Missed opportunities for guidance on sexually transmitted infection services: a global review of national HIV PrEP guidance.

OBJECTIVES: People who use or would benefit from pre-exposure prophylaxis (PrEP) for HIV infection are disproportionately affected by sexually transmitted infections (STIs). Integrating STI services when offering PrEP fosters synergies and efficiencies in response to HIV/STI and promotes people-centred care. Including guidance on STI interventions for people on PrEP may facilitate implementation and uptake. We conducted a global review of national PrEP guidance documents and analysed the inclusion of recommendations for the provision of STI services by country level of income. METHODS: We searched national PrEP guidance documents published by WHO Member States through the WHO, the Joint United Nations Programme on HIV/AIDS (UNAIDS) databases, the PrEPWatch repository and Google. Information on a range of STI-related interventions was extracted from documents available by October 2023. RESULTS: Of the 113 national PrEP guidance documents retrieved, STIs were mentioned in 77% (90/117). Viral hepatitis B testing and vaccination were recommended by most high-income countries (HICs) and low-income and middle-income countries (LMICs). Recommendation for syphilis testing was prominent in HICs (91%) and moderately noted in LMICs (68%). Gonorrhoea and chlamydia testing was recommended frequently in HICs (88%) and 42% in LMICs. However, the review noted that, to a much lesser extent, specific type of testing for these pathogens was mentioned. Recommendation for quarterly STI testing for syphilis, gonorrhoea and chlamydia was ubiquitous, while the need to offer STI partner services was rarely mentioned. CONCLUSIONS: PrEP services offer an opportunity for improved and expanded STI services, increasing person-centred care and addressing STI epidemics alongside HIV. Our review highlights the strengths and gaps in incorporating critical STI interventions into national PrEP normative guidance. Addressing these gaps through a stepwise approach and increasing targeted testing and partner services can help improve quality of care and support an effective response to HIV and other STIs.

Determining reinfection rates by hepatitis C testing interval among key populations: A systematic review and meta-analysis.

BACKGROUND & AIMS: Detecting hepatitis C virus (HCV) reinfection among key populations helps prevent ongoing transmission. This systematic review aims to determine the association between different testing intervals during post-SVR follow-up on the detection of HCV reinfection among highest risk populations. METHODS: We searched electronic databases between January 2014 and February 2023 for studies that tested individuals at risk for HCV reinfection at discrete testing intervals and reported HCV reinfection incidence among key populations. Pooled estimates of reinfection incidence were calculated by population and testing frequency using random-effects meta-analysis. RESULTS: Forty-one single-armed observational studies (9453 individuals) were included. Thirty-eight studies (8931 individuals) reported HCV reinfection incidence rate and were included in meta-analyses. The overall pooled estimate of HCV reinfection incidence rate was 4.13 per 100 per person-years (py) (95% confidence interval [CI]: 3.45-4.81). The pooled incidence estimate among people who inject drugs (PWID) was 2.84 per 100 py (95% CI: 2.19-3.50), among men who have sex with men (MSM) 7.37 per 100 py (95% CI: 5.09-9.65) and among people in custodial settings 7.23 per 100 py (95% CI: 2.13-16.59). The pooled incidence estimate for studies reporting a testing interval of ≤6 months (4.26 per 100 py; 95% CI: 2.86-5.65) was higher than studies reporting testing intervals >6 months (5.19 per 100 py; 95% CI: 3.92-6.46). CONCLUSIONS: HCV reinfection incidence was highest in studies of MSM and did not appear to change with retesting interval. Shorter testing intervals are likely to identify more reinfections, help prevent onward transmission where treatment is available and enable progress towards global HCV elimination, but additional comparative studies are required.

Protocol for a cluster randomised controlled trial of secondary distribution of hepatitis C self-testing within the context of a house-to-house hepatitis C micro-elimination programme in Karachi, Pakistan.

BACKGROUND: Globally, just 21% of the estimated 58 million people living with hepatitis C virus (HCV) know their status. Thus, there is considerable need to scale-up HCV testing if the World Health Organization (WHO) 2030 hepatitis elimination goals are to be achieved. HCV self-testing may assist with this; however, there are currently no data on the real-world impact of HCV self-testing. With an estimated 5% of the general population living with HCV, Pakistan has the second highest HCV burden in the world. This study aims to evaluate the acceptability and impact of home delivery of HCV self-testing for secondary distribution in the context of a house-to-house HCV micro-elimination programme in Pakistan. METHODS: This is a parallel group, non-blinded, cluster randomised trial comparing secondary distribution of HCV self-testing with secondary distribution of information pamphlets encouraging individuals to visit a testing facility for HCV screening. The cluster allocation ratio is 1:1. Clusters will be randomised either to HCV self-testing distributed via study staff or control clusters where information on HCV will be given and the participant will be requested to attend their local hospital for HCV screening. In both clusters, only households with a member who has not yet been screened as part of the larger micro-elimination project will be included. The primary outcome is the number and proportion of participants who report completion of testing. Secondary outcomes include the number and proportion of participants who a) receive a positive result and are made aware of their status, b) are referred to and complete HCV RNA confirmatory testing, and c) start treatment. Acceptability, feasibility, attitudes towards HCV testing, and cost will also be evaluated. The target sample size is 2,000 participants. DISCUSSION: This study will provide the first ever evidence regarding secondary distribution of HCV self-testing. By comparing HCV self-testing with facility-based testing, we will assess whether HCV self-testing increases the uptake of HCV testing. The findings will inform micro-elimination programmes and determine whether HCV self-testing can enable individuals to be reached who may otherwise be missed. TRIAL REGISTRATION: This study and was registered on clinicaltrials.gov ( NCT04971538 ) 21 July 2021.

Web-Based Service Provision of HIV, Viral Hepatitis, and Sexually Transmitted Infection Prevention, Testing, Linkage, and Treatment for Key Populations: Systematic Review and Meta-analysis.

BACKGROUND: Despite the growth of web-based interventions for HIV, viral hepatitis (VH), and sexually transmitted infections (STIs) for key populations, the evidence for the effectiveness of these interventions has not been reported. OBJECTIVE: This study aimed to inform the World Health Organization guidelines for HIV, VH, and STI prevention, diagnosis, and treatment services for key populations by systematically reviewing the effectiveness, values and preferences, and costs of web-based outreach, web-based case management, and targeted web-based health information for key populations (men who have sex with men, sex workers, people who inject drugs, trans and gender-diverse people, and people in prisons and other closed settings). METHODS: We searched CINAHL, PsycINFO, PubMed, and Embase in May 2021 for peer-reviewed studies; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials (RCTs) and observational studies. We assessed the risk of bias using the Cochrane Collaboration tool for RCTs and the Evidence Project and Risk of Bias in Non-randomized Studies of Interventions tools for non-RCTs. Values and preferences and cost data were summarized descriptively. RESULTS: Of 2711 records identified, we included 13 (0.48%) articles in the effectiveness review (3/13, 23% for web-based outreach; 7/13, 54% for web-based case management; and 3/13, 23% for targeted web-based health information), 15 (0.55%) articles in the values and preferences review, and 1 (0.04%) article in the costs review. Nearly all studies were conducted among men who have sex with men in the United States. These articles provided evidence that web-based approaches are as effective as face-to-face services in terms of reaching new people, use of HIV, VH, and STI prevention services, and linkage to and retention in HIV care. A meta-analysis of 2 RCTs among men who have sex with men in China found increased HIV testing after web-based outreach (relative risk 1.39, 95% CI 1.21-1.60). Among men who have sex with men in the United States, such interventions were considered feasible and acceptable. One cost study among Canadian men who have sex with men found that syphilis testing campaign advertisements had the lowest cost-per-click ratio on hookup platforms compared with more traditional social media platforms. CONCLUSIONS: Web-based services for HIV, VH, and STIs may be a feasible and acceptable approach to expanding services to key populations with similar outcomes as standard of care, but more research is needed in low-resource settings, among key populations other than men who have sex with men, and for infections other than HIV (ie, VH and STIs).

Comparison of cervical cancer screening by self-sampling papillomavirus test versus pap-smear in underprivileged women in France.

BACKGROUND: The purpose of this study was to compare cervical cancer screening by pap smear (PS) versus preliminary HPV testing based on self-collected samples (SC-HPV). METHODS: Interventional study among underprivileged women from 25 to 65 years old in four French cities. The control group (CG) was referred for a PS. The experimental group (EG) conducted a SC-HPV test followed by a PS in case of positivity. Differences on screening completion and cytological abnormalities were analysed by logistic and Cox regression. RESULTS: 383 women were assigned to the EG and 304 to the CG. The screening completion proportion was 39.5% in the CG compared to 71.3% in the EG (HR = 2.48 (CI 95% [1.99-3.08]; p < 0.001). The proportion of cytological abnormalities was 2.0% in the CG and 2.3% in the EG (OR = 1.20 (CI 95% [0.42-3.40]; p = 0.7). The proportion of participants lost to follow-up was 60.5% in the CG and 63.2% in the EG HPV positive (p = 0.18). CONCLUSION: Providing an SC-HPV-test increased the participation of underprivileged women in CCS. Nevertheless, the significant number of lost to follow-up in both groups can undermine the initial benefits of the strategy for HPV positive women. Registration: Clinicaltrials.gov: NCT03118258.

HIV and other sexually transmitted infections among female sex workers in Moscow (Russia): prevalence and associated risk factors.

To estimate the prevalence and factors associated with HIV and five other STIs among outdoor female sex workers (OSFW) and indoor FSW (IFSW). METHODS: Cross-sectional survey using respondent-driven sampling methodology. Participants answered a bio-behavioural questionnaire and were tested for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), syphilis (lifetime contact) and Mycoplasma genitalium (MG). Weighted HIV and other STIs prevalence and 95% CIs were calculated. Weighted multivariate logistic regression was performed to identify factors associated with having at least one STI (including HIV). RESULTS: Between October 2017 and July 2018, 385 FSW participants were recruited, among whom 206 (53.5%) were IFSW and 179 (46.5%) were OFSW. The mean age was 31.4 years. Weighted HIV prevalence was 3.1% (95% CI 1.5 to 7.0). Weighted prevalence of other STIs was: 4.1% (95% CI 2.2 to 8.0) for NG, 8.8% (95% CI 5.9 to 13.0) for CT, 12.7% (95% CI 8.6 to 18.0) for TV, 13.9% (95% CI 9.9 to 19.0) for syphilis (lifetime contact) and 14.9% (95% CI 10.5 to 21.0) for MG. STI prevalence was significantly higher among OFSW for CT, TV and MG (p<0.001). In total, 43.2% of the participants had at least one HIV/STI. Factors associated with having HIV/STI were being an OFSW (OR 3.29; 95% CI 1.72 to 6.27); being registered in another Russian region (2.61 (95% CI 1.05 to 6.48)); having never been tested for HIV (2.51 (95% CI 0.98 to 6.41)) and having a low level of knowledge regarding HIV transmission (4.88 (95% CI 0.96 to 24.78)). CONCLUSION: Prevalence of HIV and STIs was high among FSW in Moscow. OFSW were more vulnerable to STIs. There is an urgent need to tailor programmes for sexual and reproductive health for FSW in Russia.

Staying hepatitis C negative: A systematic review and meta-analysis of cure and reinfection in people who inject drugs.

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C. However, there is concern that cure rates may be lower, and reinfection rates higher, among people who inject drugs. We conducted a systematic review of treatment outcomes achieved with DAAs in  people who inject drugs (PWID). METHODS: A search strategy was used to identify studies that reported sustained viral response (SVR), treatment discontinuation, adherence or reinfection in recent PWID and/or opioid substitution therapy (OST) recipients. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of proportions was used to estimate pooled SVR and treatment discontinuation rates. The pooled relative risk of achieving SVR and pooled reinfection rate were calculated using generalized mixed effects linear models. RESULTS: The search identified 8075 references; 26 were eligible for inclusion. The pooled SVR for recent PWID was 88% (95% CI, 83%-92%) and 91% (95% CI 88%-95%) for OST recipients. The relative risk of achieving SVR for recent PWID compared to non-recent PWID was 0.99 (95% CI, 0.94-1.06). The pooled treatment discontinuation was 2% (95% CI, 1%-4%) for both recent PWID and OST recipients. Amongst recent PWID, the pooled incidence of reinfection was 1.94 per 100 person years (95% CI, 0.87-4.32). In OST recipients, the incidence of reinfection was 0.55 per 100 person years (95% CI, 0.17-1.76). CONCLUSIONS: Treatment outcomes were similar in recent PWID compared to non-PWID treated with DAAs. People who report recent injecting or OST recipients should not be excluded from hepatitis C treatment.

Survey of programmatic experiences and challenges in delivery of hepatitis B and C testing in low- and middle-income countries.

BACKGROUND: There have been few reports on programmatic experience of viral hepatitis testing and treatment in resource-limited settings. To inform the development of the 2017 World Health Organization (WHO) viral hepatitis testing guidance and in particular the feasibility of proposed recommendations, we undertook a survey across a range of organisations engaged with hepatitis testing in low- and middle-income countries (LMICs). Our objective was to describe current hepatitis B and C testing practices across a range of settings in different countries, as well as key barriers or challenges encountered and proposed solutions to promote testing scale-up. METHODS: Hepatitis testing programmes in predominantly LMICs were identified from the WHO Global Hepatitis Programme contacts database and through WHO regional offices, and invited to participate. The survey comprised a six-part structured questionnaire: general programme information, description of hepatitis testing, treatment and care services, budget and funding, data on programme outcomes, and perceptions on key barriers encountered and strategies to address these. RESULTS: We interviewed 22 viral hepatitis testing programmes from 19 different countries. Nine were from the African region; 6 from the Western Pacific; 4 from South-East Asia; and 3 from Eastern Europe. All but four of the programmes were based in LMICs, and 10 (45.5%) were supported by non-governmental or international organizations. All but two programmes undertook targeted testing of specific affected populations such as people living with HIV, people who inject drugs, sex workers, health care workers, and pregnant women. Only two programmes focussed on routine testing in the general population. The majority of programmes were testing in hospital-based or other health facilities, particularly HIV clinics, and community-based testing was limited. Nucleic acid testing (NAT) for confirmation of HCV and HBV viraemia was available in only 30% and 18% of programmes, respectively. Around a third of programmes required some patient co-payment for diagnosis. The most commonly identified challenges in scale-up of hepatitis testing were: limited community awareness about viral hepatitis; lack of facilities or services for hepatitis testing; no access to low cost treatment, particularly for HCV; absence of national guidance and policies; no dedicated budget for hepatitis; and lack of trained health care and laboratory workers. CONCLUSIONS: At this early stage in the global scale-up of testing for viral hepatitis, there is a wide variation in testing practices and approaches across different programmes. There remains limited access to NAT to confirm viraemia, and patient self-payment for testing and treatment is common. There was consensus from implementing organizations that scale-up of testing will require increased community awareness, health care worker training, development of national strategies and guidelines, and improved access to low cost NAT virological testing.

Do Peer Navigators Improve Initiation and Retention in HIV/VH/STI Treatment Programs for People From Key Populations? A Systematic Review of Effectiveness, Values and Preferences, and Cost.

BACKGROUND: Key populations are disproportionately affected by HIV, viral hepatitis (VH), and sexually transmitted infections (STIs) and face barriers to care. Peer navigation programs are widely used, but evidence supporting their use has not been synthesized. SETTING: Peer navigation programs for sex workers, men who have sex with men, people who inject drugs, prisoners, and trans and gender diverse people globally. METHODS: To inform World Health Organization guidelines, we conducted a systematic review of effectiveness, values and preferences, and cost studies published between January 2010 and May 2021. We searched CINAHL, PsycINFO, PubMed, and EMBASE; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials and comparative observational studies evaluating time to diagnosis or linkage to care, treatment initiation, treatment retention/completion, viral load, cure, or mortality. We assessed risk of bias and summarized findings in GRADE evidence profiles. Values and preferences and cost data were summarized descriptively. RESULTS: Four studies evaluated the effectiveness of peer navigators for key populations. All were focused on HIV; none were designed for VH or STIs. These studies showed mixed effects on linkage to care, treatment retention/completion, and viral load; no studies measured treatment initiation, cure, or mortality. Two values and preferences studies with community-based organization staff and health workers suggested peer navigators for key populations were acceptable and valued, although continued challenges remained. No cost studies were identified. CONCLUSIONS: Although limited, available studies provide moderate certainty evidence for benefits of HIV/VH/STI peer navigation programs for key populations. Further evaluations are needed.

Nanoelectromechanical Infrared Spectroscopy with In Situ Separation by Thermal Desorption: NEMS-IR-TD.

We present a novel method for the quantitative analysis of mixtures of semivolatile chemical compounds. For the first time, thermal desorption is integrated directly with nanoelectromechanical infrared spectroscopy (NEMS-IR-TD). In this new technique, an analyte mixture is deposited via nebulization on the surface of a NEMS sensor and subsequently desorbed using heating under vacuum. The desorption process is monitored in situ via infrared spectroscopy and thermogravimetric analysis. The resulting spectro-temporal maps allow for selective identification and analysis of the mixture. In addition, the corresponding thermogravimetric data allow for analysis of the desorption dynamics of the mixture components. As a demonstration, caffeine and theobromine were selectively identified and quantified from a mixture with a detection limit of less than 6 pg (about 30 fmol). With its exceptional sensitivity, NEMS-IR-TD allows for the analysis of low abundance and complex analytes with potential applications ranging from environmental sensing to life sciences.

Counselling behavioural interventions for HIV, STI and viral hepatitis among key populations: a systematic review of effectiveness, values and preferences, and cost studies.

INTRODUCTION: Key populations (sex workers, men who have sex with men, people who inject drugs, people in prisons and other closed settings, and trans and gender diverse individuals) are disproportionately affected by HIV, sexually transmitted infections (STIs) and viral hepatitis (VH). Counselling behavioural interventions are widely used, but their impact on HIV/STI/VH acquisition is unclear. METHODS: To inform World Health Organization guidelines, we conducted a systematic review and meta-analysis of effectiveness, values and preferences, and cost studies about counselling behavioural interventions with key populations. We searched CINAHL, PsycINFO, PubMed and EMBASE for studies published between January 2010 and December 2022; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials (RCTs) with HIV/STI/VH incidence outcomes; secondary review outcomes of unprotected sex, needle/syringe sharing and mortality were captured if studies also included primary review outcomes. We assessed the risk of bias using the Cochrane Collaboration tool, generated pooled risk ratios through random effects meta-analysis and summarized findings in GRADE evidence profiles. Values and preferences and cost data were summarized descriptively. RESULTS: We identified nine effectiveness, two values and preferences, and two cost articles. Meta-analysis of six RCTs showed no statistically significant effect of counselling behavioural interventions on HIV incidence (1280 participants; combined risk ratio [RR]: 0.70, 95% confidence interval [CI]: 0.41-1.20) or STI incidence (3783 participants; RR: 0.99; 95% CI: 0.74-1.31). One RCT with 139 participants showed possible effects on hepatitis C virus incidence. There was no effect on secondary review outcomes of unprotected (condomless) sex (seven RCTs; 1811 participants; RR: 0.82, 95% CI: 0.66-1.02) and needle/syringe sharing (two RCTs; 564 participants; RR 0.72; 95% CI: 0.32-1.63). There was moderate certainty in the lack of effect across outcomes. Two values and preferences studies found that participants liked specific counselling behavioural interventions. Two cost studies found reasonable intervention costs. DISCUSSION: Evidence was limited and mostly on HIV, but showed no effect of counselling behavioural interventions on HIV/VH/STI incidence among key populations. CONCLUSIONS: While there may be other benefits, the choice to provide counselling behavioural interventions for key populations should be made with an understanding of the potential limitations on incidence outcomes.

Immediate treatment for recent hepatitis C infection in people with high-risk behaviors: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) are almost exclusively approved for the treatment of chronic HCV. This poses a significant barrier to the treatment of recently acquired HCV because of the limited access to DAAs. This review seeks to address this issue by synthesizing evidence of the benefits and harms of immediate treatment after the detection of recently acquired HCV in people at higher risk of infection. APPROACH AND RESULTS: A systematic review and meta-analysis were conducted reporting on populations with recently acquired HCV at higher risk of infection. Studies were included if they assessed standard duration DAA treatment regimens and reported on the benefits and harms of immediate treatment (within one year of diagnosis). Outcomes included sustained virological response at 12 weeks post-treatment (SVR12), incidence, treatment initiation and adherence, overtreatment, engagement in care, and adverse events. Eight cohort studies, 3 open-label trials, and 1 case series study were included, reporting on 2085 participants with recently acquired HCV infection. No studies included a comparison group. Eight studies assessed DAA treatment in either men who have sex with men or men who have sex with men with HIV, 2 studies assessed treatment in people who inject drugs, and 2 among people living with HIV. Immediate treatment of HCV was associated with a pooled SVR12 of 95.9% (95% CI, 92.6%-99.3%). Three studies reported on hepatitis C incidence, where most participants were treated in the chronic phase of infection. A treatment completion rate of 100% was reported in 2 studies, and only 1 serious adverse event was described. CONCLUSIONS: High rates of cure were achieved with the treatment of recently acquired hepatitis C in people at higher risk of infection. Serious adverse events were rare, highlighting individual benefits consistent with the treatment of chronic hepatitis C. The impact of immediate treatment on HCV incidence requires further evaluation.

Cost-effectiveness of Hepatitis C virus self-testing in four settings.

Globally, there are approximately 58 million people with chronic hepatitis C virus infection (HCV) but only 20% have been diagnosed. HCV self-testing (HCVST) could reach those who have never been tested and increase uptake of HCV testing services. We compared cost per HCV viraemic diagnosis or cure for HCVST versus facility-based HCV testing services. We used a decision analysis model with a one-year time horizon to examine the key drivers of economic cost per diagnosis or cure following the introduction of HCVST in China (men who have sex with men), Georgia (men 40-49 years), Viet Nam (people who inject drugs, PWID), and Kenya (PWID). HCV antibody (HCVAb) prevalence ranged from 1%-60% across settings. Model parameters in each setting were informed by HCV testing and treatment programmes, HIV self-testing programmes, and expert opinion. In the base case, we assume a reactive HCVST is followed by a facility-based rapid diagnostic test (RDT) and then nucleic acid testing (NAT). We assumed oral-fluid HCVST costs of $5.63/unit ($0.87-$21.43 for facility-based RDT), 62% increase in testing following HCVST introduction, 65% linkage following HCVST, and 10% replacement of facility-based testing with HCVST based on HIV studies. Parameters were varied in sensitivity analysis. Cost per HCV viraemic diagnosis without HCVST ranged from $35 2019 US dollars (Viet Nam) to $361 (Kenya). With HCVST, diagnosis increased resulting in incremental cost per diagnosis of $104 in Viet Nam, $163 in Georgia, $587 in Kenya, and $2,647 in China. Differences were driven by HCVAb prevalence. Switching to blood-based HCVST ($2.25/test), increasing uptake of HCVST and linkage to facility-based care and NAT testing, or proceeding directly to NAT testing following HCVST, reduced the cost per diagnosis. The baseline incremental cost per cure was lowest in Georgia ($1,418), similar in Viet Nam ($2,033), and Kenya ($2,566), and highest in China ($4,956). HCVST increased the number of people tested, diagnosed, and cured, but at higher cost. Introducing HCVST is more cost-effective in populations with high prevalence.

Global reporting of progress towards elimination of hepatitis B and hepatitis C.

BACKGROUND: The 69th World Health Assembly endorsed the global health sector strategy on viral hepatitis to eliminate viral hepatitis as a public health threat by 2030. Achieving and measuring the 2030 targets requires a substantial increase in the capacity to test and treat viral hepatitis infections and a mechanism to monitor the progress of hepatitis elimination. This study aimed to identify the gaps in data availability or quality and create a new mechanism to monitor the progress of hepatitis elimination. METHODS: In 2020, using a questionnaire, we collected empirical, systematic, modelled, or surveyed data-reported by WHO country and WHO regional offices-on indicators of progress towards elimination of viral hepatitis, including burden of infection, incidence, mortality, and the cascade of care, and validated these data. FINDINGS: WHO received officially validated country-provided data from 130 countries or territories, and used partner-provided data for 70 countries or territories. We estimated that in 2019, globally, 295·9 million (3·8%) people were living with chronic hepatitis B virus (HBV) infection and 57·8 million (0·8%) people were living with chronic hepatitis C virus (HCV) infection. Globally, there were more than 3·0 million new infections with HBV and HCV and more than 1·1 million deaths due to the viruses in 2019. In 2019, 30·4 million (95% CI 24·3-38·0) individuals living with hepatitis B knew their infection status and 6·6 million (5·3-8·3) people diagnosed with hepatitis B received treatment. Among people with HCV infection, 15·2 million (95% CI 12·1-19·0) had been diagnosed between 2015 and 2019, and 9·4 million (7·5-11·7) people diagnosed with hepatitis C infection were treated with direct-acting antiviral drugs between 2015 and 2019. INTERPRETATION: There has been notable global progress towards hepatitis elimination. In 2019, 30·4 million (10·3%) people living with hepatitis B knew their infection status, which was slightly higher than in 2015 (22·0 million; 9·0%), and 6·6 million (22·7%) of those diagnosed with hepatitis B received treatment, compared with 1·7 million (8·0%) in 2015. Mortality from hepatitis C has declined since 2019, driven by an increase in HCV treatment ten times that of the strategy baseline. However, an estimated 89·7% of HBV infections and 78·6% of HCV infections remain undiagnosed. A new global strategy for 2022-30, based on these new estimates, should be implemented urgently to scale up the screening and treatment of viral hepatitis. FUNDING: World Health Organization.

Incidence of HIV and hepatitis C virus among people who inject drugs, and associations with age and sex or gender: a global systematic review and meta-analysis.

BACKGROUND: Measuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender. METHODS: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions. We contacted authors of identified studies for unpublished or updated data. We included studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection. We pooled incidence and relative risk (RR; young [generally defined as ≤25 years] vs older PWID; women vs men) estimates using random-effects meta-analysis and assessed risk of bias with a modified Newcastle-Ottawa scale. This study is registered with PROSPERO, CRD42020220884. FINDINGS: Our updated search identified 9493 publications, of which 211 were eligible for full-text review. An additional 377 full-text records from our existing database and five records identified through cross-referencing were assessed. Including 28 unpublished records, 125 records met the inclusion criteria. We identified 64 estimates of HIV incidence (30 from high-income countries [HICs] and 34 from low-income or middle-income countries [LMICs]) and 66 estimates of HCV incidence (52 from HICs and 14 from LMICs). 41 (64%) of 64 HIV and 42 (64%) of 66 HCV estimates were from single cities rather than being multi-city or nationwide. Estimates were measured over 1987-2021 for HIV and 1992-2021 for HCV. Pooled HIV incidence was 1·7 per 100 person-years (95% CI 1·3-2·3; I2=98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0-14·6; I2=97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2-1·8; I2=66·9%) and HCV (1·5, 1·3-1·8; I2=70·6%) acquisition than older PWID. Women had a greater risk of HIV (RR 1·4, 95% CI 1·1-1·6; I2=55·3%) and HCV (1·2, 1·1-1·3; I2=43·3%) acquisition than men. For both HIV and HCV, the median risk-of-bias score was 6 (IQR 6-7), indicating moderate risk. INTERPRETATION: Although sparse, available HIV and HCV incidence estimates offer insights into global levels of HIV and HCV transmission among PWID. Intensified efforts are needed to keep track of the HIV and HCV epidemics among PWID and to expand access to age-appropriate and gender-appropriate prevention services that serve young PWID and women who inject drugs. FUNDING: Canadian Institutes of Health Research, Fonds de recherche du Québec-Santé, Canadian Network on Hepatitis C, UK National Institute for Health and Care Research, and WHO.

The World Health Organization's work and recommendations for improving the health of trans and gender diverse people.

INTRODUCTION: The World Health Organization (WHO) is guided by its global programme of work and the goal that a billion more people have universal health coverage (UHC). To achieve UHC, access for those most vulnerable must be guaranteed and prioritized. WHO is committed to developing evidence-based guidance to work towards UHC for trans and gender diverse (TGD) people. This commentary describes WHO's work related to TGD people over the last decade. DISCUSSION: In 2011, WHO developed guidelines for the prevention and treatment of HIV and sexually transmitted infections (STIs) in men who have sex with men and TGD people. In 2013, the "HIV civil society reference group" called on WHO to provide specific guidance for TGD people. Values and preferences of TGD people were considered by WHO for the first time, which informed the development of the 2014 WHO Consolidated Guidelines on HIV Prevention, Diagnosis, Treatment and Care for Key Populations. The 2014 Guidelines included a comprehensive package of HIV-related health and enabling interventions with specific considerations for TGD people, as well as a specific policy brief in 2015. Regional WHO offices developed and/or supported the development of blueprints on transgender health and HIV in 2014 and 2016. A 2015 WHO report on sexual health, human rights and the law elucidated the harmful impacts of discriminatory laws on the basis of sexual orientation and gender identity. In 2019, the 11th edition of the international classification of diseases saw the removal of "transsexualism" as a mental and behavioural disorder. WHO's first guideline on self-care interventions, updated in 2021, included key considerations concerning TGD people. In 2022, WHO's updated key populations guidelines include a prioritized package of not just HIV, but also viral hepatitis and STI health interventions for TGD people. Still, a broader and more specific health approach and a greater focus on social issues are needed to better serve the health needs of TGD people. CONCLUSIONS: WHO's understanding and commitment to TGD people's health has evolved and improved over the past decade. Together with professional and community trans health organizations, WHO should now start developing evidence-informed global guidance on TGD health as part of its remit to support UHC to all.

Home-based hepatitis C self-testing in people who inject drugs and men who have sex with men in Georgia: a protocol for a randomised controlled trial.

INTRODUCTION: Globally, it is estimated that more than three-quarters of people with chronic hepatitis C virus (HCV) are unaware of their HCV status. HCV self-testing (HCVST) may improve access and uptake of HCV testing particularly among key populations such as people who inject drugs (PWID) and men who have sex with men (MSM) where HCV prevalence and incidence are high and barriers to accessing health services due to stigma and discrimination are common. METHODS AND ANALYSIS: This randomised controlled trial compares an online programme offering oral fluid-based HCVST delivered to the home with referral to standard-of-care HCV testing at HCV testing sites. Eligible participants are adults self-identifying as either MSM or PWID who live in Tbilisi or Batumi, Georgia, and whose current HCV status is unknown. Participants will be recruited through an online platform and randomised to one of three arms for MSM (courier delivery, peer delivery and standard-of-care HCV testing (control)) and two for PWID (peer delivery and standard-of-care HCV testing (control)). Participants in the postal delivery group will receive an HCVST kit delivered by an anonymised courier. Participants in the peer delivery groups will schedule delivery of the HCVST by a peer. Control groups will receive information on how to access standard-of-care testing at a testing site. The primary outcome is the number and proportion of participants who report completion of testing. Secondary outcomes include the number and proportion of participants who (a) receive a positive result and are made aware of their status, (b) are referred to and complete HCV RNA confirmatory testing, and (c) start treatment. Acceptability, feasibility, and attitudes around HCV testing and cost will also be evaluated. The target sample size is 1250 participants (250 per arm). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the National Centers for Disease Control and Public Health Georgia Institutional Review Board (IRB) (IRB# 2021-049). Study results will be disseminated by presentations at conferences and via peer-reviewed journals. Protocol version 1.1; 14 July 2021. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04961723).

A quasi-randomised controlled trial of online distribution of home-based hepatitis C self-testing for key populations in Malaysia: a study protocol.

BACKGROUND: Malaysia has an estimated hepatitis C virus (HCV) prevalence of 1.9% among its adult population and a history of providing HCV treatment in the public sector. In 2019, Malaysia launched a 5-year national strategic plan for viral hepatitis control and has been expanding HCV testing and treatment to the primary care and community levels, while actively engaging key populations in services for hepatitis care. The Ministry of Health (MoH) is seeking to specifically understand how to better target HCV services at men who have sex with men (MSM); HCV self-testing could increase the uptake of HCV testing among this group. METHODS: We aim to integrate HCV antibody self-testing into an existing online platform used for HIV self-testing, to evaluate the acceptability and impact of an online HCV self-testing programme in Malaysia. This is a non-blinded parallel group quasi-randomised superiority study comparing HCV self-testing via an online distribution model with the standard care, which involves attending a clinic for facility-based HCV antibody testing (control, 2:1). Participants will be randomised to either the HCV self-testing via online distribution arm, in which either an oral fluid- or blood-based HCV self-test kit will be mailed to them, or the control arm, where they will be provided with information about the nearest centre with HCV testing. The primary outcome is the number and proportion of participants who report completion of testing. Secondary outcomes include the number and proportion of participants who (a) receive a positive result and are made aware of their status, (b) are referred to and complete HCV RNA confirmatory testing, and (c) start treatment. Acceptability, feasibility, attitudes around HCV testing, and cost will also be evaluated. The target sample size is 750 participants. DISCUSSION: This study is one of the first in the world to explore the real-world impact of HCV self-testing on key populations using online platforms and compare this with standard HCV testing services. The outcomes of this study will provide critical evidence about testing uptake, linkage to care, acceptability, and any social harms that may emerge due to HCV self-testing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04982718.

Methods and indicators to validate country reductions in incidence of hepatitis C virus infection to elimination levels set by WHO.

One of the main goals of the 2016 Global Health Sector Strategy on viral hepatitis is the elimination of hepatitis C virus (HCV) as a public health problem by 2030, defined as an 80% reduction in incidence and 65% reduction in mortality relative to 2015. Although monitoring HCV incidence is key to validating HCV elimination, use of the gold-standard method, which involves prospective HCV retesting of people at risk, can be prohibitively resource-intensive. Additionally, few countries collected quality data in 2015 to enable an 80% decrease by 2030 to be calculated. Here, we first review different methods of monitoring HCV incidence and discuss their resource implications and applicability to various populations. Second, using mathematical models developed for various global settings, we assess whether trends in HCV chronic prevalence or HCV antibody prevalence or scale-up levels for HCV testing, treatment, and preventative interventions can be used as reliable alternative indicators to validate the HCV incidence target. Third, we discuss the advantages and disadvantages of an absolute HCV incidence target and suggest a suitable threshold. Finally, we propose three options that countries can use to validate the HCV incidence target, depending on the available surveillance infrastructure.

Modelling the impact of HIV and hepatitis C virus prevention and treatment interventions among people who inject drugs in Kenya.

OBJECTIVES: People who inject drugs (PWID) in Kenya have high HIV (range across settings: 14-26%) and hepatitis C virus (HCV; 11-36%) prevalence. We evaluated the impact of existing and scaled-up interventions on HIV and HCV incidence among PWID in Kenya. DESIGN: HIV and HCV transmission model among PWID, calibrated to Nairobi and Kenya's Coastal region. METHODS: For each setting, we projected the impact (percent of HIV/HCV infections averted in 2020) of existing coverages of antiretroviral therapy (ART; 63-79%), opioid agonist therapy (OAT; 8-13%) and needle and syringe programmes (NSP; 45-61%). We then projected the impact (reduction in HIV/HCV incidence over 2021-2030), of scaling-up harm reduction [Full harm reduction ('Full HR'): 50% OAT, 75% NSP] and/or HIV (UNAIDS 90-90-90) and HCV treatment (1000 PWID over 2021-2025) and reducing sexual risk (by 25/50/75%). We estimated HCV treatment levels needed to reduce HCV incidence by 90% by 2030. RESULTS: In 2020, OAT and NSP averted 46.0-50.8% (range of medians) of HIV infections and 50.0-66.1% of HCV infections, mostly because of NSP. ART only averted 12.9-39.8% of HIV infections because of suboptimal viral suppression (28-48%). Full HR and ART could reduce HIV incidence by 51.5-64% and HCV incidence by 84.6-86.6% by 2030. Also halving sexual risk could reduce HIV incidence by 68.0-74.1%. Alongside full HR, treating 2244 PWID over 2021-2025 could reduce HCV incidence by 90% by 2030. CONCLUSION: Existing interventions are having substantial impact on HIV and HCV transmission in Kenya. However, to eliminate HIV and HCV, further scale-up is needed with reductions in sexual risk and HCV treatment.