Tenofovir, ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir use were independent predictors of chronic renal impairment in HIV-positive persons without preexisting renal impairment. Increased tenofovir discontinuation rates with decreasing eGFR may have prevented further deteriorations. After discontinuation, the ARV-associated incidence rates decreased.

Objectives To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC) and high-income (HIC) countries. Methods Patients aged ≥16 years starting cART in a clinic participating in a multi-cohort collaboration spanning six continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multi-level linear regression models were adjusted for age, gender and calendar year; missing CD4 counts were imputed. Findings 379,865 patients from nine LIC, four LMIC, four UMIC and six HIC were included. In LIC the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/μl between 2002 and 2009. Corresponding increases in LMIC, UMIC and HIC were from 87 to 155 cells/μl (76% increase), 88 to 135 cells/μl (53%) and 209 to 274 cells/μl (31%). In 2009, compared to LIC, median counts were 13 cells/μl (95% CI -56 to +30) lower in LMIC, 22 cells/μl (-62 to +18) lower in UMIC and 112 /μl (+75 to +149) higher in HIC. They were 23 cells/μl (95% CI +18 to +28) higher in women than men. Median counts were 88 cells/μl (95% CI +35 to +141) higher in countries with an estimated national cART coverage >80%, compared to countries with <40% coverage. Conclusions Median CD4 cell counts at start of cART increased 2000-2009 but remained below 200 cells/μl in LIC and MIC and below 300 cells/μl in HIC. Earlier start of cART will require substantial efforts and resources globally.

The burden of HCV-related liver disease has increased markedly. Although the proportion diagnosed was high, treatment uptake remained low, with no increase over the last 7 years. Reducing the HCV burden in Australia requires scale-up of interferon-free HCV therapies.

Background: Limited empirical evidence exists for hepatitis C virus (HCV) treatment-asprevention. The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study assessed HCV treatment-as-prevention in four Australian prisons.Methods: SToP-C is a non-randomised trial, including a pre/post analysis within a prospective longitudinal cohort of people incarcerated in two maximum-(male) and two medium-security prisons (one male, one female). All prison inmates at least 18 years were eligible for enrolment.Participants were enrolled from late-2014 to 2019. Following HCV testing, participants were monitored for risk behaviors and HCV, among three sub-populations: 1) uninfected (HCV antibody negative); 2) previously infected (HCV antibody positive, HCV RNA negative); 3) infected (HCV antibody and HCV RNA positive). Uninfected and previously infected (at-risk) participants were followed every 3-6 months for HCV primary infection and re-infection, respectively. Infected participants were assessed for treatment, initially standard of care treatment (by prison health services), followed by direct-acting antiviral (DAA) treatment scale-up from mid-2017 (12 weeks sofosbuvir/velpatasvir, through SToP-C). Participants were followed until study closure in November 2019. The primary study outcome was HCV incidence compared between pre-and post-treatment scale-up periods among participants at risk of HCV primary infection or re-infection. The trial was registered with ClinicalTrials.gov (identifier: NCT02064049) Findings: Of 3,691 participants enrolled, 719 (19%) had detectable HCV RNA and 2,965 were at-risk of primary infection (n=2,240) or re-infection (n=725) at baseline. DAA treatment was initiated in 349/499 eligible participants during the treatment scale-up period. Among at-risk population with longitudinal follow-up (n=1,643; median age 33 years; 82% male), 31% reported injecting drug use in prison. HCV incidence declined by 48%, from 8.31 to 4.35/100 person-years between pre-and post-treatment scale-up periods [Incidence Rate Ratio (IRR): 4 0.52, 95%CI: 0.36, 0.78]. Incidence of primary infection declined from 6.64 to 2.85/100 personyears (IRR: 0.43, 95%CI: 0.25, 0.74), while incidence of re-infection declined from 12.36 to 7.27/100 person-years (IRR: 0.59, 95%CI: 0.35, 1.00). Among participants reporting injecting drug use in the current imprisonment, incidence of primary infection declined from 39.08 to 14.03/100 person-years (IRR: 0.36, 95%CI: 0.16, 0.80), and incidence of re-infection declined from 15.26 to 9.34/100 person-years (IRR: 0.61, 95%CI: 0.34, 1.09). Adjusted analysis indicated a significant reduction in HCV risk between pre-and post-treatment scale-up periods (adjusted Hazard Ratio: 0.50, 95% CI: 0.33, 0.76).Interpretation: DAA treatment scale-up was associated with reduced HCV incidence in prison, indicative of HCV treatment-as-prevention. The findings support broad DAA treatment scale-up among incarcerated populations.

BackgroundLife expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models.MethodsData were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models.ResultsThe overall SMR for all-cause mortality was 3.5 (95% CI: 3.0–4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2–10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5–2.9) for CD4 = 350–499 cells/µl; and 1.5 (95% CI: 1.1–2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment.ConclusionObserved mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.

Introduction We conducted a detailed analysis of trends in new HIV diagnoses in Australia by country of birth, to understand any changes in epidemiology, relationship to migration patterns and implications for public health programs. Methods Poisson regression analyses were performed, comparing the age-standardised HIV diagnosis rates per 100,000 estimated resident population between 2006–2010 and 2011–2015 by region of birth, with stratification by exposure (male-to-male sex, heterosexual sex–males and females). Correlation between the number of permanent and long-term arrivals was also explored using linear regression models. Results Between 2006 and 2015, there were 6,741 new HIV diagnoses attributed to male-to-male sex and 2,093 attributed to heterosexual sex, with the proportion of diagnoses attributed to male-to-male sex who were Australian-born decreasing from 72.5% to 66.5%. Compared with 2006–2010, the average annual HIV diagnosis rate per 100,000 in 2011–15 attributed to male-to-male sex was significantly higher in men born in South-East Asia (summary rate ratio (SRR) = 1.37, p = 0.001), North-East Asia (SRR = 2.18, p<0.001) and the Americas (SRR = 1.37, p = 0.025), but significantly lower as a result of heterosexual sex in men born in South-East Asia (SRR = 0.49, p = 0.002), Southern and Central Asia (SRR = 0.50, p = 0.014) and Sub-Saharan Africa (SRR = 0.39, p<0.001) and women born in South-East Asia (SRR = 0.61, p = 0.002) and Sub-Saharan Africa (SRR = 0.61, p<0.001). Positive associations were observed between the number of permanent and long-term arrivals and HIV diagnoses particularly in relation to diagnoses associated with male-to-male sex in men from North Africa and the Middle East, North Asia, Southern and Central Asia and the Americas. Conclusion The epidemiology of HIV in Australia is changing, with an increase in HIV diagnosis rates attributed to male-to-male sex amongst men born in Asia and the Americas. Tailored strategies must be developed to increase access to, and uptake of, prevention, testing and treatment in this group.

Background Gonorrhoea notifications continue to rise among gay and bisexual men in Australia and around the world. More information is needed on infection trends, accounting for testing and complimented by demographics and risk practices. Methods: A retrospective cohort analysis was undertaken using repeat gonorrhoea testing data among gay and bisexual men from 2010 to 2017, which was extracted from a network of 47 sexual health clinics across Australia. Poisson and Cox regression analyses were used to determine temporal trends in gonorrhoea incidence rates, as well as associated demographic and behavioural factors. Results: The present analysis included 46904 gay and bisexual men. Gonorrhoea incidence at any anatomical site increased from 14.1/100 person years (PY) in 2010 to 24.6/100 PY in 2017 (P&lt;0.001), with the greatest increase in infections of the pharynx (5.6-15.9/100 PY, P&lt;0.001) and rectum (6.6–14.8/100 PY, P&lt;0.001). After adjusting for symptomatic and contact-driven presentations, the strongest predictors of infection were having more than 20 sexual partners in a year (hazard ratio (HR)=1.9, 95% confidence interval (CI): 1.7–2.2), using injecting drugs (HR=1.7, 95%CI: 1.4–2.0), being HIV positive (HR=1.4, 95%CI: 1.2–1.6) and being aged less than 30 years old (HR=1.4, 95%CI: 1.2–1.6). Conclusions: Gonorrhoea has increased dramatically among gay and bisexual men in Australia. Enhanced prevention efforts, as well as more detailed, network-driven research are required to combat gonorrhoea among young men, those with HIV and those who use injecting drugs.

IMPORTANCEThere have been concerns that HIV preexposure prophylaxis (PrEP) may be associated with increases in sexually transmitted infections (STIs) because of subsequent reductions in condom use and/or increases in sexual partners. OBJECTIVE To determine trends in STI test positivity among high-risk men who have sex with men (MSM) before and after the start of HIV PrEP. DESIGN, SETTING, AND PARTICIPANTSA before-after analysis was conducted using a subcohort of a single-group PrEP implementation study cohort in New South Wales, Australia (Expanded PreEP Implementation in Communities in New South Wales [EPIC-NSW]), from up to 1 year before enrollment if after January 1, 2015, and up to 2 years after enrollment and before December 31, 2018. STI testing data were extracted from a network of 54 sexual health clinics and 6 primary health care clinics Australia-wide, using software to deidentify, encrypt, and anonymously link participants between clinics. A cohort of MSM dispensed PrEP for the first time during the study, with 2 or more STI tests in the prior year and who tested during follow-up, were included from the EPIC-NSW cohort of HIV-negative participants with high-risk sexual behavior. Data analysis was performed from June to December 2019. EXPOSURES Participants were dispensed coformulated tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) as HIV PrEP. MAIN OUTCOMES AND MEASURESThe main outcome was STI, measured using test positivity, defined as the proportion of participants testing positive for an STI at least once per quarter of follow-up. Outcomes were calculated for Chlamydia trachomatis and Neisseria gonorrhoea by site of infection (anorectal, pharyngeal, urethral, or any) and for syphilis. RESULTSOf the EPIC-NSW cohort of 9709 MSM, 2404 were included in the before-after analysis.The mean (SD) age of the participants was 36 (10.4) years, and 1192 (50%) were Australia-born. STI positivity was 52% in the year after PrEP (23.3% per quarter; 95% CI, 22.5%-24.2% per quarter) with no significant trend (mean rate ratio [RR] increase of 1.01 per quarter [95% CI, 0.99-1.02]; P = .29), compared with 50% positivity in the year prior to PrEP (20.0% per quarter [95% CI, 19.04%-20.95% per quarter]; RR for overall STI positivity, 1.17 [95% CI, 1.10-1.24]; P < .001), with an increase in quarterly STI positivity (mean RR of 1.08 per quarter, or an 8% increase per quarter [95% CI, 1.05-1.11]; P < .001; RR, 0.93 [95% CI, 0.90-0.96]; P < .001). Findings were similar when stratified by specific STIs and anatomical site. (continued) Key Points Question Is access to HIV preexposure prophylaxis (PrEP) associated with the trajectory of preexisting trends in sexually transmitted infections (STIs) among high-risk men who have sex with men (MSM)? Findings In a before-after cohort study of high-risk MSM participating in a population-based PrEP implementation project, STI positivity was high while men were taking PrEP with no increasing trend in quarterly STI positivity, compared with similar high positivity before P...