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Transcription factors regulate multiple processes during brain development and in the adult brain, from brain patterning to differentiation and maturation of highly specialized neurons as well as establishing and maintaining the functional neuronal connectivity. The members of the zinc-finger transcription factor family Bcl11 are mainly expressed in the hematopoietic and central nervous systems regulating the expression of numerous genes involved in a wide range of pathways. In the brain Bcl11 proteins are required to regulate progenitor cell proliferation as well as differentiation, migration, and functional integration of neural cells. Mutations of the human Bcl11 genes lead to anomalies in multiple systems including neurodevelopmental impairments like intellectual disabilities and autism spectrum disorders.

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.

Background Existing tools for measuring blood-borne virus (BBV) and sexually transmitted infection (STI) transmission risk behaviours in substance use interventions have limited capacity to assess risk behaviours across varied social, cultural and epidemiological contexts; have not evolved alongside HIV treatment and prevention innovations; or accounted for sexual contexts of drug use including among a range of lesbian, gay, bisexual, transgender, intersex and queer (LGBTIQ) sub-communities. The Substance Use and Sex Index (SUSI) is a new brief, simple tool being developed to assess change in HIV and STI risk behaviours for substance use treatment studies. Methods A 26-item questionnaire was piloted online among community volunteers (n = 199). Concurrent and predictive validity were assessed against risk-taking (RT-18) and STI testing items (Gay Community Periodic Surveys). Results The developed scale comprised nine items measuring: condomless penile (anal or vaginal) sex, unprotected oral sex, shared toy use, bloodplay, chemsex (consumption of drugs for the facilitation of sex), trading sex for drugs, being ‘too out of it' to protect self, injecting risk and group sex. Factor-analytic approaches demonstrated that items met good fit criteria for a single scale. Significant, moderate magnitude, positive relationships were identified between total SUSI score and both RT-18 risk-taking and recent STI testing. Qualitative feedback underscored the importance of culturally-embedded question formulation. Conclusion The results support the conceptual basis for the instrument, highlighting the need for further scale content refinement to validate the tool and examine sensitivity to change. SUSI is a step towards improving outcome measurement of HIV/BBV/STI transmission risk behaviours in substance use treatment studies with greater inclusiveness of experiences across different population groups.

Background This paper examines a methamphetamine treatment and peer support program for gay men and other men who have sex with men (MSM) who use methamphetamine. Australian MSM use illicit drugs including methamphetamine at significantly higher rates than the broader community.1,2 Methamphetamine rates are higher again amongst HIV positive MSM. Methamphetamine in the MSM community is associated with sexual activity and may be associated with psychosocial harms including risk of the transmission of HIV and sexually transmissible infections.3,4,7,8 Methods: This paper presents the formal evaluation of Re-Wired, Australia’s first structured methamphetamine treatment and support program for MSM, consisting of a free, six week therapeutic group and Re-Wired 2.0, a follow up peer support group. Data collection included baseline and post intervention administration of the Kessler Scale of Psychological Distress (K10) and the Drug Use Disorders Identification Test (DUDIT), the Personal Wellbeing Index (PWI) and the Readiness to Change Questionnaire (RCQ). This was complemented with qualitative session feedback and a small number of post intervention participant interviews. Results: Program evaluation demonstrated modest improvements in participant psychological distress, personal well-being and stage of change and reductions in methamphetamine use post intervention. Qualitative data revealed benefits of a specialised harm reduction intervention for this population through addressing fear of discrimination and stigma. Conclusions: The presented harm reduction program for MSM who use methamphetamine demonstrates the potential for a specialist peer-based approach to reduce harm in this vulnerable population. This approach may be suitable for adaptation with MSM populations in similar high-income settings.

Background: Australia has increased coverage of antiretroviral treatment (ART) over the past decade, reaching 73% uptake in 2014. While ART reduces AIDS-related deaths, accumulating evidence suggests that it could also bolster prevention efforts by reducing the risk of HIV transmission ('treatment as prevention'). While promising, evidence of community-level impact of treatment as prevention on reducing HIV incidence among gay and bisexual men is limited. We describe a study protocol that aims to determine if scale up of testing and treatment for HIV leads to a reduction in community viraemia and, in turn, if this reduction is temporally associated with a reduction in HIV incidence among gay and bisexual men in Australia's two most populous states. Methods: Over the period 2009 to 2017, we will establish two cohorts making use of clinical and laboratory data electronically extracted retrospectively and prospectively from 73 health services and laboratories in the states of New South Wales and Victoria. The 'positive cohort' will consist of approximately 13,000 gay and bisexual men (>90% of all people living with HIV). The 'negative cohort' will consist of at least 40,000 HIV-negative gay and bisexual men (approximately half of the total population). Within the negative cohort we will use standard repeat-testing methods to calculate annual HIV incidence. Community prevalence of viraemia will be defined as the proportion of men with a viral load ≥200RNA copies/mm3, which will combine viral load data from the positive cohort and viraemia estimates among those with an undiagnosed HIV infection. Using regression analyses and adjusting for behavioural and demographic factors associated with infection, we will assess the temporal association between the community prevalence of viraemia and the incidence of HIV infection. Further analyses will make use of these cohorts to assess incidence and predictors of treatment initiation, repeat HIV testing, and viral suppression. Discussion: This study will provide important information on whether 'treatment as prevention' is associated with a reduction in HIV incidence at a community level among gay and bisexual men.