HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults.

People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV1-5. In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population6-10, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study, the ARCHIVE study (NCT04641013), in which 220 HIV-positive and 226 HIV-negative participants aged 55 years or older were recruited in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess the presence of CH mutations and to identify potential risk factors for and clinical sequelae of CH. In total, 135 CH mutations were identified in 100 (22.4%) of 446 participants. CH was more prevalent in HIV-positive participants than in HIV-negative participants (28.2% versus 16.8%, P = 0.004), overall and across all age groups; the adjusted odds ratio for having CH in those with HIV was 2.16 (95% confidence interval 1.34-3.48, P = 0.002). The most common genes mutated overall were DNMT3A (47.4%), TET2 (20.0%) and ASXL1 (13.3%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.

Characteristics of Agreements to have Condomless Anal Intercourse in the Presence of an Undetectable Viral Load Among HIV Serodiscordant Male Couples in Australia, Brazil and Thailand.

The use of undetectable viral load (VL) to negotiate condomless anal intercourse (CLAI) in HIV serodiscordant male relationships has become more common as more data regarding the effectiveness of antiretroviral treatments for the prevention of HIV transmission has been described. We examined viral load agreements (VLAs) for condomless sex in the presence of an undetectable VL in 343 HIV serodiscordant male couples in Australia, Brazil and Thailand. Factors associated with having a VLA included having agreements for the HIV-positive partner to report his VL result (p < 0.001), agreeing that VL affects agreements about sexual practice (p < 0.001), the HIV-negative partner's perception of his partner's undetectable VL (p < 0.001), the couple's belief in the efficacy of undetectable VL in preventing HIV transmission (p < 0.001), and the couple engaging in CLAI with each other (p < 0.001). Over time, these agreements became more common although 49.3% of couples in the sample never had a viral load agreement. As these agreements become more common, further education is required to support male couples in using them safely.

High Adherence to HIV Pre-exposure Prophylaxis and No HIV Seroconversions Despite High Levels of Risk Behaviour and STIs: The Australian Demonstration Study PrELUDE.

PrELUDE study evaluated daily pre-exposure prophylaxis (PrEP) in high-risk individuals in Australia. This open-label, single-arm study tested participants for HIV/STI and collected behavioural information three-monthly. We report trends over 18 months in medication adherence, side-effects, HIV/STI incidence and behaviour. 320 gay/bisexual men (GBM), 4 women and 3 transgender participants, followed on average 461 days, reported taking seven pills/week on 1,591 (88.5%) occasions and 4-6 pills/week on 153 (8.5%) occasions. No HIV infections were observed. STI incidence was high and stable, while gonorrhoea infections declined from 100.0 to 25.8/100 person-years between 6 and 15 months (p < 0.001). The number of HIV-positive and unknown-status sex partners, and condomless anal intercourse, significantly increased. In this high-risk cohort of mainly GBM, increases in risk behaviours and high STI incidence were not accompanied by HIV infections due to high adherence to daily PrEP. The study informed policy and further PrEP implementation among Australian GBM.

Assessing the Impacts of Integrated Decision Support Software on Sexual Orientation Recording, Comprehensive Sexual Health Testing, and Detection of Infections Among Gay and Bisexual Men Attending General Practice: Observational Study.

BACKGROUND: Gay and bisexual men are disproportionately affected by HIV and other sexually transmissible infections (STIs), yet opportunities for sexual health testing of this population are often missed or incomplete in general practice settings. Strategies are needed for improving the uptake and completeness of sexual health testing in this setting. OBJECTIVES: The goal of the research was to evaluate the impact of an intervention centered around integrated decision support software and routine data feedback on the collection of sexual orientation data and sexual health testing among gay and bisexual men attending general practice. METHODS: A study using before/after and intervention/comparison methods was undertaken to assess the intervention's impact in 7 purposively sampled Australian general practice clinics located near the urban centers of Sydney and Melbourne. The software was introduced at staggered points between April and August 2012; it used patient records to prompt clinicians to record sexual orientation and accessed pathology testing history to generate prompts when sexual health testing was overdue or incomplete. The software also had a function for querying patient management system databases in order to generate de-identified data extracts, which were used to report regularly to participating clinicians. We calculated summary rate ratios (SRRs) based on quarterly trends and used Poisson regression analyses to assess differences between the 12-month preintervention and 24-month intervention periods as well as between the intervention sites and 4 similar comparison sites that did not receive the intervention. RESULTS: Among 32,276 male patients attending intervention clinics, sexual orientation recording increased 19% (from 3213/6909 [46.50%] to 5136/9110 [56.38%]) during the intervention period (SRR 1.10, 95% CI 1.04-1.11, P<.001) while comprehensive sexual health testing increased by 89% (305/1159 [26.32%] to 690/1413 [48.83%]; SRR 1.38, 95% CI 1.28-1.46, P<.001). Comprehensive testing increased slightly among the 7290 gay and bisexual men attending comparison sites, but the increase was comparatively greater in clinics that received the intervention (SRR 1.12, 95% CI 1.10-1.14, P<.001). In clinics that received the intervention, there was also an increase in detection of chlamydia and gonorrhea that was not observed in the comparison sites. CONCLUSIONS: Integrated decision support software and data feedback were associated with modest increases in sexual orientation recording, comprehensive testing among gay and bisexual men, and the detection of STIs. Tests for and detection of chlamydia and gonorrhea were the most dramatically impacted. Decision support software can be used to enhance the delivery of sexual health care in general practice.

Viral suppression and HIV transmission in serodiscordant male couples: an international, prospective, observational, cohort study.

BACKGROUND: Evidence on viral load and HIV transmission risk in HIV-serodiscordant male homosexual couples is limited to one published study. We calculated transmission rates in couples reporting condomless anal intercourse (CLAI), when HIV-positive partners were virally suppressed, and daily pre-exposure prophylaxis (PrEP) was not used by HIV-negative partners. METHODS: In the Opposites Attract observational cohort study, serodiscordant male homosexual couples were recruited from 13 clinics in Australia, one in Brazil, and one in Thailand. At study visits, HIV-negative partners provided information on sexual behaviour and were tested for HIV and sexually transmitted infections; HIV-positive partners had HIV viral load tests, CD4 cell count, and sexually transmitted infection tests done. Viral suppression was defined as less than 200 copies per mL. Linked within-couple HIV transmissions were identified with phylogenetic analysis. Incidence was calculated per couple-year of follow-up, focusing on periods with CLAI, no use of daily PrEP, and viral suppression. One-sided upper 95% CI limits for HIV transmission rates were calculated with exact Poisson methods. FINDINGS: From May 8, 2012, to March 31, 2016, in Australia, and May 7, 2014, to March 31, 2016, in Brazil and Thailand, 358 couples were enrolled. 343 couples had at least one follow-up visit and were followed up for 588·4 couple-years. 258 (75%) of 343 HIV-positive partners had viral loads consistently less than 200 copies per mL and 115 (34%) of 343 HIV-negative partners used daily PrEP during follow-up. 253 (74%) of 343 couples reported within-couple CLAI during follow-up, with a total of 16 800 CLAI acts. Three new HIV infections occurred but none were phylogenetically linked. There were 232·2 couple-years of follow-up and 12 447 CLAI acts in periods when CLAI was reported, HIV-positive partners were virally suppressed, and HIV-negative partners did not use daily PrEP, resulting in an upper CI limit of 1·59 per 100 couple-years of follow-up for transmission rate. INTERPRETATION: HIV treatment as prevention is effective in men who have sex with men. Increasing HIV testing and linking to immediate treatment is an important strategy in HIV prevention in homosexual men. FUNDING: National Health and Medical Research Council; amfAR, The Foundation for AIDS Research; ViiV Healthcare; and Gilead Sciences.

Risk factors for genital and anal warts in a prospective cohort of HIV-negative homosexual men: the HIM study.

OBJECTIVE: The objective of this study was to determine the prevalence, incidence, and risk factors for genital and anal warts in HIV-negative homosexual men in Sydney. STUDY DESIGN: The authors conducted a prospective cohort study. Participants were asked whether they had had genital and anal warts at each interview. Details of lifetime sexual contacts and sexual behaviors in the last 6 months were collected. RESULTS: Among 1,427 men recruited, 8.9% and 19.6% reported a history of genital and anal warts at baseline, respectively. Incidence rates for genital and anal warts were 0.94 and 1.92 per 100 person-years, respectively. In multivariate analysis, both incident genital and anal warts were associated with younger age. In addition, incident genital warts was associated with insertive fingering (P trend = 0.018), whereas incident anal warts was associated with insertive fingering (P trend = 0.007) and insertive fisting (P trend = 0.039). CONCLUSIONS: Anal warts were twice as common as genital warts. Fingering and other manual sexual practices may be an important transmission route for both.

Transmission of herpes simplex virus types 1 and 2 in a prospective cohort of HIV-negative gay men: the health in men study.

BACKGROUND: Despite increasing reports of herpes simplex virus (HSV) type 1 (HSV-1)-associated anogenital herpes, there are very limited data comparing the seroepidemiological profile of and risk factors for HSV-1 and HSV type 2 (HSV-2) infection. METHODS: Sexual behaviors were examined as risk factors for prevalent and incident HSV-1 and HSV-2 infections in a community-based cohort of 1,427 HIV-negative gay men in Australia. RESULTS: The prevalence of HSV-1 and HSV-2 at baseline was 75% and 23%, respectively. The rate of prevalent infection with HSV-1, as well as the rate of prevalent infection with HSV-2, was much lower in individuals <25 years of age, and each type of infection was associated with a higher number of both male and female sex partners. The median duration of follow-up of the cohort was 2.0 years. Among participants who were susceptible to infection, the incidence rates for HSV-1 and HSV-2 infection were 5.58 and 1.45 cases per 100 person-years, respectively. In multivariate analysis, incident infection with HSV-1 was significantly associated with younger age (P=.027) and reports of frequent insertive oral sex with casual partners (hazard ratio, 3.91 [95% confidence interval, 1.23-12.44]; P=.021). Incident infection with HSV-2 was significantly associated with a variety of anal sex practices with casual partners. CONCLUSIONS: Both HSV-1 and HSV-2 were commonly sexually transmitted, and there were more HSV-1 than HSV-2 seroconversions. Public-health strategies targeted against anogenital herpes increasingly need to take into account the importance of HSV-1 infection.

Epidemic syphilis among homosexually active men in Sydney.

OBJECTIVES: To describe trends in the notification of infectious syphilis in New South Wales, the characteristics of homosexually active men recently notified with early syphilis, and the seroprevalence and incidence of syphilis, as well as associated risk factors, in a Sydney cohort of HIV-negative homosexually active men. DESIGN, SETTING AND PARTICIPANTS: Secondary analysis of New South Wales infectious syphilis surveillance data from 1998 to 2003; a case series of 57 homosexually active men diagnosed with early syphilis in inner Sydney from December 2002 to January 2004; and a prospective cohort study of syphilis among 1333 HIV-negative homosexually active men in Sydney recruited from June 2001 to December 2003. MAIN OUTCOME MEASURES: Rates of notification of infectious syphilis in New South Wales and in areas of inner Sydney; behavioural and clinical features of men with syphilis in the case series; and incidence of syphilis and hazard ratios (HRs) associated with sexual behaviours in the cohort study. RESULTS: Infectious syphilis notifications in inner Sydney rose more than 10-fold (from 6 in 1999 to 162 in 2003), and the increase was confined to men. Of 57 men with early syphilis in the case series, 54% were HIV-positive and 32% reported no symptoms of syphilis. These 57 men were highly sexually active and likely to report recreational drug use. In the cohort study, 1292 men (97% of participants) consented to syphilis testing; the incidence of syphilis was 0.78 per 100 person-years, and risk factors included reporting unprotected anal intercourse with HIV-positive partners (HR, 5.31; 95% CI, 2.00-184.93) and insertive oral sex (HR, 4.55; 95% CI, 1.14-18.18). CONCLUSION: Syphilis has been re-established among homosexually active men in Sydney, and HIV-positive men are over-represented. Frequent screening is needed in this population to curb the transmission of both syphilis and HIV.

Hepatitis A and B infection and vaccination in a cohort of homosexual men in Sydney.

OBJECTIVES: To determine the prevalence and incidence of hepatitis A (HAV) and B (HBV) infection and vaccination in HIV-negative homosexual men in Sydney, and associated risk factors. METHODS: An open prospective cohort study was conducted among a community-based sample of HIV-negative homosexual men in Sydney in 2001-02. Participants underwent a face-to-face interview, regarding demographics, sexual behavioural risk factors and sexually transmitted infections, and blood samples were collected. They were followed annually. RESULTS: Nine hundred and three men completed a baseline interview by the end of 2002. Among them, 68% were seropositive to hepatitis A. The seroprevalence of prior hepatitis B infection was 19%, and 53% had serological evidence of HBV vaccination. Younger men were much more likely to be seronegative, with 48% and 46% of <25-year-olds being seronegative to HAV and HBV respectively. In multivariate analysis HAV and HBV infection were associated with increasing age, greater number of lifetime sex partners and HBV infection was also associated with previous sexually transmitted infections. HAV vaccination was associated with increasing age, greater number of lifetime sex partners, overseas travel in the last year and self-reported anogenital warts. HBV vaccination was associated with higher occupational status, greater lifetime number of sex partners and previous sexually transmitted infections. CONCLUSION: Substantial proportions of gay community-attached young homosexual men are still at risk of HAV and HBV infection. This study points to a need for vaccination strategies which ensure high levels of hepatitis A and B immunity in young sexually active gay men.