Long-term HIV care outcomes under universal HIV treatment guidelines: A retrospective cohort study in 25 countries.

BACKGROUND: While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. METHODS AND FINDINGS: For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged ≥15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change-associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with ≥12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p < .001) compared with enrollment before guideline adoption, with no before-after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. CONCLUSIONS: In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality.

Weight changes, metabolic syndrome and all-cause mortality among Asian adults living with HIV.

OBJECTIVES: We investigated weight changes following antiretroviral therapy (ART) initiation, the development of metabolic syndrome (MetS) and its association with all-cause mortality among Asian adults living with HIV. METHODS: Participants enrolled in a regional Asian HIV-infected cohort with weight and height measurements at ART initiation were eligible for inclusion in the analysis. Factors associated with weight changes and incident MetS (according to the International Diabetic Federation (IDF) definition) were analysed using linear mixed models and Cox regression, respectively. Competing-risk regression models were used to investigate the association of MetS with all-cause mortality. RESULTS: Among 4931 people living with HIV (PLWH), 66% were male. At ART initiation, the median age was 34 [interquartile range (IQR) 29-41] years, and the median (IQR) weight and body mass index (BMI) were 55 (48-63) kg and 20.5 (18.4-22.9) kg/m2 , respectively. At 1, 2 and 3 years of ART, overall mean (± standard deviation) weight gain was 2.2 (±5.3), 3.0 (±6.2) and 3.7 (±6.5) kg, respectively. Participants with baseline CD4 count ≤ 200 cells/µL [weight difference (diff) = 2.2 kg; 95% confidence interval (CI) 1.9-2.5 kg] and baseline HIV RNA ≥ 100 000 HIV-1 RNA copies/mL (diff = 0.6 kg; 95% CI 0.2-1.0 kg), and those starting with integrase strand transfer inhibitor (INSTI)-based ART (diff = 2.1 kg; 95% CI 0.7-3.5 kg vs. nonnucleoside reverse transcriptase inhibitors) had greater weight gain. After exclusion of those with abnormal baseline levels of MetS components, 295/3503 had incident MetS [1.18 (95% CI 1.05-1.32)/100 person-years (PY)]. The mortality rate was 0.7 (95% CI 0.6-0.8)/100 PY. MetS was not significantly associated with all-cause mortality in the adjusted model (P = 0.236). CONCLUSIONS: Weight gain after ART initiation was significantly higher among those initiating ART with lower CD4 count, higher HIV RNA and an INSTI-based regimen after controlling for baseline BMI. Greater efforts to identify and manage MetS among PLWH are needed.

Assessing the Impact of HIV Preexposure Prophylaxis Scale-Up on Gonorrhea Incidence Among Gay and Bisexual Men in Sydney: A Mathematical Modeling Study.

BACKGROUND: The rollout of preexposure prophylaxis (PrEP) for HIV prevention among gay and bisexual men (GBM) is associated with increases in condomless anal intercourse, potentially increasing the incidence of other sexually transmissible infections (STIs). METHODS: We developed an individual-based mathematical model to simulate the transmission of Neisseria gonorrhoeae among GBM in Sydney, accounting for changes in sexual practices, STI testing, and PrEP use. We calibrated and validated the model using reported incidence rates for HIV-positive and HIV-negative GBM from 2010 to 2019. Scenarios were run with varying PrEP uptake, PrEP-related STI testing, and PrEP-related sexual behavior and testing intervals up to 2030 to assess the impact of PrEP use on gonorrhea incidence. RESULTS: Preexposure prophylaxis uptake and associated 3-monthly STI testing from 2015 onward resulted in a predicted increase from 20 to 37 N. gonorrhoeae infections per 100 person-years among HIV-negative GBM by the end of 2020. This is lower than the counterfactual predictions of 45 per 100 person-years if PrEP were not scaled up and 48 per 100 person-years with nonadherence to 3-monthly STI testing. Increasing the time between STI tests for PrEP users by 1 month from 2018 results in the incidence rate among HIV-negative GBM increasing by 8% by 2030. If PrEP coverage doubles from 24% to 53%, incidence among HIV-negative GBM declines by ~25% by 2030. CONCLUSIONS: Behavior change due to widespread PrEP use may lead to significant increases in gonorrhea incidence in GBM, but the recommended quarterly STI testing recommended for PrEP users should reduce incidence by 18% by 2030.

Modelling response strategies for controlling gonorrhoea outbreaks in men who have sex with men in Australia.

The ability to treat gonorrhoea with current first-line drugs is threatened by the global spread of extensively drug resistant (XDR) Neisseria gonorrhoeae (NG) strains. In Australia, urban transmission is high among men who have sex with men (MSM) and importation of an XDR NG strain in this population could result in an epidemic that would be difficult and costly to control. An individual-based, anatomical site-specific mathematical model of NG transmission among Australian MSM was developed and used to evaluate the potential for elimination of an imported NG strain under a range of case-based and population-based test-and-treat strategies. When initiated upon detection of the imported strain, these strategies enhance the probability of elimination and reduce the outbreak size compared with current practice (current testing levels and no contact tracing). The most effective strategies combine testing targeted at regular and casual partners with increased rates of population testing. However, even with the most effective strategies, outbreaks can persist for up to 2 years post-detection. Our simulations suggest that local elimination of imported NG strains can be achieved with high probability using combined case-based and population-based test-and-treat strategies. These strategies may be an effective means of preserving current treatments in the event of wider XDR NG emergence.

Physical function limitation among gay and bisexual men aged ≥55years with and without HIV: findings from the Australian Positive and Peers Longevity Evaluation Study (APPLES).

BACKGROUND: As people living with HIV now have a life expectancy approaching that of the general population, clinical care focuses increasingly on the management and prevention of comorbidities and conditions associated with aging. We aimed to assess the prevalence of physical function (PF) limitation among gay and bisexual men (GBM) and determine whether HIV is associated with severe PF limitation in this population. METHODS: We analysed cross-sectional data from GBM aged ≥55years in the Australian Positive and Peers Longevity Evaluation Study who completed a self-administered survey on health and lifestyle factors. PF was measured using the Medical Outcomes Study-Physical Functioning scale. Factors associated with severe PF limitation were assessed using logistic regression. RESULTS: The survey was completed by 381 men: 186 without HIV and 195 with HIV. Median age was 64.3years for GBM without HIV and 62.1years for GBM with HIV. Compared with men without HIV, those with HIV had higher proportions of severe (13.3% vs 8.1%) and moderate-to-severe (26.7% vs 24.2%) PF limitation. Severe PF limitation commonly involved difficulty with vigorous activity (95% with severe PF limitation described being limited a lot), climbing several flights of stairs (68.4% limited a lot), bending, kneeling or stooping (60.5% limited a lot), and walking 1km (55.0% limited a lot). In a model adjusted for age, body mass index, typical duration of physical activity, psychological distress, and number of comorbidities, we found a significant association between HIV and severe PF limitation (adjusted odds ratio 3.3 vs not having HIV, 95% confidence interval 1.3-8.7). CONCLUSIONS: The biological mechanisms underlying this association require further investigation, particularly given the growing age of the HIV population and inevitable increase in the burden of PF limitation.

Can Australia Reach the World Health Organization Hepatitis C Elimination Goal by 2025 Among Human Immunodeficiency Virus-positive Gay and Bisexual Men?

BACKGROUND: Human immunodeficiency virus (HIV)-positive gay and bisexual men (GBM) in Australia are well engaged in care. The World Health Organization's (WHO) hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030 may be reachable ahead of time in this population. METHODS: We predicted the effect of treatment and behavioral changes on HCV incidence among HIV-positive GBM up to 2025 using a HCV transmission model parameterized with Australian data. We assessed the impact of changes in behavior that facilitate HCV transmission in the context of different rates of direct-acting antiviral (DAA) use. RESULTS: HCV incidence in our model increased from 0.7 per 100 person-years in 2000 to 2.5 per 100 person-years in 2016 and had the same trajectory as previously reported clinical data. If the proportion of eligible (HCV RNA positive) patients using DAAs stays at 65% per year between 2016 and 2025, with high-risk sexual behavior and injecting drug use remaining at current levels, HCV incidence would drop to 0.4 per 100 person-years (85% decline from 2016). In the same treatment scenario but with substantial increases in risk behavior, HCV incidence would drop to 0.6 per 100 person-years (76% decline). If the proportion of eligible patients using DAAs dropped from 65% per year in 2016 to 20% per year in 2025 and risk behavior did not change, HCV incidence would drop to 0.7 per 100 person-years (70% reduction). CONCLUSIONS: Reaching the WHO HCV elimination target by 2025 among HIV-positive GBM in Australia is achievable.

Supplemental Trichomonas vaginalis testing is required to maintain control following a transition from Pap smear to HPV DNA testing for cervical screening: a mathematical modelling study.

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.

Cardiovascular disease among people living with HIV in Brazil.

OBJECTIVES: There is a paucity of data on cardiovascular disease (CVD) among people living with HIV (PLHIV) in resource-limited countries. We assessed factors associated with CVD and the impact of prevalent CVD on all-cause mortality in PLHIV on antiretroviral therapy in Brazil. METHODS: Competing risk regression to assess factors associated with CVD and all-cause mortality in the HIV-Brazil Cohort Study between 2003 and 2014. RESULTS: Among 5614 patients, the rate of CVD was 3.5 (95% confidence interval [95% CI] 2.9-4.3) per 1000 person-years. CVD was associated with older age (adjusted hazard ratio [aHR] 6.4 for ≥55 years vs. <35 years, 95% CI: 2.5-16.3, P < 0.01), black race (aHR 1.8 vs. white race, 95% CI: 1.0-3.1, P = 0.04), past CVD (aHR 3.0 vs. no past CVD, 95% CI: 1.4-6.2, P < 0.01), hypertension (aHR 1.8 vs. no hypertension, 95% CI: 1.0-3.1, P = 0.04), high-grade dyslipidemia (aHR 9.3 vs. no high-grade dyslipidemia, 95% CI: 6.0-14.6, P < 0.01), ever smoking (aHR 2.4 vs. never, 95% CI: 1.2-5.0, P = 0.02) and low nadir CD4 cell count (aHR 1.8 for 100-250 cells/mm3 vs. >250 cells/mm3 , 95% CI: 1.0-3.2, P = 0.05). The rate of death was 16.6 (95% CI: 15.1-18.3) per 1000 person-years. Death was strongly associated with having had a past CVD event (aHR 1.7 vs. no past CVD event, 95% CI: 1.1-2.7, P = 0.01). CONCLUSIONS: Traditional and HIV-specific factors associated with CVD among PLHIV in Brazil are similar to those identified among PLHIV in high-income countries. PLHIV in Brazil with a history of CVD have a high risk of death. CVD care and treatment remain priorities for PLHIV in Brazil as this population ages and antiretroviral therapy use expands.

OBJECTIFS: Il existe peu de données sur les maladies cardiovasculaires (MCV) chez les personnes vivant avec le VIH (PVVIH) dans les pays à ressources limitées. Nous avons évalué les facteurs associés aux MCV et l'impact des MCV prévalentes sur la mortalité toutes causes confondues des PVVIH sous le traitement antirétroviral au Brésil. MÉTHODES: Régression des risques concurrente pour évaluer les facteurs associés aux MCV et à la mortalité toutes causes confondues dans l'étude de cohorte VIH-Brésil entre 2003 et 2014. RÉSULTATS: Parmi 5.614 patients, le taux de MCV était de 3,5 (intervalle de confiance à 95% [IC95%] 2,9-4,3) pour 1.000 personnes-années. Les MCV étaient associées à un âge plus avancé (rapport de risque ajusté [aHR] 6,4 chez les ≥55 ans versus chez les <35 ans, IC95%: 2,5-16,3 ; p <0,01), race noire (aHR: 1,8 versus race blanche, IC95%: 1,0-3,1 ; p = 0,04), MCV passée (aHR: 3,0 versus pas de MCV passée, IC95%: 1,4-6,2 ; p <0,01), hypertension (aHR: 1,8 versus pas d'hypertension, IC95%: 1,0-3,1 ; p = 0,04), dyslipidémie de grade élevé (aHR 9,3 versus absence de dyslipidémie de grade élevé, IC95%: 6,0-14,6 ; p <0,01), tabagisme (aHR 2,4 versus n'avoir jamais fumé, IC95%: 1,2-5,0 ; p = 0,02) et faible nombre de CD4 au nadir (aHR: 1,8 pour 100-250 cellules/mm3 versus >250 cellules/mm3 , IC95%: 1,0-3,2 ; p = 0,05). Le taux de décès était de 16,6 (IC95%: 15,1-18,3) pour 1.000 personnes-années. Le décès était fortement associé à un événement MCV antérieur (aHR: 1,7 versus aucun événement MCV antérieur, IC95%: 1,1-2,7 ; p = 0,01). CONCLUSIONS: Les facteurs traditionnels et spécifiques au VIH associés aux MCV chez les PVVIH au Brésil sont similaires à ceux identifiés chez les PVVIH dans les pays à revenu élevé. Les PVVIH au Brésil ayant des antécédents de MCV ont un risque élevé de décès. Les soins et le traitement des MCV restent des priorités pour les PVVIH au Brésil à mesure que cette population vieillit et que l'utilisation des thérapies antirétrovirales augmente.

Treating male partners of women with bacterial vaginosis (StepUp): a protocol for a randomised controlled trial to assess the clinical effectiveness of male partner treatment for reducing the risk of BV recurrence.

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 treatments directed solely to women result in unacceptably high rates of BV recurrence. If proven to be effective the findings from this trial will directly inform the development of new treatment strategies to impact on BV recurrence. TRIAL REGISTRATION: The trial was prospectively registered on 12 February 2019 on the Australian and New Zealand Clinical Trial Registry (ACTRN12619000196145, Universal Trial Number: U1111-1228-0106, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376883&isReview=true ).

Declining hepatitis C virus-related liver disease burden in the direct-acting antiviral therapy era in New South Wales, Australia.

BACKGROUND & AIMS: Population-level evidence for the impact of direct-acting antiviral (DAA) therapy on hepatitis C virus (HCV)-related disease burden is lacking. We aimed to evaluate trends in HCV-related decompensated cirrhosis and hepatocellular carcinoma (HCC) hospitalisation, and liver-related and all-cause mortality in the pre-DAA (2001-2014) and DAA therapy (2015-2017) eras in New South Wales, Australia. METHODS: HCV notifications (1993-2016) were linked to hospital admissions (2001-2017) and mortality (1995-2017). Segmented Poisson regressions and Poisson regression were used to assess the impact of DAA era and factors associated with liver-related mortality, respectively. RESULTS: Among 99,910 people with an HCV notification, 3.8% had a decompensated cirrhosis diagnosis and 1.8% had an HCC diagnosis, while 3.3% and 10.5% died of liver-related and all-cause mortality, respectively. In the pre-DAA era, the number of decompensated cirrhosis and HCC diagnoses, and liver-related and all-cause mortality consistently increased (incidence rate ratios 1.04 [95% CI 1.04-1.05], 1.08 [95% CI 1.07-1.08], 1.07 [95% CI 1.06-1.07], and 1.05 [95% CI 1.04-1.05], respectively) over each 6-monthly band. In the DAA era, decompensated cirrhosis diagnosis and liver-related mortality numbers declined (incidence rate ratios 0.97 [95% CI 0.95-0.99] and 0.96 [95% CI 0.94-0.98], respectively), and HCC diagnosis and all-cause mortality numbers plateaued (incidence rate ratio 1.00 [95% CI 0.97-1.03] and 1.01 [95% CI 1.00-1.02], respectively) over each 6-monthly band. In the DAA era, alcohol-use disorder (AUD) was common in patients diagnosed with decompensated cirrhosis and HCC (65% and 46% had a history of AUD, respectively). AUD was independently associated with liver-related mortality (incidence rate ratio 3.35; 95% CI 3.14-3.58). CONCLUSIONS: In the DAA era, there has been a sharp decline in liver disease morbidity and mortality in New South Wales, Australia. AUD remains a major contributor to HCV-related liver disease burden, highlighting the need to address comorbidities. LAY SUMMARY: Rising hepatitis C-related morbidity and mortality is a major public health issue. However, development of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) means hepatitis C could be eliminated as a public health threat by 2030. This study shows a sharp decline in liver disease morbidity and mortality since the introduction of DAAs in New South Wales, Australia. Despite this, heavy alcohol use remains an important risk factor for liver disease among people with hepatitis C. To ensure that the benefits of new antiviral treatments are not compromised, management of major comorbidities, including heavy alcohol use must improve among people with hepatitis C.

The contribution of alcohol use disorder to decompensated cirrhosis among people with hepatitis C: An international study.

BACKGROUND & AIMS: The advent of direct-acting antivirals (DAAs) has led to ambitious targets for hepatitis C virus (HCV) elimination. However, in the context of alcohol use disorder the ability of DAAs to achieve these targets may be compromised. The aim of this study was to evaluate the contribution of alcohol use disorder to HCV-related decompensated cirrhosis in three settings. METHODS: HCV notifications from British Columbia, Canada; New South Wales, Australia, and Scotland (1995-2011/2012/2013, respectively) were linked to hospital admissions (2001-2012/2013/2014, respectively). Alcohol use disorder was defined as non-liver-related hospitalisation due to alcohol use. Age-standardised decompensated cirrhosis incidence rates were plotted, associated factors were assessed using Cox regression, and alcohol use disorder-associated population attributable fractions (PAFs) were computed. RESULTS: Among 58,487, 84,529, and 31,924 people with HCV in British Columbia, New South Wales, and Scotland, 2,689 (4.6%), 3,169 (3.7%), and 1,375 (4.3%) had a decompensated cirrhosis diagnosis, and 28%, 32%, and 50% of those with decompensated cirrhosis had an alcohol use disorder, respectively. Age-standardised decompensated cirrhosis incidence rates were considerably higher in people with alcohol use disorder in New South Wales and Scotland. Decompensated cirrhosis was independently associated with alcohol use disorder in British Columbia (aHR 1.92; 95% CI 1.76-2.10), New South Wales (aHR 3.68; 95% CI 3.38-4.00) and Scotland (aHR 3.88; 95% CI 3.42-4.40). The PAFs of decompensated cirrhosis-related to alcohol use disorder were 13%, 25%, and 40% in British Columbia, New South Wales and Scotland, respectively. CONCLUSIONS: Alcohol use disorder was a major contributor to HCV liver disease burden in all settings, more distinctly in Scotland. The extent to which alcohol use would compromise the individual and population-level benefits of DAA therapy needs to be closely monitored. Countries, where appropriate, must develop strategies combining promotion of DAA treatment uptake with management of alcohol use disorders, if World Health Organization 2030 HCV mortality reduction targets are going to be achieved. LAY SUMMARY: The burden of liver disease has been rising among people with hepatitis C globally. The recent introduction of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) has brought renewed optimism to the sector. DAA scale-up could eliminate hepatitis C as a public health threat in the coming decades. However, our findings show heavy alcohol use is a major risk factor for liver disease among people with hepatitis C. If continued, heavy alcohol use could compromise the benefits of new antiviral treatments at the individual- and population-level. To tackle hepatitis C as a public health threat, where needed, DAA therapy should be combined with management of heavy alcohol use.

Impact of replacing cytology with human papillomavirus testing for cervical cancer screening on the prevalence of Trichomonas vaginalis: a modelling study.

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. METHODS: A mathematical model was developed to describe the transmission of TV in the general population and used to evaluate scenarios that capture the switch from cytology-based screening to HR HPV testing. Under these scenarios, individuals with asymptomatic TV who test negative for HR HPV will remain undiagnosed and untreated. We estimate the change in TV prevalence expected to occur due to the switch from cytology to HR HPV testing and changes to the frequency and age at commencement of screening. RESULTS: Our results suggest that with the transition to HR HPV testing, TV prevalence may increase from the current ~0.4% to 2.8% within 20 years if TV testing coverage is not increased and HR HPV prevalence does not decline further. If HR HPV prevalence continues to decline at its current rate with ongoing vaccination, TV prevalence is predicted to increase to 3.0% within this time frame. CONCLUSIONS: Our modelling suggests that in a setting like Australia, where TV can be detected incidentally through cytology-based cervical screening, a transition to HPV testing is likely to result in increasing TV prevalence over time unless additional measures are implemented to increase TV testing and treatment.

Mortality trends among people with hepatitis B and C: a population-based linkage study, 1993-2012.

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.

Attrition and Mortality of Children Receiving Antiretroviral Treatment through the Universal Coverage Health Program in Thailand.

OBJECTIVE: To assess mortality and loss to follow-up of children with HIV infection who started antiretroviral therapy (ART) through the Universal Coverage Health Program (UC) in Thailand. STUDY DESIGN: Children with HIV infection who initiated ART at age <15 years through the UC between 2008 and 2013 were included in the analysis. Death was ascertained through linkage with the National Death Registry. A competing-risks method was used to calculate subdistribution hazard ratios (SHRs) of predictors for loss to follow-up. Death was considered a competing risk. Cox proportional hazards models were used to assess predictors of mortality. RESULTS: A total of 4618 children from 497 hospitals in Thailand were included in the study. Median age at ART initiation was 9 years (IQR, 6-12 years), and the median duration of tracking was 4.1 years (a total of 18 817 person-years). Three hundred and ninety-five children (9%) died, for a mortality rate of 2.1 (95% CI, 1.9-2.3) per 100 person-years, and 525 children (11%) were lost to follow-up, for a lost to follow-up rate of 2.9 (95% CI, 2.7-3.2) per 100 person-years. The cumulative incidence of loss to follow-up increased from 4% at 1 year to 8.8% at 3 years. Children who started ART at age ≥12 years were at the greatest risk of loss to follow-up. The probability of death was 3.2% at 6 months and 6.4% at 3 years. Age ≥12 years at ART initiation, lower baseline CD4%, advanced HIV staging, and loss to follow-up were associated with mortality. CONCLUSION: The Thai national HIV treatment program has been very effective in treating children with HIV infection, with low mortality and modest rates of loss to follow-up.

Identifying factors that lead to the persistence of imported gonorrhoeae strains: a modelling study.

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.

Growing challenges for HIV programmes in Asia: clinic population trends, 2003-2013.

The scale-up of antiretroviral therapy (ART) has led to a substantial change in the clinical population of HIV-positive patients receiving care. We describe the temporal trends in the demographic and clinical characteristics of HIV-positive patients initiating ART in 2003-13 within an Asian regional cohort. All HIV-positive adult patients that initiated ART between 2003 and 2013 were included. We summarized ART regimen use, age, CD4 cell count, HIV viral load, and HIV-related laboratory monitoring rates during follow-up by calendar year. A total of 16 962 patients were included in the analysis. Patients in active follow-up increased from 695 patients at four sites in 2003 to 11,137 patients at eight sites in 2013. The proportion of patients receiving their second or third ART regimen increased over time (5% in 2003 to 29% in 2013) along with patients aged ≥50 years (8% in 2003 to 18% in 2013). Concurrently, CD4 monitoring has remained stable in recent years, whereas HIV viral load monitoring, although varied among the sites, is increasing. There have been substantial changes in the clinical and demographic characteristics of HIV-positive patients receiving ART in Asia. HIV programmes will need to anticipate the clinical care needs for their aging populations, expanded viral load monitoring, and, the eventual increase in second and third ART regimens that will lead to higher costs and more complex drug procurement needs.

Hepatitis C testing and re-testing among people attending sexual health services in Australia, and hepatitis C incidence among people with human immunodeficiency virus: analysis of national sentinel surveillance data.

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-positive individuals in Australia will assist strategies to achieve HCV elimination through rapid treatment scale up. Continued monitoring of HCV incidence in this population is essential for guiding both HCV prevention and treatment strategies.

A multicentre double-blind randomised controlled trial evaluating the efficacy of daily use of antibacterial mouthwash against oropharyngeal gonorrhoea among men who have sex with men: the OMEGA (Oral Mouthwash use to Eradicate GonorrhoeA) study protocol.

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 Zealand Clinical Trials Registry ACTRN12616000247471 , registered on 23rd February 2016.

Time to decompensated cirrhosis and hepatocellular carcinoma after an HBV or HCV notification: A population-based study.

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, are required. Late hepatitis notification as described in this study could be used as a measure of population-level HBV/HCV screening.

Patterns of Drug Use and Drug-related Hospital Admissions in HIV-Positive and -Negative Gay and Bisexual Men.

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.