Human immunodeficiency virus (HIV) infection can lead to various neurologic complications affecting central and peripheral nervous systems. Rarely, patients on combined anti-retroviral therapy (CART) with peripheral virologic suppression may develop compartmentalised central nervous system infection with cerebrospinal fluid (CSF) viral escape. We report the case of a 42-year-old man with chronic HIV infection and a previous diagnosis of Parkinson's disease referred for neurologic evaluation with diffuse hyperreflexia including brisk jaw jerk. He was adherent to combined anti-retroviral therapy (CART). During follow-up, he developed mild upper and lower limb weakness and gait instability. Electromyography was consistent with a motor neuropathy or neuronopathy. Neuraxial MRI showed non-specific supratentorial white matter lesions. Plasma HIV viral load was suppressed (<20 copies/mL) whereas CSF viral load was 35 copies/mL, consistent with CSF viral escape. CSF neopterin level was elevated indicating neuroinflammation. HIV-associated neurological overlap syndrome, with parkinsonism and an amyotrophic lateral sclerosis-like syndrome, in the context of neurosymptomatic CSF escape was diagnosed. The patient's HIV CART regime was adjusted to improve CNS penetration. Neurosymptomatic HIV CSF escape is a rare and likely under-recognised complication which can occur despite compliance with CART. When suspected, CSF viral load should be tested. CART optimisation to improve CNS penetration may be potentially beneficial in neurosymptomatic CSF viral escape and to reduce HIV-associated neurotoxicity, but these require further study to confirm.

ABSTRACT:Given injectable HIV preexposure prophylaxis (PrEP) has unique service-delivery requirements, there is a need to investigate the feasibility of its implementation and equitable access for people at risk of HIV. Data were collected from 45 informants (nurses, physicians, general practitioners, policy makers, and community representatives) to identify barriers to and facilitators of implementing long-acting injectable cabotegravir (CAB-LA) in Australian settings. Findings were mapped onto the domains of the updated Consolidated Framework for Implementation Research. Informants welcomed new PrEP options as a way of addressing issues of access equity. However, they questioned the benefits of CAB-LA over oral PrEP, given its dose-scheduling requirements and long pharmacokinetic tail, as well as its cost, complexity, and potential to "remedicalize" PrEP, reversing current trends in PrEP prescribing and consumption. Other concerns included increased resource and capacity implications for clinics resulting from initial assessments and the increased number (and complexity) of subsequent visits.

Introduction: HIV preexposure prophylaxis (PrEP) is highly effective at preventing HIV. We aimed to assess mental and physical health among long-term PrEP users in Australia's X-PLORE cohort. Methods: In early 2021, 1485 X-PLORE participants were emailed a survey covering demographics, sexual practices, ongoing PrEP use, physical and psychological diagnoses received since commencing PrEP, substance use, and impacts of the COVID-19 pandemic. Current anxiety and depression were assessed using GAD-7 and PHQ-9 questionnaires. Results: Of 476 participants (completion rate 32.1%), 99.8% were cis-gender men. Median PrEP use duration was 48 months (2002 person-years), with 81.7% currently using PrEP. PrEP-related toxicity was uncommon: 2.9% reported bone fractures, 1.3% low bone density, and 4.0% reported kidney problems, largely not necessitating PrEP cessation. Most (92.0%) rated their health as ‘good’ to ‘excellent’, and 22.6% reported improved health since starting PrEP, often because of improved mental health. Only 6.2% reported deterioration in health since starting PrEP, largely unrelated to PrEP. The most common diagnoses were hypertension (9.9%), depression (13.2%) and anxiety (14.9%); 17% had PHQ-9 scores indicating current moderate-to-severe depression, which was associated with unemployment [adjusted odds ratio (aOR) 3.90], regular cannabis use (aOR 2.49), and having ceased PrEP (aOR 2.13). Conclusion: Among long-term PrEP users, of which over 80% were currently using PrEP, self-reported PrEP toxicity was uncommon. With almost one in five PrEP users categorized as having depression, and with higher risk among those having ceased PrEP, we recommend routine screening for depression and anxiety in PrEP users and corresponding follow-up of patients no longer attending for PrEP.

The emergency phase of the coronavirus disease 2019 (COVID-19) pandemic is over. Still, the work goes on in understanding the SARS-CoV-2 virus and its evolution, infection impacts - acute and long term - as well as therapeutics and the lessons for preventing and responding to future pandemics. Research into the long-term post-infection effects and therapeutic interventions also expands as the post-infection period lengthens. We provide an overview of the leading edge of COVID-19 research across clinical, epidemiological and social domains.

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.

Background In mid-2022, a global mpox (formerly ‘monkeypox’) outbreak affecting predominantly gay and bisexual men emerged in non-endemic countries. Australia had never previously recorded mpox cases and there was no prior research on knowledge or attitudes to mpox among gay and bisexual men across Australia. Methods We conducted a national, online cross-sectional survey between August 2022 and September 2022. Participants were recruited through community organisation promotions, online advertising, and direct email invitations. Eligible participants were gay, bisexual or queer; identified as male (cisgender or transgender) or non-binary; aged 16 years or older; and lived in Australia. The main outcome measures were: knowledge and concern about mpox; recognition of mpox symptoms and transmission routes; vaccination history; acceptability of behavioural changes to reduce mpox risk, and willingness to be vaccinated. Results Of 2287 participants, most participants were male (2189/2287; 95.7%) and gay (1894/2287; 82.8%). Nearly all had heard about mpox (2255/2287; 98.6%), and the majority were concerned about acquiring it (1461/2287; 64.4%). Most of the 2268 participants not previously diagnosed with mpox correctly identified skin lesions (2087; 92%), rash (1977; 87.2%), and fever (1647; 72.6%) as potential symptoms, and prolonged and brief skin-to-skin contact as potential ways to acquire mpox (2124, 93.7%; and 1860, 82%, respectively). The most acceptable behavioural changes were reducing or avoiding attendance at sex parties (1494; 65.9%) and sex-on-premises venues (1503; 66.4%), and having fewer sexual partners (1466; 64.6%). Most unvaccinated and undiagnosed participants were willing to be vaccinated (1457/1733; 84.1%). Conclusions People at risk of mpox should be supported to adopt acceptable risk reduction strategies during outbreaks and to seek vaccination.

Background Although data from large implementation trials suggest that sexually transmissible infection (STI) risk increases among gay and bisexual men who initiate HIV pre-exposure prophylaxis (PrEP), there are few data on the trends in population-level STI incidence in the years following widespread PrEP implementation. We aimed to describe trends in bacterial STI incidence among gay and bisexual men using PrEP across Australia in the context of broad PrEP availability through Australia's subsidised medicines scheme. Methods We analysed linked clinical data from HIV-negative gay and bisexual men aged 16 years or older who had been prescribed PrEP across a sentinel surveillance clinical network, including 37 clinics in Australia, between Jan 1, 2016, and Dec 31, 2019. Patients were included if they had STI testing at least twice during the observation period. Repeat testing methods were used to calculate chlamydia, gonorrhoea, syphilis, and any STI incidence rates during individuals' periods of PrEP use. Incidence rate ratios (IRRs) for estimated change in incidence per half calendar year (6-month) period were calculated using negative binomial regression. Secondary analyses compared STI incidence rates across individuals initiating PrEP in each year from 2016 to 2019, as well as by length of time using PrEP (per each additional 6 months of PrEP use). Findings 22 730 men were included in the analyses. During the observation period, 11 351 chlamydia infections were diagnosed in 6630 (30.1%) of 22 034 men over 25 991.2 person-years of PrEP use (incidence rate 43.7 cases [95% CI 42.9-44.5] per 100 person-years). Chlamydia incidence decreased from 48.7 cases per 100 person-years in July-December, 2016, to 42.0 cases per 100 person-years in July-December, 2019 (IRR for estimated change per 6-month period 0.98 [95% CI 0.97-0.99]; p=0.0031). 9391 gonorrhoea infections were diagnosed in 5885 (26.9%) of 21 845 men over 24 858.7 person-years of PrEP use (incidence rate 37.8 cases [95% CI 37.0-38.5] per 100 person-years). Gonorrhoea incidence decreased from 45.5 cases per 100 person-years in July-December, 2016, to 37.2 cases per 100 person-years in July-December, 2019 (IRR 0.97 [95% CI 0.96-0.98]; p<0.0001). Declines in chlamydia and gonorrhoea incidence were most prominent in the first 18 months of observation and incidence was stable thereafter. 2062 syphilis infections were diagnosed in 1488 (7.7%) of 19 262 men over 21 978.9 person-years of PrEP use (incidence rate 9.4 cases [95% CI 9.0-9.8] per 100 person-years). Syphilis incidence increased from 6.2 cases per 100 person-years in July-December, 2016, to 9.8 cases per 100 person-years in July-December, 2019 (IRR 1.08 [95% CI 1.05-1.10]; p<0.0001). Interpretation Chlamydia and gonorrhoea incidence among gay and bisexual men using PrEP were highest in the early months of PrEP implementation in Australia and stabilised at slightly lower rates thereafter following wider PrEP uptake. Lower prospective STI risk among people initiating PrEP in later years contributed to the observed trends in STI incidence. Widespread PrEP implementation can contribute to increased STI screening and detection. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

Background. Identifying factors that determine the frequency of latently infected CD4+ T cells on antiretroviral therapy (ART) may inform strategies for human immunodeficiency virus (HIV) cure. We investigated the role of CD4+ count at ART initiation for HIV persistence on ART. Methods. Among participants of the Strategic Timing of Antiretroviral Treatment Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500-599, 600-799, or >= 800 cells/mm(3). After 36-44 months on ART, the levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA), and two-long terminal repeat HIV-DNA in CD4+ T cells were quantified and plasma HIV-RNA was measured by single-copy assay. We measured T-cell expression of Human Leucocyte Antigen-DR Isotype (HLA-DR), programmed death-1, and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata. Results. We enrolled 146 PWH, 36 in the 500-599, 60 in the 600-799, and 50 in the >= 800 CD4 strata. After 36-44 months of ART, total HIV-DNA, plasma HIV-RNA, and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count = 800 cells/mm3 at ART initiation compared with 600-799 or 500-599 cells/mm3. The median level of HIV-DNA after 36-44 months of ART was lower by 75% in participants initiating ART with >= 800 vs 500-599 cells/mm(3) (median [interquartile range]: 16.3 [7.01-17.6] vs 68.4 [13.7-213.1] copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females. Conclusions. Initiating ART with a CD4+ count = 800 cells/mm3 compared with 600-799 or 500-599 cells/mm3 was associated with achieving a substantially smaller HIV reservoir on ART.

IntroductionOverseas-born and newly arrived gay and bisexual men and men who have sex with men (GBMSM) are at higher risk of acquiring HIV in comparison to Australian-born GBMSM. Pre-exposure prophylaxis (PrEP) is subsidized by the Australian government under Medicare, Australia's universal health insurance scheme, however many members of this population are Medicare-ineligible, which could prevent them from accessing PrEP. We wanted to explore participants' knowledge of and attitudes toward PrEP and their opinions of new PrEP modalities, namely injectable PrEP and PrEP implants.MethodsWe conducted in-depth qualitative interviews between February 2021 to September 2021 with 22 overseas-born, newly arrived (<5 years in Australia) GBMSM of varying PrEP use. We asked their opinions of PrEP and their preferences of new PrEP modalities. Interviews were audio recorded and transcribed verbatim. We conducted a reflexive thematic analysis to interpret the data.ResultsParticipants' views reflect the intersections between systemic factors, such as Medicare ineligibility and the high cost of PrEP, with socio-cultural factors, such as lack of knowledge about PrEP, internalized stigma stemming from homo- and sex-negativity, and stigmatizing attitudes toward PrEP and PrEP users. For participants who were on PrEP, being community connected, having a positive relationship with doctors and nurses, and being informed of the option to purchase PrEP from overseas pharmacies at a low cost helped them to overcome some of these barriers. Additionally, there was a strong preference for injectable PrEP but not PrEP implants. Participants stressed the importance of providing a comprehensive information about PrEP specific to this population and to make PrEP free for all.ConclusionsWe concluded that resources about PrEP specific to this population that address both systemic and socio-cultural factors are needed, and for these resources to be available in languages other than English. This is to coincide with on-going advocacy to increase the capacity of publicly funded sexual health clinics to provide multilingual PrEP services for people without Medicare, and to make PrEP free for all. These combined strategies have the potential to increase PrEP knowledge and uptake among this population.

To the Editor: People without Medicare coverage cannot access Pharmaceutical Benefits Scheme (PBS)subsidised human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) or associated clinical care. Rates of HIV infection diagnosis are disproportionately higher among overseasborn gay and bisexual men compared with Australianborn gay and bisexual men.1 In response, in June 2020, the Alfred Hospital and the Victorian Infectious Diseases Reference Laboratory established the free PrEPMe Clinic for Medicareineligible people. Data were collected using proformas after patients provided verbal consent (Alfred Health Ethics Committee approval No. 656/18).

Abstract Background Identifying factors that determine the frequency of latently infected CD4+ T-cells on antiretroviral therapy (ART) may inform strategies for HIV cure. We investigated the role of CD4 count at ART initiation for HIV persistence on ART. Methods Among participants of the Strategic Timing of Antiretroviral Treatment (START) Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500-599, 600-799 or ≥800 cells/mm 3. After 36-44 months on ART, we quantified levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA) and 2-long terminal repeat HIV-DNA in CD4+ T-cells and measured plasma HIV-RNA by single-copy assay. We measured T-cell expression of HLA-DR, programmed death-1, phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata. Results We enrolled 146 PWH, 36 in the 500-599, 60 in the 600-799 and 50 in the ≥800 CD4 strata. After 36-44 months of ART, total HIV-DNA, plasma HIV-RNA and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count ≥800 cells/mm 3 at ART initiation compared to 600-799 or 500-599 cells/mm 3. The median level of HIV-DNA after 36-44 months of ART was lower by 75% in participants initiating ART with ≥800 vs. 500-599 cells/mm 3 [median (IQR): 16.3 (7.0-117.6) vs. 68.4 (13.7-213.1) copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females.. Conclusion Initiating ART with a CD4+ count ≥800 cells/mm 3 compared to 600-799 or 500-599 cells/mm 3 was associated with achieving a substantially smaller HIV reservoir on ART.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) affect approximately half of people living with HIV despite viral suppression with antiretroviral therapies and represent a major cause of morbidity. HAND affects activities of daily living including driving, using the Internet and, importantly, maintaining drug adherence. Whilst viral suppression with antiretroviral therapies (ART) has reduced the incidence of severe dementia, mild neurocognitive impairments continue to remain prevalent. The neuropathogenesis of HAND in the context of viral suppression remains ill-defined, but underlying neuroinflammation is likely central and driven by a combination of chronic intermittent low-level replication of whole virus or viral components, latent HIV infection, peripheral inflammation possibly from a disturbed gut microbiome or chronic cellular dysfunction in the central nervous system. HAND is optimally diagnosed by clinical assessment with imaging and neuropsychological testing, which can be difficult to perform in resource-limited settings. Thus, the identification of biomarkers of disease is a key focus of the field. In this chapter, recent advances in the pathogenesis of HAND and biomarkers that may aid its diagnosis and treatment will be discussed.

Gay and bisexual men (GBM) who use pre-exposure prophylaxis (PrEP) are at increased risk of sexually transmitted infections (STIs) compared to those who don’t use PrEP. Since the implementation of PrEP in Australia, it is possible that attitudes towards STIs have shifted in line with changes in risk and transmission dynamics in the context of increased screening. As the extent to which GBM utilise STI prevention strategies likely depends on their attitudes towards STIs and STI prevention, the aims of this study were to use latent class analysis (LCA) to classify GBM using PrEP on the basis of their attitudes towards STIs and reported risk behaviours, and examine how these categorisations relate to risk of STI acquisition. 1225 GBM who were previously enrolled in a PrEP implementation study (The PrEPX Study) completed a survey focused on sexual behaviours and attitudes towards STIs 1 year post-study follow-up. Data on chlamydia, gonorrhoea and syphilis testing and positivity were available through a sentinel network of participating study clinics. Using LCA, participants were allocated into four classes; Class 1, “Some concern and lowest risk”; Class 2, “Low concern and lower risk”; Class 3, “ High concern and higher risk”; and Class 4, “Low concern and highest risk”. The majority (78%) of participants were classified into Class 3 or Class 4, two groups which were distinguished by highly disparate attitudes towards STIs but with a similar proportion of participants diagnosed with a bacterial STI in the last 12 months (48% and 57%, respectively). Findings suggest that attitudes towards STIs among GBM using PrEP in Australia vary considerably, and this will likely influence their receptivity to different STI prevention strategies.

We aimed to estimate how often urethral gonorrhoea is symptomatic among men in the Pre-Exposure Prophylaxis Expanded Victoria study. Eighty-seven percent of 213 cases of urethral gonorrhoea were symptomatic. Ensuring men with urethral gonorrhoea both recognize and present early for treatment is critical to reduce transmission.

Background The aim of this review is to explore acceptability, barriers, and facilitators to PrEP use among African migrants in high-income countries. Methods: A systematic review was conducted to explore reasons that contribute to low PrEP uptake in this population. Three online databases, abstracts from key conferences and reference lists of relevant studies articles published between the 2 July 2018 and 3 March 2019 were searched. Narrative synthesis was performed on quantitative data and thematic synthesis was performed on qualitative data. Results: Of 1779 titles retrieved, two cross-sectional studies (United States (US) (n = 1), United Kingdom (UK) (n = 1)) and six qualitative studies (US (n = 2), UK (n = 3), Australia (n = 1)) met inclusion criteria. PrEP acceptability was reported in one cross-sectional article and two qualitative articles. Cross-sectional studies measured acceptability and willingness to use PrEP; in one study, 46% of African migrant men found PrEP use acceptable, and following PrEP education, another study categorised 60% of participants as willing to use PrEP if it were cost-free. Qualitative studies reported mixed acceptability, with higher acceptability reported for serodiscordant couples. Barriers and facilitators to PrEP use were coded into five themes: cultural aspects of stigma; knowledge gap in health literacy; risks unrelated to HIV transmission; practical considerations for PrEP use; and the impact of PrEP use on serodiscordant couples. Conclusions: Several common barriers to PrEP use, including stigma, health literacy and risk perception and cost, were identified. Findings were limited by there being no published data on uptake. Additional work is needed to understand PrEP acceptability and uptake among African migrants.

BACKGROUND:PrEPX was an Australian HIV pre-exposure prophylaxis (PrEP) study conducted between 2016 and 2018. This analysis aimed to estimate hepatitis C (HCV) incidence and explore likely modes of transmission.SETTING:Cohort study of PrEP users in Victoria, Australia.METHODS:HCV tests were conducted at enrollment and every 12 months thereafter. HCV incident cases were identified from laboratory data. Likely modes of transmission were inferred from computer-assisted self-interviews, medical records, and interviews.RESULTS:Among 3202 PrEPX participants tested for HCV at baseline, HCV RNA-positive prevalence was 0.22% (95% confidence interval: 0.09 to 0.45). Among participants testing HCV antibody-negative or RNA-negative at baseline, 2058 had at least one follow-up HCV test. Eight incident HCV cases were identified during 2111 person-years of follow-up (incidence 0.38/100 person-years); all were primary infections in men who had sex with men. Clinical, laboratory, and computer-assisted self-interviews data were available for all, and 6 cases were interviewed. Three cases were attributable to injecting drug use (IDU). A fourth case reported IDU, but his HCV was attributable to sexual transmission. Four other cases reported no IDU and probably acquired HCV sexually. Most cases reported anal trauma in the context of condomless receptive anal intercourse during group sex at sex-on-premises venues.CONCLUSIONS:In PrEPX, HCV incidence was low compared to international PrEP studies, and most cases were transmitted sexually. Our findings highlight the need for HCV prevention messaging by clinicians, in sex-on-premises venues, and on digital platforms used to arrange group sex; and the need for HCV screening among some PrEP-using men who have sex with men.

OBJECTIVES:This paper aims to address the concerns around ongoing immune activation, inflammation, and resistance in those ageing with HIV that represent current challenges for clinicians.METHODS:Presentations at a symposium addressing issues of ageing with HIV infection were reviewed and synthesised.RESULTS:The changing natural history and demographics of human immunodeficiency virus (HIV)-infected individuals means new challenges in contemporary management. In the early years of the epidemic,management was focussed on acute, potentially life-threatening AIDS-related complications. From initial monotherapy with first-generation antiretroviral therapy (ART), the development of combination highly active ART (HAART) allowed HIV control but ART toxicities, treatment adherence and drug resistance emerged as major issues. Today, the availability of potent and tolerable ART has made viral suppression achievable in most people living with HIV (PLHIV), and clinicians are confronted with managing a chronic condition among an ageing population. The combination of diseases of ageing and the co-morbidities associated with HIV-infection, even when well controlled, results in a complex set of challenges for many older PLHIV. There is a growing appreciation that many non-AIDS-related co-morbidities are caused, at least in part, by persistent, low-grade immune activation, inflammation, and hypercoagulability, despite suppressive ART.CONCLUSIONS:In order to further improve HIV management, it is important to understand the enduring effects of chronically suppressed HIV infection, the potential contribution of these factors to the ageing process, the possibility of drug resistance, and the impact of different treatment strategies, including early ART initiation.