Individual Heterogeneity and Trends in Hepatitis C Infection Risk Among People Who Inject Drugs: A Longitudinal Analysis.

Hepatitis C virus (HCV) causes substantial morbidity and mortality, particularly among people who inject drugs (PWID). While elimination of HCV as a public health problem may be possible through treatment-as-prevention, reinfection can attenuate the impact of treatment scale-up. There is a need to better understand the distribution and temporal trends in HCV infection risk, including among HCV-seropositive individuals who will be eligible for treatment and at risk for subsequent reinfection. In this analysis of 840 seronegative and seropositive PWID in Baltimore, MD USA, we used random forest methods to develop a composite risk score of HCV infection from sociodemographic and behavioural risk factors. We characterised the individual heterogeneity and temporal trajectories in this composite risk score using latent class methods and compared that index with a simpler, conventional measure, injection drug use frequency. We found that 15% of the population remained at high risk of HCV infection and reinfection by the composite metric for at least 10 years from study enrolment, while others experienced transient periods of moderate and low risk. Membership in this high-risk group was strongly associated with higher rates of HCV seroconversion and post-treatment viraemia, as a proxy of reinfection risk. Injection frequency alone was a poor measure of risk, evidenced by the weak associations between injection frequency classes and HCV-associated outcomes. Together, our results indicate HCV infection risk is not equally distributed among PWID nor well captured by injection frequency alone. HCV elimination programmes should consider targeted, multifaceted interventions among high-risk individuals to reduce reinfection.

An Increase in the Prevalence of Clinically Relevant Resistance-Associated Substitutions in Four Direct-Acting Antiviral Regimens: A Study Using GenBank HCV Sequences.

Direct-acting antivirals (DAAs) revolutionized the therapeutics of chronic hepatitis C. The emergence and transmission of HCV variants with resistance-associated substitutions (RASs) can undermine HCV treatment. This study aimed to assess the prevalence and temporal trends of RASs in HCV, with a particular focus on clinically relevant RASs (cr-RASs). Near-complete HCV GenBank sequences archived in the Los Alamos HCV Database were analyzed. The study period was divided into two phases: before 2011 and from 2011 onward. Identification of RASs across three DAA classes (NS3, NS5A, and NS5B inhibitors) was based on the 2020 EASL guidelines. The AASLD-IDSA recommendations were used to identify cr-RASs for three HCV genotypes/subtypes (1a, 1b, and 3) and four DAA regimens: ledipasvir/sofosbuvir; elbasvir/grazoprevir; sofosbuvir/velpatasvir; and glecaprevir/pibrentasvir. The final HCV dataset comprised 3443 sequences, and the prevalence of RASs was 50.4%, 60.2%, and 25.3% in NS3, NS5A, and NS5B, respectively. In subtype 1a, resistance to ledipasvir/sofosbuvir was 32.8%, while resistance to elbasvir/grazoprevir was 33.0%. For genotype 3, resistance to sofosbuvir/velpatasvir and glecaprevir/pibrentasvir was 4.2% and 24.9%, respectively. A significant increase in cr-RASs was observed across the two study phases as follows: for ledipasvir/sofosbuvir in subtype 1a, cr-RASs increased from 30.2% to 35.8% (p = 0.019); for elbasvir/grazoprevir in subtype 1a, cr-RASs increased from 30.4% to 36.1% (p = 0.018); In subtype 1b, neither ledipasvir/sofosbuvir nor elbasvir/grazoprevir showed any cr-RASs in the first phase, but both were present at a prevalence of 6.5% in the second phase (p < 0.001); for sofosbuvir/velpatasvir in genotype 3, cr-RASs increased from 0.9% to 5.2% (p = 0.006); and for glecaprevir/pibrentasvir, cr-RASs increased from 12.0% to 29.1% (p < 0.001). The rising prevalence of HCV RASs and cr-RASs was discernible. This highlights the necessity for ongoing surveillance and adaptation of novel therapeutics to manage HCV resistance effectively. Updating the clinical guidelines and treatment regimens is recommended to counteract the evolving HCV resistance to DAAs.

Evaluating the effect of direct-acting antiviral agent treatment scale-up on Hepatitis C virus prevalence among people who inject drugs in UK.

BACKGROUND: There is limited empirical work assessing the effectiveness of treatment as prevention (TasP) in reducing HCV prevalence among people who inject drugs (PWID). Here, we used survey data from the UK during 2010-2020, to evaluate the impact of direct-acting antiviral agent (DAA) treatment scale-up, which started in 2015, on HCV prevalence among PWID. METHODS: We fitted a logistic regression to time/location specific data on prevalence from the Needle Exchange Surveillance Initiative in Scotland and Unlinked Anonymous Monitoring programme in England. For each post-intervention year and location, we quantified the effect of TasP as the difference between estimated prevalence and its counterfactual (prevalence in the absence of scale-up). Progress to elimination was assessed by comparing most recent prevalence against one in 2015. RESULTS: In 2015, prevalence ranged from 0.44 to 0.71 across the 23 locations (3 Scottish, 20 English). Compared to counterfactuals, there was an absolute reduction of 46% (95% credible interval [32%,59%]) in Tayside in 2020, 35% ([24%,44%]) in Glasgow in 2019, and 25% ([10%,39%]) in the Rest of Scotland in 2020. The English sites with highest estimated absolute reductions in 2021 were South Yorkshire (45%, [29%,58%]), Thames Valley (49%, [34%,59%]) and West London (41%, [14%,59%]). Compared to 2015, there was 80% probability that prevalence had fallen by 65% in Tayside, 53% in Glasgow and 36% in the Rest of Scotland. The English sites with highest % prevalence decrease compared to 2015, achieved with probability 80%, were Chesire & Merseyside (70%), South Yorkshire (65%) and Thames Valley (71%). Higher treatment intensity was associated with higher reductions in prevalence. CONCLUSION: Conclusion. Real-world evidence showing substantial reductions in chronic HCV associated with increase of HCV treatment scale-up in the community thus supporting the effectiveness of HCV treatmen as prevention in people who inject drugs.

Implementation of a safer conception programme for HIV-affected men and women in rural Uganda.

We integrated safer conception care into a Ugandan HIV clinic. People with HIV (PWH), or partnered with a PWH, and desiring children were eligible for the Healthy Families Clinic Program. Clients completed quarterly safer conception counselling visits and questionnaires to provide information around method preferences and outcomes (partner pregnancy, partner seroconversion). We used clinic level data to evaluate longitudinal viral suppression among PWH. Between November 2016 and January 2020, 361 clients (53% men) accessed services. 75% were PWH (51% women, 96% men): 99% were on antiretroviral therapy (ART) and most reported HIV-sero-different partnerships (97%). Frequently selected safer conception methods included ART (86%), timed condomless sex (74%), and PrEP (40%) with important differences by HIV-serostatus and gender. 22.5% reported pregnancy. Most (97%) PWH were virally suppressed at enrolment and 81% of non-virally suppressed PWH were virally suppressed at 15 months. Two HIV-negative clients (2%) had HIV seroconversion. There is demand for safer conception care in a public sector HIV-clinic in Uganda. Men and women have unique safer conception care preferences. The majority of clients engaged in safer conception care had viral suppression at follow up.

Integrating 'undetectable equals untransmittable' into HIV counselling in South Africa: the development of locally acceptable communication tools using intervention mapping.

BACKGROUND: The global campaign for "Undetectable equals Untransmittable" (U = U) seeks to spread awareness of HIV treatment as prevention, aiming to enhance psychological well-being and diminish stigma. Despite its potential benefits, U = U faces challenges in Sub-Saharan Africa, with low awareness and hesitancy to endorse it. We sought to develop a U = U communications intervention to support HIV counselling in primary healthcare settings in South Africa. METHODS: We used Intervention Mapping (IM), a theory-based framework to develop the "Undetectable and You" intervention for the South African context. The six steps of the IM protocol were systematically applied to develop the intervention including a needs assessment consisting of a systematic review and qualitative research including focus group discussions (FGD) and key informant (KI) interviews. Program objectives and target population were determined before designing the intervention components and implementation plan. RESULTS: The needs assessment indicated low global U = U awareness, especially in Africa, and scepticism about its effectiveness. Lay counsellors and clinic managers stressed the need for a simple and standardized presentation of U = U addressing both patients' needs for encouragement and modelling of U = U success but also clear guidance toward ART adherence behaviour. Findings from each step of the process informed successive steps. Our final intervention consisted of personal testimonials of PLHIV role models and their partners, organized as an App to deliver U = U information to patients in primary healthcare settings. CONCLUSIONS: We outline an intervention development strategy, currently in evaluation stage, utilizing IM with formative research and input from key U = U stakeholders and people living with HIV (PLHIV).

Knowledge of HIV transmission, prevention strategies and U = U among adult sexual and gender minorities in Brazil.

INTRODUCTION: Although strong scientific evidence of the efficacy and effectiveness of treatment-as-prevention (TasP) is available, full endorsement of the "Undetectable = Untransmittable" (U = U) and "zero-risk" messages could be improved. Increasing knowledge about HIV transmission, prevention and treatment is a critical component of care efforts. The study assessed knowledge of HIV transmission and prevention strategies, and the perceived accuracy of the slogan U = U among sexual and gender minorities (SGM) in Brazil. METHODS: Cross-sectional web-based survey targeting adult SGM living in Brazil (2021-2022) recruited on social media and dating apps. We used the 12-item HIV Knowledge Assessment (HIV-KA) questionnaire to assess HIV knowledge, three items of which address pre-exposure prophylaxis (PrEP), post-exposure prophylaxis and TasP. Perceived accuracy of the U = U slogan was assessed with the question: "With regards to HIV-positive individuals transmitting HIV through sexual contact, how accurate do you believe the slogan U = U is?". We a priori grouped the study population into three mutually exclusive groups: people living with HIV (PLHIV), HIV negative and HIV unknown. We used logistic regression models to assess factors associated with high HIV knowledge and perception of the U = U as completely accurate. RESULTS: Of 50,222 individuals accessing the questionnaire, 23,981 were included: 5071 (21.0%) PLHIV, 17,257 (71.5%) HIV negative and 1653 (6.9%) HIV unknown. The proportion of participants with high knowledge was significantly higher for PLHIV and HIV negative (48.1% and 45.5%, respectively) compared to 26.1% of HIV unknown. More PLHIV perceived U = U as completely accurate (80.4%), compared to 60.0% of HIV negative and 42.9% of HIV unknown. HIV knowledge correlates with perceived accuracy of the U = U slogan across all groups. Higher HIV knowledge was associated with higher income and education regardless of HIV status. Among HIV-negative participants, PrEP awareness and use were associated with higher knowledge and accurate perception of the U = U slogan. CONCLUSIONS: Our findings show that HIV knowledge and perceived accuracy of U = U are strongly correlated, that knowledge differs according to HIV status, and that poor socio-economic is linked to poor knowledge among SGM from Brazil. Educational strategies regarding TasP, U = U and zero risk targeting socio-economically vulnerable populations are urgent in Brazil.

The Potential Role of Undetectable = Untransmittable (U = U) in Reducing HIV Stigma among Sexual Minority Men in the US.

The Undetectable = Untransmittable (U = U) message and its scientific underpinnings have been widely suggested to reduce HIV stigma. However, misunderstanding and skepticism about U = U may prevent this destigmatizing potential from being fully realized. This cross-sectional study examined associations between U = U belief (belief that someone with a sustained undetectable viral load has zero risk of sexually transmitting HIV) and HIV stigma among US sexual minority men. Differences by serostatus and effects of brief informational messaging were also explored. The survey was completed online by 106 men living with HIV and 351 HIV-negative/status-unknown men (2019-2020). Participants were 18-83 years old (M[SD] = 41[13.0]). Most were non-Hispanic White (70.0%) and gay (82.9%). Although nearly all participants (95.6%) were aware of U = U, only 41.1% believed U = U. A greater percentage of participants living with HIV (66.0%) believed U = U compared with HIV-negative/status-unknown participants (33.6%). Among participants living with HIV, U = U belief was not significantly associated with perceived, internalized, or experienced HIV stigma or with viral load prejudice (prejudice against people who have a detectable HIV viral load). Among HIV-negative/status-unknown participants, U = U belief was associated with less frequently enacted HIV discrimination, more positive feelings toward people with an undetectable viral load, and lower personal endorsement of stigmatizing beliefs. Brief informational messaging about U = U did not affect most stigma dimensions and did not favorably affect any. Interventions are needed to correct commonly held, outdated misconceptions about HIV transmission risk. Such initiatives must not only engage people living with HIV but also engage HIV-negative/status-unknown people to maximize the destigmatizing potential of U = U.

RESUMEN: Para reducir el estigma del VIH se ha recomendado difundir extensivamente el mensaje Indetectable = Intransmisible (U = U) y sus fundamentos científicos. Sin embargo, falta de comprensión y escepticismo acerca de U = U pueden impedir que se realice plenamente su potencial desestigmatizante. Este estudio transversal examinó las asociaciones entre la creencia U = U (creencia de que alguien con una carga viral indetectable sostenida tiene cero riesgo de transmitir sexualmente el VIH) y el estigma del VIH entre hombres de minorías sexuales estadounidenses. También se exploró si el efecto de los mensajes informativos breves dependía del estatus serológico. La encuesta fue completada en línea por 106 hombres que viven con el VIH y 351 hombres VIH negativos o de estatus desconocido (2019­2020). Los participantes tenían entre 18 y 83 años (M[DS] = 41[13,0]). La mayoría eran blancos no hispanos (70,0%) y gay (82,9%). Aunque casi todos los participantes (95,6%) sabían sobre U = U, sólo el 41,1% creían en U = U. Un mayor porcentaje de participantes con VIH (66,0%) creían que U = U en comparación con los participantes VIH negativos o de estatus desconocido (33,6%). Entre los participantes con VIH, la creencia U = U no se asoció significativamente con el estigma del VIH percibido, interiorizado o experimentado ni con el prejuicio sobre la carga viral (prejuicio contra las personas que tienen una carga viral de VIH detectable). Entre los participantes VIH negativos/con estatus desconocido, la creencia U = U se asoció con menor frecuencia de discriminación por VIH, sentimientos más positivos hacia las personas con una carga viral indetectable y menor respaldo personal a las creencias estigmatizantes. Los mensajes informativos breves sobre U = U no afectaron la mayoría de las dimensiones del estigma y no afectó favorablemente a ninguno. Se necesitan intervenciones para corregir conceptos frecuentes sobre el riesgo de transmisión del VIH que son erróneos y obsoletos. Para maximizar el potencial desestigmatizador de U = U, estas iniciativas no sólo deben involucrar a las personas que viven con el VIH, sino también a las personas VIH-negativas o de estatus desconocido.

Rapid Initiation of Antiretroviral Therapy With Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide Versus Efavirenz, Lamivudine, and Tenofovir Disoproxil Fumarate in HIV-Positive Men Who Have Sex With Men in China: Week 48 Results of the Multicenter, Randomized Clinical Trial.

BACKGROUND: Most international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for people newly diagnosed with human immunodeficiency virus (HIV)-1 infection, but experiences with rapid ART initiation remain limited in China. We aimed to evaluate the efficacy and safety of efavirenz (400 mg) plus lamivudine and tenofovir disoproxil fumarate (EFV + 3TC + TDF) versus coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in rapid ART initiation among men who have sex with men (MSM) who have been diagnosed with HIV. METHODS: This multicenter, open-label, randomized clinical trial enrolled MSM aged ≥18 years to start ART within 14 days of confirmed HIV diagnosis. The participants were randomly assigned in a 1:1 ratio to receive EFV (400 mg) + 3TC + TDF or BIC/FTC/TAF. The primary end point was viral suppression (<50 copies/mL) at 48 weeks per US Food and Drug Administration Snapshot analysis. RESULTS: Between March 2021 and July 2022, 300 participants were enrolled; 154 were assigned to receive EFV + 3TC + TDF (EFV group) and 146 BIC/FTC/TAF (BIC group). At week 48, 118 (79.2%) and 140 (95.9%) participants in the EFV and BIC group, respectively, were retained in care with viral suppression, and 24 (16.1%) and 1 (0.7%) participant in the EFV and BIC group (P < .001), respectively, discontinued treatment because of adverse effects, death, or lost to follow-up. The median increase of CD4 count was 181 and 223 cells/µL (P = .020), respectively, for the EFV and BIC group, at week 48. The overall incidence of adverse effects was significantly higher for the EFV group (65.8% vs 37.7%, P < .001). CONCLUSIONS: BIC/FTC/TAF was more efficacious and safer than EFV (400 mg) + 3TC + TDF for rapid ART initiation among HIV-positive MSM in China.

Evaluating experiences of HIV-related stigma among people living with HIV diagnosed in different treatment eras in British Columbia, Canada.

There is mixed evidence on whether experiences of HIV-related stigma are mitigated with lived experience. We sought to examine whether people living with HIV (PLWH) with longer living experience reported varying levels of HIV-related stigma. Between January 2016-September 2018, we used purposive sampling to enrol PLWH aged ≥19 across British Columbia, Canada, where participants completed the 10-item Berger HIV Stigma Scale. We conducted bivariate analyzes examining key sociodemographic characteristics and HIV-related stigma scores. Multivariable linear regression modelled the association between year of HIV diagnosis by treatment era and HIV-related stigma scores. We enrolled 644 participants; median age at enrolment was 50 years (Q1-Q3: 42-56), with 37.4% (n = 241) diagnosed before the year 2000. The median HIV-stigma scores of all participants (19.0, Q1-Q3: 13-25, range 0-40) stratified by treatment era were: 17.0 (pre-1996), 20.0 (1996-1999), 20.0 (2000-2009), 19.0 (2010-2018) (p = 0.03). While there was a significant association at the univariate level, year of HIV diagnosis by treatment era was not associated with stigma scores after controlling for age, gender, HIV key populations, ethnicity, relationship status, social support, and ever having a mental health disorder diagnosis. This suggests that PLWH still experience HIV-related stigma today, compared to those diagnosed in earlier time periods.

The Perils of Overly Sensitive Viral Load Testing for Persons With Human Immunodeficiency Virus.

The concept of "undetectable = untransmittable (U = U)" has been revolutionary in both the prevention and treatment of persons with human immunodeficiency virus (HIV). Most studies proving the concept of U = U used an HIV RNA (viral load [VL]) cutoff of 200 copies/mL to define being undetectable. Since then, increasingly sensitive commercial VL assays, sometimes down to a lower limit of detection (LLD) of 20 copies/mL, lead to confusion about the definition of "undetectable" and when someone is truly considered untransmittable. VLs between the LLD and 200 copies/mL have been associated with future virologic failure; however, no data exist to suggest that intervening in those patients leads to any meaningful benefits. In the absence of a demonstrable benefit of reporting such low VLs, we view this practice as harmful. We suggest recommendations for adjusting VL reporting and improving provider counseling, and call for research designs to mitigate the harms of overly sensitive VL testing.

Improving HIV testing, linkage, and retention in care among South African men through U=U messaging: A study protocol for two sequential hybrid type 1 effectiveness- implementation randomized controlled trials.

BACKGROUND: Increasing HIV testing and treatment coverage among people living with HIV (PLHIV) is essential for achieving global AIDS epidemic control. However, compared to women, cis-gender heterosexual men living with HIV are significantly less likely to know their HIV status, initiate anti-retroviral therapy (ART) and achieve viral suppression. This is particularly true in South Africa, where men are also at increased risk of mortality resulting from AIDS-related illnesses. While there is growing knowledge of Treatment as Prevention or the concept Undetectable=Untransmittable (U=U) among PLHIV in Western and high-income countries, the reach and penetration of the U=U message in sub-Saharan Africa remains limited, and few studies have evaluated the impact of accessible and relatable U=U messages on ART initiation and adherence. To address these gaps, rigorous evaluations of interventions that incorporate U=U messages are needed, especially among men in high prevalence settings. METHODS: Building on our U=U messages that we previously developed for men using behavioral economics insights and a human-centered design, we will conduct two sequential hybrid type 1 effectiveness-implementation trials to evaluate the impact of U=U messages on men's uptake of community-based HIV testing and ART initiation (Trial 1), and retention in care and achievement of viral suppression (Trial 2). A cluster randomized trial will be implemented for Trial 1, with HIV testing service site-days randomized to U=U or standard-of-care (SoC) messages inviting men to test for HIV. An individual-level randomized control trial will be implemented for Trial 2, with men initiating ART at six government clinics randomized to receive U=U counselling or SoC treatment adherence messaging. We will incorporate a multi-method evaluation to inform future implementation of U=U messaging interventions. The study will be conducted in the Buffalo City Metro Health District of the Eastern Cape Province and in the Cape Town Metro Health District in the Western Cape Province in South Africa. DISCUSSION: These trials are the first to rigorously evaluate the impact of U=U messaging on HIV testing uptake, ART initiation and achievement of viral suppression among African men. If effective, these messaging interventions can shape global HIV testing, treatment and adherence counselling guidelines and practices.

Bridging the knowledge gap of biomedical HIV prevention tools among sub-saharan african immigrants in France. Results from an empowerment-based intervention.

Introduction: Biomedical HIV prevention tools are available in France to prevent new infections. However, evidence suggests a lack of knowledge of these tools among sub-Saharan African immigrants, who are particularly affected by HIV due to social hardship, an indirect factor of HIV acquisition. We analysed the impact of an empowerment-based intervention on the knowledge of treatment as prevention (TasP), pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) in a population of precarious sub-Saharan African immigrants. Methods: Data were collected throughout the MAKASI project. Following an outreach approach, participants were recruited in public places based on their precarious situations and followed for six months (0, 3, 6 months) between 2018 and 2021. Participants were randomized into two groups and received an empowerment intervention sequentially (stepped wedge design). We used random-effects logistic regression models to evaluate the intervention effect on the knowledge of biomedical HIV prevention tools. ClinicalTrials.gov Identifier: NCT04468724. Results: The majority of the participants were men (77.5%), and almost half of them had arrived in France within 2 years prior to inclusion (49.3%). At baseline, 56% of participants knew about TasP, 6% knew about PEP and 4% knew about PrEP. Receiving the intervention increased the odds of knowing about PEP (aOR = 2.02 [1.09-3.75]; p < 0.026). Intervention effects were observed for TasP and PrEP only after 6 months. We found significant time effects for PEP (at 3 months, aOR = 4.26 [2.33-7.80]; p < 0.001; at 6 months, aOR = 18.28 [7.39-45.24]; p < 0.001) and PrEP (at 3 months, aOR = 4.02 [2.10-7.72]; p < 0.001; at 6 months, aOR = 28.33 [11.16-71.91]; p < 0.001). Conclusions: We showed that the intervention increased the knowledge of biomedical HIV prevention tools. The effect of the intervention was coupled with an important time effect. This suggested that exposure to the intervention together with other sources of information contributed to increased knowledge of biomedical HIV prevention tools among precarious sub-Saharan African immigrants.

Behaviour changes following HIV diagnosis among men who have sex with men in the era of treatment as prevention: data from a prospective study.

We described the longitudinal changes in sexual behaviour and associated factors among newly diagnosed with HIV men who have sex with men participating in a prospective observational study from a London HIV clinic (2015-2018). Participants self-completed questionnaires at baseline, months 3 and 12. Information collected included socio-demographic, sexual behaviour, health, lifestyle and social support. Trends in sexual behaviours over one year following diagnosis and associated factors were assessed using generalized estimating equations with logit link. Condomless sex (CLS) dropped from 62.2% at baseline to 47.6% at month-three but increased again to 61.8% at month-12 (p-trend = 0.790). Serodiscordant-CLS increased between month-three and month-12 (from 13.1% to 35.6%, p-trend < 0.001). The prevalence of serodiscordant-CLS with high risk of transmitting to their partners at month-three was 10.7%. CLS was higher among men who reported recreational drug use (adjusted Odds Ratio (aOR) 3.03, 95%CI 1.47-6.24, p = 0.003), those with undetectable viral load (aOR 2.17, 95%CI 1.22-3.84, p = 0.008) and those who agreed with a statement "condoms are not necessary when HIV viral load is undetectable" (aOR 3.41, 95%CI 1.58-7.38, p = 0.002). MSM continued to engage in CLS after HIV diagnosis, which coincided with U = U publications and increased throughout the study.

Treatment as prevention for hepatitis C virus in the Middle East and North Africa: a modeling study.

Background: Direct-acting antivirals opened an opportunity for eliminating hepatitis C virus (HCV) infection in the Middle East and North Africa (MENA), the region most affected by HCV infection. Impact of HCV treatment as prevention (HCV-TasP) was investigated in 19 MENA countries. Methods: An age-structured mathematical model was used to assess program impact using epidemiologic and programming measures. The model was fitted to a database of systematically gathered HCV antibody prevalence data. Two main scenarios were investigated for the treatment roll-out to achieve (i) 80% reduction in HCV incidence by 2030, and (ii) incidence rate < 1 per 100,000 person-years by 2030. Results: In the target-80%-incidence-reduction scenario, number of treatments administrated by 2030 ranged from 2,610 in Lebanon to 180,416 in Sudan with a median of 53,079, and treatment coverage ranged between 40.2 and 78.4% with a median of 60.4%. By 2030, prevalence of chronic infection ranged between 0.0 and 0.3% with a median of 0.1%, and incidence rate, per 100,000 person-years, ranged between 0.9 and 16.3 with a median of 3.2. Program-attributed reduction in incidence rate ranged between 47.8 and 81.9% with a median of 68.5%, and number of averted infections ranged between 401 and 68,499 with a median of 8,703. Number of treatments needed to prevent one new infection ranged from 1.7 in Oman to 25.9 in Tunisia with a median of 6.5. In the target incidence rate < 1 per 100,000 person-years scenario, number of treatments administrated by 2030 ranged from 3,470 in Lebanon to 211,912 in Sudan with a median of 54,479, and treatment coverage ranged between 55.5 and 95.9% with a median of 87.5%. By 2030, prevalence of chronic infection was less than 0.1%, and incidence rate, per 100,000 person-years, reached less than 1. Program-attributed reduction in incidence rate ranged between 61.0 and 97.5% with a median of 90.7%, and number of averted infections ranged between 559 and 104,315 with a median of 12,158. Number of treatments needed to prevent one new infection ranged from 1.3 in Oman to 25.9 in Tunisia with a median of 5.5. Conclusion: HCV-TasP is an effective and indispensable prevention intervention to control MENA's HCV epidemic and to achieve elimination by 2030.

Biomedical bargains: Negotiating "safe sex" on antiretroviral treatment in rural South Africa.

Wide-scale availability of antiretroviral treatment (ART) has transformed the global landscape for HIV prevention, shifting emphasis away from a strictly behavioral focus on changing sexual practices towards a biomedical approach. Successful ART management is measured by an undetectable viral load, which helps maintain overall health and prevent onward viral transmission. The latter utility of ART, however, must be understood in the context of its implementation. In South Africa, ART has become easily accessible - yet ART knowledge spreads unevenly, while counseling advice and normative expectations and experiences of gender and aging interact to inform sexual practices. As ART enters the sexual lives of middle-aged and older people living with HIV (MOPLH), a population growing rapidly, how has it informed sexual decisions and negotiations? Drawing on in-depth interviews with MOPLH on ART, corroborated with focus group discussions and national ART-related policies and guidelines, we find that for MOPLH, sexual decisions increasingly feature compliance with biomedical directives and concern for ART efficacy. Seeking consensus regarding the biological risks of sex on ART becomes an important feature of sexual negotiations, and anticipated disagreements can pre-empt sexual relationships altogether. We introduce the concept of biomedical bargains to explain what happens when disagreements arise, and the terms of sex are negotiated using competing interpretations of biomedical information. For both men and women, ostensibly gender-neutral biomedical discourses provide new discursive resources and strategies for sexual decisions and negotiations, yet biomedical bargains are still embedded in gender dynamics-women invoke the dangers of jeopardizing treatment efficacy and longevity to insist on condoms or justify abstinence, while men utilize biomedical arguments in an effort to render condomless sex safe. While the full therapeutic benefits of ART are critical for the efficacy and equity of HIV programs, they will nonetheless always affect, and be affected by, social life.

Attitudes and Beliefs About HIV Treatment as Prevention Among People Who are Not Engaged in HIV Care, 2018-2019.

Treatment as prevention (TasP) is an effective HIV prevention strategy. Our objectives were to explore TasP attitudes and beliefs among people with HIV (PWH) who are not engaged in care and to examine attitudes and beliefs by selected characteristics. We sampled PWH who had participated in the Medical Monitoring Project (MMP), a structured interview survey, from June 2018-May 2019 to participate in 60-minute semi-structured telephone interviews. We obtained sociodemographic and behavioral quantitative data from the MMP structured interview. We used applied thematic analysis to analyze the qualitative data and integrated the qualitative and quantitative data during analysis. Negative attitudes and beliefs, especially skepticism and mistrust, about TasP were pervasive. Only one participant who identified as female, was not sexually active, and had not heard of TasP held positive attitudes and beliefs about TasP. TasP messages should use clear and unambiguous language, address mistrust, and reach people who are not engaged in medical care.

Attitudes Towards Treatment as Prevention Among PrEP-Experienced Gay and Bisexual Men in Australia.

The introduction of HIV pre-exposure prophylaxis (PrEP) has the potential to impact the attitudes gay and bisexual men (GBM) who consequently choose to take PrEP have towards treatment as prevention (TasP), and the extent to which they are willing to have condomless anal intercourse (CLAI) with an HIV-positive sexual partner who has an undetectable viral load (UVL). Using a cross-sectional sample from an observational cohort study conducted from August 2018 to March 2020, we examined the extent to which PrEP-experienced GBM are willing to have CLAI with a partner who has a UVL. Simple and multiple logistic regression models were used to identify associated variables. Of the 1386 participants included in the analyses, 79.0% believed in the effectiveness of TasP, and 55.3% were willing to have CLAI with a partner who has a UVL. Wiling participants were less worried about getting HIV when taking PrEP and more likely to believe in TasP. Further research is needed to better understand the gap between belief in TasP and willingness to have CLAI with a partner who has a UVL among PrEP-experienced GBM.

Attitudes Toward HIV-Positive Status Disclosure Among U=U-Aware Sexual and Gender Minority Individuals in the USA: a Consensual Qualitative Research Approach.

Introduction: The U=U (i.e., undetectable equals untransmittable) campaign is founded upon biomedical advancements that have positioned HIV as a manageable condition with effectively zero risk of transmission. In spite of these developments, attitudes of sexual and gender minority populations regarding the necessity of seropositive status disclosure remain unexamined. Methods: The current study analyzed qualitative data regarding the necessity of seropositive status disclosure from 62 sexual minority men as well as transgender and gender non-conforming individuals who have sex with men from 2020 to 2021. Results: The majority of participants believed disclosure to be necessary and invoked several social and structural factors that informed their attitudes. Participants cited HIV criminalization laws, the ethics of non-disclosure, and disclosure as a means of educating sex partners when appraising the necessity of disclosure. Participants also presented concerns regarding U=U efficacy and HIV stigma. Conclusions: Findings indicate that the disclosure of seropositive status to sex partners is still important to U=U-aware sexual and gender minority individuals. The majority of the study sample, irrespective of HIV status, believed seropositive status disclosure was necessary in advance of sex. Policy Implications: Findings suggest opportunities for public health messaging to remediate concerns about U=U efficacy, combat misinformation, and clarify out-of-date information on HIV criminalization.

Achieving the UNAIDS 90-90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa.

BACKGROUND: Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012-2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90-90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90-90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90-90-90 targets. METHODS: Estimates were based predominantly on "process" data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field. RESULTS: The estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~ 3%) of the target. CONCLUSIONS: All four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings. All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90-90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95-95-95 by 2030 and fast-track the end of the HIV epidemic.

Same-day and rapid initiation of antiretroviral therapy in people living with HIV in Asia. How far have we come?

Human immunodeficiency virus (HIV) continues to be a major public health issue, and the effectiveness of HIV prevention, diagnosis, treatment, and care varies, particularly in the Asia-Pacific region. The rapid initiation of antiretroviral therapy (ART) is important to control the HIV epidemic and to optimize the health of people living with HIV; many guidelines now recommend ART initiation within 7 days of HIV diagnosis, with same-day initiation for people diagnosed with HIV who feel ready. Many countries in the Asia-Pacific region have already implemented or are moving towards implementation of rapid or same-day ART initiation. However, there are many obstacles and challenges to its implementation, which vary substantially across the region. This article summarizes the latest evidence on rapid and same-day ART initiation and discusses lessons learned and barriers to implementation in Asian countries, particularly focusing on Taiwan, Thailand, Singapore, and the Republic of Korea.