Publications by authors named "Andrew E Grulich"

270 Publications

Protective efficacy of the anti-HIV broadly neutralizing antibody PGT121 in the context of semen exposure.

EBioMedicine 2021 Aug 9;70:103518. Epub 2021 Aug 9.

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia; ARC Centre for Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Victoria, Australia; Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia. Electronic address:

Background: HIV-1 infections occur following viral exposure at anogenital mucosal surfaces in the presence of semen. Semen contains immunosuppressive and pro-inflammatory factors. Semen from HIV-1-infected donors contains anti-HIV-1 antibodies. We assessed if passively infused anti-HIV-1 neutralizing antibody conferred protection from rectal SHIV challenge at semen exposed mucosae.

Methods: We pooled seminal plasma from HIV-1-infected donors. The pool was screened by ELISA for antibodies against HIV-1 gp140. The ability of seminal plasma to inhibit macaque NK cells from responding to direct and antibody-dependent stimulation was assessed. The ability of seminal plasma to inhibit macaque granulocytes from mediating oxidative burst was also assessed. To demonstrate viral infectivity in the presence of seminal plasma, macaques (n = 4) were rectally challenged with SHIV following exposure to 2.5 mL of seminal plasma. To evaluate if anti-HIV-1 neutralizing antibody confers protection against rectal SHIV challenge at semen exposed mucosae, eight macaques were intravenously infused with PGT121, either wild type (n = 4) or the Fc receptor binding deficient LALA variant (n = 4), and rectally challenged with SHIV following exposure to 2.5 mL of seminal plasma.

Findings: Anti-HIV-1 gp140 antibodies were detected in seminal plasma. Seminal plasma inhibited direct and antibody-dependent NK cell activation and granulocyte oxidative burst in vitro. Rectal SHIV challenge of control macaques following seminal plasma exposure resulted in infection of all animals. All macaques infused with wild type or LALA PGT121 and challenged with SHIV following seminal plasma exposure were protected.

Interpretation: PGT121 conferred protection against rectal SHIV challenge at semen exposed mucosae. Future research should investigate if semen alters protection conferred by antibodies more dependent on non-neutralizing functions.

Funding: This work was supported by a grant from the Australian National Health and Medical Research Council (APP1124680).
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http://dx.doi.org/10.1016/j.ebiom.2021.103518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361295PMC
August 2021

Effect on genital warts in Australian female and heterosexual male individuals after introduction of the national human papillomavirus gender-neutral vaccination programme: an analysis of national sentinel surveillance data from 2004-18.

Lancet Infect Dis 2021 Jul 30. Epub 2021 Jul 30.

The Kirby Institute, University of New South Wales Sydney, Sydney, NSW, Australia; Sydney Sexual Health Centre, Sydney Hospital, Sydney, NSW, Australia.

Background: In Australia, the government-funded human papillomavirus (HPV) vaccination programme was introduced in April, 2007, for girls and young women, and in February, 2013, for boys. As of Dec 31, 2018, all Australian-born female individuals younger than 38 years and male individuals younger than 21 years have been eligible for the free quadrivalent or nonavalent HPV vaccine. We aimed to examine the trends in genital wart diagnoses among Australian-born female and heterosexual male individuals who attended sexual health clinics throughout Australia before and after the introduction of the gender-neutral HPV vaccination programme in February, 2013.

Methods: We did a serial cross-sectional analysis of genital wart diagnoses among Australian-born female and heterosexual male individuals attending a national surveillance network of 35 clinics between Jan 1, 2004, and Dec 31, 2018. We calculated prevalence ratios of genital warts, using log-binomial regression models, for the female-only vaccination period (July 1, 2007, to Feb 28, 2013), gender-neutral vaccination period (March 1, 2013, to Dec 31, 2018), and the whole vaccination period (July 1, 2007, to Dec 31, 2018) compared with the pre-vaccination period (Jan 1, 2004, to June 30, 2007).

Findings: We included 121 038 men and 116 341 women in the analysis. Overall, we observed a 58% reduction (prevalence ratio 0·42, 95% CI 0·40-0·44) in genital wart diagnoses in female individuals and a 45% reduction (0·55, 0·53-0·57) in genital wart diagnoses in heterosexual male individuals after the introduction of the vaccination programme in 2007. The largest reduction in genital warts was observed in younger individuals, and there was a decreasing magnitude of reduction with increasing age (80%, 72%, 61%, 41%, and 16% reductions in female individuals aged 15-20 years, 21-25 years, 26-30 years, 31-35 years, and ≥36 years, respectively; 70%, 61%, 49%, 37%, and 29% reductions in male individuals aged 15-20 years, 21-25 years, 26-30 years, 31-35 years, and ≥36 years, respectively). Significant reductions observed in female individuals (0·32, 0·28-0·36) and male individuals (0·51, 0·43-0·61) aged 15-20 years in the female-only vaccination period were followed by a more substantial reduction in female individuals (0·07, 0·06-0·09) and male individuals (0·11, 0·08-0·15) aged 15-20 years in the gender-neutral vaccination period.

Interpretation: The national gender-neutral HPV vaccination programme has led to substantial and ongoing reduction in genital warts among Australian female and heterosexual male individuals, with a marked reduction in young individuals who received the vaccine at school.

Funding: Seqirus Australia and the Australian Government Department of Health.
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http://dx.doi.org/10.1016/S1473-3099(21)00071-2DOI Listing
July 2021

Renal impairment in a large-scale HIV pre-exposure prophylaxis implementation cohort.

AIDS 2021 Jul 22. Epub 2021 Jul 22.

Central Clinical School, University of Sydney, Camperdown, NSW 2050, Australia Wagga Wagga Base Hospital, Wagga Wagga, NSW, 2650 Australia Kirby Institute, UNSW Sydney, Sydney, NSW 2052, Australia Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Westmead, NSW 2145, Australia Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead, NSW 2145, Australia Western Sydney Sexual Health Centre, Western Sydney Local Health District, Parramatta, NSW, 2150, Australia Holdsworth House Medical Practice, Darlinghurst, NSW 2010, Australia.

Background: HIV pre-exposure prophylaxis (PrEP) with fixed-dose tenofovir disoproxil fumarate (TDF) and emtricitabine has been associated with low rates of renal impairment in clinical trials. Large-scale PrEP implementation may result in higher rates, as the prevalence of associated risk factors may be higher than in trial populations.

Methods: A post-hoc analysis of EPIC-NSW, a large Australian multi-centre PrEP implementation trial for patients at high-risk of HIV infection. Participants were eligible for inclusion if they commenced PrEP between 1 March 2016 and of 30 April 2018, and had renal function assessed at baseline and at least once more before the censor date. The primary outcome was new onset renal impairment, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2.

Results: 6808 participants were eligible for inclusion. Almost all were male (99%), with a median age of 35 years (IQR: 28 to 44). Approximately one-quarter (26%) had a baseline eGFR < 90 mL/min/1.73m2. Over a median follow-up period of 1.2 years (IQR 0.6 to 1.7), the rate of renal impairment was 5.8 episodes per 1000 person years (95%CI: 4.0 to 7.8). In multivariable Cox regression, there was higher risk of renal impairment in participants aged ≥50 years (HR 14.7, 95%CI: 5.0 to 43.3, p< 0.001) and those with an eGFR < 90 mL/min/1.73m2 (HR 28.9, 95%CI: 6.9 to 121.9) at baseline.

Conclusion: In a large-scale implementation study, TDF-containing PrEP was associated with a low risk of renal impairment overall, while older patients and those with pre-existing renal dysfunction were at substantially increased risk.
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http://dx.doi.org/10.1097/QAD.0000000000003035DOI Listing
July 2021

Understanding and managing HIV infection risk among men who have sex with men in rural Uganda: a qualitative study.

BMC Public Health 2021 07 4;21(1):1309. Epub 2021 Jul 4.

Kirby Institute, UNSW Sydney, Kensington, NSW, 2052, Australia.

Background: Same-sex sexual relations are criminalised in Uganda, and men who have sex with men (MSM) experience a high burden of HIV infection. In Uganda, health promotion policies focus on equity in healthcare and creating enabling environments. At present there is limited evidence upon which to enhance engagement of MSM in rural settings into effective HIV prevention. To fill this gap, our study explored MSM's understandings of HIV risk and strategies used to reduce HIV risk in their sexual lives.

Methods: In-depth interviews were conducted with sixteen MSM in rural communities in Southwestern Uganda. Inductive thematic analysis examined men's perceptions of HIV risk and strategies of reducing their own HIV risks.

Results: Understandings of HIV risk and risk practices were framed by lack of access to condoms, challenges negotiating condom and pre-exposure prophylaxis (PrEP) use, and condomless sex being reported as more pleasurable than sex with condoms. Strategies men perceived as enabling them to manage HIV risk included: PrEP use; condom use; knowing partners' HIV status; avoiding partners associated with HIV risk; oral sex; withdrawal before ejaculation and washing one's penis after sex. There were several misconceptions arising from poor HIV prevention knowledge. Strategies reliant on communication and negotiation with sexual partners were inhibited by gendered powered imbalances.

Conclusions: Our findings illustrate that MSM in rural settings in Uganda are making concerted efforts to implement strategies that might reduce risk of HIV transmission and infection within their sexual relationships. Key HIV health promotion and service-related strategies to support MSM with these efforts include an effective condom and lubricant supply chain; a PrEP program in trusted local health units, implemented via discreet community-outreach mechanisms; and same-sex specific HIV-related health promotion.
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http://dx.doi.org/10.1186/s12889-021-11365-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254907PMC
July 2021

Long-term protection from HIV infection with oral HIV pre-exposure prophylaxis in gay and bisexual men: findings from the expanded and extended EPIC-NSW prospective implementation study.

Lancet HIV 2021 08 1;8(8):e486-e494. Epub 2021 Jul 1.

Clinic 16, St Leonards, NSW, Australia.

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.

Funding: New South Wales Ministry of Health, Australian Capital Territory Health Directorate, Gilead Sciences.
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http://dx.doi.org/10.1016/S2352-3018(21)00074-6DOI Listing
August 2021

Preferences for Current and Future PrEP Modalities Among PrEP-Experienced Gay and Bisexual Men in Australia.

AIDS Behav 2021 Jun 17. Epub 2021 Jun 17.

The Kirby Institute, UNSW Sydney, Sydney, NSW, 2052, Australia.

Alternatives to daily dosing of HIV pre-exposure prophylaxis (PrEP) are continuing to emerge. From October 2019 to March 2020, we conducted an online survey of PrEP-experienced gay and bisexual men in Australia about interest in and preference for four different PrEP modalities: daily dosing, event-driven dosing, long-acting injectable (LAI)-PrEP and subdermal PrEP implants. Using data from 1477 participants, we measured interest and preference of different modalities using multivariate logistic regression. High proportions of participants were interested in LAI-PrEP (59.7%), daily PrEP (52.0%), PrEP implants (45.3%) and event-driven PrEP (42.8%). LAI-PrEP was the most frequently selected preference (30.5%), followed by PrEP implants (26.3%), daily PrEP (21.4%) and event-driven PrEP (21.2%). Higher interest and preference for non-daily PrEP modalities were associated with being concerned about side effects and perceived difficulties with daily adherence. As novel modalities emerge, attitudes to them should be considered in public health messaging to facilitate informed decision-making.
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http://dx.doi.org/10.1007/s10461-021-03344-3DOI Listing
June 2021

Adherence to daily HIV pre-exposure prophylaxis in a large-scale implementation study in New South Wales, Australia.

AIDS 2021 Oct;35(12):1987-1996

The Kirby Institute, UNSW Sydney.

Objectives: To examine patterns of long-term pre-exposure prophylaxis (PrEP) adherence and its association with HIV seroconversion in NSW, Australia.

Design: Population-based HIV PrEP implementation study.

Methods: Expanded PrEP Implementation in Communities in New South Wales was an open-label study of daily oral PrEP which recruited participants from March 2016 to April 2018. Adherence was measured using dispensing records. PrEP discontinuation was defined as an at least 120-day period without PrEP coverage. Long-term adherence patterns were identified using group-based trajectory modelling.

Results: Participants dispensed at least once (n = 9586) were almost all male (98.5%), identified as gay (91.3%), with a median age of 34 years (range: 18-86). Of the 6460 (67.4%) participants who had at least 9 months of follow-up since first dispensing, 1942 (30.1%) discontinued. Among these, 292 (15.0%) restarted later. Four distinct groups were identified ['Steep decline' in adherence (15.8%), 'Steady decline' (11.6%), 'Good adherence' (37.4%), and 'Excellent adherence' (35.2%)]. Older (P < 0.001) and gay-identified (P < 0.001) participants were more likely to have higher adherence, so were those living in postcodes with a higher proportion of gay-identified male residents (P < 0.001). Conversely, those who at baseline reported recent crystal methamphetamine use and had a recent diagnosis of sexually transmitted infection (STI) had lower adherence (P < 0.001). Overall HIV incidence was 0.94 per 1000 person-years (95% confidence interval: 0.49-1.81; n = 9) and was highest in the 'steep decline' group (5.45 per 1000 person-years; P = 0.001).

Conclusion: : About 15% of participants stopped PrEP during study follow-up and were at increased risk of HIV infection. They were more likely to be younger and report a recent STI or methamphetamine use prior to PrEP initiation.
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http://dx.doi.org/10.1097/QAD.0000000000002970DOI Listing
October 2021

HIV pre-exposure prophylaxis: scaling up for impact now and in the future.

Lancet Public Health 2021 07 2;6(7):e528-e533. Epub 2021 Jun 2.

Kirby Institute, University of New South Wales, Sydney, NSW, Australia.

More than a decade after the first efficacy evidence for oral HIV pre-exposure prophylaxis (PrEP) was reported, PrEP uptake globally has been inadequate and global HIV prevention targets have been missed. Access to PrEP is still highly concentrated in a fairly small number of countries and, even within countries with widespread PrEP access, inequalities have emerged. More ambitious, high-priority global targets for PrEP uptake are required and could accelerate the HIV prevention response in a similar way to the success of the 90-90-90 testing and treatment targets. Health systems must be PrEP-friendly and allow PrEP to be prescribed in settings already attended by large numbers of HIV-negative individuals who are at risk. Several models have been advanced for the greater demedicalisation of PrEP. Individual-level barriers to PrEP uptake and persistence have been characterised, such as low awareness, low willingness to use PrEP, and the gap between self-perceived and actual HIV risk. Overcoming these barriers will require further efforts to understand and address them first. New PrEP modalities are emerging; as more options become available, we need to develop a greater understanding of the long-term patterns of PrEP use in different populations and to develop models of such use that can accommodate people alternating through periods of use and non-use, as well as switching between dosing regimens or modalities as they become available. Scaling up PrEP is crucial to achieving the UNAIDS prevention targets for 2030. Simply getting more people onto PrEP cannot be the only goal: the big-picture definition of success for PrEP programmes must be their impact on the HIV epidemic.
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http://dx.doi.org/10.1016/S2468-2667(21)00112-2DOI Listing
July 2021

HIV pre-exposure prophylaxis: scaling up for impact now and in the future.

Lancet Public Health 2021 07 2;6(7):e528-e533. Epub 2021 Jun 2.

Kirby Institute, University of New South Wales, Sydney, NSW, Australia.

More than a decade after the first efficacy evidence for oral HIV pre-exposure prophylaxis (PrEP) was reported, PrEP uptake globally has been inadequate and global HIV prevention targets have been missed. Access to PrEP is still highly concentrated in a fairly small number of countries and, even within countries with widespread PrEP access, inequalities have emerged. More ambitious, high-priority global targets for PrEP uptake are required and could accelerate the HIV prevention response in a similar way to the success of the 90-90-90 testing and treatment targets. Health systems must be PrEP-friendly and allow PrEP to be prescribed in settings already attended by large numbers of HIV-negative individuals who are at risk. Several models have been advanced for the greater demedicalisation of PrEP. Individual-level barriers to PrEP uptake and persistence have been characterised, such as low awareness, low willingness to use PrEP, and the gap between self-perceived and actual HIV risk. Overcoming these barriers will require further efforts to understand and address them first. New PrEP modalities are emerging; as more options become available, we need to develop a greater understanding of the long-term patterns of PrEP use in different populations and to develop models of such use that can accommodate people alternating through periods of use and non-use, as well as switching between dosing regimens or modalities as they become available. Scaling up PrEP is crucial to achieving the UNAIDS prevention targets for 2030. Simply getting more people onto PrEP cannot be the only goal: the big-picture definition of success for PrEP programmes must be their impact on the HIV epidemic.
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http://dx.doi.org/10.1016/S2468-2667(21)00112-2DOI Listing
July 2021

High Levels of Prevention-Effective Adherence to HIV PrEP: An Analysis of Substudy Data From the EPIC-NSW Trial.

J Acquir Immune Defic Syndr 2021 08;87(4):1040-1047

Kirby Institute, UNSW Sydney, Sydney, Australia.

Background: Preexposure prophylaxis (PrEP) prevents HIV infection but relies on good adherence at times of risk, termed "prevention-effective adherence." Most studies assess adherence without reference to sexual behaviur, making it challenging to determine if poor adherence coincides with HIV risk.

Setting: We examined data from a behavioral substudy of a large-scale PrEP implementation trial in New South Wales, Australia.

Methods: Trial participants completed optional brief quarterly surveys, reporting the number of pills taken and sexual behavior with male partners for each day of the "last full week" before each survey. Condomless sex (CLS) was defined as "higher risk" for HIV when with HIV-positive men with detectable/unknown viral loads or unknown HIV status men. Adequate PrEP protection was defined as ≥4 pills for participants assigned male sex at birth and ≥6 pills for participants assigned female sex at birth (including transgender men).

Results: Of 9596 participants dispensed PrEP, 4401 completed baseline and ≥1 follow-up survey. Participants reported on 12,399 "last full weeks": 7485 weeks (60.4%) involved CLS and 2521 weeks (33.7% of CLS-weeks) involved higher risk CLS. There were 103 weeks in which participants did not have adequate PrEP protection and had higher risk CLS: 4.1% of higher-risk CLS weeks (n = 103/2521), 1.4% of all CLS weeks (n = 103/7485), and 0.8% of all observed weeks (n = 103/12,399).

Conclusions: In a large PrEP trial, prevention-effective adherence to PrEP was very high at 99%. Our findings illustrate the importance of measuring pill-taking and sexual behavior in the same period so that prevention-effective adherence can be better estimated.
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http://dx.doi.org/10.1097/QAI.0000000000002691DOI Listing
August 2021

Sexual behaviours associated with incident high-risk anal human papillomavirus among gay and bisexual men.

Sex Transm Infect 2021 Mar 16. Epub 2021 Mar 16.

The Kirby Insitute, UNSW Sydney, Sydney, New South Wales, Australia.

Objective: High-risk human papillomavirus (HRHPV) causes anal cancer, which disproportionately affects gay and bisexual men (GBM). We examined sexual behaviours associated with incident anal HRHPV in an observational cohort study of GBM in Sydney, Australia.

Methods: GBM aged 35 years and above were enrolled in the Study of the Prevention of Anal Cancer. Detailed information on sexual practices in the last 6 months, including receptive anal intercourse (RAI) and non-intercourse receptive anal practices, was collected. Anal human papillomavirus (HPV) testing was performed at the baseline and three annual follow-up visits. Risk factors for incident HRHPV were determined by Cox regression using the Wei-Lin-Weissfeld method.

Results: Between 2010 and 2015, 617 men were recruited and 525 who had valid HPV results at baseline and at least one follow-up visit were included in the analysis. The median age was 49 years (IQR 43-56) and 188 (35.8%) were HIV-positive. On univariable analysis, incident anal HRHPV was associated with being HIV-positive (p<0.001), having a higher number of recent RAI partners regardless of condom use (p<0.001 for both), preference for the receptive position during anal intercourse (p=0.014) and other non-intercourse receptive anal sexual practices, including rimming, fingering and receptive use of sex toys (p<0.05 for all). In multivariable analyses, being HIV-positive (HR 1.46, 95% CI 1.09 to 1.85, p=0.009) and reporting condom-protected RAI with a higher number of sexual partners (p<0.001) remained significantly associated with incident HRHPV. When stratified by recent RAI, non-intercourse receptive anal practices were not associated with incident HRHPV in men who reported no recent RAI.

Conclusion: GBM living with HIV and those who reported RAI were at increased of incident anal HRHPV. Given the substantial risk of anal cancer and the difficulty in mitigating the risk of acquiring anal HRHPV, HPV vaccination should be considered among sexually active older GBM.

Trial Registration Number: ANZCTR365383.
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http://dx.doi.org/10.1136/sextrans-2020-054851DOI Listing
March 2021

Antiseptic mouthwash for gonorrhoea prevention (OMEGA): a randomised, double-blind, parallel-group, multicentre trial.

Lancet Infect Dis 2021 05 4;21(5):647-656. Epub 2021 Mar 4.

Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia; Central Clinical School, Monash University, Melbourne, VIC, Australia; China-Australia Joint Research Centre for Infectious Diseases, School of Public Health, Xi'an Jiaotong University, Xi'an, China.

Background: To address the increasing incidence of gonorrhoea and antimicrobial resistance, we compared the efficacy of Listerine and Biotène mouthwashes for preventing gonorrhoea among men who have sex with men (MSM).

Methods: The OMEGA trial was a multicentre, parallel-group, double-blind randomised controlled trial among MSM, done at three urban sexual health clinics and one general practice clinic in Australia. Men were eligible if they were diagnosed with oropharyngeal gonorrhoea by nucleic acid amplification test (NAAT) in the previous 30 days or were aged 16-24 years. They were randomly assigned to receive Listerine (intervention) or Biotène (control) via a computer-generated sequence (1:1 ratio, block size of four). Participants, clinicians, data collectors, data analysts, and outcome adjudicators were masked to the interventions after assignment. Participants were instructed to rinse and gargle with 20 mL of mouthwash for 60 s at least once daily for 12 weeks. Oropharyngeal swabs were collected by research nurses every 6 weeks, and participants provided saliva samples every 3 weeks, to be tested for Neisseria gonorrhoeae with NAAT and quantitative PCR. The primary outcome was proportion of MSM diagnosed with oropharyngeal N gonorrhoeae infection at any point over the 12-week period, defined as a positive result for either oropharyngeal swabs or saliva samples by NAAT, and the cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit. A modified intention-to-treat analysis for the primary outcome was done that included men who provided at least one follow-up specimen over the 12-week study period. The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12616000247471).

Findings: Between March 30, 2016, and Oct 26, 2018, 786 MSM were screened and 256 were excluded. 264 MSM were randomly assigned to the Biotène group and 266 to the Listerine group. The analysis population included 227 (86%) men in the Biotène group and 219 (82%) in the Listerine group. Oropharyngeal gonorrhoea was detected in ten (4%) of 227 of MSM in the Biotène group and in 15 (7%) of 219 in the Listerine group (adjusted risk difference 2·5%, 95% CI -1·8 to 6·8). The cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit did not differ between the two mouthwash groups (adjusted risk difference 3·1%, 95% CI -1·4 to 7·7).

Interpretation: Listerine did not reduce the incidence of oropharyngeal gonorrhoea compared with Biotène. However, previous research suggests that mouthwash might reduce the infectivity of oropharyngeal gonorrhoea; therefore, further studies of mouthwash examining its inhibitory effect on N gonorrhoeae are warranted to determine if it has a potential role for the prevention of transmission.

Funding: Australian National Health and Medical Research Council.
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http://dx.doi.org/10.1016/S1473-3099(20)30704-0DOI Listing
May 2021

Increasing preexposure prophylaxis use and 'net prevention coverage' in behavioural surveillance of Australian gay and bisexual men.

AIDS 2021 04;35(5):835-840

The Kirby Institute, UNSW Sydney.

Objectives: To assess trends in HIV prevention strategies among Australian gay and bisexual men (GBM) since the introduction of preexposure prophylaxis (PrEP), the level of net prevention coverage (the use of safe strategies), and the characteristics of HIV-negative and untested GBM who remain at risk of HIV.

Design: Repeated behavioural surveillance of GBM recruited from venues, events and online in seven Australian states and territories.

Methods: Participants with casual male partners were included. Trends in sexual practices, prevention strategies, net prevention coverage and the characteristics of 'at risk' participants were assessed with binary and multivariate logistic regression.

Results: A total of 32 048 survey responses (2014-2019) were included. The proportion of participants who reported consistent condom use declined (44.6-23.2%). The proportion who reported any condomless anal intercourse with casual partners increased (37.4-62.0%) but net prevention coverage also increased (68.1-74.9%), with higher levels of undetectable viral load among HIV-positive participants and rapidly increasing PrEP use by HIV-negative participants. PrEP became the most commonly reported prevention strategy in 2019 (31.1%). The analysis of 'at risk' participants showed that they became more likely to report frequent condomless anal intercourse with casual partners but had fewer partners and more partners with undetectable viral load or on PrEP. 'At risk' participants became more likely to identify as bisexual and to be born overseas.

Conclusion: There has been a rapid, historic shift in HIV prevention among GBM in Australia. Net prevention coverage has increased among GBM and 'at risk' GBM have become less at risk of HIV, facilitating reductions in HIV transmission.
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http://dx.doi.org/10.1097/QAD.0000000000002797DOI Listing
April 2021

A New Method for Estimating the Incidence of Infectious Diseases.

Am J Epidemiol 2021 07;190(7):1386-1395

Ambitious World Health Organization targets for disease elimination require monitoring of epidemics using routine health data in settings of decreasing and low incidence. We evaluated 2 methods commonly applied to routine testing results to estimate incidence rates that assume a uniform probability of infection between consecutive negative and positive tests based on 1) the midpoint of this interval and 2) a randomly selected point in this interval. We compared these with an approximation of the Poisson binomial distribution, which assigns partial incidence to time periods based on the uniform probability of occurrence in these intervals. We assessed bias, variance, and convergence of estimates using simulations of Weibull-distributed failure times with systematically varied baseline incidence and varying trend. We considered results for quarterly, half-yearly, and yearly incidence estimation frequencies. We applied the methods to assess human immunodeficiency virus (HIV) incidence in HIV-negative patients from the Treatment With Antiretrovirals and Their Impact on Positive and Negative Men (TAIPAN) Study, an Australian study of HIV incidence in men who have sex with men, between 2012 and 2018. The Poisson binomial method had reduced bias and variance at low levels of incidence and for increased estimation frequency, with increased consistency of estimation. Application of methods to real-world assessment of HIV incidence found decreased variance in Poisson binomial model estimates, with observed incidence declining to levels where simulation results had indicated bias in midpoint and random-point methods.
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http://dx.doi.org/10.1093/aje/kwab014DOI Listing
July 2021

Subtype-specific differences in transmission cluster dynamics of HIV-1 B and CRF01_AE in New South Wales, Australia.

J Int AIDS Soc 2021 01;24(1):e25655

The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.

Introduction: The human immunodeficiency virus 1 (HIV-1) pandemic is characterized by numerous distinct sub-epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses.

Methods: We used HIV-1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV-1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW-specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi-Square statistics.

Results: We identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2-fold increase in the number of NSW-specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p < 0.01). CRF01_AE infections clusters were associated with infections among individuals diagnosed during the early stage of infection (p < 0.05) and CRF01_AE singletons were more likely to be from infections among individuals reporting heterosexual transmission (p < 0.05). We found six subtype B clusters with an above-average growth rate (>1.5 sequences / 6-months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals.

Conclusions: The large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.
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http://dx.doi.org/10.1002/jia2.25655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817915PMC
January 2021

HIV diagnoses in Australia fall as clinicians embrace pre-exposure prophylaxis.

Aust Prescr 2020 Dec 1;43(6):182-183. Epub 2020 Dec 1.

The Kirby Institute, University of New South Wales, Sydney.

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http://dx.doi.org/10.18773/austprescr.2020.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738688PMC
December 2020

Comparison of Trends in Rates of Sexually Transmitted Infections Before vs After Initiation of HIV Preexposure Prophylaxis Among Men Who Have Sex With Men.

JAMA Netw Open 2020 12 1;3(12):e2030806. Epub 2020 Dec 1.

Kirby Institute, University of New South Wales Sydney, Sydney, New South Wales, Australia.

Importance: There have been concerns that HIV preexposure prophylaxis (PrEP) may be associated with increases in sexually transmitted infections (STIs) because of subsequent reductions in condom use and/or increases in sexual partners.

Objective: To determine trends in STI test positivity among high-risk men who have sex with men (MSM) before and after the start of HIV PrEP.

Design, Setting, And Participants: A before-after analysis was conducted using a subcohort of a single-group PrEP implementation study cohort in New South Wales, Australia (Expanded PreEP Implementation in Communities in New South Wales [EPIC-NSW]), from up to 1 year before enrollment if after January 1, 2015, and up to 2 years after enrollment and before December 31, 2018. STI testing data were extracted from a network of 54 sexual health clinics and 6 primary health care clinics Australia-wide, using software to deidentify, encrypt, and anonymously link participants between clinics. A cohort of MSM dispensed PrEP for the first time during the study, with 2 or more STI tests in the prior year and who tested during follow-up, were included from the EPIC-NSW cohort of HIV-negative participants with high-risk sexual behavior. Data analysis was performed from June to December 2019.

Exposures: Participants were dispensed coformulated tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) as HIV PrEP.

Main Outcomes And Measures: The main outcome was STI, measured using test positivity, defined as the proportion of participants testing positive for an STI at least once per quarter of follow-up. Outcomes were calculated for Chlamydia trachomatis and Neisseria gonorrhoea by site of infection (anorectal, pharyngeal, urethral, or any) and for syphilis.

Results: Of the EPIC-NSW cohort of 9709 MSM, 2404 were included in the before-after analysis. The mean (SD) age of the participants was 36 (10.4) years, and 1192 (50%) were Australia-born. STI positivity was 52% in the year after PrEP (23.3% per quarter; 95% CI, 22.5%-24.2% per quarter) with no significant trend (mean rate ratio [RR] increase of 1.01 per quarter [95% CI, 0.99-1.02]; P = .29), compared with 50% positivity in the year prior to PrEP (20.0% per quarter [95% CI, 19.04%-20.95% per quarter]; RR for overall STI positivity, 1.17 [95% CI, 1.10-1.24]; P < .001), with an increase in quarterly STI positivity (mean RR of 1.08 per quarter, or an 8% increase per quarter [95% CI, 1.05-1.11]; P < .001; RR, 0.93 [95% CI, 0.90-0.96]; P < .001). Findings were similar when stratified by specific STIs and anatomical site.

Conclusions And Relevance: STI rates were high but stable among high-risk MSM while taking PrEP, compared with a high but increasing trend in STI positivity before commencing PrEP. These findings suggest the importance of considering trends in STIs when describing how PrEP use may be associated with STI incidence.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.30806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758809PMC
December 2020

Effect of age on the association between recreational drug use and sexual risk behaviour: a cross-sectional observational analysis.

Sex Health 2020 12;17(6):538-542

Sexual Health Service, Sydney Local Health District, Camperdown, NSW 2050, Australia; and The Kirby Institute, UNSW Australia, Sydney, NSW 2052, Australia; and Central Clinical School, The University of Sydney, Sydney, NSW 2006, Australia.

Recreational drug use (RDU) among gay and bisexual men (GBM) is associated with higher-risk sexual behaviours, however this has not been well defined among older GBM. We investigated the association between RDU and sexual behaviours among older GBM in Sydney, Australia. 617 GBM aged 35-79 years self-reported their RDU in the past 6 months and sexual behaviours. Age-stratified univariable associations between RDU and behaviour were examined. GBM aged 35-44 years were the most likely to report RDU, with rates decreasing with increasing age (Ptrend < 0.001). Associations between RDU and higher-risk sexual behaviours were most consistently found among GBM aged 35-54 years.
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http://dx.doi.org/10.1071/SH20115DOI Listing
December 2020

Increased HIV Subtype Diversity Reflecting Demographic Changes in the HIV Epidemic in New South Wales, Australia.

Viruses 2020 12 6;12(12). Epub 2020 Dec 6.

The Kirby Institute, The University of New South Wales, Sydney 2052, Australia.

Changes over time in HIV-1 subtype diversity within a population reflect changes in factors influencing the development of local epidemics. Here we report on the genetic diversity of 2364 reverse transcriptase sequences from people living with HIV-1 in New South Wales (NSW) notified between 2004 and 2018. These data represent >70% of all new HIV-1 notifications in the state over this period. Phylogenetic analysis was performed to identify subtype-specific transmission clusters. Subtype B and non-B infections differed across all demographics analysed ( < 0.001). We found a strong positive association for infections among females, individuals not born in Australia or reporting heterosexual transmission being of non-B origin. Further, we found an overall increase in non-B infections among men who have sex with men from 50 to 79% in the last 10 years. However, we also found differences between non-B subtypes; heterosexual transmission was positively associated with subtype C only. In addition, the majority of subtype B infections were associated with clusters, while the majority of non-B infections were singletons. However, we found seven non-B clusters (≥5 sequences) indicative of local ongoing transmission. In conclusion, we present how the HIV-1 epidemic has changed over time in NSW, becoming more heterogeneous with distinct subtype-specific demographic associations.
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http://dx.doi.org/10.3390/v12121402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762219PMC
December 2020

HIV, Immune Dysfunction, and the Natural History of Anal High-Risk Human Papillomavirus Infection in Gay and Bisexual Men.

J Infect Dis 2021 Jul;224(2):246-257

The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.

Background: Incidence of anal cancer is highest in gay and bisexual men (GBM). Better understanding of the natural history of anal high-risk human papillomavirus (hrHPV) infection is needed for anal cancer prevention.

Methods: The Study of the Prevention of Anal Cancer was a 3-year study of Australian GBM, aged 35 years or older. We examined incidence, clearance, and risk factors for 13 hrHPV types at baseline and 3 annual visits.

Results: In 525 men with ≥ 2 visits, 348 (66.3%) acquired ≥ 1 incident hrHPV infection. HPV16 incidence rates were similar, but non-16 hrHPV incidence was higher in HIV-positive (51.8/100 person years [PY]) than HIV-negative men (36.5/100 PY, P < .001). Annual clearance rates of HPV16 (13.21/100 PY, 95% confidence interval, 10.53-16.56) were lower than for other hrHPV types. hrHPV clearance rates were not associated with HIV overall but were significantly lower in those with a lower nadir CD4 (<200 cells/µL) for HPV16 (P = .015) and other hrHPV types (P = .007).

Conclusions: Higher incidence of non-16 hrHPV types, coupled with lower clearance of non-16 hrHPV types in those with past impaired immune function, is consistent with the greater role of non-16 hrHPV in anal cancer in HIV-positive people.

Australia New Zealand Clinical Trials Registry: ANZCTR365383.
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http://dx.doi.org/10.1093/infdis/jiaa723DOI Listing
July 2021

Prevalence and incidence of hepatitis C virus infection in men who have sex with men: a systematic review and meta-analysis.

Lancet Gastroenterol Hepatol 2021 01 18;6(1):39-56. Epub 2020 Nov 18.

The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.

Background: WHO has set targets for hepatitis C virus (HCV) elimination by 2030. We did a global systematic review of HCV prevalence and incidence in men who have sex with men (MSM) to provide updated estimates that can guide community education and public health policy.

Methods: We did a systematic review and meta-analysis of studies published and listed on MEDLINE or Embase between Jan 1, 2000, and Oct 31, 2019, including conference proceedings. Studies were eligible if they reported measures of HCV prevalence or HCV incidence (or both) among MSM. Studies that relied on participants' self-reported HCV status with no laboratory confirmation were excluded. Pooled HCV estimates in MSM were stratified by HIV status and by injecting drug use, then by WHO region and by income level. Random-effects meta-analysis was done to account for between-study heterogeneity and examined using the I statistic. Pooled HCV prevalence was also compared with HCV estimates in the general population and presented as prevalence ratios (PRs). In HIV-negative MSM, incidence estimates were stratified by use of HIV pre-exposure prophylaxis (PrEP). The systematic review was registered with PROSPERO, number CRD42020156262.

Findings: Of 1221 publications identified, 194 were deemed to be eligible and included in the systematic review and meta-analysis. Overall, the pooled HCV prevalence in MSM was 3·4% (95% CI 2·8-4·0; I=98·0%) and was highest in Africa (5·8%, 2·5-10·4) and South-East Asia (5·0%, 0·0-16·6). Globally, HCV prevalence was 1·5% (1·0-2·1) in HIV-negative MSM and 6·3% (5·3-7·5) in HIV-positive MSM. Compared with the general population, HCV prevalence was slightly higher in HIV-negative MSM (PR 1·58, 95% CI 1·14-2·01) and markedly higher (6·22, 5·14-7·29) in HIV-positive MSM. Pooled HCV prevalence was substantially higher in MSM who had ever injected drugs (30·2%, 22·0-39·0) or currently injected drugs (45·6%, 21·6-70·7) than in those who never injected drugs (2·7%, 2·0-3·6). In HIV-negative MSM, the pooled HCV incidence was 0·12 per 1000 person-years (95% CI 0·00-0·72) in individuals not on PrEP and 14·80 per 1000 person-years (9·65-20·95) in individuals on PrEP. HCV incidence in HIV-positive MSM was 8·46 per 1000 person-years (6·78-10·32).

Interpretation: HIV-positive MSM are at substantially increased risk of HCV. Overall, HIV-negative MSM had a slightly higher prevalence of HCV than the general population but had a lower prevalence than HIV-positive MSM. High HCV incidence in more recent PrEP studies suggests that as PrEP use increases, greater HCV transmission might occur. HCV burden in MSM varies considerably by region, which is likely to be associated with variation in the prevalence of injecting drug use and HIV.

Funding: World Health Organization.
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http://dx.doi.org/10.1016/S2468-1253(20)30303-4DOI Listing
January 2021

Prevalence and Association of Perianal and Intra-Anal Warts with Composite High-Grade Squamous Intraepithelial Lesions Among Gay and Bisexual Men: Baseline Data from the Study of the Prevention of Anal Cancer.

AIDS Patient Care STDS 2020 10 21;34(10):436-443. Epub 2020 Sep 21.

The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.

Human papillomavirus (HPV) causes anal warts and anal squamous cell carcinoma (SCC). A higher incidence of anal cancer has been found among individuals previously diagnosed with anogenital warts. We aimed to investigate the association between anal warts and the presumed anal SCC precursor high-grade squamous intraepithelial lesion (HSIL), among participants in the Study of the Prevention of Anal Cancer (SPANC). SPANC was a longitudinal study of anal HPV infections and related lesions among gay and bisexual men (GBM) age 35 years and older, in Sydney, Australia. Anal cytology and high-resolution anoscopy were performed. Logistic regression was used to investigate the association between clinically diagnosed anal warts and intra-anal composite-HSIL (cytology and/or histology) at the baseline visit. The prevalence of HSIL within biopsies from intra-anal warts was calculated. Laser capture microdissection (LCM) and HPV-genotyping was performed on HSIL lesions. Among 616 participants at study entry, 165 (26.8%) and 51 (8.3%) had intra-anal and perianal warts, respectively. Warts were associated with composite-HSIL, even after adjustment for HIV status, age, lifetime receptive anal intercourse partner number, and smoking (perianal: aOR 2.13, 95% CI 1.17-3.87,  = 0.013; intra-anal: aOR 1.69, 95% CI 1.16-2.46,  = 0.006). HSIL was detected in 24 (14.5%) of 165 biopsies from intra-anal warts. Of 17 HSIL lesions, 16 (94.1%) had high-risk HPV detected by LCM. Anal warts were common. Prevalent anal warts were associated with composite-HSIL. HSIL may be detected within biopsies of intra-anal warts. Anal warts may be a useful addition to risk stratification for HSIL among GBM.
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http://dx.doi.org/10.1089/apc.2020.0067DOI Listing
October 2020

Human Papillomavirus Genotypes in Anal High-Grade Squamous Intraepithelial Lesion (HSIL): Anal Intraepithelial Neoplasia Grades 2 (AIN2) and 3 (AIN3) Are Different.

Cancer Epidemiol Biomarkers Prev 2020 10 30;29(10):2078-2083. Epub 2020 Jul 30.

Centre for Women's Infectious Diseases, The Royal Women's Hospital, Parkville, Melbourne, Victoria, Australia.

Background: Anal high-grade squamous intraepithelial lesion (HSIL) can be histomorphologically categorized into anal intraepithelial neoplasia (AIN) grade 2 (AIN2) and grade 3 (AIN3). Different risk factors for these two categories have been described. We investigated whether there were also differences in lesion-specific human papillomavirus (HPV) genotypes.

Methods: The Study of the Prevention of Anal Cancer (SPANC) recruited 617 gay and bisexual men (GBM); 36% of participants were HIV positive. At baseline, 196 men (31.8%) had histologic HSIL lesions. Tissue was available for genotyping in 171, with a total of 239 HSIL lesions (183 AIN3 and 56 AIN2). Using laser capture microdissection, each lesion revealed a maximum of one genotype.

Results: High-risk HPV (HR-HPV) genotypes were found in 220 (92.1%) HSIL lesions, with no significant difference between AIN3 (93.4%) and AIN2 (87.5%). AIN3 lesions had significantly more HPV16 (42.1%) than AIN2 lesions (12.5%; < 0.001) and AIN2 lesions had significantly more non-16 HR-HPV types (75.0%) than AIN3 lesions (51.4%; = 0.002). These associations were similar for HIV-negative men with HPV16 in 51.1% AIN3 and 18.2% AIN2 ( = 0.001) and non-16 HR-HPV in 40.0% AIN3 and 75.8% AIN2 ( < 0.001). For HIV-positive men, HPV16 remained more frequently detected in AIN3 (33.3% vs. 4.4% for AIN2; = 0.004), but there was no difference between AIN3 and AIN2 for non-16 HR-HPV (62.4% vs. 73.9%; = 0.300).

Conclusions: As HPV16 has the strongest link with anal cancer, the subcategorization of HSIL may enable stratification of lesions for anal cancer risk and guide anal HSIL management.

Impact: Stratification of anal cancer risk by histologic HSIL grade.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0664DOI Listing
October 2020

Sustained, Low Prevalence of Undiagnosed HIV Among Gay and Bisexual Men in Sydney, Australia Coincident With Increased Testing and Pre-exposure Prophylaxis Use: Results From Repeated, Bio-Behavioral Studies 2014-2018.

J Acquir Immune Defic Syndr 2020 11;85(3):e41-e47

Centre for Social Research in Health, UNSW Sydney, Sydney, Australia.

Background: Gay and bisexual men with undiagnosed HIV contribute disproportionately to HIV transmission in Australia.

Methods: In 2014 and 2018, we recruited men at gay venues and events in Sydney. Participants self-completed surveys and provided oral fluid samples for HIV testing. We calculated the prevalence of HIV and undiagnosed infection, and assessed changes in behavior, HIV testing, and the use of pre-exposure prophylaxis. We weighted the samples to adjust for differences in where participants were recruited between rounds. Two-sample tests of proportion were used to compare prevalence estimates and χ tests to assess differences between the samples.

Results: In 2014, 944 men were recruited, and 890 men were recruited in 2018. In 2014, the weighted estimate of HIV prevalence was 6.1% [95% confidence intervals (CI): 4.6 to 7.6], of which 13.8% (95% CI: 5.0 to 22.7) was undiagnosed. In 2018, weighted HIV prevalence was 6.4% (95% CI: 4.8 to 8.0), of which 5.3% (95% CI: 0.5 to 11.1) was undiagnosed. Between 2014 and 2018 among all participants, men reporting at least 10 recent casual partners increased from 22.3% to 27.7% (P = 0.008), condomless anal intercourse with casual partners in the previous 6 months increased from 23.9% to 37.3% (P < 0.001), and sexually transmitted infection diagnoses in the previous year increased from 14.4% to 27.5% (P < 0.001). HIV testing and the use of pre-exposure prophylaxis in the previous 6 months increased from 49.6% to 56.3% (P = 0.004) and 2.0%-21.0% (P < 0.001), respectively.

Conclusions: Repeated, bio-behavioral surveillance suggests the prevalence of undiagnosed HIV remains low in Sydney, despite gay and bisexual men reporting more casual sex partners, condomless sex, and sexually transmitted infections.
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http://dx.doi.org/10.1097/QAI.0000000000002451DOI Listing
November 2020

Clinical characteristics and prognosis of anal squamous cell carcinoma: a retrospective audit of 144 patients from 11 cancer hospitals in southern China.

BMC Cancer 2020 Jul 21;20(1):679. Epub 2020 Jul 21.

School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China.

Background: The incidence of anal squamous cell carcinoma (SCC) has been steadily growing globally in the past decade. Clinical data on anal SCC from China are rare. We conducted this study to describe the clinical and epidemiological characteristics of anal SCC in China and explore prognostic factors of outcomes among patients with anal SCC.

Methods: We audited demographic characteristics, relevant symptoms, risk factors, treatment modalities and outcomes for patients diagnosed with anal SCC at 11 medical institutions in China between January 2007 and July 2018.

Results: A total of 144 patients (109 females) were diagnosed with SCC during this period. Median age at initial diagnosis was 52.0 (interquartile range: 46.0-61.8) years. The most common symptoms were bleeding (n = 93, 64.6%), noticing a lump (n = 49, 34.0%), and pain (n = 47, 32.6%). The proportion of patients at the American Joint Committee on Cancer (AJCC) stages I-IV were 10 (6.9%), 22 (15.3%), 61 (42.4%) and 8 (5.6%), respectively, and AJCC stages in 43 (29.9%) patients were unknown. Thirty-six patients (25.0%) underwent abdominoperineal resection initially. Univariable analysis showed that T stage predicted recurrence-free survival (RFS) (Hazard ratio [HR] = 3.03, 95% Confidence interval [CI]: 1.10-8.37, p = 0.032), and age group (HR = 2.90, 95% CI: 1.12-7.49, p = 0.028), AJCC stage (HR = 4.56, 95% CI: 1.02-20.35, p = 0.046), and N stage (HR = 3.05, 95% CI: 1.07-8.74, p = 0.038) predicted overall survival (OS).

Conclusions: T stage was identified as prognostic factor of RFS, and age, AJCC stage, and N stage were identified as prognostic factors of OS. Improving symptom awareness and earlier presentation among patients potentially at risk for anal SCC should be encouraged. Familiarity with the standard treatment among health care providers in China should be further improved.
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http://dx.doi.org/10.1186/s12885-020-07170-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372759PMC
July 2020

The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men.

Clin Infect Dis 2021 03;72(5):853-861

The Kirby Institute, University of New South Wales, New South Wales, Australia.

Background: Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL).

Methods: The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs.

Results: Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5-13.5 per 100 PY). Significant bivariate predictors of higher incidence included age <45 years (HR 1.64, 95% CI 1.11-2.41), HIV positivity (HR 1.43, 95% CI .99-2.06), prior SIL diagnosis (P-trend < .001) and human papillomavirus (HPV)16 (HR 3.39, 2.38-4.84). Over 695.3 PY follow-up, 153 HSIL cleared (clearance 22.0, 95% CI 18.8-25.8 per 100 PY). Predictors were age < 45 years (HR 1.52, 1.08-2.16), anal intraepithelial neoplasia (AIN)2 rather than AIN3 (HR 1.79, 1.29-2.49), smaller lesions (HR 1.62, 1.11-2.36) and no persistent HPV16 (HR 1.72, 1.23-2.41). There was 1 progression to cancer (incidence 0.224, 95% CI .006-1.25 per 100 PY).

Conclusion: These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments.

Clinical Trials Registration: Australia New Zealand Clinical Trials Registry (ANZCTR365383).
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http://dx.doi.org/10.1093/cid/ciaa166DOI Listing
March 2021

Increases in HIV Testing Frequency in Australian Gay and Bisexual Men are Concentrated Among PrEP Users: An Analysis of Australian Behavioural Surveillance Data, 2013-2018.

AIDS Behav 2020 Sep;24(9):2691-2702

The Centre for Social Research in Health, UNSW Sydney, Sydney, NSW, Australia.

Increasing HIV testing frequency in gay and bisexual men (GBM) is critical to reducing the time between HIV infection and diagnosis. Using anonymous national behavioural surveillance data (2013-2018) from 43,753 surveys of Australian GBM, we examined HIV testing frequency trends and factors differentiating PrEP-users, non-PrEP-users reporting two or more tests in the previous year, and non-PrEP-users reporting less frequent testing. The proportion tested at least annually increased from 64.4% in 2013 to 70.8% in 2018 (p-trend < 0.001), and from 73.9% to 84.6% among the 51.6% of men classified as higher-risk. Among higher-risk men, having two or more tests in the previous year increased from 48.0% to 69.3% (p-trend < 0.001). Among higher-risk non-PrEP-users, it increased from 47.2% to 54.8% (p-trend < 0.001), however, there was a decrease since 2016 (p-trend < 0.001). Among PrEP-users, it increased from 82.1% in 2013 to 97.3% in 2018 (p-trend < 0.001). Non-PrEP-using higher-risk men having less frequent tests reported lower risk than PrEP-users and non-PrEP-using men reporting two or more tests in the previous year. However, recent risk behaviour was not uncommon: nearly half reported condomless sex; one-fifth reported receptive condomless sex with ejaculation; over half reported group sex; one-quarter used drugs for the purposes of sex; and one-fifth had more than ten sex partners. Efforts are needed to encourage frequent testing and PrEP use among non-PrEP-users who are at higher-risk.
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http://dx.doi.org/10.1007/s10461-020-02826-0DOI Listing
September 2020

HIV treatment and anal cancer: emerging clarity.

Lancet HIV 2020 04 25;7(4):e220-e221. Epub 2020 Feb 25.

The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.

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http://dx.doi.org/10.1016/S2352-3018(20)30027-8DOI Listing
April 2020
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