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.

Pre-exposure prophylaxis (PrEP) for HIV prevention among people who inject drugs: a global mapping of service delivery.

BACKGROUND: The World Health Organization (WHO) recommends oral pre-exposure prophylaxis (PrEP) for all people at substantial risk of HIV as part of combination prevention. The extent to which this recommendation has been implemented globally for people who inject drugs is unclear. This study mapped global service delivery of PrEP for people who inject drugs. METHODS: Between October and December 2021, a desk review was conducted to obtain information on PrEP services for people who inject drugs from drug user-led networks and HIV, harm reduction, and human rights stakeholders. Websites of organizations involved in HIV prevention or services for people who inject drugs were searched. Models of service delivery were described in terms of service location, provider, and package. RESULTS: PrEP services were identified in 27 countries (15 high-income). PrEP delivery models varied within and across countries. In most services, PrEP services were implemented in healthcare clinics without direct links to other harm reduction services. In three countries, PrEP services were also provided at methadone clinics. In 14 countries, PrEP services were provided through community-based models (outside of clinic settings) that commonly involved peer-led outreach activities and integration with harm reduction services. CONCLUSIONS: This study indicates limited PrEP availability for people who inject drugs. There is potential to expand PrEP services for people who inject drugs within harm reduction programs, notably through community-based and peer-led services. PrEP should never be offered instead of evidence-based harm reduction programs for people who inject drugs; however, it could be offered as an additional HIV prevention choice as part of a comprehensive harm reduction program.

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).

Guidelines are needed for studies of pre-treatment HIV drug resistance: a methodological study.

BACKGROUND: The expansion of access to antiretroviral therapy (ART) has been accompanied by an increase in pre-treatment drug resistance (PDR). While it is critical to monitor the increasing prevalence of PDR across countries and populations to inform optimal regimen selection, the completeness of reporting is often suboptimal, limiting the interpretation and generalizability of the results. Indeed, there is no formal guidance on how studies investigating the prevalence of drug resistance should be reported. Thus, we sought to determine the completeness of reporting in studies of PDR and the factors associated with sub-optimal reporting to ascertain the need for guidelines. METHODS: As part of a systematic review on the global prevalence of PDR in key populations (men who have sex with men, sex workers, transgender people, people who inject drugs and people in prisons), we searched 10 electronic databases until January 2019. We extracted information on selected study characteristics useful for interpreting prevalence data. Data were extracted in duplicate. Analyses of variance and correlation were used to explore factors that may explain the number of items reported. RESULTS: We found 650 studies of which 387 were screened as full text and 234 were deemed eligible. The included studies were published between 1997 and 2019 and included a median of 239 (quartile 1 = 101; quartile 3 = 778) participants. Most studies originated from high-income countries (125/234; 53.0%). Of 23 relevant data items, including study design, setting, participant sociodemographic characteristics, HIV risk factors, type of resistance test conducted, definition of resistance, the mean (standard deviation) number of items reported was 13 (2.2). We found that more items were reported in studies published more recently (r = 0.20; p < 0.002) and in studies at low risk of bias (F [2231] = 8.142; p < 0.001). CONCLUSIONS: Incomplete reporting in studies on PDR makes characterising levels of PDR in subpopulations across countries challenging. Hence, guidelines are needed to define a minimum set of variables to be included in such studies.

Piloting a simplified bio-behavioural survey methodology, the BBS-Lite, among people who inject drugs in Georgia.

BACKGROUND: During 2021 and 2023 two simplified Biological and Behavioural Study (BBS-Lite) surveys, and in 2022 one Standard Integrated Biological and Behavioural Study (IBBS), were conducted among people who inject drugs in seven cities in Georgia. From these, an opportunity to compare the implementation of these survey methods and results was able to be gained. METHODS: The two survey types were compared to find points of similarity and difference in their methodologies. The methodologies of the IBBS and BBS-Lite studies shared many characteristics, including the cities where they were implemented, recruitment criteria, sample sizes, and common questionnaire items. All studies were multi-centre cross-sectional involving administration of a face-to-face behavioural questionnaire and collection of biological specimens for testing of HIV, syphilis, hepatitis B virus (HBV), and hepatitis C virus (HCV). The main differences were in the sampling methods. The IBBS utilised respondent-driven sampling (RDS) while participants of the BBS-Lite studies were enrolled through consecutive recruitment at the harm reduction (HR) programme sites and on outreach and through snowball sampling. We compared the results from each study as well as the implementation modalities such as time taken and budgetary requirements, and the complexity of implementation. RESULTS: Considerably less time was required for recruitment, as well as for interviewing, data entry (4 times less) and the analysis for the BSS-Lite studies compared to the IBBS. The BSS-Lite study budgets were at least 2.5 times less than of the IBBS study. The recruited samples were comparable for age distribution, median age at first injection, the last drug injected, sharing of drug injecting equipment or receiving opioid agonist maintenance treatment (OAMT) during the last 12 months. HIV and HCV prevalence were similar including for stratifications by age, client status and city of recruitment. CONCLUSION: Our findings have demonstrated that if implemented on a regular basis, the BBS-Lite can be a complementary solution for systematic data collection, filling surveillance gaps and addressing the challenges that persist in obtaining important data on people who inject drugs (PWID) between IBBS rounds in the country. The methodology is recommended for testing in other settings and in other key populations. In addition, the data collected on a routine base can help the harm reduction (HR) program to better understand the changes in the drug scene and observe new trends in HIV risks and drug injecting behaviours, possible barriers for access to harm reduction, drug treatment, and HIV and/or viral hepatitis testing and treatment services.

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.

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.

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.

Cost-effectiveness of implementing HIV and HIV/syphilis dual testing among key populations in Viet Nam: a modelling analysis.

OBJECTIVES: Key populations, including sex workers, men who have sex with men, and people who inject drugs, have a high risk of HIV and sexually transmitted infections. We assessed the health and economic impacts of different HIV and syphilis testing strategies among three key populations in Viet Nam using a dual HIV/syphilis rapid diagnostic test (RDT). SETTING: We used the spectrum AIDS impact model to simulate the HIV epidemic in Viet Nam and evaluated five testing scenarios among key populations. We used a 15-year time horizon and a provider perspective for costs. PARTICIPANTS: We simulate the entire population of Viet Nam in the model. INTERVENTIONS: We modelled five testing scenarios among key populations: (1) annual testing with an HIV RDT, (2) annual testing with a dual RDT, (3) biannual testing using dual RDT and HIV RDT, (4) biannual testing using HIV RDT and (5) biannual testing using dual RDT. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is incremental cost-effectiveness ratios. Secondary outcomes include HIV and syphilis cases. RESULTS: Annual testing using a dual HIV/syphilis RDT was cost-effective (US$10 per disability-adjusted life year (DALY)) and averted 3206 HIV cases and treated 27 727 syphilis cases compared with baseline over 15 years. Biannual testing using one dual test and one HIV RDT (US$1166 per DALY), or two dual tests (US$5672 per DALY) both averted an additional 875 HIV cases, although only the former scenario was cost-effective. Annual or biannual HIV testing using HIV RDTs and separate syphilis tests were more costly and less effective than using one or two dual RDTs. CONCLUSIONS: Annual HIV and syphilis testing using dual RDT among key populations is cost-effective in Vietnam and similar settings to reach global reduction goals for HIV and syphilis.

Cortical atrophy differentiates Richardson's syndrome from the parkinsonian form of progressive supranuclear palsy.

To determine whether brain atrophy differs between the two subtypes of progressive supranuclear palsy (PSP), Richardson's syndrome (PSP-RS), and PSP parkinsonism (PSP-P), and whether such atrophy directly relates to clinical deficits and the severity of tau deposition. We compared 24 pathologically confirmed PSP cases (17 PSP-RS and 7 PSP-P) with 22 controls from a Sydney brain donor program. Volume loss was analyzed in 29 anatomically discrete brain regions using a validated point-counting technique, and tau-immunoreactive neurons, astrocytes and oligodendrocytes/threads semiquantified. Correlations between the two pathological measures and the presence or absence of cardinal PSP symptoms were investigated. Cortical atrophy was more severe in PSP-RS than PSP-P and affected more frontal lobe regions (frontal pole, inferior frontal gyrus). The supramarginal gyrus was atrophic in both subtypes. Additionally, atrophy of the internal globus pallidus, amygdala, and thalamus was more severe in PSP-RS. As expected, more severe frontal lobe tau pathology differentiated PSP-RS from PSP-P. No correlations were found between the degree of atrophy and severity of tau pathology in any region assessed, or between the severity of atrophy or tau pathology and the presence or absence of cardinal PSP symptoms. Our study shows that thalamocortical atrophy is a defining feature of PSP-RS, but this atrophy does not correlate with the presence of any specific cardinal clinical feature. Interestingly, there is a disassociation between tau pathology and atrophy in the brain regions affected in PSP-RS that requires further investigation.

Values and preferences of contraceptive methods: a mixed-methods study among sex workers from diverse settings.

There is limited information on contraceptive values and preferences of sex workers. We conducted a mixed-method study to explore contraceptive values and preferences among sex workers. We conducted an online survey with individuals from 38 countries (n = 239), 6 focus group discussions (FGD, n = 68) in Zimbabwe, and 12 in-depth phone interviews (IDI) across 4 world regions, in June and July of 2019. Participants were asked about awareness of contraceptives, methods they had used in the past, and the determinants of their choices. Differences between respondents from high-, low- and middle- income countries were examined. Qualitative data were analysed thematically. Survey participants reported an awareness of modern contraceptive methods. FGDs found that younger women had lower awareness. Reports of condomless sex were common and modern contraceptive use was inconsistent. Determinants of contraceptive choices differed by setting according to results of the survey, FGD, and IDI. Regardless of country income level, determinants of contraceptive choices included ease of use, ease of access to a contraceptive method, and fewer side effects. Healthcare provider attitudes, availability of methods, and clinic schedules were important considerations. Most sex workers are aware of contraceptives, but barriers include male partners/clients, side effects, and health system factors such as access and clinic attitudes towards sex workers.

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

BACKGROUND: WHO has set targets for hepatitis C virus (HCV) elimination by 2030. We did a global systematic review of HCV prevalence and incidence in men who have sex with men (MSM) to provide updated estimates that can guide community education and public health policy. METHODS: We did a systematic review and meta-analysis of studies published and listed on MEDLINE or Embase between Jan 1, 2000, and Oct 31, 2019, including conference proceedings. Studies were eligible if they reported measures of HCV prevalence or HCV incidence (or both) among MSM. Studies that relied on participants' self-reported HCV status with no laboratory confirmation were excluded. Pooled HCV estimates in MSM were stratified by HIV status and by injecting drug use, then by WHO region and by income level. Random-effects meta-analysis was done to account for between-study heterogeneity and examined using the I2 statistic. Pooled HCV prevalence was also compared with HCV estimates in the general population and presented as prevalence ratios (PRs). In HIV-negative MSM, incidence estimates were stratified by use of HIV pre-exposure prophylaxis (PrEP). The systematic review was registered with PROSPERO, number CRD42020156262. FINDINGS: Of 1221 publications identified, 194 were deemed to be eligible and included in the systematic review and meta-analysis. Overall, the pooled HCV prevalence in MSM was 3·4% (95% CI 2·8-4·0; I2=98·0%) and was highest in Africa (5·8%, 2·5-10·4) and South-East Asia (5·0%, 0·0-16·6). Globally, HCV prevalence was 1·5% (1·0-2·1) in HIV-negative MSM and 6·3% (5·3-7·5) in HIV-positive MSM. Compared with the general population, HCV prevalence was slightly higher in HIV-negative MSM (PR 1·58, 95% CI 1·14-2·01) and markedly higher (6·22, 5·14-7·29) in HIV-positive MSM. Pooled HCV prevalence was substantially higher in MSM who had ever injected drugs (30·2%, 22·0-39·0) or currently injected drugs (45·6%, 21·6-70·7) than in those who never injected drugs (2·7%, 2·0-3·6). In HIV-negative MSM, the pooled HCV incidence was 0·12 per 1000 person-years (95% CI 0·00-0·72) in individuals not on PrEP and 14·80 per 1000 person-years (9·65-20·95) in individuals on PrEP. HCV incidence in HIV-positive MSM was 8·46 per 1000 person-years (6·78-10·32). INTERPRETATION: HIV-positive MSM are at substantially increased risk of HCV. Overall, HIV-negative MSM had a slightly higher prevalence of HCV than the general population but had a lower prevalence than HIV-positive MSM. High HCV incidence in more recent PrEP studies suggests that as PrEP use increases, greater HCV transmission might occur. HCV burden in MSM varies considerably by region, which is likely to be associated with variation in the prevalence of injecting drug use and HIV. FUNDING: World Health Organization.

Prevalence of pretreatment HIV drug resistance in key populations: a systematic review and meta-analysis.

INTRODUCTION: WHO's 2019 report on HIV drug resistance (HIVDR) documents a high prevalence of pretreatment drug resistance (PDR) among populations initiating first-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC). However, systematic evidence on the prevalence of PDR among key populations remains limited. We performed a systematic review to characterize levels of PDR in key population groups and compared them to levels of PDR in the "general population" across different geographical regions. METHODS: Ten electronic databases were searched for papers published until February 2019 that included predefined search terms. We included studies that reported the number of successfully tested genotypes and the number of genotypes with drug resistance mutations among antiretroviral therapy treatment naïve people, recently infected people, or people initiating first-line ART from key populations. To assess the prevalence of PDR for each key population, we pooled estimates using random-effects meta-analysis of proportions. Where possible, we computed the differences in the odds of PDR (any, and by drug class) present in each key population compared to the "general population". The I2 statistic (a measure of heterogeneity between studies) is reported. RESULTS AND DISCUSSION: A total of 332 datasets (from 218 studies) and 63,111 people with successful HIVDR genotyping were included in the analysis. The pooled prevalence estimate of any PDR was high among men who have sex with men (13.0%, 95% CI 11.0 to 14.0%, I2  = 93.19), sex workers (17.0%, 95% CI 6.0 - 32.0, I2  = 87.31%) and people in prisons (18.0%, 95% CI 11.0 to 25.0, I2  = 70.18%), but less so among people who inject drugs (7.0%, 95% CI 5.0 to 10.0, I2  = 90.23). Overall, men who have sex with men were more likely to carry any PDR compared to the "general population," a finding which was statistically significant (odds ratio (OR) 1.28, 95% CI 1.13 - 1.46, I2 48.9%). CONCLUSIONS: High prevalence of PDR found in key populations highlights the need to increase access to effective first-line HIV treatment. The low prevalence of nucleotide reverse transcriptase inhibitor (NRTI) PDR suggests that current WHO recommendations for pre-exposure prophylaxis (PrEP) regimens will remain effective and can be scaled up to prevent new HIV infections in high-risk groups.

Universal health coverage and key populations.

PURPOSE OF REVIEW: There is renewed focus at global and national level to adopt commitments to ensure universal access to health services. The present study highlights key considerations to ensure that the commitment to 'leave no one behind' includes key populations, recognizing the specific impact of marginalization, stigma, discrimination, and criminalization on their access to health. RECENT FINDINGS: Universal health coverage (UHC) means that all people can use the promotive, preventive, curative, rehabilitative, and palliative health services they need, of sufficient quality to be effective, while also ensuring that the use of these services does not expose the user to financial hardship. Countries commit to UHC through Sustainable Development Goals (SDG Target 3.8 Achieve universal health coverage, including financial risk protection, access to quality essential health-care services and access to well tolerated, effective, quality, and affordable essential medicines). SUMMARY: UHC cannot be achieved without addressing the needs of key populations. At the same time, the goal of UHC provides new opportunities to improve health equity and the health of key populations. Political commitment, defining and including essential high-impact, evidence-based interventions for key populations, and their full integration into national health benefit packages; integrated, decentralized, and differentiated health services with involvement, ownership, and acceptance of communities to ensure equity and quality; ensuring financing for UHC provides coverage for key populations, including those who may be undocumented, are needed. Developing more effective interventions and service delivery approaches, providing a supportive policy and legal environment; and measuring progress against clear targets for accountability and programme adjustment will also be required for key populations to benefit fully from UHC.

Transforming lives and empowering communities: evidence, harm reduction and a holistic approach to people who use drugs.

PURPOSE OF REVIEW: We reviewed the global state of harm reduction for people who use and/or inject drugs. KEY FINDINGS: Although harm reduction is now the key response to HIV among people who use drugs globally, intervention coverage remains suboptimal, exacerbated by chronic under-funding, declining donor support and limited domestic investment, particularly in low-income and middle-income countries. We describe the current environment and review recent innovations and responses, including peer distribution of naloxone, low dead space syringes, drug consumption rooms and drug-checking services. However, despite efforts by people who use drugs and supporting partners to sustain harm reduction services and to develop and implement novel interventions, programmes are often under-scaled and under-resourced and people who use drugs continue to face significant barriers to accessing services. SUMMARY: There is an urgent need to bring existing harm reduction programmes to scale and to broaden their scope, as well to complement them with innovative interventions targeting new populations and new substances. Under and disinvestment in harm reduction and the absence of enabling legal environments threatens to undermine the global HIV response and exacerbate the morbidity and mortality associated with the current epidemic of opioid overdose.

Gaps and opportunities: measuring the key population cascade through surveys and services to guide the HIV response.

INTRODUCTION: The UNAIDS 90-90-90 targets to diagnose 90% of people living with HIV, put 90% of them on treatment, and for 90% of them to have suppressed viral load have focused the international HIV response on the goal of eliminating HIV by 2030. They are also a constructive tool for measuring progress toward reaching this goal but their utility is dependent upon data availability. Though more than 25% of new infections are among key populations (KP)- sex workers, men who have sex with men, transgender people, people who inject drugs, and prisoners- and their sex partners, there is a dearth of treatment cascade data for KP. We assess the availability of cascade data and review the opportunities offered by biobehavioral and programme data to inform the HIV response. DISCUSSION: The emphasis on the collection of treatment cascade data among the general population in higher prevalence countries has not led to a similar increase in the availability of cascade data for KP. The limited data available for KP highlight large gaps in service uptake across the cascade, particularly in the first 90, awareness of HIV status. Biobehavioral surveys (BBS), with linked population size estimation, provide population-based data on the treatment cascade and should be conducted every two to three years in locations with services for KP. With the inclusion of viral load testing, these surveys are able to monitor the entire treatment cascade among KP regardless of whether these populations access HIV services targeting the general population or KP. BBS also reach people accessing services and those who do not, thereby providing a unique opportunity to learn about barriers to service uptake including stigma and discrimination. At the same time high-quality programme data can play a complementary role in identifying missed opportunities that can be addressed in real-time. CONCLUSIONS: Data are more important than ever for guiding the HIV response toward reaching 90-90-90 targets and eliminating HIV, particularly in the face of decreased funding for HIV and specifically for KP. Timely high-quality BBS data can be triangulated with high-quality programme data to provide a comprehensive picture of the epidemic response for KP.

A call for differentiated approaches to delivering HIV services to key populations.

INTRODUCTION: Key populations (KPs) are disproportionally affected by HIV and have low rates of access to HIV testing and treatment services compared to the broader population. WHO promotes the use of differentiated approaches for reaching and recruiting KP into the HIV services continuum. These approaches may help increase access to KPs who are often criminalized or stigmatized. By catering to the specific needs of each KP individual, differentiated approaches may increase service acceptability, quality and coverage, reduce costs and support KP members in leading the HIV response among their communities. DISCUSSION: WHO recommends the implementation of community-based and lay provider administered HIV testing services. Together, these approaches reduce barriers and costs associated with other testing strategies, allow greater ownership in HIV programmes for KP members and reach more people than do facility-based services. Despite this evidence availability and support for them is limited. Peer-driven interventions have been shown to be effective in engaging, recruiting and supporting clients. Some programmes employ HIV-positive or non-PLHIV "peer navigators" and other staff to provide case management, enrolment and/or re-enrolment in care and treatment services. However, a better understanding of the impact, cost effectiveness and potential burden on peer volunteers is required. Task shifting and non-facility-based service locations for antiretroviral therapy (ART) initiation and maintenance and antiretroviral (ARV) distribution are recommended in both the consolidated HIV treatment and KP guidelines of WHO. These approaches are accepted in generalized epidemics and for the general population where successful models exist; however, few organizations provide or initiate ART at KP community-based services. CONCLUSIONS: The application of a differentiated service approach for KP could increase the number of people who know their status and receive effective and sustained prevention and treatment for HIV. However, while community-based and lay provider testing are effective and affordable, they are not implemented to scale. Furthermore regulatory barriers to legitimizing lay and peer providers as part of healthcare delivery systems need to be overcome in many settings. WHO recommendations on task shifting and decentralization of ART treatment and care are often not applied to KP settings.

Differences in regional brain atrophy in genetic forms of Alzheimer's disease.

Multiple degenerative hallmarks characterize Alzheimer's disease: insoluble protein deposition, neuronal loss and cortical atrophy. Atrophy begins in the medial temporal lobe and becomes global by end stage. In a small proportion of cases, these tissue changes are caused by mutations in three known genes. These cases are affected earlier in life and have more abundant protein deposition, which may indicate greater tissue atrophy and degeneration. This issue remains unresolved. Grey matter atrophy in different cortical regions was determined in genetic cases of Alzheimer's disease (N = 13) and compared to sporadic cases (N = 13) and non-diseased controls (N = 23). Genetic mutations were found to influence the degree and regional pattern of atrophy. The majority of cases had greater medial temporal atrophy than sporadic disease, suggesting that abnormalities affecting Abeta metabolism selectively increase hippocampal degeneration. Cases with mutations in presenilin-1 demonstrated additional increased frontotemporal atrophy. This effect may be due to the influence of presenilin-1 on tau phosphorylation and metabolism. These differences may explain the earlier onset ages in these different forms of Alzheimer's disease.