Background Daily pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but few long-term data are available on effectiveness and adherence in real-world settings. Here, we report trends in HIV incidence over 3 years in individuals at high risk who were prescribed PrEP in New South Wales (NSW), as well as adherence before the transition to subsidised PrEP. Methods Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) was a pragmatic, prospective, single-arm, implementation study of daily, oral PrEP in 31 sites (sexual health clinics, general practices, and a hospital) in NSW, Australia. Eligible participants were HIV-negative adults (aged >= 18 years) who were at high risk of HIV infection as defined in local PrEP guidelines. Participants were prescribed coformulated (once-daily, oral tablet) tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) as HIV PrEP and were followed up with HIV testing, sexually transmitted infection testing, and PrEP dispensing. Originally planned for 3700 participants followed for 1 year, the study was expanded so that all eligible participants in the state could obtain PrEP and extended until publicly subsidised PrEP became available in Australia. The primary outcome was new HIV infection among all participants who were dispensed PrEP at least once and had at least one follow-up HIV test result. Adherence was estimated by medication possession ratio (MPR), defined as the proportion of PrEP pills dispensed in 90 days, assuming daily dosing. This study is registered with ClinicalTrials.gov, NCT02870790. Findings Between March 1, 2016, and April 30, 2018, we enrolled 9709 participants. 9596 participants were dispensed PrEP, of whom 9448 (98.3%) were gay or bisexual men. Participants were followed up until March 31, 2019, with at least one follow-up HIV test available in 9520 (99.2%) participants. Mean MPR declined from 0.93 to 0.64 from the first to the ninth quarter. There were 30 HIV seroconversions over 18 628 person-years, an incidence of 1.61 per 1000 person-years (95% CI 1.13-2.30). Being younger, living in a postcode with fewer gay men, reporting more risk behaviours at baseline, and having an MPR of less than 0.6 were each univariately associated with increased HIV incidence. In the final year of follow-up, when PrEP was mostly purchased rather than provided free by the study, HIV incidence remained low at 2.24 per 1000 person-years (1.46-3.44). Interpretation HIV incidence remained low over up to 3 years of follow-up, including during a transition from study-provided to publicly subsidised PrEP. In a setting of affordable PrEP and associated health-care services, very low HIV incidence of 1 to 2 per 1000 person-years can be maintained in gay and bisexual men who were previously at high risk.

Background: HCV elimination among people living with HIV may be feasible in Australia, given unrestricted access to direct-acting antiviral (DAA) therapy (from March 2016). Our aim was to evaluate HCV treatment uptake, outcome, and HCV RNA prevalence among HIV/HCV co-infected adults in Australia following the availability of DAA therapy.

Introduction ENCORE1 compared the efficacy and safety of reduced versus standard dose efavirenz (EFV) with tenofovir/emtricitabine (TDF/FTC) as first‐line HIV therapy. The primary analysis at 48 weeks showed 400 mg EFV was safe and virologically non‐inferior to 600 mg. This analysis explores over 96 weeks the durability of efficacy and safety. Materials and Methods A multinational, double‐blind, placebo‐controlled, non‐inferiority trial in treatment‐naïve HIV‐positive adults randomized to TDF/FTC plus reduced (400 mg, EFV400) or standard dose (600 mg, EFV600) EFV. The difference between proportions of participants with plasma HIV RNA (VL) <200 log 10 copies/mL by intention‐to‐treat (ITT missing=failure) was compared using a non‐inferiority margin of −10%. Non‐inferiority was also examined in per protocol (PP) and non‐completer = failure (NC=F) populations. Adverse events (AEs) and serious adverse events (SAEs) were summarized by treatment arm. Results The ITT population comprised 630 patients (EFV400 = 321; EFV600 = 309); 32% were female; 37%, 33% and 30% were African, Asian and Caucasian, respectively. A total of 585 (EFV400 = 299; EFV600 = 286) completed 96 weeks on randomized therapy. At 96 weeks, proportions with VL <200 copies/mL were EFV400 (90.0%) and EFV600 (90.6%) (difference −0.6; 95% CI −5.2 to 4.0; p =0.72) demonstrating continued non‐inferiority. Non‐inferior efficacy was also observed for VL thresholds of <50 and <400 copies/mL irrespective of baseline VL (<100,000 versus ≥100,000 copies/mL). There was no between‐arm difference in time to loss of virological response (>200 copies/mL) ( p =0.47) or mean change from baseline VL ( p =0.74). Mean change from baseline in CD4 T‐cell counts at week 96 remained significantly higher for EFV400 than EFV600 (difference 25 cells/µL; 95% CI 2–48; p =0.03). There was no difference in the frequency or severity of AEs (EFV400 = 89.4%, EFV600 = 89.3%; difference 0.09; 95% CI −4.73 to 4.90; p =0.97). The proportions ever reporting an AE definitely or probably EFV‐related were EFV400 (37.7%) and EFV600 (47.9%) (difference −10.2%; 95% CI −17.9 to −2.51; p =0.01). SAEs did not differ in frequency (EFV400 = 7.5%, EFV600 = 10.4%; difference −2.9%; 95% CI −7.3 to 1.6; p =0.20). Conclusions Non‐inferiority of EFV 400 mg to EFV 600 mg when combined with TDF/FTC as initial HIV therapy was confirmed at week 96. Both doses demonstrated similar safety profiles. These results support the use of a lower EFV dose as part of routine HIV management.

Objectives The aim of this study was to evaluate the feasibility, safety and efficacy of treatment for chronic hepatitis C virus (HCV) infection through a primary care-based model for the delivery of HCV services in New South Wales (NSW), Australia. Participants and methods This observational cohort study recruited participants through seven primary care clinics in NSW, Australia, between November 2010 and June 2013. Patients with HCV genotype 2/3 were treated without specialist review, whereas those with genotype 1 required an initial specialist review. Treatment consisted of pegylated interferon-&agr;-2a/2b and ribavirin. Sustained virological response and adverse events were evaluated. Results Among 41 participants (mean age 44 years, 73% men) initiating treatment with pegylated interferon-&agr;-2a/2b and ribavirin, 90% had injected drugs ever, 16% had injected drugs in the past 30 days and 56% had ever received opioid substitution treatment. HCV genotype 1 and genotype 2/3 occurred in 17% (n=7) and 83% (n=34). Treatment was completed in 83% (34 of 41), with seven discontinuations [adverse event (depression), n=1; patient decision, n=1; lost to follow-up, n=3; virological nonresponse, n=2]. In an intent-to-treat analysis, sustained virological response was 71% overall (29 of 41), 43% in genotype 1 (three of seven) and 76% in genotype 2/3 (26 of 34). Conclusion Initiation of HCV treatment in the primary care setting is an effective alternative for selected patients and may contribute towards increasing access to HCV care.

Background: The brief period of viral replication in recurrent genital herpes lesions suggests shorter therapeutic regimens may be as effective as standard 5-day courses. Objective: To demonstrate that a 2-day course of famciclovir 500 mg statim, then 250 mg twice daily was non-inferior to the standard 5-day course of 125 mg twice daily. Methods: Patients were randomly assigned either the 2-day or 5-day famciclovir course and initiated therapy within 12 h of onset of prodromal symptoms. They were instructed to complete daily questionnaires on herpes-related symptoms and functioning and to attend the clinic for assessment of healing 5.5 days after initiating therapy. Results: A total of 873 patients were randomised at least once and 1038 recurrences were treated. The proportion of evaluable recurrences with lesions present at 5.5 days was less in the 2-day arm (24%) than in the 5-day (28%) arm. The upper 97.5% confidence limit (CL) for this difference in favour of the 2-day arm was 2% in favour of the 5-day arm, well within the 10% predefined for non-inferiority. The upper 97.5% CL was similar in the intent-to-treat, evaluable and per-protocol recurrence populations and when adjusted for baseline differences (in gender, age, herpes history and HIV infection) or for clustering of recurrences within patients. Both treatments had similar side-effects; proportion of lesions aborted; time to next recurrence; patient-reported symptoms; and impact on daily functioning. Conclusions: The 2-day course was as safe and effective as the standard 5-day course and can only enhance patient convenience and compliance.

Background ESPRIT is a randomized trial comparing the clinical impact of interleukin (IL)-2 plus antiretrovirals vs antiretrovirals alone. Identification of factors that influence the relationship between IL-2 and CD4 count recovery will enable better personalization of treatment with IL-2 in HIV-1-positive individuals. The IL-2 induction phase consists of three dosing cycles over 6-8 months (7.5 MIU twice a day, for 5 days every 8 weeks).Methods We included patients initiating IL-2 at the 7.5 MIU dose with an 8-month CD4 count, measured at least 30 days after their last cycle. We identified baseline predictors of CD4 count changes over 8 months using linear regression.Results Of 2090 patients assigned IL-2, 1673 (80%) were included in the analysis. The median (interquartile range) baseline CD4 count was 461 (370, 587) cells/mu L with a median increase of 233 (90, 411) cells/mu L at month 8. After adjustments, significant predictors of CD4 count change included CD4 nadir (29.8 cells/mu L greater increase per 100 cells/mu L higher; P < 0.0001), last CD4 count before baseline (mean 36.0 cells/mu L greater increase per 100 cells/mu L higher; P < 0.0001), time from antiretroviral start to baseline (8.3 cells/mu L smaller increase per year longer; P=0.001), age (11.7 cells/mu L smaller increase per 5 years older; P=0.005) and race (79.7 cells/mu L greater increase for black patients vs white patients; P=0.003). A linear relationship existed between total IL-2 dose in the first cycle and CD4 count change (73.1 cells/mu L greater increase per 15 MIU higher; P < 0.0001).Conclusions Prior nadir and current CD4 counts, age and IL-2 dose are major determinants of CD4 increases induced by with intermittent administration of IL-2 in HIV-1-positive individuals on antiretrovirals. The clinical function of these induced CD4 cells is under study.