Investigating rates and predictors of viral blips, low-level viraemia and virological failure in the Australian HIV observational database.

OBJECTIVES: Australia has made significant progress towards achieving the UNAIDS's 95-95-95 cascade targets including HIV viral suppression. To investigate the burden of HIV viraemia, we assessed viral blips, low-level viraemia (LLV) and virologic failure (VF) in an Australian cohort. METHODS: We studied the proportion of people with viral suppression, viral blips, LLV and VF in the Australian HIV observational database (AHOD) between 2010 and 2021. The association between blips or LLV, and VF was investigated using Cox regression, and predictors of viral blips and LLV were assessed using repeated-measured logistic regression. RESULTS: Among 2544 AHOD participants who were in follow-up and on antiretroviral therapy (ART) from 1 January 2010 (88.7% male), 444 had experienced VF (incidence rate: 2.45 [95% CI: 2.23-2.69] per 100 person-years [PY]) during 18,125 PY of follow-up (a median of 7.6 years). The proportion of people with VF decreased over time, whereas rates of blips and LLV remained stable. Participants with blips (hazard ratio, 2.89; 95% CI: 2.31-3.61) and LLV (4.46; 95% CI: 3.38-5.89) were at increased risk of VF. Hepatitis B co-infection, longer documented treatment interruption duration, younger age and lower CD4 at ART initiation, and protease inhibitors-based initial regimen were associated with an increased risk of VF. Common predictors of blips and LLV such as higher HIV-1 RNA and lower CD4 at ART initiation, longer treatment interruption, more VL testing and types of care settings (hospitals vs. sexual health services) were identified. CONCLUSIONS: Blips and LLV predict subsequent VF development. We identified important predictors of HIV viraemia including VF among individuals on INSTI-based regimens to help direct HIV management plans.

HIV-1 subtype variability and transmitted drug resistance in a culturally diverse population in Western Sydney, New South Wales, Australia.

Background Transmitted human immunodeficiency virus type 1 (HIV-1) drug resistance (TDR) is an important contributor to antiretroviral treatment failure, and is associated with HIV-1 transmission among men who have sex with men (MSM), non-MSM clusters and individuals diagnosed with concurrent sexually transmissible infections (STI). Western Sydney has a culturally diverse population, with a high proportion of non-Australian-born individuals. This study describes the prevalence of TDR and non-B HIV-1 subtypes in a clinic-based population. METHODS: A clinic database was examined for all newly diagnosed treatment-naïve HIV-1 patients and information on their HIV-1 resistance and subtype, demographics including country of birth and diagnosis of a bacterial sexually transmissible infection was collected. RESULTS: Data were available from 74/79 individuals (62 cis-male, 16 cis-female and 1 transgender woman). Of the 74 genotypes, the prevalence of non-B subtypes and TDR was 43/74 (58%; 95%CI = 46.9-69.3) and 14/74 (19%; 95%CI = 10.0 to 27.8). It was also found that 30/79 (38%) had a concurrent bacterial STI. TDR was associated with subtype B infection (OR 3.53; 95%CI = 1.41-8.82; P = 0.007) and being born in Australia (OR 12.0; 95%CI = 2.45-58.86; P = 0.002). CONCLUSION: The relative prevalence of non-B HIV-1 subtypes and TDR is higher in Western Sydney than in the rest of Australia. TDR is associated with subtype B HIV-1 and being Australian born, suggesting ongoing local transmission. This highlights the diversity of the HIV epidemic locally and the need for interventions to prevent ongoing HIV transmission.

Population-level effectiveness of rapid, targeted, high-coverage roll-out of HIV pre-exposure prophylaxis in men who have sex with men: the EPIC-NSW prospective cohort study.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is highly effective in men who have sex with men (MSM) at the individual level, but data on population-level impact are lacking. We examined whether rapid, targeted, and high-coverage roll-out of PrEP in an MSM epidemic would reduce HIV incidence in the cohort prescribed PrEP and state-wide in Australia's most populous state, New South Wales. METHODS: The Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) study is an implementation cohort study of daily co-formulated tenofovir disoproxil fumarate and emtricitabine as HIV PrEP. We recruited high-risk gay men in a New South Wales-wide network of 21 clinics. We report protocol-specified co-primary outcomes at 12 months after recruitment of the first 3700 participants: within-cohort HIV incidence; and change in population HIV diagnoses in New South Wales between the 12-month periods before and after PrEP roll-out. The study is registered with ClinicalTrials.gov, number NCT02870790. FINDINGS: We recruited 3700 participants in the 8 months between March 1, 2016, and Oct 31, 2016. 3676 (99%) were men, 3534 (96%) identified as gay, and 149 (4%) as bisexual. Median age was 36 years (IQR 30-45 years). Overall, 3069 (83%) participants attended a visit at 12 months or later. Over 4100 person-years, two men became infected with HIV (incidence 0·048 per 100 person-years, 95% CI 0·012-0·195). Both had been non-adherent to PrEP. HIV diagnoses in MSM in New South Wales declined from 295 in the 12 months before PrEP roll-out to 221 in the 12 months after (relative risk reduction [RRR] 25·1%, 95% CI 10·5-37·4). There was a decline both in recent HIV infections (from 149 to 102, RRR 31·5%, 95% CI 11·3 to 47·3) and in other HIV diagnoses (from 146 to 119, RRR 18·5%, 95% CI -4·5 to 36·6). INTERPRETATION: PrEP implementation was associated with a rapid decline in HIV diagnoses in the state of New South Wales, which was greatest for recent infections. As part of a combination prevention approach, rapid, targeted, high-coverage PrEP implementation is effective to reduce new HIV infections at the population level. FUNDING: New South Wales Ministry of Health, Gilead Sciences.

Non-AIDS complexity amongst patients living with HIV in Sydney: risk factors and health outcomes.

OBJECTIVE: To assess the prevalence of non-AIDS co-morbidities (NACs) and predictors of adverse health outcomes amongst people living with HIV in order to identify health needs and potential gaps in patient management. DESIGN: Retrospective, non-consecutive medical record audit of patients attending a publicly funded HIV clinic in metropolitan Sydney analysed for predictors of adverse health outcomes. We developed a scoring system based on the validated Charlson score method for NACs, mental health and social issues and confounders were selected using directed acyclic graph theory under the principles of causal inference. RESULTS: 211 patient files were audited non-consecutively over 6 weeks. 89.5% were male; 41.8% culturally and linguistically diverse and 4.1% were of Aboriginal/Torres Strait Islander origin. Half of patients had no general practitioner and 25% were ineligible for Medicare subsidised care. The most common NACs were: cardiovascular disease (25%), hepatic disease (21%), and endocrinopathies (20%). One-third of patients had clinical anxiety, one-third major depression and almost half of patients had a lifetime history of tobacco smoking. Five predictors of poor health outcomes were identified: (1) co-morbidity score was associated with hospitalisation (odds ratio, OR 1.58; 95% CI 1.01-2.46; p = 0.044); (2) mental health score was associated with hospitalisation (OR 1.79; 95% CI 1.22-2.62; p = 0.003) and poor adherence to ART (OR 2.34; 95% CI 1.52-3.59; p = 0.001); (3) social issues score was associated with genotypic resistance (OR 2.61; 95% CI 1.48-4.59; p = 0.001), co-morbidity score (OR 1.69; 95% CI 1.24-2.3; p = 0.001) and hospitalisation (OR 1.72; 95% CI 1.1-2.7; p = 0.018); (4) body mass index < 20 was associated with genotypic resistance (OR 6.25; 95% CI 1.49-26.24; p = 0.012); and (5) Medicare eligibility was associated with co-morbidity score (OR 2.21; 95% CI 1.24-3.95; p = 0.007). CONCLUSION: Most HIV patients are healthy due to effective antiretroviral therapy; however, NACs and social/mental health issues are adding to patient complexity. The current findings underpin the need for multidisciplinary management beyond routine viral load and CD4 count monitoring.

Capacity of non-invasive hepatic fibrosis algorithms to replace transient elastography to exclude cirrhosis in people with hepatitis C virus infection: A multi-centre observational study.

INTRODUCTION: Achievement of the 2030 World Health Organisation (WHO) global hepatitis C virus (HCV) elimination targets will be underpinned by scale-up of testing and use of direct-acting antiviral treatments. In Australia, despite publically-funded testing and treatment, less than 15% of patients were treated in the first year of treatment access, highlighting the need for greater efficiency of health service delivery. To this end, non-invasive fibrosis algorithms were examined to reduce reliance on transient elastography (TE) which is currently utilised for the assessment of cirrhosis in most Australian clinical settings. MATERIALS AND METHODS: This retrospective and prospective study, with derivation and validation cohorts, examined consecutive patients in a tertiary referral centre, a sexual health clinic, and a prison-based hepatitis program. The negative predictive value (NPV) of seven non-invasive algorithms were measured using published and newly derived cut-offs. The number of TEs avoided for each algorithm, or combination of algorithms, was determined. RESULTS: The 850 patients included 780 (92%) with HCV mono-infection, and 70 (8%) co-infected with HIV or hepatitis B. The mono-infected cohort included 612 men (79%), with an overall prevalence of cirrhosis of 16% (125/780). An 'APRI' algorithm cut-off of 1.0 had a 94% NPV (95%CI: 91-96%). Newly derived cut-offs of 'APRI' (0.49), 'FIB-4' (0.93) and 'GUCI' (0.5) algorithms each had NPVs of 99% (95%CI: 97-100%), allowing avoidance of TE in 40% (315/780), 40% (310/780) and 40% (298/749) respectively. When used in combination, NPV was retained and TE avoidance reached 54% (405/749), regardless of gender or co-infection. CONCLUSIONS: Non-invasive algorithms can reliably exclude cirrhosis in many patients, allowing improved efficiency of HCV assessment services in Australia and worldwide.

Sex differences in the significance of isolated reactive treponemal chemiluminescence immunoassay results.

OBJECTIVES: The significance of sera with isolated reactive treponemal chemiluminescence immunoassay (IRTCIA) results is unclear. Women have this phenotype more commonly than men. Most cohorts examining this phenotype have included predominantly men and have demonstrated evidence of past or subsequently confirmed syphilis infection in a significant proportion of cases. We hypothesised that a proportion of sera with IRTCIA results would be positive on immunoblot testing and that sera from women with IRTCIA would have different results in immunoblot testing than men. METHODS: IRTCIA sera from a tertiary referral serology laboratory serving multiple clinical sites were analysed with a syphilis line immunoblot assay (LIA) and analysed by sex. Logistic regression was undertaken to assess factors associated with LIA status. Medical record review and descriptive analysis of a separate cohort of women with the IRTCIA phenotype from a single campus was also undertaken. RESULTS: Overall, 19/63 (30.1%) subjects with the IRTCIA phenotype were positive in the LIA, including 13 men and 6 women. Women were significantly less likely to have definitive results (positive or negative) than men (p=0.015). Pregnant women were less likely than non-pregnant women to have a negative LIA result (OR 0.57; p=0.03). Record review of 22 different women with IRTCIA reactivity showed that 2/22 (9.1%) had HIV and previous syphilis infection, 15/22 (68.2%) were pregnant and 3 (13.6%) had autoimmune disease. CONCLUSIONS: A significant proportion of sera with IRTCIA results on serological tests are reactive on LIA testing and some may not be false positive results. The interpretation of IRTCIA results should be undertaken in conjunction with an assessment of factors such as sex, pregnancy, a history of syphilis and other STIs and syphilis risk.

Antiretroviral Use in the CEASE Cohort Study and Implications for Direct-Acting Antiviral Therapy in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection.

Background. Interferon-free direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) provide a major advance in clinical management, including in human immunodeficiency virus (HIV)/HCV coinfection. Drug-drug interactions (DDIs) with combination antiretroviral therapy (cART) require consideration. This study aimed to characterize the cART regimens in HIV/HCV-coinfected individuals and assess the clinical significance of DDIs with DAAs in a real-world cohort. Methods. This analysis included participants enrolled in CEASE-D, a prospective cohort of HIV/HCV-coinfected individuals in Sydney, Australia, between July 2014 and December 2015. A simulation of potential DDIs between participants' cART and interferon-free DAA regimens was performed using www.hep-druginteractions.org and relevant prescribing information. Results. In individuals on cART with HCV genotype (GT) 1 and 4 (n = 128), category 3 DDIs (contraindicated or not recommended) were noted in 0% with sofosbuvir/ledipasvir, 0% with sofosbuvir plus daclatasvir, 17% with sofosbuvir/velpatasvir, 36% with ombitasvir/paritaprevir/ritonavir ± dasabuvir, 51% with grazoprevir/elbasvir, and 51% with sofosbuvir plus simeprevir; current cART regimens were suitable for coadministration in 100%, 100%, 73%, 64%, 49%, and 49%, respectively. In individuals with HCV GT 2 or 3 (n = 53), category 3 DDIs were evident in 0% with sofosbuvir plus daclatasvir, 0% with sofosbuvir and ribavirin, and 13% with sofosbuvir/velpatasvir; current cART regimens were suitable in 100%, 100%, and 81%, respectively. Conclusions. Potential DDIs are expected and will impact on DAA prescribing in HIV/HCV coinfection. Sofosbuvir in combination with an NS5A inhibitor or ribavirin appeared to be the most suitable regimens in this cohort. Evaluation of potential DDIs is required to prevent adverse events or treatment failure.