Mpox (monkeypox) knowledge, concern, willingness to change behaviour, and seek vaccination: results of a national cross-sectional survey.

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 16years 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.

Antiretroviral Initiation at ≥800 CD4+ Cells/mm3 Associated With Lower Human Immunodeficiency Virus Reservoir Size.

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/mm3. 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/mm3 (median [interquartile range]: 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. 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.

Latent Class Analysis of Sexual Behaviours and Attitudes to Sexually Transmitted Infections Among Gay and Bisexual Men Using PrEP.

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.

The Potential Impact of a Gel-Based Point-of-Sex Intervention in Reducing Gonorrhea Incidence Among Gay and Bisexual Men: A Modeling Study.

BACKGROUND: Increases in sexually transmitted infections among gay and bisexual men (GBM) over the past decade have coincided with declines in condom use and rapid uptake of HIV preexposure prophylaxis (PrEP). We explored the impact of an antimicrobial gel-based point-of-sex intervention (gel-PSI) with a lower efficacy for reducing gonorrhea transmission risk than condoms on population-level gonorrhea incidence among GBM in Victoria, Australia. METHODS: A deterministic compartmental model of HIV and gonorrhea transmission was used to project annual gonorrhea incidence from 2020 to 2025. Individuals were classified as HIV-negative (PrEP or non-PrEP users) or HIV-positive, and further stratified by gonorrhoea risk (high/low). All possible scenarios where between 0% and 100% of GBM using condoms transitioned to gel-PSI (considered a downgrade in protection) and 0% and 100% of GBM not using condoms transitioned to gel-PSI (considered an upgrade in protection), with gel-PSI efficacy ranging from 20% to 50%, were run. RESULTS: The baseline scenario of no gel-PSI uptake (status quo) projected 94,367 gonorrhea infections between 2020 and 2025, with an exponentially increasing trend in annual infections. For a gel-PSI efficacy of 30%, a net reduction in cumulative gonorrhea incidence was projected, relative to the status quo, for any ratio of proportion of condom users "downgrading" to proportion of noncondom users "upgrading" to gel-PSI use of less than 2.6. Under the supposition of equal proportions of condom users and noncondom users switching to gel-PSI, a relative reduction was projected for any gel-PSI efficacy greater than 16%. CONCLUSIONS: Our model suggests that the introduction of a gel-PSI could have benefits for controlling gonorrhea transmission among GBM, even in scenarios where the gel-PSI is considerably less efficacious than condoms and when gel-PSI uptake leads to consequent reductions in consistent condom use.

Association of HIV Preexposure Prophylaxis With Incidence of Sexually Transmitted Infections Among Individuals at High Risk of HIV Infection.

Importance: Emerging evidence suggests that risk of bacterial sexually transmitted infections (STIs) increases among gay and bisexual men following initiation of HIV preexposure prophylaxis (PrEP). Objective: To describe STI incidence and behavioral risk factors among a cohort of predominantly gay and bisexual men who use PrEP, and to explore changes in STI incidence following PrEP commencement. Design, Setting, and Participants: The Pre-exposure Prophylaxis Expanded (PrEPX) Study, a multisite, open-label intervention study, was nested within the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) clinic network. A total of 4275 participants were enrolled (July 26, 2016-April 1, 2018) in Victoria, Australia. Of these, 2981 enrolled at 5 ACCESS clinics (3 primary care, 1 sexual health, and 1 community-based HIV rapid testing service), had at least 1 follow-up visit, and were monitored until April 30, 2018. Exposures: Upon enrollment, participants received daily oral tenofovir disoproxil fumurate and emtricitabine for HIV PrEP, quarterly HIV and STI testing, and clinical monitoring. Main Outcomes and Measures: The primary outcome was incidence of chlamydia, gonorrhea, or syphilis. Incidence rates and hazard ratios describing behavioral risk factors of STI diagnosis were calculated. Incidence rate ratios (IRRs), adjusted for change in testing frequency, described changes in STI incidence from 1-year preenrollment to study follow-up among participants with preenrollment testing data (n = 1378). Results: Among the 2981 individuals (median age, 34 years [interquartile range, 28-42]), 98.5% identified as gay or bisexual males, 29% used PrEP prior to enrollment, 89 (3%) withdrew and were censored at date of withdrawal, leaving 2892 (97.0%) enrolled at final follow-up. During a mean follow-up of 1.1 years (3185.0 person-years), 2928 STIs were diagnosed among 1427 (48%) participants (1434 chlamydia, 1242 gonorrhea, 252 syphilis). STI incidence was 91.9 per 100 person-years, with 736 participants (25%) accounting for 2237 (76%) of all STIs. Among 2058 participants with complete data for multivariable analysis, younger age, greater partner number, and group sex were associated with greater STI risk, but condom use was not. Among 1378 participants with preenrollment testing data, STI incidence increased from 69.5 per 100 person-years prior to enrollment to 98.4 per 100 person-years during follow-up (IRR, 1.41 [95% CI, 1.29-1.56]). After adjusting for testing frequency, the increase in incidence from 1 year preenrollment to follow-up was significant for any STI (adjusted IRR, 1.12 [95% CI, 1.02-1.23]) and for chlamydia (adjusted IRR, 1.17 [95% CI, 1.04-1.33]). Conclusions and Relevance: Among gay and bisexual men using PrEP, STIs were highly concentrated among a subset, and receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with preenrollment. These findings highlight the importance of frequent STI testing among gay and bisexual men using PrEP.

Effects of Pre-exposure Prophylaxis for the Prevention of Human Immunodeficiency Virus Infection on Sexual Risk Behavior in Men Who Have Sex With Men: A Systematic Review and Meta-analysis.

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.

Evaluation of Preexposure (PrEP) Eligibility Criteria, Using Sexually Transmissible Infections as Markers of Human Immunodeficiency Virus (HIV) Risk at Enrollment in PrEPX, a Large Australian HIV PrEP Trial.

Background: To determine participants' human immunodeficiency virus (HIV) risk, the Australian preexposure prophylaxis (PreEPX) trial used 6 eligibility criteria derived from the US Centers for Disease Control and Prevention PrEP guidelines. Participants who fulfilled no eligibility criteria could be enrolled if clinically assessed to need PrEP. This study evaluated whether PREPX eligibility criteria correlated with biological HIV risk markers-namely, syphilis, anorectal chlamydia, or anorectal gonorrhea (sexually transmitted infections [STIs]). Methods: We calculated adjusted odds ratios (aORs) to assess whether eligibility criteria predicted STI diagnoses at enrollment. Results: We included 1774 participants, of whom 10.2% tested positive for STIs. Eligibility criteria predicted STI diagnoses as follows: (1) aOR 2.5 (95% confidence interval [CI], 1.4-4.4) for condomless anal intercourse (CLAI) with an HIV-positive regular sexual partner (RSP) with detectable viral load; (2) aOR 1.8 (95% CI, 1.3-2.5) for receptive CLAI with casual sexual partners; (3) aOR 1.8 (95% CI, 1.3-2.5) for previous STIs; (4) aOR 2.1 (95% CI, 1.4-3.0) for methamphetamine use; (5) aOR 0.8 (95% CI, .6-1.1) for unsuccessful condom use; and (6) aOR 1.0 (95% CI, .7-1.4) for insertive CLAI when uncircumcised. Of participants enrolled outside eligibility criteria, 7.1% had STIs. Conclusions: Eligibility criteria 1-4 predicted diagnoses of STIs, but eligibility criteria 5 and 6 did not. Our findings support the use of PrEP eligibility criteria recommended in current guidelines. Participants enrolled outside the eligibility criteria had substantial prevalence of STIs, suggesting that people who request PrEP but do not fulfill eligibility criteria may nonetheless need PrEP.

Monitoring HIV-Associated Neurocognitive Disorder Using Screenings: a Critical Review Including Guidelines for Clinical and Research Use.

Screening tools to identify HIV-associated neurocognitive disorder (HAND) are primarily devised to detect cognitive impairment on a single occasion. With the chronicity of HIV infection and the risk of HAND developing or progressing despite viral control, it may be pertinent to repeat HAND screening at more than one time point. Despite this, there are limited data on longitudinal use of such screening tools, particularly with regard to the role of practice effects. Additionally, no guidelines currently exist on the timeframe between testing intervals, or recommendation of the magnitude of baseline impairment that warrants follow-up testing. The aim of the current paper was to review existing evidence for longitudinal validity of HAND screening tools. Only those HAND screening tools previously found to have high cross-sectional criterion validity were included. Preliminary recommendations for clinical use and future research are proposed including in international settings.

Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy.

BACKGROUND: The relationship between the timing of the initiation of antiretroviral therapy (ART) after infection with human immunodeficiency virus type 1 (HIV-1) and the recovery of CD4+ T-cell counts is unknown. METHODS: In a prospective, observational cohort of persons with acute or early HIV-1 infection, we determined the trajectory of CD4+ counts over a 48-month period in partially overlapping study sets: study set 1 included 384 participants during the time window in which they were not receiving ART and study set 2 included 213 participants who received ART soon after study entry or sometime thereafter and had a suppressed plasma HIV viral load. We investigated the likelihood and rate of CD4+ T-cell recovery to 900 or more cells per cubic millimeter within 48 months while the participants were receiving viral-load-suppressive ART. RESULTS: Among the participants who were not receiving ART, CD4+ counts increased spontaneously, soon after HIV-1 infection, from the level at study entry (median, 495 cells per cubic millimeter; interquartile range, 383 to 622), reached a peak value (median, 763 cells per cubic millimeter; interquartile range, 573 to 987) within approximately 4 months after the estimated date of infection, and declined progressively thereafter. Recovery of CD4+ counts to 900 or more cells per cubic millimeter was seen in approximately 64% of the participants who initiated ART earlier (≤4 months after the estimated date of HIV infection) as compared with approximately 34% of participants who initiated ART later (>4 months) (P<0.001). After adjustment for whether ART was initiated when the CD4+ count was 500 or more cells per cubic millimeter or less than 500 cells per cubic millimeter, the likelihood that the count would increase to 900 or more cells per cubic millimeter was lower by 65% (odds ratio, 0.35), and the rate of recovery was slower by 56% (rate ratio, 0.44), if ART was initiated later rather than earlier. There was no association between the plasma HIV RNA level at the time of initiation of ART and CD4+ T-cell recovery. CONCLUSIONS: A transient, spontaneous restoration of CD4+ T-cell counts occurs in the 4-month time window after HIV-1 infection. Initiation of ART during this period is associated with an enhanced likelihood of recovery of CD4+ counts. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Evolving views and practices of antiretroviral treatment prescribers in Australia.

OBJECTIVE: To examine whether there have been recent changes in Australian antiretroviral treatment (ART) prescribers' perceptions and practices relating to early ART initiation, which was defined as commencing ART when a patient's CD4+ T-cell count approaches 500 cells/mm3 or immediately after a patient is diagnosed with HIV. DESIGN, PARTICIPANTS AND SETTING: Self-completed, anonymous, cross-sectional surveys, targeting all ART prescribers in Australia, were conducted online in 2012 and 2013. The surveys included questions on prescriber factors, CD4+ T-cell count at which prescribers would most strongly recommend ART initiation, and perceived patient characteristics that could change prescribers' practices of early initiation of ART. MAIN OUTCOME MEASURES: Proportions of ART prescribers recommending early ART initiation. RESULTS: We analysed responses from 108 participants in 2012 and 82 participants in 2013. In both years, more male than female prescribers participated. The median age of participants was 49 years in 2012 and 50 years in 2013. In both rounds, over 60% had more than 10 years' experience in treating HIV-positive patients. More prescribers in 2013 stated that they would most strongly recommend early ART initiation compared with those in 2012 (50.0% [95% CI, 38.7%-61.3%] v 26.9% [95% CI, 18.8%-36.2%]; P=0.001). The prescribers' primary concern was more about individual patient than public health benefit. Out of 824 patients for whom ART was initiated, as reported by prescribers in 2013, only 108 (13.1% [95% CI, 10.9%-15.6%]) were given ART primarily to prevent onward HIV transmission. The number of patients for whom ART was initiated was significantly associated with prescribers' HIV caseload even after adjusting for prescriber type (adjusted odds ratio, 1.73 [95% CI, 1.47-2.03]; P<0.001); of the 37 who had initiated ART for 10 or more patients, 29 had a high HIV caseload. In 2013, 60 prescribers (73.2% [95% CI, 62.2%-82.4%]) reported that they routinely recommended ART to treatment-naive, asymptomatic patients with a CD4+ T-cell count of 350-500 cells/mm3. CONCLUSION: Our findings show increasing acceptance of and support for early ART initiation primarily as treatment and not as prevention.

Physical and mental health of long-term users of HIV preexposure prophylaxis in Australia.

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.

Improved neurocognitive test performance in both arms of the SMART study: impact of practice effect.

We evaluated factors associated with improvement in neurocognitive performance in 258 HIV-infected adults with baseline CD4 lymphocyte counts above 350 cells/mm³ randomized to intermittent, CD4-guided antiretroviral therapy (ART) (128 participants) versus continuous therapy (130) in the Neurology substudy of the Strategies for Management of Antiretroviral Therapy trial. Participants were enrolled in Australia, North America, Brazil, and Thailand, and neurocognitive performance was assessed by a five-test battery at baseline and month 6. The primary outcome was change in the quantitative neurocognitive performance z score (QNPZ-5), the average of the z scores of the five tests. Associations of the 6-month change in test scores with ART use, CD4 cell counts, HIV RNA levels, and other factors were determined using multiple regression models. At baseline, median age was 40 years, median CD4 cell count was 513 cells/mm³, 88 % had plasma HIV RNA ≤ 400 copies/mL, and mean QNPZ-5 was -0.68. Neurocognitive performance improved in both treatment groups by 6 months; QNPZ-5 scores increased by 0.20 and 0.13 in the intermittent and continuous ART groups, respectively (both P < 0.001 for increase and P = 0.26 for difference). ART was used on average for 3.6 and 5.9 out of the 6 months in the intermittent and continuous ART groups, respectively, but the increase in neurocognitive test scores could not be explained by ART use, changes in CD4, or plasma HIV RNA, which suggests a practice effect. The impact of a practice effect after 6 months emphasizes the need for a control group in HIV studies that measure intervention effects using neurocognitive tests similar to ours.

A cross-disciplinary view of current and emerging COVID-19 developments.

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.

Incidence and Prevalence of Hepatitis C Virus Among HIV-Negative Gay and Bisexual Men Using HIV Pre-exposure Prophylaxis (PrEP): A Systematic Review and Meta-analysis.

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.

"How PrEPared are you?": Knowledge of and attitudes toward PrEP among overseas-born and newly arrived gay, bisexual, and other men who have sex with men in Australia.

Introduction: Overseas-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. Methods: We 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. Results: Participants' 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. Conclusions: We 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.

Real-world trends in incidence of bacterial sexually transmissible infections among gay and bisexual men using HIV pre-exposure prophylaxis (PrEP) in Australia following nationwide PrEP implementation: an analysis of sentinel surveillance data.

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. FUNDING: Australian Department of Health, National Health and Medical Research Council.

Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women.

BACKGROUND: The Duffy-null trait and ethnic netropenia are both highly prevalent in Africa. The influence of pre-seroconversion levels of peripheral blood cell counts (PBCs) on the risk of acquiring human immunodeficiency virus (HIV)-1 infection among Africans is unknown. METHODS: The triangular relationship among pre-seroconversion PBC counts, host genotypes, and risk of HIV acquisition was determined in a prospective cohort of black South African high-risk female sex workers. Twenty-seven women had seroconversion during follow-up, and 115 remained HIV negative for 2 years, despite engaging in high-risk activity. RESULTS: Pre-seroconversion neutrophil counts in women who subsequently had seroconversion were significantly lower, whereas platelet counts were higher, compared with those who remained HIV negative. Comprising 27% of the cohort, subjects with pre-seroconversion neutrophil counts of <2500 cells/mm(3) had a ∼3-fold greater risk of acquiring HIV infection. In a genome-wide association analyses, an African-specific polymorphism (rs2814778) in the promoter of Duffy Antigen Receptor for Chemokines (DARC -46T > C) was significantly associated with neutrophil counts (P = 7.9 × 10(-11)). DARC -46C/C results in loss of DARC expression on erthyrocytes (Duffy-null) and resistance to Plasmodium vivax malaria, and in our cohort, only subjects with this genotype had pre-seroconversion neutrophil counts of <2500 cells/mm(3). The risk of acquiring HIV infection was ∼3-fold greater in those with the trait of Duffy-null-associated low neutrophil counts, compared with all other study participants. CONCLUSIONS: Pre-seroconversion neutrophil and platelet counts influence risk of HIV infection. The trait of Duffy-null-associated low neutrophil counts influences HIV susceptibility. Because of the high prevalence of this trait among persons of African ancestry, it may contribute to the dynamics of the HIV epidemic in Africa.

The Duffy-null state is associated with a survival advantage in leukopenic HIV-infected persons of African ancestry.

Persons of African ancestry, on average, have lower white blood cell (WBC) counts than those of European descent (ethnic leukopenia), but whether this impacts negatively on HIV-1 disease course remains unknown. Here, in a large natural history cohort of HIV-infected subjects, we show that, although leukopenia (< 4000 WBC/mm(3) during infection) was associated with an accelerated HIV disease course, this effect was more prominent in leukopenic subjects of European than African ancestry. The African-specific -46C/C genotype of Duffy Antigen Receptor for Chemokines (DARC) confers the malaria-resisting, Duffy-null phenotype, and we found that the recently described association of this genotype with ethnic leukopenia extends to HIV-infected African Americans (AAs). The association of Duffy-null status with HIV disease course differed according to WBC but not CD4(+) T-cell counts, such that leukopenic but not nonleukopenic HIV(+) AAs with DARC -46C/C had a survival advantage compared with all Duffy-positive subjects. This survival advantage became increasingly pronounced in those with progressively lower WBC counts. These data highlight that the interaction between DARC genotype and the cellular milieu defined by WBC counts may influence HIV disease course, and this may provide a partial explanation of why ethnic leukopenia remains benign in HIV-infected AAs, despite immunodeficiency.

New Potential Axes of HIV Neuropathogenesis with Relevance to Biomarkers and Treatment.

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.