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Background Approximately 10% of people with HIV in Australia had active hepatitis C virus (HCV) infection prior to availability of government-subsidized direct-acting antiviral (DAA) therapy in 2016. This analysis evaluated progress toward HCV elimination among people with HIV in Australia between 2014 and 2023. Methods The CEASE cohort study enrolled adults with HIV with past or current HCV infection (anti-HCV antibody positive) from 14 primary and tertiary clinics. Biobehavioral, clinical, and virologic data were collected at enrollment (2014–2016), follow-up 1 (2017–2018), and follow-up 2 (2021–2023). HCV treatment uptake, outcome, and HCV RNA prevalence (current infection) were evaluated. Death and HCV reinfection incidence and risk were assessed. Results Of 402 participants, 341 (85%) had current HCV infection (RNA positive) at enrollment. Among the sample, 83% were gay and bisexual men, 13% had cirrhosis, and 80% had a history of injecting drug use (42%, past 6 months). DAA treatment was scaled up rapidly, with cumulative treatment uptake increasing from 12% in 2014 to 2015 to 92% in 2022 to 2023. HCV RNA prevalence declined from 85% (95% CI, 81%–88%) at enrollment (2014–2016) to 8% (95% CI, 6%–12%) at follow-up 1 (2017–2018) and 0.5% (95% CI, 0%–3%) at follow-up 2 (2020–2023). Sixteen reinfections occurred (incidence, 1.41 per 100 person-years; 95% CI,.81–2.29) as well as 30 deaths (incidence, 1.64 per 100 person-years; 95% CI, 1.11–2.34). HCV reinfection incidence declined over time while mortality remained stable. Conclusions Universal access and rapid DAA uptake were associated with a dramatic reduction in HCV prevalence and reinfection incidence among people with HIV to levels consistent with microelimination. Registration: NCT02102451 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Hepatitis C is a global public health threat, affecting 56 million people worldwide. The World Health Organization has committed to eliminating hepatitis C by 2030. Although new treatments have revolutionised the treatment and care of people with hepatitis C, treatment uptake has slowed in recent years, drawing attention to the need for innovative approaches to reach elimination targets. One approach involves using existing notifiable disease data to contact people previously diagnosed with hepatitis C. Within these disease surveillance systems, however, competing tensions exist, including protecting individual rights to privacy and autonomy, and broader public health goals. We explore these issues using hepatitis C and Australia's legislative and regulatory frameworks as a case study. We examine emerging uses of notification data to contact people not yet treated, and describe some of the ethical dilemmas associated with the use and non-use of this data and the protections that exist to preserve individual rights and public health. We reveal weaknesses in rights protections and processes under Australian public health and human rights legislation and argue for consultation with and involvement of affected communities in policy and intervention design before notification data is used to increase hepatitis C treatment coverage. [ABSTRACT FROM AUTHOR]

Background In Australia, the incidence of hepatitis C virus (HCV) has declined among gay and bisexual men (GBM) with human immunodeficiency virus (HIV) since 2015 and is low among GBM using HIV preexposure prophylaxis (PrEP). However, ongoing HCV testing and treatment remains necessary to sustain this. To assess the potential utility of sexually transmissible infections (STIs) to inform HCV testing among GBM with HIV and GBM using PrEP, we examined the association between bacterial STI diagnoses and subsequent primary HCV infection. Methods Data were from a national network of 46 clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance. GBM included had ≥1 HCV antibody negative test result and ≥1 subsequent HCV antibody and/or RNA test. Discrete time survival analysis was used to estimate the association between a positive syphilis, rectal chlamydia, and rectal gonorrhea diagnosis in the previous 2 years and a primary HCV diagnosis, defined as a positive HCV antibody or RNA test result. Results Among 6529 GBM with HIV, 92 (1.4%) had an incident HCV infection. A prior positive syphilis diagnosis was associated with an incident HCV diagnosis (adjusted hazard ratio, 1.99 [95% confidence interval, 1.11–3.58]). Among 13 061 GBM prescribed PrEP, 48 (0.4%) had an incident HCV diagnosis. Prior rectal chlamydia (adjusted hazard ratio, 2.75 [95% confidence interval, 1.42–5.32]) and rectal gonorrhea (2.54 [1.28–5.05]) diagnoses were associated with incident HCV. Conclusions Diagnoses of bacterial STIs in the past 2 years was associated with HCV incidence. These findings suggest that STIs might be useful for informing HCV testing decisions and guidelines for GBM with HIV and GBM using PrEP. [ABSTRACT FROM AUTHOR]

Background Gay and bisexual men using HIV pre-exposure prophylaxis (PrEP) are at increased risk for sexually transmissible infections. Hepatitis C virus (HCV) risk among PrEP users is less clear. We explored HCV prevalence and incidence among cohorts of gay and bisexual men using PrEP and sources of heterogeneity across studies. Methods This was a systematic review and meta-analysis of open-label PrEP studies to April 2022 reporting HCV prevalence at baseline or incidence during follow-up among gay and bisexual men using PrEP. Pooled prevalence and incidence estimates were calculated using random-effects meta-analysis, and subgroup analyses were performed by study- and country-level characteristics, including availability of HCV direct-acting antiviral (DAA) therapy at time of study. Results Twenty-four studies from 9 countries were included, with a total sample of 24 733 gay and bisexual men. Pooled HCV antibody baseline prevalence was 0.97% (95% CI, 0.63%–1.31%), and pooled HCV RNA baseline prevalence was 0.38% (95% CI, 0.19%–0.56%). Among 19 studies reporting HCV incidence, incidence ranged from 0.0 to 2.93/100 person-years (py); the pooled estimate was 0.83/100py (95% CI, 0.55–1.11). HCV incidence was higher in 12 studies that began follow-up before broad DAA availability (1.27/100py) than in 8 studies that began follow-up after broad DAA availability (0.34/100py) and higher in studies in Europe compared with North America and Australia. Conclusions Early reports of high HCV incidence among PrEP-using cohorts likely reflect enrollment of individuals based on specific risk-based eligibility criteria for smaller studies and enrollment before DAA scale-up. In contexts where both DAAs and PrEP have been implemented at scale, studies report lower HCV incidence. PrEP-specific HCV testing guidelines should be guided by local epidemiology. [ABSTRACT FROM AUTHOR]

Background Prison-based hepatitis C treatment is safe and effective; however, many individuals are released untreated due to time or resource constraints. On community re-entry, individuals face a number of immediate competing priorities, and in this context, linkage to hepatitis C care is low. Interventions targeted at improving healthcare continuity after prison release have yielded positive outcomes for other health diagnoses; however, data regarding hepatitis C transitional care are limited. Methods We conducted a prospective randomized controlled trial comparing a hepatitis C care navigator intervention with standard of care for individuals released from prison with untreated hepatitis C infection. The primary outcome was prescription of hepatitis C direct-acting antivirals (DAA) within 6 months of release. Results Forty-six participants were randomized. The median age was 36 years and 59% were male. Ninety percent (n  = 36 of 40) had injected drugs within 6 months before incarceration. Twenty-two were randomized to care navigation and 24 were randomized to standard of care. Individuals randomized to the intervention were more likely to commence hepatitis C DAAs within 6 months of release (73%, n  = 16 of 22 vs 33% n  = 8 of 24, P  < .01), and the median time between re-entry and DAA prescription was significantly shorter (21 days [interquartile range {IQR}, 11–42] vs 82 days [IQR, 44–99], P  = .049). Conclusions Care navigation increased hepatitis C treatment uptake among untreated individuals released from prison. Public policy should support similar models of care to promote treatment in this high-risk population. Such an approach will help achieve hepatitis C elimination as a public health threat. [ABSTRACT FROM AUTHOR]

Background Hepatitis C virus (HCV) infection has been reported among gay, bisexual, and other men who have sex with men (GBM) globally including GBM with human immunodeficiency virus (HIV) and HIV-negative GBM, particularly those using HIV preexposure prophylaxis (PrEP). In Australia, HCV direct-acting antiviral treatment (DAA) was government-funded from 2016. Large implementation studies of PrEP also began in 2016. We examined HCV incidence among GBM to assess whether HCV incidence has changed since 2015. Methods Data were drawn from the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance. We included GBM who tested HCV antibody negative at their first test and had ≥1 subsequent test. Generalized linear modeling (Poisson distribution) was used to examine HCV incidence from 2009 to 2019 stratified by HIV status, and among HIV-negative GBM prescribed PrEP from 2016 to 2019. Results Among 6744 GBM with HIV, HCV incidence was 1.03 per 100 person-years (PY). Incidence declined by 78% in 2019 compared to 2015 (incidence rate ratio [IRR], 0.22 [95% confidence interval {CI}:.09–.55]). Among 20 590 HIV-negative GBM, HCV incidence was 0.20/100 PY, with no significant change over time. Among 11 661 HIV-negative GBM prescribed PrEP, HCV incidence was 0.29/100 PY. Compared to 2016, incidence among GBM prescribed PrEP declined by 80% in 2019 (IRR, 0.20 [95% CI:.06–.64]). Conclusions HCV incidence among GBM living with HIV declined following DAA availability. There was no observed change in HCV incidence among HIV-negative GBM overall. Among GBM prescribed PrEP, incidence declined since the early years of PrEP implementation in Australia. Australia is on track to eliminate HCV among GBM before global 2030 targets. [ABSTRACT FROM AUTHOR]

Ambitious World Health Organization targets for disease elimination require monitoring of epidemics using routine health data in settings of decreasing and low incidence. We evaluated 2 methods commonly applied to routine testing results to estimate incidence rates that assume a uniform probability of infection between consecutive negative and positive tests based on 1) the midpoint of this interval and 2) a randomly selected point in this interval. We compared these with an approximation of the Poisson binomial distribution, which assigns partial incidence to time periods based on the uniform probability of occurrence in these intervals. We assessed bias, variance, and convergence of estimates using simulations of Weibull-distributed failure times with systematically varied baseline incidence and varying trend. We considered results for quarterly, half-yearly, and yearly incidence estimation frequencies. We applied the methods to assess human immunodeficiency virus (HIV) incidence in HIV-negative patients from the Treatment With Antiretrovirals and Their Impact on Positive and Negative Men (TAIPAN) Study, an Australian study of HIV incidence in men who have sex with men, between 2012 and 2018. The Poisson binomial method had reduced bias and variance at low levels of incidence and for increased estimation frequency, with increased consistency of estimation. Application of methods to real-world assessment of HIV incidence found decreased variance in Poisson binomial model estimates, with observed incidence declining to levels where simulation results had indicated bias in midpoint and random-point methods. [ABSTRACT FROM AUTHOR]

Background The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT). Methods Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models. Results Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2–2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6–6.3) overall and 17.9/100 person-years (95% CI, 5.8–55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection. Conclusions These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination. Clinical Trials Registration NCT02336139 and NCT02498015. [ABSTRACT FROM AUTHOR]

Background This study investigated adherence and associated factors among people with recent injection drug use (IDU) or current opioid agonist therapy (OAT) and compared once-daily to twice-daily hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy. Methods SIMPLIFY and D3FEAT are international, multicenter studies that recruited participants with recent IDU (previous 6 months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in 8 countries. Participants received sofosbuvir/velpatasvir (once daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice daily) ± ribavirin (D3FEAT) for 12 weeks administered in electronic blister packs. We evaluated overall adherence (proportion of prescribed doses taken) and nonadherence (<90% adherent) between dosing patterns. Results Of 190 participants, 184 (97%) completed treatment. Median adherence was 92%, with higher adherence among those receiving once-daily vs twice-daily therapy (94% vs 87%, P =.005). Overall, 40% of participants (n = 76) were nonadherent (<90% adherent). Recent stimulant injecting (odds ratio [OR], 2.48 [95% confidence interval {CI}, 1.28–4.82]), unstable housing (OR, 2.18 [95% CI, 1.01–4.70]), and twice-daily dosing (OR, 2.81 [95% CI, 1.47–5.36]) were associated with nonadherence. Adherence decreased during therapy. Sustained virologic response was high in nonadherent (89%) and adherent populations (95%, P =.174), with no difference in SVR between those who did and did not miss 7 consecutive doses (92% vs 93%, P =.897). Conclusions This study demonstrated high adherence to once- and twice-daily DAA therapy among people with recent IDU or currently receiving OAT. Nonadherence described did not impact treatment outcomes, suggesting forgiveness to nonadherence. [ABSTRACT FROM AUTHOR]

Background Microelimination of hepatitis C virus (HCV) among people living with human immunodeficiency virus (HIV) may be feasible in Australia, given unrestricted access to direct-acting antiviral (DAA) therapy from 2016. Our aim was to evaluate progress towards elimination goals within HIV/HCV-coinfected adults in Australia following universal DAA access. Methods The CEASE prospective cohort study enrolled adults with HIV/HCV, irrespective of viremic status, from 14 primary and tertiary clinics in Australia. Annual and cumulative HCV treatment uptake, outcome, and HCV RNA prevalence were evaluated, with follow-up through May 2018 (median follow-up, 2.63 years). Factors associated with DAA uptake were analyzed. Results Between July 2014 and March 2017, 402 participants who were HIV/HCV antibody positive were enrolled (95% male [80% gay and bisexual men,], 13% cirrhosis, 80% history of injecting drug use [39% currently injecting]). Following universal DAA access, annual HCV treatment uptake in those eligible increased from 7% and 11% per year in 2014 and 2015, respectively, to 80% in 2016. By 2018, cumulative HCV treatment uptake in those ever eligible for treatment was 91% (336/371). HCV viremic prevalence declined from 82% (95% CI, 78–86%) in 2014 to 8% (95% CI, 6–12%) in 2018. Reinfection was reported in only 5 participants for a reinfection incidence of 0.81 per 100 person-years (95% CI, 0.34–1.94). Conclusions High uptake and effectiveness of unrestricted DAA therapy in Australia have permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden and low reinfection rate among people living with HIV, suggesting that microelimination is feasible. Clinical Trials Registration NCT02102451. [ABSTRACT FROM AUTHOR]

Background In many settings, recent or prior injection drug use remains a barrier to accessing direct-acting antiviral treatment (DAA) for hepatitis C virus (HCV) infection. We examined patterns of drug and alcohol use and injection equipment sharing among people with recent injecting drug use or receiving opioid agonist treatment (OAT) during and following DAA-based treatment. Methods SIMPLIFY and D3FEAT are phase 4 trials evaluating the efficacy of DAA among people with past 6-month injecting drug use or receiving OAT through a network of 25 international sites. Enrolled in 2016–2017, participants received sofosbuvir/velpatasvir (SIMPLIFY) or paritaprevir/ritonavir/dasabuvir/ombitasvir ± ribavirin (D3FEAT) for 12 weeks and completed behavioral questionnaires before, during, and up to 2 years posttreatment. The impact of time in HCV treatment and follow-up on longitudinally measured longitudinally measured behaviors was estimated using generalized estimating equations. Results At screening, of 190 participants (mean age, 47 years; 74% male), 62% reported any past-month injecting 16% past-month injection equipment sharing, and 61% current OAT. Median alcohol use was 2 (Alcohol Use Disorders Identification Test–Consumption; range, 1–12). During follow-up, opioid injecting (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.92–0.99) and sharing (OR, 0.87; 95% CI, 0.80–0.94) decreased, whereas no significant changes were observed for stimulant injecting (OR, 0.98; 95% CI, 0.94–1.02) or alcohol use (OR, 0.99; 95% CI, 0.95–1.04). Conclusions Injecting drug use and risk behaviors remained stable or decreased following DAA-based HCV treatment. Findings further support expanding HCV treatment to all, irrespective of injection drug use. Clinical Trials Registration SIMPLIFY, NCT02336139; D3FEAT, NCT02498015. [ABSTRACT FROM AUTHOR]

Background To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to direct-acting antivirals (DAAs), especially among people who inject drugs (PWID). We aimed to determine the effectiveness of providing DAAs in primary care, compared with hospital-based specialist care. Methods We randomized PWID with HCV attending primary care sites in Australia or New Zealand to receive DAAs at their primary care site or local hospital (standard of care [SOC]). The primary outcome was to determine whether people treated in primary care had a noninferior rate of sustained virologic response at Week 12 (SVR12), compared to historical controls (consistent with DAA trials at the time of the study design); secondary outcomes included comparisons of treatment initiation, SVR12 rates, and the care cascade by study arm. Results We recruited 140 participants and randomized 136: 70 to the primary care arm and 66 to the SOC arm. The SVR12 rate (100%, 95% confidence interval [CI] 87.7–100) of people treated in primary care was noninferior when compared to historical controls (85% assumed). An intention-to-treat analysis revealed that the proportion of participants commencing treatment in the primary care arm (75%, 43/57) was significantly higher than in the SOC arm (34%, 18/53; P <.001; relative risk [RR] 2.48, 95% CI 1.54–3.95), and the proportion of participants with SVR12 was significantly higher in the primary care arm, compared to in the SOC arm (49% [28/57] and 30% [16/53], respectively; P =.043; RR 1.63, 95% CI 1.0–2.65). Conclusions Providing HCV treatment in primary care increases treatment uptake and cure rates. Approaches that increase treatment uptake among PWID will accelerate elimination strategies. Clinical Trials Registration NCT02555475. [ABSTRACT FROM AUTHOR]

Background While opioid agonist therapy (OAT) reduces the risk of hepatitis C virus (HCV) acquisition among people who inject drugs (PWID), protective effects may be attenuated in females. We used pooled data from an international collaboration of prospective cohorts to assess sex disparities in HCV incidence among PWID exposed to OAT. Methods Independent predictors of HCV infection were identified using Cox regression models with random effects after accounting for the clustering effect of study sites. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented in sex‐specific analyses. Results Among 701 participants exposed to OAT, HCV incidence was 16.5/100 person-years of observation (PYO) (95% CI, 13.1–20.7) in females and 7.6/100 PYO (95% CI, 6.0–9.5) in males (female:male adjusted HR [aHR], 1.80 [95% CI, 1.37–2.22]; P <.001). Factors associated with HCV acquisition among females exposed to OAT included nonwhite race (aHR, 1.79 [95% CI, 1.25–2.56]; P =.001), unstable housing (aHR, 4.00 [95% CI, 3.62–4.41]; P <.001), daily or more frequent injection (aHR, 1.45 [95% CI, 1.01–2.08]; P =.042), and receptive syringe sharing (aHR, 1.43 [95% CI, 1.33–1.53]; P <.001). Conclusions Female PWID exposed to OAT are twice as likely as their male counterparts to acquire HCV. While there is a need for better understanding of sex differences in immune function and opioid pharmacokinetic and pharmacodynamic parameters, structural and behavioral interventions that target women are required to bolster the efficacy of OAT in preventing HCV transmission. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is effective in reducing HIV risk in men who have sex with men (MSM). However, concerns remain that risk compensation in PrEP users may lead to decreased condom use and increased incidence of sexually transmitted infections (STIs). We assessed the impact of PrEP on sexual risk outcomes in MSM. Methods We conducted a systematic review of open-label studies published to August 2017 that reported sexual risk outcomes in the context of daily oral PrEP use in HIV-negative MSM and transgender women. Pooled effect estimates were calculated using random-effects meta-analysis, and a qualitative review and risk of bias assessment were performed. Results Sixteen observational studies and 1 open-label trial met selection criteria. Eight studies with a total of 4388 participants reported STI prevalence, and 13 studies with a total of 5008 participants reported change in condom use. Pre-exposure prophylaxis use was associated with a significant increase in rectal chlamydia (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19–2.13) and an increase in any STI diagnosis (OR, 1.24; 95% CI,.99–1.54). The association of PrEP use with STI diagnoses was stronger in later studies. Most studies showed evidence of an increase in condomless sex among PrEP users. Conclusion Findings highlight the importance of efforts to minimize STIs among PrEP users and their sexual partners. Monitoring of risk compensation among MSM in the context of PrEP scale-up is needed to assess the impact of PrEP on the sexual health of MSM and to inform preventive strategies. [ABSTRACT FROM AUTHOR]

Background. We estimated the human immunodeficiency virus (HIV) incidence reduction in Australia that would correspond to achieving the United Nations Program on HIV and AIDS (UNAIDS) 90-90-90 targets by 2020 and extended targets of 95-95-95 by 2030. This was done in combination with various scale-ups of HIV testing, primary prevention, and preexposure prophylaxis (PrEP) among high-risk men who have sex with men (MSM). These projections were evaluated against the target of achieving a 90% reduction in HIV incidence by 2030 compared with 2010 levels. Methods. A mathematical model. Results. Achieving 90-90-90 by 2020 was estimated to reduce incidence by 10% from 2010 levels. Achieving 95-95-95 by 2030 was estimated to reduce incidence by 17% from 2010 levels, with the first "95" being achievable by testing low- and high-risk MSM 2 and 4 times per year, respectively. This was improved to a 34% reduction by including a 5-year scale-up of PrEP to 30% coverage among high-risk MSM and to 45% by also increasing MSM condom use from 42% to 60%. However, even with 95-95-95, 2 and 4 tests per year for low- and high-risk MSM, 100% high-risk MSM PrEP coverage, and 100% MSM condom use, only an 80% reduction in incidence was possible by 2030. Conclusions. Many countries, particularly those with low HIV prevalence, will struggle to achieve a 90% reduction in HIV incidence by 2030, even if UNAIDS targets are met. Most will require substantially higher levels of prevention coverage and higher testing frequencies to reach this target. [ABSTRACT FROM AUTHOR]

Background. Syphilis rates have increased markedly among men who have sex with men (MSM) internationally. We examined trends in syphilis testing and detection of early syphilis among MSM in Australia. Methods. Serial cross-sectional analyses on syphilis testing and diagnoses among MSM attending a national sentinel network of 46 clinics in Australia between 2007 and 2014. Results. 359313 clinic visits were included. The proportion of MSM serologically tested for syphilis annually increased in HIV-negative (48% to 91%; Ptrend < .0001) and HIV-positive MSM (42% to 77%; Ptrend < .0001). The mean number of tests per man per year increased from 1.3 to 1.6 in HIV-negative MSM (Ptrend < .0001) and from 1.6 to 2.3 in HIV-positive MSM (Ptrend < .0001). 2799 and 1032 syphilis cases were detected in HIV-negative and HIV-positive MSM, respectively. Among HIV-negative MSM, the proportion of infections that were early latent increased from 27% to 44% (Ptrend < .0001), while the proportion that were secondary decreased from 24% to 19% (Ptrend = .030). Among HIV-positive MSM, early latent infections increased from 23% to 45% (Ptrend < .0001), while secondary infections decreased from 45% to 26% (Ptrend = .0003). Among HIV-positive MSM, decreasing secondary syphilis correlated with increasing testing coverage (r = −0.87; P = .005) or frequency (r = −0.93; P = .001). Conclusions. Increases in syphilis screening were associated with increased detection of asymptomatic infectious syphilis and relative falls in secondary syphilis for both HIV-positive and HIV-negative MSM nationally, suggesting interruption of syphilis progression. [ABSTRACT FROM AUTHOR]

New combination human acquired deficiency (HIV) prevention strategies that include biomedical and primary prevention approaches add complexity to the task of measuring sexual risk. Latent transition models are beneficial for understanding complex phenomena; therefore, we trialed the application of latent class and latent transition models to HIV surveillance data. Our aims were to identify sexual risk states and model individuals' transitions between states. A total of 4,685 HIV-negative men who have sex with men (MSM) completed behavioral questionnaires alongside tests for HIV and sexually transmissible infections at one of 2 Melbourne, Victoria, Australia, general practices (2007-2013). We found 4 distinct classes of sexual risk, which we labeled "monogamous" (n = 1,224), "risk minimizer" (n = 1,443), "risk potential" (n = 1,335), and "risk taker" (n = 683). A positive syphilis, gonorrhea, or chlamydia test was significantly associated with class membership. Among a subset of 516 MSM who had at least 3 clinic visits, there was general stability across risk classes; MSM had on average a 0.70 (i.e., 70%) probability of remaining in the same class between visits 1 and 2 and between visits 2 and 3. Monogamous MSM were one exception; the probability of remaining in the monogamous class was 0.51 between visits 1 and 2. Latent transition analyses identified unobserved risk patterns in surveillance data, characterized high-risk MSM, and quantified transitions over time. [ABSTRACT FROM AUTHOR]

Background. We determined temporal trends (1985-2011) in hepatitis C virus (HCV) incidence and associated behavioral exposures for people who inject drugs (PWID) from the United States (Boston, Baltimore, and San Francisco), Canada (Montreal), the Netherlands (Amsterdam), and Australia (Sydney and Melbourne). Methods. Using population-based cohort data from HCV-negative PWID, we calculated overall and within-city HCV incidence trends, HCV rates by study enrollment period (1985-2011), and temporal trends in exposure behaviors. Poisson regression models estimated trends in HCV incidence over calendar-time. Survival models identified risk factors for HCV incidence across cities and estimated independent effects of city and calendar period on HCV infection risk. Results. Among 1391 initially HCV-negative participants followed prospectively (1644.5 person-years of observation [PYO]), 371 HCV incident infections resulted in an overall incidence of 22.6 per 100 PYO (95% confidence interval [CI], 20.4-25.0). Incidence was highest and remained elevated in Baltimore (32.6/100 PYO), San Francisco (24.7/100 PYO), and Montreal (23.5/100 PYO), lowest in Melbourne and Amsterdam (7.5/100 PYO and 13.1/100 PYO, respectively), and moderate (21.4/100 PYO) in Sydney. Higher rates of syringe and equipment sharing and lower prevalence of opioid agonist therapy were associated with HCV incidence in cities with the highest incidence. Risk for infection dropped by 18% for every 3-year increase in calendar-time (adjusted hazard ratio, 0.8 [95% CI, .8-.9]) in the multivariable model. Conclusions. Differences in prevention strategies and injecting contexts may explain the ongoing high HCV incidence in these North American cities and emphasize the need for scale-up of opioid agonist therapy and increased coverage of needle and syringe programs in North America. [ABSTRACT FROM AUTHOR]

Background:  Bayesian evolutionary analysis (coalescent analysis) based on genetic sequences has been used to describe the origins and spread of rapidly mutating RNA viruses, such as influenza, Ebola, human immunodeficiency virus (HIV), and hepatitis C virus (HCV).Methods:  Full-length subtype 1a and 3a sequences from early HCV infections from the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC3), as well as from public databases from a time window of 1977-2012, were used in a coalescent analysis with BEAST software to estimate the origin and progression of the HCV epidemics in Australia and North America. Convergent temporal trends were sought via independent epidemiological modeling.Results:  The epidemic of subtype 3a had more recent origins (around 1950) than subtype 1a (around 1920) in both continents. In both modeling approaches and in both continents, the epidemics underwent exponential growth between 1955 and 1975, which then stabilized in the late 20th century.Conclusions:  Historical events that fuelled the emergence and spread of injecting drug use, such as the advent of intravenous medical therapies and devices, and growth in the heroin trade, as well as population mixing during armed conflicts, were likely drivers for the cross-continental spread of the HCV epidemics. [ABSTRACT FROM AUTHOR]

Background: Mechanisms by which spontaneous clearance of acute hepatitis C occurs are unclear. A critical role for the innate immune system and IFNL4 polymorphisms has been proposed. This study investigates whether Toll-like receptor (TLR) expression and signaling during acute hepatitis C correlates with clinical outcomes.Methods: Participants identified from the Australian Trial in Acute Hepatitis C and the Networks study were followed longitudinally from the time of diagnosis of acute hepatitis C. Peripheral blood mononuclear cells (PBMCs) and plasma were collected at and 2 time points after diagnosis. At each time point, TLR2, TLR4, and CD86 expression on peripheral blood monocytes, natural killer (NK) cells, and NK T cells was measured, as well as the response of PBMCs to stimulation with TLR ligands. Cytokine and chemokine levels were measured in stimulated PBMCs and plasma.Results: We identified 20 participants with acute hepatitis C (10 with hepatitis C virus [HCV] monoinfection and 10 with HCV and human immunodeficiency virus coinfection). Eleven participants (55%) spontaneously cleared HCV. Acute hepatitis C and spontaneous clearance was associated with lower TLR4 expression on monocytes (P = .009) and NK cells (P = .029). Acute hepatitis C and spontaneous clearance was also associated with a reduced interferon γ response to TLR4 (P = .038) and TLR7/8 stimulation (P = .035), a reduced interleukin 6 response to TLR7/8 stimulation (P = .037), and reduced IFN-γ-inducible protein 10 (IP-10) response to TLR2 stimulation (P = .042). Lower plasma IP-10 levels were associated with spontaneous clearance (P = .001).Conclusions: These findings implicate TLR4 signaling as playing a critical role in the outcome of acute hepatitis C. [ABSTRACT FROM AUTHOR]

Background: We aimed to characterize the natural history of hepatitis C virus (HCV) reinfection and spontaneous clearance following reinfection (reclearance), including predictors of HCV reclearance.Methods: Data were synthesized from the 9 prospective cohorts of the International Collaboration of Incident Human Immunodeficiency Virus and HCV in Injecting Cohorts study, which evaluated HCV infection outcomes among people who inject drugs. Participants with primary HCV infection were classified as having achieved viral suppression if they had negative results of at least 1 subsequent HCV RNA test. Those with positive results of an HCV RNA test following viral suppression were investigated for reinfection. Viral sequence analysis was used to identify reinfection (defined as detection of heterologous virus with no subsequent detection of the original viral strain).Results: Among 591 participants with acute primary HCV infection, 118 were investigated for reinfection. Twenty-eight participants were reinfected (12.3 cases/100 person-years; 95% confidence interval [CI], 8.5-17.8). Peak HCV RNA level was lower during reinfection than primary infection (P = .011). The proportion of individuals with reclearance 6 months after reinfection was 52% (95% CI, 33%-73%). After adjustment for study site, females with the IFNL4 (formerly IFNL3 and IL28B) rs12979860 CC genotype detected were more likely to have reclearance (hazard ratio, 4.16; 95% CI, 1.24-13.94; P = .021).Conclusions: Sex and IFNL4 genotype are associated with spontaneous clearance after reinfection. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis of 58 studies found that antiretroviral therapy is not associated with increased sexual or injecting risk-taking behavior among HIV-infected individuals undergoing treatment.Background. Increased global access and use of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) has been postulated to undermine HIV prevention efforts by changing individual risk-taking behavior. This review aims to determine whether ART use is associated with changes in sexual or injecting risk-taking behavior or diagnosis of sexually transmitted infections (STIs).Methods. A systematic review and meta-analysis was conducted of HIV-seropositive participants receiving ART compared with no ART use in experimental or observational studies. Primary outcomes included (1) any unprotected sexual intercourse, (2) STI diagnoses, and (3) any unsafe injecting behavior.Results. Fifty-eight studies met the selection criteria. Fifty-six studies containing 32 857 participants reported unprotected sex; 11 studies containing 16 138 participants reported STI diagnoses; and 4 studies containing 1600 participants reported unsafe injecting behavior. All included studies were observational. Unprotected sex was lower in participants receiving ART than in those not receiving ART (odds ratio [OR], 0.73; 95% confidence interval [CI], .64–.83; P < .001; heterogeneity I2 = 79%) in both high-income (n = 38) and low-/middle-income country (n = 18) settings, without any evidence of publication bias. STI diagnoses were also lower among individuals on ART (OR, 0.58; 95% CI, .33–1.01; P = .053; I2 = 92%); however, there was no difference in injecting risk-taking behavior with antiretroviral use (OR, 0.90; 95% CI, .60–1.35; P = .6; I2 = 0%).Conclusions. Despite concerns that use of ART might increase sexual or injecting risk-taking, available research suggests that unprotected sex is reduced among HIV-infected individuals on treatment. The reasons for this are not yet clear, although self-selection and mutually reinforcing effects of HIV treatment and prevention messages among people on ART are likely. [ABSTRACT FROM PUBLISHER]

Background Needle and syringe programmes (NSP) aim to reduce the risk of HIV by providing people who inject drugs (PWID) with sterile injecting equipment. A recent review of reviews (ROR) concluded that there was only tentative evidence to support the effectiveness of NSP in reducing HIV. We carried out a systematic review and meta-analysis to assess the association between NSP and HIV transmission.Methods Relevant primary articles presenting data on the risk of HIV transmission associated with NSP were identified in two stages: (i) from reviews identified in two published RORs (covering the period 1980–2008); and (ii) a literature search of CINAHL, Cochrane Library, EMBASE, MEDLINE and PsychINFO for primary articles published since the most recent high quality review (covering the period 2008–12). Study results were synthesized using random-effects meta-analysis.Results There were 12 studies comprising at least 12 000 person-years of follow-up. Exposure to NSP was associated with a reduction in HIV transmission: pooled effect size 0·66 [95% confidence interval (CI) 0·43, 1·01] across all studies, and 0·42 (95% CI 0·22, 0·81) across six higher quality studies (according to the Newcastle-Ottawa tool).Conclusions There is evidence to support the effectiveness of NSP in reducing the transmission of HIV among PWID, although it is likely that other harm reduction interventions have also contributed to the observed reduction in HIV risk. NSP should be considered as just one component of a programme of interventions to reduce both injecting risk and other types of HIV risk behaviour. [ABSTRACT FROM PUBLISHER]

The International Collaboration of Incident HIV and Hepatitis C in Injecting Cohorts (InC3) Study is an international multi-cohort project of pooled biological and behavioural data from nine prospective cohorts of people who inject drugs (PWID). InC3 brings together researchers from Australia, Canada, USA and the Netherlands with expertise in epidemiology, biostatistics, clinical and behavioural sciences, virology and immunology to investigate research questions relevant to hepatitis C virus (HCV) and HIV outcomes. InC3 was established to: (i) create a merged multi-cohort study of pooled data from well-characterized cohorts of PWID with prospective data on HIV and HCV infections, with a particular focus on HCV; (ii) facilitate new studies not possible within individual cohorts; and (iii) bring together researchers across disciplines to answer a broad range of research questions. Study cohorts identify acute HCV cases through follow-up of high-risk HCV antibody–negative PWID or through clinical referral networks. To date, data from 1986 to 2010 have been received from all contributing cohorts, with 821 HCV-infected and 1216 HCV-uninfected participants (overall, n = 2037). Data collected include demographics, host genetics, HCV ribonucleic acid testing, alanine aminotransferase testing, HIV/hepatitis B virus testing, HCV therapy, loss to follow-up and mortality. Potential collaborators should contact the InC3 PI Dr Kimberley Page (kPage@psg.ucsf.edu) for further information. [ABSTRACT FROM PUBLISHER]

Studies examining the effect of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) on the HCV-specific immune response in acute HCV infection are limited. This study directly compared acute HCV-specific T-cell responses and cytokine profiles between 20 HIV/HCV-coinfected and 20 HCV-monoinfected subjects, enrolled in the Australian Trial in Acute Hepatitis C (ATAHC), using HCV peptide enzyme-linked immunospot (ELISPOT) and multiplex in vitro cytokine production assays. HIV/HCV coinfection had a detrimental effect on the HCV-specific cytokine production in acute HCV infection, particularly on HCV-specific interferon γ (IFN-γ) production (magnitude P = .004; breadth P = .046), which correlated with peripheral CD4(+) T-cell counts (ρ = 0.605; P = .005) but not with detectable HIV viremia (ρ = 0.152; P = .534). [ABSTRACT FROM AUTHOR]

Introduction. Studies have explored whether spontaneous clearance of hepatitis C virus (HCV) infection decreases the likelihood of reinfection or increases the probability of clearance. This analysis investigates whether the conflicting findings from these studies could be due to differences in frequency of HCV RNA testing. Methods. A model simulated the dynamics of HCV reinfection and clearance among a cohort of injection drug users. For different reinfection incidence and clearance rates, the model evaluated the accuracy of epidemiological studies that used different HCV testing frequencies. Results. Experimental estimates for the reinfection incidence and clearance probability will be accurate (<20% error) if the testing interval is less than the reinfection clearance duration. Otherwise, experimental estimates can greatly underestimate the real values (<66% error if reinfection duration is 1 month and the testing interval is 3 months). Uncertainty in experimental estimates also increases at lower reinfection incidences, whereas for lower clearance probabilities the uncertainty in the estimated clearance probability increases but estimated reinfection incidence decreases. Discussion. Differences in HCV testing interval could account for most between-study variability in the estimated probability of clearing reinfections and is likely to have biased reinfection incidence estimates. Our findings suggest that a high reinfection clearance probability (>75%) is consistent with data. [ABSTRACT FROM AUTHOR]

The relation between sporadic gastroenteritis and recreational swimming was examined in a cohort of 2,811 people in Melbourne, Australia, over a 15-month period (September 1997–February 1999). Data from a prospective community-based study of gastroenteritis were used for a Poisson analysis of temporality between reported swimming (in public or private pools/spas and in marine or freshwater settings) and a highly credible gastroenteritis (HCG) event. Overall, HCG events were more likely in participants who had swum in a public pool/spa (incidence rate ratio (IRR) = 1.25, 95% confidence interval (CI): 1.10, 1.42; P = 0.001) or river/lake/dam (IRR = 1.77, 95% CI: 1.13, 2.79; P = 0.014) during the previous week or had swum in a public pool/spa (IRR = 1.29, 95% CI: 1.13, 1.46; P < 0.001) during the previous 2 weeks. Subanalysis by age showed that HCG episodes were also more likely in adults who had swum in a private pool/spa (IRR = 1.56, 95% CI: 1.02, 2.39; P = 0.042) during the previous week or swum at an ocean/beach (IRR = 1.78, 95% CI: 1.12, 2.81; P = 0.014) during the previous 2 weeks, demonstrating significant associations between all swimming locations and gastrointestinal symptoms. This study showed that although the incremental risk of recreational swimming is significant, it is relatively small. [ABSTRACT FROM PUBLISHER]

Globally, ~90% of new hepatitis C infections are attributed to injection drug use, but there is a continuing reluctance to treat injection drug users (IDUs). There is evidence that a sizeable proportion of IDUs who begin hepatitis C treatment achieve a sustained virological response (SVR). In chronic hepatitis C treatment trials, the SVR rate among IDUs appears to be comparable to rates among non-IDUs; in trials prescribing pegylated interferon plus ribavirin, the median rate of SVR among IDUs was 54.3% (range, 18.1%-94.1%), compared with 54%-63% in the large treatment trials. Few trials of acute hepatitis C treatment report on outcomes in IDUs; however, among these trials, the SVR among IDUs was 68.5% (np89), compared with 81.5% among non-IDUs (np65). Additional studies are required to determine the optimal circumstances for treatment (e.g., enrollment in drug treatment, the requirement of a period of abstinence from injection drug use, or the establishment of multidisciplinary treatment programs). [ABSTRACT FROM AUTHOR]

Background Without intervention, HIV, hepatitis B virus and syphilis can be transmitted from mother-to-child during pregnancy, birth and breastfeeding and these can cause adverse pregnancy and longer-term outcomes. The 22 Pacific Island countries and territories (PICTs) have among the highest global prevalence of syphilis and hepatitis B. Mother-to-child transmission remains a concern, particularly hepatitis B. Global and regional elimination targets have been set to eliminate mother-to-child transmission (EMTCT) however progress of PICTs towards meeting targets is unknown. Methods Data from 2000-2019 relating to EMTCT epidemiological, process and impact targets were extracted from peer reviewed literature, online data repositories and grey literature. Results 27 peer reviewed reports, data from online data repositories for 19 countries and twelve national demographic and/or health reports were collated. Existing online databases report data for only small number of EMTCT indicators and there are few peer-reviewed studies that report EMTCT coverage estimates for PICTs. Availability of data varied between countries and available data suggests that few countries are meeting EMTCT indicator targets. Conclusions Based on the current trach trajectory, PICTs will not reach triple elimination by 2030. Both interventions to improve EMTCT activity coverage and strengthened surveillance, monitoring and evaluation systems are required. Key messages Mother-to-child transmission of HIV, hepatitis B and syphilis is a major concern in the Pacific and increased efforts are required, including strengthened monitoring and evaluation systems. [ABSTRACT FROM AUTHOR]

The article responds to a commentary made on the article "Latent Transition Analyses in Clinical Cohorts" that presented results of latent class and latent transition analysis using sexual behavior surveillance data on gay and bisexual men (GBM) visiting primary-care clinics in Melbourne, Victoria. Topics discussed include the potential dependency between the probability of being observed and the outcome and limitations of prospective surveillance relative to conventional cohort studies.

Background HIV and bacterial sexually transmissible infection (STI) notifications among men who have sex with men (MSM) have increased in Australia and many other countries. The relationship between HIV infection and other STIs has been demonstrated previously. However, the relationship between the cumulative history of STIs and subsequent HIV infection remains largely unexplored and limits our understanding of the mechanisms underpinning the elevated HIV risk. Methods Data from HIV-negative MSM who attended high–HIV caseload primary care clinics in Melbourne, Australia, from 2007 to 2014 with 2 or more HIV and STI tests were included. Controlling for sexual behaviors self-reported at clinic visits, discrete time survival analyses using generalized linear modeling estimated the effect of an STI at the prior test event and the cumulative history of STIs (none, 1, 2, or more [repeated]) on risk of HIV infection. Results A total of 8941 MSM met the study criteria; 227 (2.5%) were diagnosed with HIV over the follow-up period. Adjusting for sexual behaviors, a cumulative history of repeated rectal gonorrhea infections (adjusted hazard ratio [aHR], 6.27; 95% confidence interval [CI], 2.68–14.50) and a single rectal gonorrhea infection (aHR, 2.09; 95% CI, 1.15–3.79) were associated with increased HIV infection risk. Conclusions Repeated and single rectal gonorrhea infections were independently associated with increased HIV infection risk. These findings suggest that MSM with any history of rectal gonorrhea, particularly repeat rectal gonorrhea, represent a group for whom preventive interventions for HIV should be emphasized. [ABSTRACT FROM AUTHOR]

Background. Although guidelines recommend that people who inject drugs (PWID) should not be excluded from hepatitis C (HCV) treatment, some services remain reluctant to treat PWID. The aim of this review was to investigate sustained virologic response (SVR), adherence, discontinuation, and HCV reinfection among PWID.Methods. A search of Medline, Embase, and Cochrane databases (between 2002 and January 2012) was conducted for primary articles/conference abstracts examining HCV treatment outcomes in PWID. Meta-analysis was used to obtain pooled estimates of SVR, adherence, discontinuation, and HCV reinfection.Results. Ten primary articles and 1 conference abstract met the inclusion criteria. Across 6 studies (comprising 314 drug users, of whom 141 [45%] were PWID), pooled SVR was 56% (95% confidence interval [CI], 50%–61%) for all genotypes, 37% (95% CI, 26%–48%) for genotypes 1/4, and 67% (95% CI, 56%–78%) for genotypes 2/3. Pooled 80/80/80 adherence was 82% (95% CI, 74%–89%) across 2 studies, and pooled treatment discontinuation was 22% (95% CI, 16%–27%) across 4 studies. Across 5 studies (comprising 131 drug users) examining reinfection, pooled risk was 2.4 (95% CI, .9–6.1) per 100 person-years.Conclusions. HCV treatment outcomes are acceptable in PWID, supporting treatment guidelines. The pooled estimate of HCV reinfection risk was low, but there was considerable uncertainty around this estimate. Further studies on the risk of reinfection are needed to assess the long-term effectiveness of HCV treatment in PWID. [ABSTRACT FROM AUTHOR]

A response by Gail V. Matthews and colleagues to a letter to the editor about their article "Characteristics and treatment outcomes among HIV-infected individuals in the Australian trial in acute hepatitis C," in the 2009 issue.

The article focuses on a study on the impact of use pornography as a source of education and information about sex by young Australians on their sexual development and health. It mentions questionnaire on influence of pornography on their life. It concludes that participants use pornography as a form of sexual education, sex positions, and creation of problems in sexual expectations with pornography use.