Antibiofilm Agents for the Treatment and Prevention of Bacterial Vaginosis: A Systematic Narrative Review.

BACKGROUND: Bacterial vaginosis (BV) is difficult to eradicate due to BV biofilms protecting BV bacteria (Gardnerella, Prevotella, and other genera). With the growing understanding of biofilms, we systematically reviewed the current knowledge on the efficacy of anti-BV biofilm agents. METHODS: We searched literature in the Scopus, Medline, and Embase databases for empirical studies investigating substances for the treatment of BV biofilms or prevention of their recurrence and their efficacy and/or safety. RESULTS: Of 201 unique titles, 35 satisfied the inclusion criteria. Most studies (89%) reported on preclinical laboratory research on the efficacy of experimental antibiofilm agents (80%) rather than their safety. Over 50% were published within the past 5 years. Agents were classified into 7 groups: antibiotics, antiseptics, cationic peptides, enzymes, plant extracts, probiotics, and surfactants/surfactant components. Enzymes and probiotics were most commonly investigated. Earlier reports of antibiotics having anti-BV biofilm activity have not been confirmed. Some compounds from other classes demonstrated promising anti-BV biofilm efficacy in early studies. CONCLUSIONS: Further research is anticipated on successful antibiofilm agents. If confirmed as effective and safe in human clinical trials, they may offer a breakthrough in BV treatment. With rising antibiotic resistance, antibiofilm agents will significantly improve the current standard of care for BV management.

Agreements, Behaviour, and Change: Sex Outside the Relationship in Male HIV-negative Partners in HIV Serodiscordant Relationships in Australia, Brazil, and Thailand.

Male HIV serodiscordant couples have diverse relationship agreements regarding sex outside the relationship. We examined the relationship agreements as described by 343 male HIV-negative partners in HIV serodiscordant relationships in Australia, Brazil and Thailand participating in a multi-year cohort study. At baseline, 125 (34.1%) HIV-negative partners reported no agreement, 115 (33.5%) had a monogamous agreement, and 103 (37.9%) had an open agreement allowing sex outside the relationship. Relationship agreements were largely stable over time, with 76% of HIV-negative men reporting the same agreement across follow up, while changes were predominantly towards having an open agreement. Behaviour largely matched relationship agreements, and the predictors of breaking an agreement by having condomless anal intercourse (CLAI) with an outside partner were CLAI within the relationship (OR = 3.17, 95%CI: 1.64-6.14, p < 0.001) and PrEP use in the last three months (OR = 3.42, 95%CI: 1.48-7.92, p = 0.004). When considering HIV transmission risk for HIV-negative men in serodiscordant relationships, greater focus needs to be placed on sex that is occurring outside the relationship and the agreements that facilitate this.

Incorrect Knowledge of Event-Driven PrEP "2-1-1" Dosing Regimen Among PrEP-Experienced Gay and Bisexual Men in Australia.

BACKGROUND: Event-driven pre-exposure prophylaxis (ED-PrEP), when taken according to the "2-1-1" dosing method, is highly effective at preventing HIV acquisition for gay, bisexual, and other men who have sex with men (GBM). Any missed doses when using ED-PrEP drastically reduce its effectiveness, so it is vital that people using this method know how to take it correctly. This study investigated Australian GBM's awareness of ED-PrEP and their knowledge of how to take it correctly. METHOD: We conducted a survey of 1471 PrEP-experienced GBM in Australia, between October 2019 and March 2020. The survey assessed awareness and knowledge of the 3 components of the "2-1-1" ED-PrEP dosing regimen (number of pills for loading dose, timing of loading dose, and number of days after sex to take PrEP pills) among GBM. Characteristics associated with ED-PrEP awareness and correct knowledge of how to take ED-PrEP were assessed with multivariate logistic regression. RESULTS: Two-thirds (n = 1004, 68.4%) had heard of ED-PrEP, of whom only one-eighth (n = 125, 12.5%) knew the correct details of the "2-1-1" ED-PrEP method; one-third (n = 339, 33.8%) did not know any of the 3 key components. Awareness of ED-PrEP and correct knowledge was associated with greater belief in PrEP efficacy, university education, and intention to take a nondaily PrEP regimen in the next 6 months. CONCLUSIONS: Although ED-PrEP awareness was considerable, most participants did not know how to use ED-PrEP correctly. Further work is needed to increase awareness and knowledge of ED-PrEP among GBM.

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

What does PrEP mean for 'safe sex' norms? A qualitative study.

While HIV pre-exposure prophylaxis (PrEP) is highly effective, it has arguably disrupted norms of 'safe sex' that for many years were synonymous with condom use. This qualitative study explored the culture of PrEP adoption and evolving concepts of 'safe sex' in Sydney, Australia, during a period of rapidly escalating access from 2015-2018, drawing on interviews with sexually active gay men (n = 31) and interviews and focus groups with key stakeholders (n = 10). Data were analysed thematically. Our results explored the decreasing centrality of condoms in risk reduction and new patterns of sexual negotiation. With regards to stigma, we found that there was arguably more stigma related to not taking PrEP than to taking PrEP in this sample. We also found that participants remained highly engaged with promoting the wellbeing of their communities through activities as seemingly disparate as regular STI testing, promotion of PrEP in their social circles, and contribution to research. This study has important implications for health promotion. It demonstrates how constructing PrEP as a rigid new standard to which gay men 'should' adhere can alienate some men and potentially create community divisions. Instead, we recommend promoting choice from a range of HIV prevention options that have both high efficacy and high acceptability.

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

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.

Potential and demonstrated impacts of the COVID-19 pandemic on sexually transmissible infections: Republication.

PURPOSE OF REVIEW: This review considers the potential and demonstrated impacts of SARS-CoV-2 on the sexually transmissible infection (STI)/HIV transmission. RECENT FINDINGS: COVID-19 increases the vulnerability of those at highest risk of acquiring STI/HIV. Altered health-seeking behaviour, reductions in STI/HIV clinic capacity, service disruptions and redeployment of human resources to assist COVID-19 control efforts have impacted on STI/HIV control programmes. Reports of reduced STI incidence are emerging, but it is hard to determine whether this is real or due to decreased testing during COVID-19 lockdown periods. Fear of COVID-19 and implemented control measures have altered STI/HIV transmission dynamics. Sexual health services adapted to the pandemic by reducing face-to-face patient encounters in favour of telehealth and mail-based initiatives as well as more stringent triage practice. Many sexual health and HIV treatment services now operate at reduced capacity and experience ongoing service disruptions, which necessarily translates into poorer outcomes for patients and their communities. SUMMARY: In the short-term, COVID-19 related sexual behaviour change is driving STI/HIV transmission downwards. However, the impacts of the global COVID-19 response on sexual health-seeking behaviour and STI/HIV services threaten to drive STI/HIV transmission upwards. Ultimately, the expected rebound in STI/HIV incidence will require an appropriate and timely public health response. VIDEO ABSTRACT: http://links.lww.com/COID/A31.

Potential and demonstrated impacts of the COVID-19 pandemic on sexually transmissible infections.

PURPOSE OF REVIEW: This review considers the potential and demonstrated impacts of SARS-CoV-2 on the sexually transmissible infection (STI)/HIV transmission. RECENT FINDINGS: COVID-19 increases the vulnerability of those at highest risk of acquiring STI/HIV. Altered health-seeking behaviour, reductions in STI/HIV clinic capacity, service disruptions and redeployment of human resources to assist COVID-19 control efforts have impacted on STI/HIV control programmes. Reports of reduced STI incidence are emerging, but it is hard to determine whether this is real or due to decreased testing during COVID-19 lockdown periods. Fear of COVID-19 and implemented control measures have altered STI/HIV transmission dynamics. Sexual health services adapted to the pandemic by reducing face-to-face patient encounters in favour of telehealth and mail-based initiatives as well as more stringent triage practice. Many sexual health and HIV treatment services now operate at reduced capacity and experience ongoing service disruptions, which necessarily translates into poorer outcomes for patients and their communities. SUMMARY: In the short-term, COVID-19 related sexual behaviour change is driving STI/HIV transmission downwards. However, the impacts of the global COVID-19 response on sexual health-seeking behaviour and STI/HIV services threaten to drive STI/HIV transmission upwards. Ultimately, the expected rebound in STI/HIV incidence will require an appropriate and timely public health response. VIDEO ABSTRACT: http://links.lww.com/COID/A31.

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.

Utilisation of hepatocellular carcinoma screening in Australians at risk of hepatitis B virus-related carcinoma and prescribed anti-viral therapy.

AIMS AND OBJECTIVES: To investigate hepatocellular carcinoma screening utilisation and factors associated with utilisation among patients prescribed hepatitis B virus anti-viral therapy and at risk of hepatocellular carcinoma. BACKGROUND: The incidence of hepatocellular carcinoma has increased in Australia over the past three decades with chronic hepatitis B virus infection a major contributor. hepatocellular carcinoma surveillance programs aim to detect cancers early enabling curative treatment options, longer survival and longer times to recurrence. DESIGN: Multi-site cross-sectional survey. METHODS: An online study questionnaire was administered to eligible participants attending three Sydney tertiary hospitals. Data were grouped into six mutually exclusive hepatocellular carcinoma risk factor categories as per American Association for the Study of Liver Diseases guidelines. All analyses were undertaken in STATA. Logistic regression was used to assess the associations between covariates and screening utilisation. Multivariate models described were assessed using the Hosmer-Lemeshow goodness of fit. RESULTS: Of the 177 participants, 137 (77.4%) self-reported that US had been performed in the last six months. Awareness that screening should be performed and knowing the correct frequency of US screening were independently associated with screening utilisation. Participants who knew that screening should be undertaken were three times more likely to have had pretreatment education or were prescribed hepatitis B virus anti-viral treatment for >4 years. Participants reporting a family history of hepatocellular carcinoma were less likely to know that screening should be undertaken every 6 months. CONCLUSION: While utilisation of hepatocellular carcinoma surveillance programs was higher in this study than in previous reports, strategies to further improve surveillance remain necessary. RELEVANCE TO CLINICAL PRACTICE: Findings from this research form the basis for proposing strategies to improve utilisation of hepatocellular carcinoma screening, inform hepatitis B virus-related clinical practice and for the delivery of care and nursing education to people receiving hepatitis B virus anti-viral therapy and at risk of developing hepatocellular carcinoma.

Factors associated with non-adherence to HBV antiviral therapy.

BACKGROUND: HBV antiviral therapy has the potential to reduce the burden of HBV-related liver disease by suppressing HBV DNA replication to undetectable levels, reducing the progression of liver fibrosis and reducing the risk of hepatocellular carcinoma (HCC) development. Treatment outcomes and long-term benefits require adherence to medication regimens. This study aimed to identify the prevalence and factors associated with non-adherence to antiviral therapy. METHODS: A cross-sectional survey of patients receiving HBV antiviral therapies was conducted in three Sydney hospitals. Participants were asked to complete an online questionnaire. Logistic regression was used to assess the associations between non-adherence (defined as missing more than 1 day of medication in the last 30 days) and demographic, socio-economic, disease, treatment, health-care system and individual-related factors. RESULTS: Of the 277 participants, 66 (23.8%) were non-adherent, missing a mean 1.7 days of medication (sd 4.8) in the last 30 days. In multivariate analysis, non-adherent behaviour declined with age (odds ratio [OR] 0.9, 95% CI 0.97, 0.99; P<0.013). Participants who reported having no established routine to take their medication (OR 5.0, 95% CI 1.4, 17.4; P<0.012) and having inadequate health literacy (OR 2.7, 95% CI 1.3, 5.5; P<0.007) were more likely to be non-adherent. CONCLUSIONS: Almost a quarter of participants in the current study were non-adherent. Adherence is potentially modifiable through person-centred education, collaborative models of patient care and interventions designed to improve health literacy and establish medication routines. Findings have the potential to improve health service delivery to patients at risk of non-adherence to HBV antiviral therapy.

Adherence to Hepatitis B Antiviral Therapy: A Qualitative Study.

Hepatitis B virus (HBV) antiviral therapies potentially suppress HBV viral load to an undetectable level reducing the risk of progressive liver disease and the development of HBV-related hepatocellular carcinoma. Adherence to antiviral therapies is imperative to achieve and maintain viral suppression. To date, there has been limited research on adherence to HBV therapies. Our study aimed to explore factors influencing adherence to antiviral therapy. A total of 29 participants consented to in-depth qualitative interviews at three outpatient clinics in Sydney, New South Wales, Australia. Interviews were digitally recorded and transcribed. Transcripts were initially classified as adherent or nonadherent and thematic analysis was used to identify dominant themes. Adherent behavior was reported by 59% (n = 17) of participants. Several themes influenced adherence including routine, fear of HBV-related disease progression, clinician-patient communication, treatment knowledge, and forgetfulness. To our knowledge, this is the first qualitative study to explore adherence to HBV antiviral therapy. An interplay of several dominant themes emerged from our data including fear of chronic HBV disease progression, clinician-patient communication, treatment knowledge, routine, and forgetfulness. Study findings have the potential to change nursing clinical practice, especially the way nurses and other clinicians target key HBV treatment messages and education, while monitoring adherence.

Barriers to access and uptake of antiretroviral therapy among HIV-positive men who have sex with men in Hanoi, Vietnam: from HIV testing to treatment.

Little is known about the experiences of Vietnamese men who have sex with men in accessing HIV testing and treatment. We aimed to explore barriers to access and uptake of antiretroviral therapy (ART) among HIV-positive men who have sex with men in Hanoi. During 2015, we conducted qualitative interviews with 35 participants recruited using snowball sampling based on previous research and social networks. Key individual impediments to ART uptake included inadequate preparation for a positive diagnosis and the dual stigmatisation of homosexuality and HIV and its consequences, leading to fear of disclosure of HIV status. Health system barriers included lack of clarity and consistency about how to register for and access ART, failure to protect patient confidentiality and a reticence by providers to discuss sexual identity and same-sex issues. Results suggest fundamental problems in the way HIV testing is currently delivered in Hanoi, including a lack of client-centred counselling, peer support and clear referral pathways. Overcoming these barriers will require educating men who have sex with men about the benefits of routine testing, improving access to quality diagnostic services and building a safe, confidential treatment environment for HIV-positive men to access, receive and remain in care.

Factors associated with HBV virological breakthrough.

BACKGROUND: Little is known about non-adherence to HBV therapy. This study aimed to investigate the relationship between self-reported missed days of antiviral therapy and HBV virological breakthrough and factors associated with virological breakthrough. METHODS: A cross-sectional survey of 211 HBV patients receiving oral antiviral therapies was undertaken at three tertiary hospitals in Sydney, Australia. Associations between 0 to >6 missed days in the last 30 days and virological breakthrough (defined as >10-fold rise in serum HBV DNA above nadir or after achieving virological response in the last 12 months) were examined. Logistic regression analyses determined the number of missed days most strongly associated with virological breakthrough and the associated factors. We report odds ratios (ORs) and relative risks (RRs). RESULTS: Of the 204, 32 participants (15.6%) had quantifiable HBV DNA levels (>20 IU/ml); 15 (46.8%) of them experienced virological breakthrough. Participants reported never missing medication (n=130, 63.7%) or missing 1 day (n=23, 11.3%), >1 day (n=23, 11.3%), 2-6 days (n=15, 7.3%) and >6 days (n=13, 6.4%). The most discriminating definition of non-adherence was missing >1 day of medication (RR=8.3; OR=10.2, 95% CI 3.1, 33.8, receiver operating characteristic curve 0.76). Factors independently associated with virological breakthrough included non-adherence (OR=9.0, 95% CI 2.5, 31.9) diagnosed with HBV ≤14 years (OR=5.3, 95% CI 1.0, 26.2) and age ≤47 years (OR=5.4, 95% CI 1.1, 26.9). CONCLUSIONS: Results provide an evidence-based definition of non-adherence to inform clinical practice and provide a basis for key patient education messages. Closer monitoring of groups at risk of viral breakthrough is required.