, to detect a 40% reduction in BV recurrence rates from 40% in the control group to 24% in the intervention group within 12 weeks. Discussion: Current treat

Objectives Using mathematical modelling, we have previously shown that the prevalence of infection with Trichomonas vaginalis (TV) is likely to increase in the general population in Australia with the transition from Pap smear-based cervical screening to human papillomavirus (HPV) DNA testing. Here we use the existing model to estimate the level of supplemental testing required to maintain TV control. Methods A compartmental mathematical model describing the transmission of TV in the general heterosexual population in Australia was used to evaluate the impact of a range of screening scenarios on TV prevalence over time following the transition to HPV DNA testing for cervical screening. Scenarios considered were the inclusion of a TV test with the HPV test and the addition of TV testing to routine chlamydia testing conducted in primary care. Results Our modelling suggests that with sufficient coverage, inclusion of TV testing with routine chlamydia screening in general practice, TV prevalence can be reduced over time, but at the current reported coverage will gradually increase following the transition to HPV testing. Inclusion of TV testing with HPV testing in the cervical screening programme is preferable to no supplemental testing but is considerably less effective in controlling TV. Conclusions These findings support the inclusion of TV testing with routine chlamydia testing of young people.

Women-who-have-sex-with-women (WSW) are at increased risk of bacterial vaginosis (BV). We investigated the impact of practices and past BV on the vaginal microbiota within a two-year longitudinal cohort of Australian WSW. Self-collected vaginal swabs were used to characterise the vaginal microbiota using 16S-rRNA gene sequencing. Hierarchical clustering defined community state types (CSTs). Bacterial diversity was calculated using the Shannon diversity index and instability of the vaginal microbiota was assessed by change of CST and Bray-Curtis dissimilarity. Sex with a new partner increased the bacterial diversity (adjusted-coefficient = 0.41, 95%CI: 0.21,0.60, p < 0.001) and instability of the vaginal microbiota, in terms of both change of CST (adjusted-odds-ratio = 2.65, 95%CI: 1.34,5.22, p = 0.005) and increased Bray-Curtis dissimilarity (adjusted-coefficient = 0.21, 95%CI: 0.11,0.31, p < 0.001). Women reporting sex with a new partner were more likely than women reporting no new partner to have a vaginal microbiota characterised by Gardnerella vaginalis (adjusted-relative-risk-ratio[aRRR] = 3.45, 95%CI: 1.42,8.41, p = 0.006) or anaerobic BV-associated bacteria (aRRR = 3.62, 95%CI: 1.43,9.14, p = 0.007) relative to a Lactobacillus crispatus dominated microbiota. Sex with a new partner altered the vaginal microbiota of WSW by increasing the diversity and abundance of BV-associated bacteria. These findings highlight the influence of practices on the development of a non-optimal vaginal microbiota and provide microbiological support for the sexual exchange of bacteria between women.

The benefit of immediate antiretroviral therapy (ART) at CD4 >500 cells/L was established in the Strategic Timing of Antiretroviral Treatment (START) study. The benefits and risks of immediate ART in participants with low pretreatment viremia, including virologic suppressors, were further assessed.Setting:Randomized prospective international study.Methods:START participants with enrollment viremia <3000 c/mL were included. We compared clinical outcomes (grade 4 adverse events, hospitalizations, or death), plasma viremia, CD4 counts, and changes in biomarkers in immediate versus deferred ART groups.Results:Participants (N = 1134 including 93 with viremia ≤50 c/mL) had a median age of 37 years, 40% were women, and median CD4 was 713 cells/L. Ninety-seven percent in the immediate and 29% in the deferred arm initiated ART at a median of 6 and 699 days, respectively. Clinical outcomes were experienced in 64 versus 61 patients in immediate and deferred arms (hazard ratio 1.10, 95% confidence interval: 0.77 to 1.56). The CD4 count difference was 125 cells/L at 12 and 235 cells/L at 36 months higher in the immediate versus deferred groups. D-dimer and VCAM levels decreased, and C-reactive protein increased, in the immediate arm at month 8. No significant changes in CD4 counts or biomarkers were observed in persons who maintained spontaneous virologic suppression.Conclusions:START participants with low enrollment viremia experienced higher CD4 counts, greater proportion with suppressed viremia, and decreases in D-dimer levels on immediate ART despite the lack of difference in serious clinical outcomes. These data support immediate ART in people with low viremia, although equipoise remains for suppressors.

OBJECTIVES: As HIV-positive people age, diagnosis and management of comorbidities associated with ageing are of increasing concern. In this study, we aimed to compare the self-reported prevalences of heart disease, stroke, thrombosis and diabetes in older Australian HIV-positive and HIV-negative gay and bisexual men (GBM). METHODS: We analysed data from the Australian Positive & Peers Longevity Evaluation Study (APPLES), a study of a prospectively recruited cross-sectional sample of 228 (51.1%) HIV-positive and 218 (48.9%) HIV-negative GBM, aged ≥ 55 years. Regression methods were used to assess the association of HIV status with self-reported comorbidities. RESULTS: Of 446 patients, 389 [200 (51.4%) HIV-positive] reported their disease history. The reported prevalence of comorbidities was higher in the HIV-positive group than in the HIV-negative group: heart disease, 19.5 versus 12.2%; stroke, 7.5 versus 4.2%; thrombosis, 10.5 versus 4.2%; and diabetes, 15.0 versus 9.0%, respectively. In adjusted analyses, HIV-positive GBM had significantly increased odds of reporting heart disease [adjusted odds ratio (aOR) 1.99; P = 0.03] and thrombosis (aOR 2.87; P = 0.01). In our analysis, HIV status was not significantly associated with either age at diagnosis of heart disease (median 53 years for HIV-positive GBM versus 55 years for HIV-negative GBM; P = 0.64) or 5-year cardiovascular disease (CVD) risk estimated using the Framingham risk score. CONCLUSIONS: HIV-positive GBM more commonly reported heart disease and thrombosis compared with their HIV-negative peers. These results further highlight the need to understand the impact of HIV on age-related comorbidities in GBM, to guide optimal screening and treatment strategies to reduce the risk of these comorbidities among the HIV-positive population.

We conducted a pilot open-label randomised controlled trial of combined (oestrogen-progesterone) oral contraceptive pill (COCP)-exposure aimed to examine its effect on BV-recurrence following first-line antibiotics compared to antibiotics alone. Ninety-five women with symptomatic BV were prescribed antibiotic therapy, randomised to COCP-exposure (intervention) or current non-hormonal contraceptive practices (control) and followed monthly for six-months or until BV-recurrence. Modified intention-to-treat methods requiring either ≥1 clinical (primary/Amsel-outcome) or ≥1 microbiological (secondary/Nugent-outcome) BV-recurrence assessment were applied to determine cumulative recurrence rates. Secondary Cox regression analyses assessed factors associated with recurrence in all women. 92/95 women randomised provided baseline requirements. BV-recurrence rates were similar in women randomised to the COCP (primary/Amsel-outcome: 10/100PY, 95%CI: 6,19/100PY) compared to controls (14/100PY, 95%CI: 9, 21/100PY, p = 0.471). In secondary analyses sex with the same pre-treatment regular sexual partner (RSP; Amsel: Adjusted Hazard Ratio [AHR] = 3.13, 95%CI: 1.41, 6.94, p = 0.005; Nugent: AHR = 2.97, 95%CI: 1.49, 5.83, p = 0.002) and BV-history (Amsel: AHR = 3.03, 95%CI: 1.14, 6.28; Nugent: AHR = 2.78, 95%CI: 1.22, 6.33) were associated with increased BV-recurrence. This pilot RCT of COCP-exposure did not improve BV cure but found sex with an RSP and BV-history were associated with recurrence, although impacted by sample size and attrition. These data indicate reinfection from an untreated RSP and persistence of BV-associated bacteria are integral to the pathogenesis of recurrence and may overwhelm potential beneficial effects of hormonal contraception on the vaginal microbiota.

© 2017 CSIRO. Background: The widespread availability of direct-acting antivirals (DAAs) is expected to drastically improve the treatment uptake and cure rate of hepatitis C virus (HCV). In this paper, rates of and factors associated with HCV treatment uptake and cure in the HIV co-infected population in Australia were assessed before access to DAAs. Methods: The medical records of patients in the Australian HIV Observational Database who were reported to be HCV antibody positive from 1999 to 2014 were reviewed for HCV treatment data. Patients with detectable HCV RNA were included in this analysis. Logistic regression models were applied to identify factors associated with treatment uptake and HCV sustained virological response (SVR) 24 weeks' post treatment. Results: The median follow-up time of those with chronic HCV/HIV co-infection was 103 months (interquartile range 51-166 months). Of 179 HCV viraemic patients, 79 (44.1%) began treatment. In the adjusted model, a higher METAVIR score was the only significant factor associated with treatment uptake (odds ratio (OR) 8.87, 95% confidence interval (CI) 2.00-39.3, P≤0.004). SVR was achieved in 37 (50%) of 74 treated patients. HCV genotypes 2/3 compared with 1/4 remained the only significant factor for SVR in an adjusted multivariable setting (OR 5.44, 95% CI 1.53-19.4, P≤0.009). Conclusions: HCV treatment uptake and SVR have been relatively low in the era of interferon-containing regimens, in Australian HIV/HCV coinfected patients. With new and better tolerated DAAs, treatment of HCV is likely to become more accessible, and identification and treatment of HCV in co-infected patients should become a priority.

Background: Increased D-dimer concentrations are associated with poor cardiovascular and other clinical outcomes in people with treated HIV infection. Proteinase activated receptor-1 (PAR-1) is activated by thrombin and overexpressed by immune cells from HIV-infected people. We aimed to study the efficacy of vorapaxar, a licensed inhibitor of PAR-1, in reducing HIV-associated hypercoagulation and inflammation. Methods: This was a multicentre, double-blind, randomised, placebo-controlled trial done in seven hospital clinics in Australia and the USA. Eligible participants were HIV-infected, aviraemic, were receiving stable antiretroviral therapy, and had D-dimer concentrations greater than 200 ng/mL. We randomly assigned participants (1:1) using computer-generated block lists of size two to receive vorapaxar (2·5 mg orally daily) or matched placebo for 12 weeks. Participants were reviewed and had a blood sample taken at weeks 1, 4, 8, and 12 during treatment, and at a final visit at week 18. The primary endpoint was treatment group difference in changes from baseline D-dimer concentrations after 8–12 weeks of treatment, and was assessed in the modified intention-to-treat population (participants who had at least one dose of study drug or one follow-up visit). This trial is registered with ClinicalTrials.gov, number NCT02394730, and is closed to new participants. Findings: Between Oct 21, 2015, and July 14, 2017, 65 eligible patients were randomly assigned to the placebo group (n=31) or vorapaxar group (n=34). One patient from the vorapaxar group did not receive any study drug, and the modified intention-to-treat population was comprised of 33 patients. D-dimer concentrations after 8–12 weeks of treatment did not differ significantly between groups (difference −0·02 log10 ng/mL, 95% CI −0·10 to 0·05; p=0·56). Vorapaxar treatment was safe and well tolerated in this cohort. There were 161 adverse events (n=84 in the placebo group and n=77 in the vorapaxar group), and fiv

Objectives: The aim of this study was to describe characteristics of perinatally HIV-infected adolescents (PHIVAs), factors associated with mortality, and outcomes at transition. Design: Ongoing observational database collating clinical data on HIV-infected children and adolescents in Asia. Methods: Data from 2001 to 2016 relating to adolescents (10-19 years) with perinatal HIV infection were analysed to describe characteristics at adolescent entry and transition and combination antiretroviral therapy (cART) regimens across adolescence. A competing risk regression analysis was used to determine characteristics at adolescent entry associated with mortality. Outcomes at transition were compared on the basis of age at cART initiation. Results: Of 3448 PHIVA, 644 had reached transition. Median age at HIV diagnosis was 5.5 years, cART initiation 7.2 years and transition 17.9 years. At adolescent entry, 35.0% hadCD4+ cell count less than 500 cells/ml and 51.1% had experience da WHO stage III/IV clinical event. At transition, 38.9% had CD4+ cell count less than 500copies/ml, and 53.4% had experienced a WHO stage III/IV clinical event. Mortality ratewas 0.71 per 100 person-years, with HIV RNA >1000copies/ml, CD4+ cell count less than 500cells/ml, height-for-ageorweight-for-agez-score less than - 2, historyofa WHO stage III/IV clinical event or hospitalization and at least second cART associated with mortality. For transitioning PHIVA, those who commenced cART age less than 5 years had better virologic and immunologic outcomes, though were more likely to be on at least second cART. Conclusion: Delayed HIV diagnosis and cART initiation resulted in considerable morbidity and poor immune status by adolescent entry. Durable first-line cART regimens to optimize disease control are key to minimizing mortality. Early cART initiation provides the best virologic and immunologic outcomes at transition.

OBJECTIVES: Trichomonas vaginalis (TV) is the most common curable STI worldwide and is associated with increased risk of HIV acquisition and serious reproductive morbidities. The prevalence of TV infection is very low in Australian cities, and this is thought to be at least partly due to incidental detection and treatment of TV in women participating in the cervical cytology screening programme. In 2017, the national cervical screening programme will transition to a new model based on testing for high-risk (HR) human papillomavirus (HPV), with a reduced frequency and commencement at an older age. We model the potential impact of this transition on TV prevalence in Australia.

BACKGROUND: This study evaluated cause-specific mortality trends including liver-related mortality among people with a hepatitis B virus (HBV) and hepatitis C virus (HCV) notification in New South Wales, Australia. METHODS: Notifications 1993-2012 were linked to cause-specific mortality records 1993-2013. RESULTS: Among 57,929 and 92,474 people with a HBV and HCV notification, 4.8% and 10.0% died since 1997. In early 2010s, 28% and 33% of HBV and HCV deaths were liver-related, 28% and 17% were cancer-related (excluding liver cancer), and 5% and 15% were drug-related, respectively. During 2002-2012, annual HBV-related liver death numbers were relatively stable (53 to 68), while HCV-related liver death numbers increased considerably (111 to 284). Age-standardised HBV-related liver mortality rates declined from 0.2 to 0.1 per 100 person-years (PY) (P < 0.001); however, HCV-related rates remained stable (0.2 to 0.3 per 100 PY, P = 0.619). In adjusted analyses, older age was the strongest predictor of liver-related mortality [birth earlier than 1945, HBV adjusted hazard ratio (aHR) 28.1, 95% CI 21.0, 37.5 and; HCV aHR 31.9, 95% CI 26.8, 37.9], followed by history of alcohol-use disorder (HBV aHR 7.0, 95% CI 5.5, 8.8 and; HCV aHR 8.3, 95% CI 7.6, 9.1). CONCLUSIONS: Declining HBV-related liver mortality rates and stable burden suggest an impact of improved antiviral therapy efficacy and uptake. In contrast, the impact of interferon-containing HCV treatment programs on liver-related mortality individual-level risk and population-level burden has been limited. These findings also highlight the importance of HBV/HCV public health interventions that incorporate increased antiviral therapy uptake, and action on health risk behaviors.

© 2017 Fritz CQ et al. Introduction: An important determinant of the effectiveness of HIV treatment programs is the capacity of sites to implement recommended services and identify systematic changes needed to ensure that invested resources translate into improved patient outcomes. We conducted a survey in 2014 of HIV care and treatment sites in the seven regions of the International epidemiologic Database to Evaluate AIDS (IeDEA) Consortium to evaluate facility characteristics, HIV prevention, care and treatment services provided, laboratory capacity, and trends in the comprehensiveness of care compared to data obtained in the 2009 baseline survey. Methods: Clinical staff from 262 treatment sites in 45 countries in IeDEA completed a site survey from September 2014 to January 2015, including Asia-Pacific with Australia (n = 50), Latin America and the Caribbean (n = 11), North America (n = 45), Central Africa (n = 17), East Africa (n = 36), Southern Africa (n = 87), and West Africa (n = 16). For the 55 sites with complete data from both the 2009 and 2014 survey, we evaluated change in comprehensiveness of care. Results: The majority of the 262 sites (61%) offered seven essential services (ART adherence, nutritional support, PMTCT, CD4+ cell count testing, tuberculosis screening, HIV prevention, and outreach). Sites that were publicly funded (64%), cared for adults and children (68%), low or middle Human Development Index (HDI) rank (68%, 68%), and received PEPFAR support (71%) were most often fully comprehensive. CD4+ cell count testing was universally available (98%) but only 62% of clinics offered it onsite. Approximately two-thirds (69%) of sites reported routine viral load testing (44-100%), with 39% having it onsite. Laboratory capacity to monitor antiretroviral-related toxicity and diagnose opportunistic infections varied widely by testing modality and region. In the subgroup of 55 sites with two surveys, comprehensiveness of services provided significantly inc

Objectives To examine the influence of sexual activity on the composition and consistency of the vaginal microbiota over time, and distribution of Gardnerella vaginalis clades in young women. Methods Fifty-two participants from a university cohort were selected. Vaginal swabs were self-collected every 3-months for up to 12 months with 184 specimens analysed. The vaginal microbiota was characterised using Roche 454 V3/4 region 16S rRNA sequencing, and G. vaginalis clade typing by qPCR. Results A Lactobacillus crispatus dominated vaginal microbiota was associated with Caucasian ethnicity (adjusted relative risk ratio[ARRR] = 7.28, 95%CI:1.37,38.57,p = 0.020). An L. iners (ARRR = 17.51, 95%CI:2.18,140.33,p = 0.007) or G.vaginalis (ARRR = 14.03, 95% CI:1.22,160.69, p = 0.034) dominated microbiota was associated with engaging in penilevaginal sex. Microbiota dominated by L.crispatus, L.iners or other lactobacilli exhibited greater longitudinal consistency of the bacterial communities present compared to ones dominated by heterogeneous non-lactobacilli (p<0.030); sexual activity did not influence consistency. Women who developed BV were more likely to have clade GV4 compared to those reporting no sex/practiced non-coital activities (OR = 11.82, 95%CI:1.87,74.82,p = 0.009). Specimens were more likely to contain multiple G.vaginalis clades rather than a single clade if women engaged in penile-vaginal sex (RRR = 9.55, 95%CI:1.33,68.38,p = 0.025) or were diagnosed with BV (RRR = 31.5, 95%CI:1.69,586.87,p = 0.021). Conclusions Sexual activity and ethnicity influenced the composition of the vaginal microbiota of these young, relatively sexually inexperienced women. Women had consistent vaginal microbiota over time if lactobacilli were the dominant spp. present. Penile-vaginal sex did not alter the consistency of microbial communities but increased G.vaginalis clade diversity in young women with and without BV, suggesting sexual transmission of commensal and potentially pathogen

Background: Direct acting antivirals are expected to drastically reduce the burden of hepatitis C virus (HCV) in people living with Human Immunodeficiency Virus (HIV). However, rates of HCV testing, re-testing and incident infection in this group remain uncertain in Australia. We assessed trends in HCV testing, re-testing and incident infection among HIV-positive individuals, and evaluated factors associated with HCV re-testing and incident infection. Methods: The study population consisted of HIV-positive individuals who visited a sexual health service involved in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) between 2007 and 2015. Poisson regression was used to assess trends and to evaluate factors associated with HCV re-testing and incident HCV infection. Results: There were 9227 HIV-positive individuals included in our testing rate analysis. Of 3799 HIV-positive/HCV-negative people that attended an ACCESS sexual health service more than once, 2079 (54.7%) were re-tested for HCV and were therefore eligible for our incidence analysis. The rate of HCV testing increased from 17.1 to 51.4 tests per 100 patient years between 2007 and 2015 (p for trend <0.01). Over the same period, HCV re-testing rates increased from 23.9 to 79.7 tests per 100 person years (p for trend <0.01). A clear increase in testing and re-testing began after 2011. Patients who identified as men who have sex with men and those with a history of injecting drug use experienced high rates of HCV re-testing over the course of the study period. Among those who re-tested, 157 incident HCV infections occurred at a rate of 2.5 events per 100 person years. Between 2007 and 2009, 2010-2011, 2012-2013 and 2014-2015, rates of incident HCV were 0.8, 1.5, 3.9 and 2.7 events per 100 person years, respectively (p for trend <0.01). Incident HCV was strongly associated with a history of injecting drug use. Conclusions: High rates of HCV testing and re-testing among HIV-positiv

Objectives: Life expectancy is an important indicator informing decision making in policies relating to HIV-infected people. Studies estimating life expectancy after starting combination antiretroviral therapy (cART) have noted differences between income regions. The objective of our study was to perform a meta-analysis to assess life expectancy of HIV-positive people after starting cART, and to quantify differences between low/middle- and high-income countries. Methods: Eight cohort studies estimating life expectancy in HIV-positive people initiating cART aged ≥ 14 years using the abridged life table method were identified. Random effects meta-analysis was used to pool estimated outcomes, overall and by income region. Heterogeneity between studies was assessed with the I2 statistic. We estimated additional years of life expected after starting cART at ages 20 and 35 years. Results: Overall life expectancy in high-income countries was an additional 43.3 years [95% confidence interval (CI) 42.5–44.2 years] and 32.2 years (95% CI 30.9–33.5 years) at ages 20 and 35 years, respectively, and 28.3 (95% CI 23.3–33.3) and 25.6 (95% CI 22.1–29.2) additional years, respectively, in low/middle-income countries. In low/middle-income countries, life expectancy after starting cART at age 20 years was an additional 22.9 years (95% CI 18.4–27.5 years) for men and 33.0 years (95% CI 30.4–35.6 years) for women, but was similar in the two sexes in high-income countries. In all income regions, life expectancy after starting cART increased over calendar time. Conclusions: Our results suggest that the life expectancy of HIV-positive people after starting cART has improved over time. Monitoring life expectancy into the future is important to assess how changes to cART guidelines will affect patient long-term outcomes.

In Australia, almost half of HIV-positive people are now aged over 50 and are predominately gay and bisexual men (GBM). Compared to the general HIV-negative population, GBM engage more in behaviours that may increase the risk of age-related comorbidities, including smoking, high alcohol consumption and recreational drug use. The objective of APPLES was to compare comorbidities and risk factors in HIV-positive older GBM with an appropriate control group of HIV-negative GBM. We undertook a prospectively recruited cross-sectional sample of HIV-positive and HIV-negative GBM ≥ 55 years. Detailed data collection included clinic data, a health and lifestyle survey, and blood sample collection. We report key demographic, laboratory markers and self-reported comorbidities by HIV status. For selected comorbidities we also adjust HIV status a priori for age, smoking and body mass index. Over 16 months 228 HIV-positive and 218 HIV-negative men were recruited. Median age was 63 years (IQR: 59–67). Although more HIV-positive men reported having ever smoked, smoking status was not statistically different between HIV positive and HIV negative men (p = 0.081). Greater alcohol use was reported by HIV-negative men (p = 0.002), and recreational drug use reported more often by HIV-positive men (p<0.001). After adjustment, HIV-positive men had significantly increased odds of diabetes (adjusted Odds ratio (aOR): 1.97, p = 0.038), thrombosis (aOR: 3.08, p = 0.007), neuropathy (aOR: 34.6, P<0.001), and non-significantly increased odds for heart-disease (aOR: 1.71, p = 0.077). In conclusion, HIV-positive GBM have significantly increased odds for key self-reported comorbidities. This study underscores the importance of an appropriate HIV-negative control group for more accurate evaluation of the risk and attribution of age-related comorbidities in HIV-positive people.

In Australia, almost half of HIV-positive people are now aged over 50 and are predominately gay and bisexual men (GBM). Compared to the general HIV-negative population, GBM engage more in behaviours that may increase the risk of age-related comorbidities, including smoking, high alcohol consumption and recreational drug use. The objective of APPLES was to compare comorbidities and risk factors in HIV-positive older GBM with an appropriate control group of HIV-negative GBM. We undertook a prospectively recruited cross-sectional sample of HIV-positive and HIV-negative GBM ≥ 55 years. Detailed data collection included clinic data, a health and lifestyle survey, and blood sample collection. We report key demographic, laboratory markers and self-reported comorbidities by HIV status. For selected comorbidities we also adjust HIV status a priori for age, smoking and body mass index. Over 16 months 228 HIV-positive and 218 HIV-negative men were recruited. Median age was 63 years (IQR: 59-67). Although more HIV-positive men reported having ever smoked, smoking status was not statistically different between HIV positive and HIV negative men (p = 0.081). Greater alcohol use was reported by HIV-negative men (p = 0.002), and recreational drug use reported more often by HIV-positive men (p<0.001). After adjustment, HIV-positive men had significantly increased odds of diabetes (adjusted Odds ratio (aOR): 1.97, p = 0.038), thrombosis (aOR: 3.08, p = 0.007), neuropathy (aOR: 34.6, P<0.001), and non-significantly increased odds for heart-disease (aOR: 1.71, p = 0.077). In conclusion, HIV-positive GBM have significantly increased odds for key self-reported comorbidities. This study underscores the importance of an appropriate HIV-negative control group for more accurate evaluation of the risk and attribution of age-related comorbidities in HIV-positive people.

OBJECTIVES: To examine the influence of sexual activity on the composition and consistency of the vaginal microbiota over time, and distribution of Gardnerella vaginalis clades in young women. METHODS: Fifty-two participants from a university cohort were selected. Vaginal swabs were self-collected every 3-months for up to 12 months with 184 specimens analysed. The vaginal microbiota was characterised using Roche 454 V3/4 region 16S rRNA sequencing, and G.vaginalis clade typing by qPCR. RESULTS: A Lactobacillus crispatus dominated vaginal microbiota was associated with Caucasian ethnicity (adjusted relative risk ratio[ARRR] = 7.28, 95%CI:1.37,38.57,p = 0.020). An L.iners (ARRR = 17.51, 95%CI:2.18,140.33,p = 0.007) or G.vaginalis (ARRR = 14.03, 95%CI:1.22,160.69, p = 0.034) dominated microbiota was associated with engaging in penile-vaginal sex. Microbiota dominated by L.crispatus, L.iners or other lactobacilli exhibited greater longitudinal consistency of the bacterial communities present compared to ones dominated by heterogeneous non-lactobacilli (p<0.030); sexual activity did not influence consistency. Women who developed BV were more likely to have clade GV4 compared to those reporting no sex/practiced non-coital activities (OR = 11.82, 95%CI:1.87,74.82,p = 0.009). Specimens were more likely to contain multiple G.vaginalis clades rather than a single clade if women engaged in penile-vaginal sex (RRR = 9.55, 95%CI:1.33,68.38,p = 0.025) or were diagnosed with BV (RRR = 31.5, 95%CI:1.69,586.87,p = 0.021). CONCLUSIONS: Sexual activity and ethnicity influenced the composition of the vaginal microbiota of these young, relatively sexually inexperienced women. Women had consistent vaginal microbiota over time if lactobacilli were the dominant spp. present. Penile-vaginal sex did not alter the consistency of microbial communities but increased G.vaginalis clade diversity in young women with and without BV, suggesting sexual transmission of commensal and potentially pathog

BACKGROUND: Gonorrhoea is one of the most common sexually transmissible infections in men who have sex with men (MSM). Gonorrhoea rates have increased substantially in recent years. There is concern that increasing gonorrhoea prevalence will increase the likelihood of worsening antibiotic resistance in Neisseria gonorrhoeae. A recent randomised controlled trial (RCT) demonstrated that a single-dose of mouthwash has an inhibitory effect against oropharyngeal gonorrhoea. We are conducting the first RCT to evaluate whether daily use of mouthwash could reduce the risk of acquiring oropharyngeal gonorrhoea. METHODS/DESIGN: The OMEGA (Oral Mouthwash use to Eradicate GonorrhoeA) study is a double-blind RCT and will be conducted at several sexual health clinics and high caseload General Practice (GP) clinics in Melbourne and Sydney, Australia. A total of 504 MSM attending the participating sites will be recruited. Participants will be randomised to either using 'Study mouthwash A' or 'Study mouthwash B' for 12 weeks. Study mouthwash A was inhibitory against N. gonorrhoeae in vitro, whereas study mouthwash B was not. Participants will be instructed to rinse and gargle the study mouthwash for 60 seconds every day. The primary outcome is the proportion of participants with oropharyngeal gonorrhoea detected by nucleic acid amplification test by 12 weeks. DISCUSSION: The results from this trial may provide a novel way to reduce gonorrhoea prevalence and transmission without the use of antibiotics that may be associated with development of resistance. If shown to be effective, the widespread use of mouthwash will reduce the prevalence of oropharyngeal gonorrhoea, which plays key role in driving the emergence of gonococcal antimicrobial resistance through DNA exchange with oral commensal bacteria. The anticipated net effect will be interruption of onward transmission of N. gonorrhoeae within high density sexual networks within MSM populations. TRIAL REGISTRATION: Australian New Ze

Background We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region. Methods Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/orHCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test. Results A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV-and HCV-positive. Conclusion In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.

Background & Aims Delayed hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis may increase risk of advanced liver disease complications, including decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC). The aim of this study was to characterise “late hepatitis notification” among people with an HBV/HCV notification and advanced liver disease in New South Wales, Australia. Methods HBV/HCV notifications 1995–2012 were linked to cancer registry and hospital admissions. Late hepatitis notification was defined by a notification after, at the time, or within two years before DC/HCC diagnosis. Results HBV and HCV cohorts comprised 50,958 and 79,727 individuals, respectively. Among people with DC (n = 3869), late HBV notification declined from 64% (88/138) during 2001–2002 to 31% (46/149) in 2011–2012 (p <0.001), and late HCV notification declined from 52% (179/341) during 2001–2002 to 22% (134/605) in 2011–2012 (p <0.001). Among people with HCC (n = 1656), late HBV notification declined from 68% (59/87) during 2001–2002 to 29% (37/128) in 2011–2012 (p <0.001), and late HCV notification declined from 51% (40/79) during 2001–2002 to 17% (49/288) in 2011–2012 (p <0.001). Conclusions Despite significant declines in late hepatitis notification since early 2000s, efforts to enhance hepatitis screening, particularly for HBV, are required. Late hepatitis notification as described in this study could be used as a measure of population-level HBV/HCV screening. Lay summary Delayed hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis may increase the risk of advanced liver disease complications, including decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC). The aim of this study was to characterise “late hepatitis notification” among people with an HBV or HCV notification in New South Wales, Australia. Late hepatitis notifications have significantly declined since early 2000s; however, efforts to enhance hepatitis screening, particularly for HBV

Several outbreaks of hepatitis A in men who have sex with men (MSM) were reported in the 1980s and 1990s in Australia and other countries. An effective hepatitis A virus (HAV) vaccine has been available in Australia since 1994 and is recommended for high-risk groups including MSM. No outbreaks of hepatitis A in Australian MSM have been reported since 1996. In this study, we aimed to estimate HAV transmissibility in MSM populations in order to inform targets for vaccine coverage in such populations. We used mathematical models of HAV transmission in a MSM population to estimate the basic reproduction number (R 0) and the probability of an HAV epidemic occurring as a function of the immune proportion. We estimated a plausible range for R 0 of 1·71-3·67 for HAV in MSM and that sustained epidemics cannot occur once the proportion immune to HAV is greater than ~70%. To our knowledge this is the first estimate of R 0 and the critical population immunity threshold for HAV transmission in MSM. As HAV is no longer endemic in Australia or in most other developed countries, vaccination is the only means of maintaining population immunity >70%. Our findings provide impetus to promote HAV vaccination in high-risk groups such as MSM.

Background: In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use. Methods: We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression. Results: Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018). Conclusions: Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.

© 2016 by the BMJ Publishing Group Ltd.Objective The importation of Neisseria gonorrhoeae (NG) strains from overseas is believed to be the main source of antimicrobial resistance in Australia. With recent sporadic cases of ceftriaxone-resistant gonorrhoea reported in Australia and elsewhere, we sought to model the potential for imported NG strains to persist in the men who have sex with men (MSM) population in Australia. Methods We developed an individual-based model to simulate the transmission of NG in a population of urban MSM, and used this model to investigate factors contributing to the probability that an imported NG strain will persist. Results The probability of the imported NG strain persisting as the result of a single importation event is less than 1%, but the probability increases to 1% if the imported NG strain is resistant to treatment, and further increases to 3.1% if the imported NG strain can also form mixed infections with the local NG strain. The probability of the imported NG strain persisting increases to 4.4% if there are at least three importation events per month within a 1-year period. Conclusion The imported NG strain is unlikely to persist as a result of a single importation event. However, the probability of persistence increases if the imported NG strain is resistant to treatment, can form mixed infections with the local NG strain or there are frequent importation events. Identification of the factors that determine the likelihood of persistence of an imported NG strain could contribute to our capacity to respond appropriately and in a timely fashion.

Objectives: The aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of cardiovascular disease (CVD) and diabetes. Methods: We analysed data from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre-ART) to 1 year after initiation (continuous variable) in treatment-naïve individuals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI [weight (kg)/(height (m))2] was categorized as underweight (<18.5), normal (18.5-25), overweight (25-30) and obese (>30). Poisson regression models were fitted stratified for each pre-ART BMI category to allow for category-specific estimates of incidence rate ratio (IRR). Models were adjusted for pre-ART BMI and CD4 count, key known risk factors (time-updated where possible) and calendar year. Results: A total of 97 CVD events occurred in 43982 person-years (n=9321) and 125 diabetes events in 43278 person-years (n=9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre-ART BMI category, was: underweight, 0.90 (0.60-1.37); normal, 1.18 (1.05-1.33); overweight, 0.87 (0.70-1.10), and obese, 0.95 (0.71-1.28) (P for interaction=0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre-ART BMI (P for interaction>0.05). Conclusions: Short-term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre-ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre-ART BMI. HIV Medicine

Objectives To examine the validity of deterministic compared to probabilistic record linkage in the ascertainment of hospitalizations in two linked cohorts. Study Design and Setting HIV-negative (HIV-ve) (n = 1,325) and HIV-positive (HIV+ve) gay and bisexual men (n = 557) recruited in Sydney, Australia, were probabilistically and deterministically linked to a statewide hospital registry (July 2000–June 2012). Results Using probabilistic linkage as the reference standard, deterministic linkage had higher specificity but much lower sensitivity [34.67% (95% confidence interval: 33.44, 35.92)]. A disproportionate number of links missed were individuals with poorer socioeconomic and health indicators, including HIV status. Risk of hospitalization compared to the general male population [HIV+ve standardized incidence ratio (SIR) = 1.45 (1.33–1.59); HIV-ve SIR = 0.72 (0.67–0.78)] was significantly underestimated when deterministic linkage was used [HIV+ve SIR = 0.46 (0.37–0.58); HIV-ve SIR = 0.29 (0.24–0.35)]. The impact of linkage strategy on the calculation of incidence rate ratios (IRRs) was less, but a greater discrepancy in IRRs was seen for diagnostic categories where event rates were low or where the sensitivity of the deterministic linkage was differential between the two cohorts. Conclusion Linkage without proven high sensitivity and specificity should be carefully considered. In circumstances of undetermined sensitivity, SIRs should not be calculated as the extent of underestimation is unknown. The comparison of linked events within or between cohorts is more robust to linkage misclassification; however, selection bias does affect estimates and should be considered before linkage.

© 2016, Springer Science+Business Media New York. We aimed to compare rates of illicit drug-related hospitalisations in HIV-negative (HIV−ve) (n = 1325) and HIV-positive (HIV+ve) (n = 557) gay and bisexual men (GBM) with rates seen in the general male population and to examine the association between self-reported illicit drug use and drug-related hospitalisation. Participants were asked how often they used a range of illicit drugs in the previous 6 months at annual interviews. Drug-related hospital admissions were defined as hospital admissions for mental or behavioural disorders due to illicit drug use (ICD 10: F11–16, F18, F19), drug poisoning (T40–T45, T50) or toxic effect of gases (T53, T59, T65). Drug-related hospitalisations were 4.8 times higher in the HIV−ve cohort [SIR 4.75 (95 % CI 3.30–6.91)] and 3.5 times higher in the HIV+ve cohort [SIR 3.51 (1.92–5.88)] compared with the general population. Periods of weekly drug use [IRR 1.86 (1.01–3.46)], poly-drug use [IRR 2.17 (1.07–4.38)] and cannabis use [low use-IRR 1.95 (1.01–3.77), high use-IRR 2.58 (1.29–5.16)] were associated with drug-related hospitalisation in both cohorts, as was being a consistently high meth/amphetamine user throughout follow-up [IRR 3.24 (1.07–9.83)] and being an inconsistent or consistent injecting drug user throughout follow-up [IRR 3.94 (1.61–9.66), IRR 4.43(1.04–18.76), respectively]. Other risk factors for drug-related hospitalisation indicated the likelihood of comorbid drug and mental health issues in GBM hospitalised for drug use.

Objectives: There is evidence that HIV-positive patients are suffering from a greater burden of morbidity as they age due to nonAIDS-related complications. To date it has been difficult to determine what part of this excess risk is due to the health effects of HIV, its treatment or to lifestyle factors common to gay and bisexual men (GBM). We calculated overall and cause-specific hospitalisation rates and risk factors for hospitalisations in HIV-negative and HIV-positive cohorts of GBM and compare these with rates in the general male population. Methods: We conducted a record linkage study, linking two cohorts of HIV-negative (n = 1325) and HIV-positive (n = 557) GBM recruited in Sydney, New South Wales (NSW), Australia with the NSW hospital discharge data register. We compared rates of hospitalisation in the two cohorts and risk factors for hospitalisation using random-effects Poisson regression methods. Hospitalisation rates for each cohort were further compared with those in the general male population using indirect standardisation. Results: We observed 2032 hospitalisations in the HIV-negative cohort during 13 016 person-years (PYs) [crude rate: 15.6/100PYs (95% CI: 14.9-16.3)] and 2130 hospitalisations in the HIV-positive cohort during 5571 PYs [crude rate: 38.2/100PYs (95% CI: 36.6-39.9)]. HIV-positive individuals had an increased risk of hospitalisation compared with the HIV-negative individuals [adjusted-IRR: 2.34 (95% CI: 1.91-2.86)] and the general population [SHR: 1.45 (95% CI: 1.33-1.59)]. Hospitalisation rates were lower in the HIV-negative cohort compared with the general population [SHR: 0.72 (95% CI: 0.67-0.78)]. The primary causes of hospitalisation differed between groups. Conclusions: HIV-positive GBM continue to experience excess morbidity compared with HIV-negative GBM men and the general population. HIV-negative GBM had lower morbidity compared with the general male population suggesting that GBM identity does not confer excess risk.

Introduction: Outbreaks of syphilis have been described among HIV-infected men who have sex with men (MSM) in Western communities, whereas reports in Asian countries are limited. We aimed to characterize the incidence and temporal trends of syphilis among HIV-infected MSM compared with HIV-infected non-MSM in Asian countries. Methods: Patients enrolled in the TREAT Asia HIV Observational Database cohort and with a negative non-treponemal test since enrolment were analyzed. Incidence of syphilis seroconversion, defined as a positive non-treponemal test after previously testing negative, was evaluated among patients at sites performing non-treponemal tests at least annually. Factors associated with syphilis seroconversion were investigated at sites doing non-treponemal testing in all new patients and subsequently testing routinely or when patients were suspected of having syphilis. Results: We included 1010 patients from five sites that performed non-treponemal tests in all new patients; those included had negative non-treponemal test results during enrolment and subsequent follow-ups. Among them, 657 patients were from three sites conducting regular non-treponemal testing. The incidence of syphilis seroconversion was 5.38/100 person-years (PY). Incidence was higher in MSM than non-MSM (7.64/100 PY vs. 2.44/100 PY, p<0.001). Among MSM, the incidence rate ratio (IRR) for every additional year from 2009 was 1.19 (p=0.051). MSM status (IRR 3.48, 95% confidence interval (CI) 1.88-6.47), past syphilis diagnosis (IRR 5.15, 95% CI 3.69-7.17) and younger age (IRR 0.84 for every additional 10 years, 95% CI 0.706-0.997) were significantly associated with syphilis seroconversion. Conclusions: We observed a higher incidence of syphilis seroconversion among HIV-infected MSM and a trend to increasing annual incidence. Regular screening for syphilis and targeted interventions to limit transmission are needed in this population.

Background: Prevalence of anxiety and mood disorders (AMDs) in HIV-infected individuals has varied widely because of the variety of measurements used and differences in risk factor profiles between different populations. We aimed to examine the relationship between HIV status and hospitalization for AMDs in gay and bisexual men (GBM). Design and Methods: HIV-infected (n 557) and HIV-uninfected (n 1325) GBM recruited in Sydney, Australia were probabilistically linked to their hospital admissions and death notifications (2000-2012). Random-effects Poisson models were used to assess HIV risk factors for hospitalization. Cox regression methods were used to assess risk factors for mortality. Results: We observed 300 hospitalizations for AMDs in 15.3% of HIV-infected and 181 in 5.4% of HIV-uninfected participants. Being infected with HIV was associated with a 2.5-fold increase in risk of hospitalization for AMDs in GBM. Other risk factors in the HIV-infected cohort included previous hospitalization for HIV-related dementia, a more recent HIV diagnosis, and a CD4 T-cell count above 350 cells per cubic millimeter. Being hospitalized for an AMD was associated with a 5.5-fold increased risk of mortality; this association did not differ by HIV status. An association between substance use and mortality was observed in individuals hospitalized for AMDs. Conclusions: There is a need to provide more effective strategies to identify and treat AMDs in HIV-infected GBM. This research highlights the importance of further examination of the effects of substance use, neurocognitive decline, and AMDs on the health of HIV-infected individuals.

OBJECTIVES: We established a subcohort of HIV-positive individuals from 10 sexual health clinics within the Australian HIV Observational Database (AHOD). The aim of this study was to assess demographic and other factors that might be associated with an incident sexually transmitted infection (STI). METHODS: The cohort follow-up was from March 2010 to March 2013, and included patients screened at least once for an STI. We used survival methods to determine time to first new and confirmed incident STI infection (chlamydia, gonorrhoea, syphilis or genital warts). Factors evaluated included sex, age, mode of HIV exposure, year of AHOD enrolment, hepatitis B or C coinfection, time-updated CD4 cell count, time-updated HIV RNA viral load, and prior STI diagnosis. RESULTS: There were 110 first incident STI diagnoses observed over 1015 person-years of follow-up, a crude rate of 10.8 [95% confidence interval (CI) 9.0-13.0] per 100 person-years. Factors independently associated with increased risk of incident STI included younger age [≥ 50 vs. 30-39 years old, adjusted hazards ratio (aHR) 0.4; 95% CI 0.2-0.8; P < 0.0001]; prior STI infection (aHR 2.5; 95% CI 1.6-3.8; P < 0.001), and heterosexual vs. men who have sex with men (MSM) as the likely route of exposure (aHR 0.2; 95% CI 0.1-0.6; P < 0.001). CONCLUSIONS: In this cohort of individualsbeing treated with antiretroviral drugs, those who were MSM, who were 30-39 years old, and who had a prior history of STI, were at highest risk of a further STI diagnosis.