Impact of simplified HCV diagnostic strategies on the HCV epidemic among men who have sex with men in the era of HIV oral pre-exposure prophylaxis in Taiwan: a modelling study.

INTRODUCTION: Simplified hepatitis C virus (HCV) diagnostic strategies have the potential to improve HCV diagnoses and treatment. We aimed to investigate the impact of simplified HCV diagnostic strategies on HCV incidence and its effect on HCV diagnosis and treatment among men who have sex with men (MSM) regardless of HIV status and use of HIV pre-exposure prophylaxis (PrEP) in Taiwan. METHODS: A compartmental deterministic model was developed to describe the natural history of HCV disease progression, the HCV care cascade and the HIV status and PrEP using among MSM. The model was calibrated to available data for HCV and HIV epidemiology and population demographics in Taiwan. We simulated the epidemic from 2004 and projected the impact of simplified testing strategies on the HCV epidemic among MSM over 2022-2030. RESULTS: Under the current testing approach in Taiwan, total HCV incidence would increase to 12.6 per 1000 person-years among MSM by 2030. Single-visit point-of-care RNA testing had the largest impact on reducing the number of new HCV infections over 2022-2030, with a 31.1% reduction (interquartile range: 24.9%-32.8%). By 2030, single-visit point-of-care HCV testing improved HCV diagnosis to 90.9%, HCV treatment to 87.7% and HCV cure to 81.5% among MSM living with HCV. Compared to status quo, prioritized simplified HCV testing for PrEP users and MSM living with diagnosed HIV had considerable impact on the broader HCV epidemic among MSM. A sensitivity analysis suggests that reinfection risk would have a large impact on the effectiveness of each point-of-care testing scenario. CONCLUSIONS: Simplified HCV diagnostic strategies could control the ongoing HCV epidemic and improve HCV testing and treatment among Taiwanese MSM. Single-visit point-of-care RNA testing would result in large reductions in HCV incidence and prevalence among MSM. Efficient risk-reduction strategies will need to be implemented alongside point-of-care testing to achieve HCV elimination among MSM in Taiwan.

We have reached single-visit testing, diagnosis, and treatment for hepatitis C infection, now what?

INTRODUCTION: Progress toward hepatitis C virus (HCV) elimination is impeded by low testing and treatment due to the current diagnostic pathway requiring multiple visits leading to loss to follow-up. Point-of-care testing technologies capable of detecting current HCV infection in one hour are a 'game-changer.' These tests enable diagnosis and treatment in a single visit, overcoming the barrier of multiple visits that frequently leads to loss to follow-up. Combining point-of-care HCV antibody and RNA tests should improve cost-effectiveness, patient/provider acceptability, and testing efficiency. However, implementing HCV point-of-care testing programs at scale requires multiple considerations. AREAS COVERED: This commentary explores the need for point-of-care HCV tests, diagnostic strategies to improve HCV testing, key considerations for implementing point-of-care HCV testing programs, and remaining challenges for point-of-care testing (including operator training, quality management, connectivity and reporting systems, regulatory approval processes, and the need for more efficient tests). EXPERT OPINION: It is exciting that single-visit testing, diagnosis, and treatment for HCV infection have been achieved. Innovations afforded through COVID-19 should facilitate the accelerated development of low-cost, rapid, and accurate tests to improve HCV testing. The next challenge will be to address barriers and facilitators for implementing point-of-care testing to deliver them at scale.

Oral meloxicam given as an ancillary treatment at respiratory disease diagnosis was not associated with growth, clinical scores, or ultrasound scores in preweaned dairy calves.

Objective: To assess the efficacy of a single dose of oral meloxicam as an ancillary therapy to an antibiotic given at the time of respiratory disease identification on average daily gain (ADG), behavioral attitude, clinical respiratory, and lung ultrasound scores in preweaned dairy calves. Animals: 215 male and female Holstein, Jersey, and crossbred preweaned calves enrolled between 1 and 14 days of age at study enrollment on a single commercial dairy in the western US. Methods: The study took place from March 4, 2021, to November 21, 2021. In this double-blind placebo-controlled study, calves were given an antibiotic (1.1 mL of tulathromycin/kg, SC, once) and either a placebo (1 mg of lactose monohydrate/kg, in a gelatin capsule) or oral meloxicam (1 mg/kg) at the time of respiratory disease identification. Behavioral attitude, clinical respiratory, and lung ultrasound scores and ADG were assessed in preweaned dairy calves at different time points including the next health examination, 1 week later, or at weaning. Results: There was no association between treatment (placebo vs meloxicam) on ADG or respiratory disease status at weaning (P > .05). There was no effect of treatment on behavioral attitude, clinical respiratory, or lung ultrasound scores at the next health examination or 1 week later (P > .05). Clinical Relevance: The present study did not provide evidence that oral meloxicam given once is beneficial for growth, behavioral attitude, or clinical or lung ultrasound scores.

National Surveillance of Home-Based HIV Testing Among Australian Gay and Bisexual Men, 2018-2020: Uptake After Commercial Availability of HIV Self-Tests.

HIV self-testing allows people to collect samples and test themselves at home, addressing known barriers to facility-based testing. We aimed to measure the uptake of home HIV testing among Australian gay and bisexual men (GBM). Using national cross-sectional data from the Australian Gay Community Periodic Surveys, we assessed trends in home HIV testing among non-HIV positive GBM between 2018 and 2020. Overall, the use of home HIV testing was low, but slightly increased during 2018-2020 (from 0.3 to 0.8%, RR = 1.54, 95%CI = 1.23-1.92, p-trend < 0.001). Testing at home was more likely among non-HIV-positive GBM who were born overseas and recently arrived in Australia, at higher risk of HIV, and infrequent HIV testers. Given the greater use of home testing by men at higher risk of HIV, recent migrants and infrequent testers, all priority groups in Australia's HIV epidemic, we recommend increasing access to HIV self-testing to enhance uptake in these and other groups of GBM.

Reinfection incidence and risk among people treated for recent hepatitis C virus infection.

OBJECTIVE: Reinfection poses a challenge to hepatitis C virus (HCV) elimination. This analysis assessed incidence of, and factors associated with reinfection among people treated for recent HCV (duration of infection <12 months). METHODS: Participants treated for recent HCV (primary infection or reinfection) in an international randomized trial were followed at 3-monthly intervals for up to 2 years to assess for reinfection. Reinfection incidence was calculated using person-time of observation. Factors associated with HCV reinfection were assessed using Cox proportional hazards regression analysis. RESULTS: Of 222 participants treated for recent HCV, 196 (62% primary infection, 38% reinfection) were included in the cohort at risk for reinfection, of whom 87% identified as gay or bisexual men, 71% had HIV and 20% injected drugs in the month prior to enrolment. During 198 person-years of follow-up, 28 cases of HCV reinfection were identified among 27 participants, for an incidence of 14.2 per 100 person-years [95% confidence interval (CI) 9.8-20.5]. Reinfection was associated with prior HCV reinfection [adjusted hazards ratio (aHR) 2.42; 95% CI 1.08-5.38], injection drug use posttreatment (aHR 2.53; 95% CI 1.14-5.59), condomless anal intercourse with casual male partners (aHR 3.32; 95% CI 1.14-9.65) and geographic region (United Kingdom, aHR 0.21; 95% CI 0.06-0.75). Among gay and bisexual men (GBM), reinfection was also associated with sexualized drug use involving injecting posttreatment (aHR 2.97; 95% CI 1.10-8.02). CONCLUSION: High reinfection incidence following treatment for recent HCV among people with ongoing sexual and drug use risk behaviour highlights the need for posttreatment surveillance, rapid retreatment of reinfection and targeted harm reduction strategies.

Hepatitis C virus transmission between eight high-income countries among men who have sex with men: a whole-genome analysis.

BACKGROUND: Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial. METHODS: For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population. FINDINGS: The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6-43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed. INTERPRETATION: Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM. FUNDING: National Institutes of Health and Dr. C.J. Vaillant Fonds.

Evaluation of Simplified HCV Diagnostics in HIV/HCV Co-Infected Patients in Myanmar.

To evaluate a decentralised testing model and simplified treatment protocol of hepatitis C virus (HCV) infection to facilitate treatment scale-up in Myanmar, this prospective, observational study recruited HIV-HCV co-infected outpatients receiving sofosbuvir/daclatasvir in Yangon, Myanmar. The study examined the outcomes and factors associated with a sustained virological response (SVR). A decentralised "hub-and-spoke" testing model was evaluated where fingerstick capillary specimens were transported by taxi and processed centrally. The performance of the Xpert HCV VL Fingerstick Assay in detecting HCV RNA was compared to the local standard of care ( plasma HCV RNA collected by venepuncture). Between January 2019 and February 2020, 162 HCV RNA-positive individuals were identified; 154/162 (95%) initiated treatment, and 128/154 (84%) returned for their SVR12 visit. A SVR was achieved in 119/154 (77%) participants in the intent-to-treat population and 119/128 (93%) participants in the modified-intent-to-treat population. Individuals receiving an antiretroviral therapy were more likely to achieve a SVR (with an odds ratio (OR) of 7.16, 95% CI 1.03-49.50), while those with cirrhosis were less likely (OR: 0.26, 95% CI 0.07-0.88). The sensitivity of the Xpert HCV VL Fingerstick Assay was 99.4% (95% CI 96.7-100.0), and the specificity was 99.2% (95% CI 95.9-99.9). A simplified treatment protocol using a hub-and-spoke testing model of fingerstick capillary specimens can achieve an SVR rate in LMIC comparable to well-resourced high-income settings.

Barriers and facilitators to HIV and syphilis rapid diagnostic testing in antenatal care settings in low-income and middle-income countries: a systematic review.

BACKGROUND: Testing and treatment during pregnancy is a well-established and cost-effective prevention strategy, which relies largely on use of rapid diagnostic tests (RDTs). Yet, in many low-income and-middle-income countries, the uptake of RDTs is suboptimal. A qualitative meta-synthesis was conducted to identify the barriers and enablers to use of HIV and syphilis RDTs among pregnant women in low-income and middle-income countries. METHODS: This review was conducted using PRISMA guidelines. Eligible studies included peer-reviewed publications, which used qualitative methods to explore HIV and syphilis RDT in antenatal care clinics in low-income and middle-income countries. Studies focusing on perspectives of pregnant women, healthcare workers and/or stakeholders were included. We used an inductive approach informed by a modified socioecological model to synthesise the data. RESULTS: 62 manuscripts met the eligibility criteria. For pregnant women, initial acceptance of the RDT and continuation in antenatal care depends on the perception that engaging in testing will be a beneficial experience for their baby and themselves, often influenced by the provision of services that are gender-sensitive, confidential, respectful, flexible and considers their well-being into the future. Local sociocultural beliefs about pregnancy and diseases, awareness of diseases and gender roles in society also influenced RDT acceptability among pregnant women. For healthcare workers, the ability to provide high-quality RDT care required ongoing training, accurate and easy to use tests, support from supervisors and communities, sufficient resources and staffing to provide services, and reliable salary. At the stakeholder level, well-developed guidelines and health system infrastructures were imperative to the delivery of RDT in antenatal clinics. CONCLUSION: Our findings highlight clear gaps to the provision of sustainable and culturally acceptable maternal HIV and/or syphilis screening using RDTs. In addition, greater attention needs to be paid to community stakeholders in promoting the uptake of RDT in antenatal clinics. PROSPERO REGISTRATION NUMBER: CRD42018112190.

Patterns and correlates of hepatitis C virus phylogenetic clustering among people living with HIV in Australia in the direct-acting antiviral era: A molecular epidemiology study among participants in the CEASE cohort.

Background and Aims: In moving towards the elimination of hepatitis C virus (HCV) infection among people living with HIV, understanding HCV transmission patterns may provide insights to guide and evaluate interventions. In this study, we evaluated patterns of, and factors associated with HCV phylogenetic clustering among people living with HIV/HCV co-infection in Australia in the direct-acting antiviral era. Methods: HCV RNA was extracted from dried blood spot (DBS) samples collected between 2014 and 2018 in the CEASE cohort study. The HCV Core-E2 region was amplified by a polymerase chain reaction and Sanger sequenced. Maximum likelihood phylogenetic trees (1000 bootstrap replicates) were used to identify patterns of clustering (3% genetic distance threshold). Mixed-effects logistic regression was used to determine correlates of phylogenetic clustering. Factors assessed were sexual risk behavior, education, injecting drug use, housing, employment, HIV viral load, age, sex, and sexuality. Results: Phylogenetic trees were reconstructed for HCV subtype 1a (n = 139) and 3a (n = 63) sequences, with 29% (58/202) in a pair or cluster. Overall (n = 202), phylogenetic clustering was positively associated with younger age (under 40; adjusted odds ratio [aOR] 2.52, 95% confidence interval [CI] 1.20-5.29), and among gay and bisexual men (n = 168), was positively associated with younger age (aOR 2.61, 95% CI 1.10-6.19), higher education (aOR 2.58, 95% CI 1.09-6.13), and reporting high-risk sexual behavior (aOR 3.94, 95% CI 1.31-11.84). During follow-up, five reinfections were observed, but none were in phylogenetic clusters. Conclusion: This study found a high proportion of phylogenetic relatedness, predominantly among younger people and gay and bisexual men reporting high-risk sexual behavior. Despite this, few reinfections were observed, and reinfections demonstrated little relationship with known clusters. These findings highlight the importance of rapid HCV treatment initiation, together with monitoring of the phylogeny.

Ureteropyeloscopic removal of a nephrolith from a 19 year old Hanoverian gelding.

OBJECTIVE: To describe the ureteropyeloscopic removal of a nephrolith in a horse. ANIMALS: A 19 year old Hanoverian gelding with history of urolithiasis requiring surgical intervention. STUDY DESIGN: Case report METHODS: The horse presented with signs of abdominal straining and stranguria. A proximal urethral calculus was palpable externally within the perineal urethra. Perineal urethrostomy (PU) at the location of the urethral calculi was performed to remove the urethral obstruction. Left nephrolithiasis was then treated by endoscopic retrieval, inserting the endoscope through the PU. The procedures were performed over 2 consecutive days, with the horse standing and sedated. Medical therapy included antimicrobial and anti-inflammatory treatment. RESULTS: The ureteropyeloscopic removal of a nephrolith from the left renal pelvis was completed. No complications were appreciated following the procedure, and the horse was able to return to athletic activity within 2 weeks. The horse had no further clinical signs referable to urinary dysfunction 7 months later. CONCLUSION: Ureteropyeloscopic removal of a nephrolith from the renal pelvis is technically feasible in the equine patient and preserves function of the affected kidney. The availability of a treatment that maintains renal function is a distinct benefit over unilateral nephrectomy, particularly when treating a condition that frequently involves both kidneys.

Preferences for HIV Testing Services and HIV Self-Testing Distribution Among Migrant Gay, Bisexual, and Other Men Who Have Sex With Men in Australia.

Background: In Australia, undiagnosed HIV rates are much higher among migrant gay, bisexual, or other men who have sex with men (GBMSM) than Australian-born GBMSM. HIV self-testing is a promising tool to overcome barriers to HIV testing and improve HIV testing uptake among migrant GBMSM. We compared the preferences for HIV testing services, including HIV self-testing, among migrant and Australian-born GBMSM. Methods: Preferences were assessed via two discrete choice experiments (DCEs). Participants were recruited between December 2017 and January 2018 using online and offline advertising and randomly assigned to complete one of two online DCE surveys. Migrant GBMSM were classified as being born in a country with a reciprocal healthcare agreement (RHCA) with Australia (providing free or subsided health care) or not. Latent class analysis and mixed logit models were used to explore heterogeneity in preferences. Findings: We recruited 1,606 GBMSM, including 583 migrant men of whom 419 (72%) were born in non-RHCA countries. Most participants preferred a free or cheap oral test with higher accuracy and a shorter window period to facilitate early detection of infections. Cost was more important for men born in non-RHCA countries than for men from RHCA countries or Australia. All groups preferred accessing kits through online distributers or off the shelf purchasing from pharmacies. Men born in RHCA countries least preferred accessing HIV self-testing kits from a medical clinic, while more than half of men from non-RHCA countries most preferred sourcing kits from a clinic. Sex-on-premises venues were the least preferred location to access test kits among all groups. In addition, two latent class analyses explored heterogeneity in preferences among men from non-RHCA countries and we found four latent classes for HIV testing services and two latent classes for HIVST distribution. Interpretation: Our findings emphasise the need for high-performing and low-cost HIV self-testing kits that are accessible from a variety of distribution points as a component of Australia's HIV response, especially for those who do not have access to free or subsidised health care in Australia.

Evaluation of the 4-point regional nerve block using 2% lidocaine in sheep.

PURPOSE: To determine whether a single 4-point regional nerve block using 2% lidocaine administered distal to the fetlock of sheep with a single distal limb lameness will result in analgesia of the digits. ANIMALS: Eighteen adult ewes with a single limb lameness originating from distal to the metacarpo/metatarsophalangeal joint were enrolled in the study. PROCEDURES: Digital lameness was confirmed and scored based on clinical examination. Pain associated with digital lesions was assessed in triplicate using a pressure algometer to quantify mechanical nociceptive threshold. The same procedure was repeated on the contralateral limb as a control, and maximum force and time to response recorded. A 4-point regional nerve block was performed using 8 mL of 2% lidocaine. Mechanical nociception was again applied in triplicate to both limbs as described above, by a blinded investigator. Following appropriate medical treatment, the ewe was released and lameness scoring repeated.Median values for pressure and time to withdrawal were determined for affected and control limbs, and differences between pre- and post-lidocaine block measures were compared using Friedman's ANOVA test. The Wilcoxon Signed-Rank test was used to compare lameness score pre- and post-block. Statistical significance was set at α = 0.05. MAIN FINDINGS: Application of the 4-point block resulted in a change in pressure required to elicit withdrawal (F-value 17.7; P < 0.0001) as well as time to withdrawal (F-value 20.4; P < 0.0001), for the affected limb as compared to the control limb. Lameness scores decreased following the block (Signed-rank statistic 85.5; P < 0.0001). PRINCIPAL CONCLUSION: The 4-point nerve block resulted in anesthesia of the distal limb in sheep in this clinical model.

Évaluation du bloc nerveux régional en quatre points avec de la lidocaïne à 2 % chez le mouton. OBJECTIF: Déterminer si un seul bloc nerveux régional en quatre points utilisant de la lidocaïne à 2 % administrée distalement du boulet d'un mouton présentant une boiterie d'un seul membre distal entraînera une analgésie des doigts. ANIMAUX: Dix-huit brebis adultes avec une boiterie d'un seul membre provenant de la partie distale de l'articulation métacarpo/métatarsophalangienne ont été incluses dans l'étude. PROCÉDURES: La boiterie digitale a été confirmée et notée sur la base d'un examen clinique. La douleur associée aux lésions digitales a été évaluée en triple à l'aide d'un algomètre à pression pour quantifier le seuil nociceptif mécanique. La même procédure a été répétée sur le membre controlatéral en tant que témoin, et la force maximale et le temps de réponse ont été enregistrés. Un bloc nerveux régional en quatre points a été réalisé avec 8 ml de lidocaïne à 2 %. La nociception mécanique a de nouveau été appliquée en triple exemplaire aux deux membres comme décrit ci-dessus, par un chercheur en aveugle. Suite à un traitement médical approprié, la brebis a été relâchée et le score de boiterie répété.Les valeurs médianes de la pression et du temps de retrait ont été déterminées pour les membres affectés et les membres témoins, et les différences entre les mesures du bloc avant et après le bloc de lidocaïne ont été comparées à l'aide du test ANOVA de Friedman. Le test de Wilcoxon (signed-rank) a été utilisé pour comparer le score de boiterie avant et après le bloc. Le seuil de signification statistique a été fixé à α = 0,05. PRINCIPAUX RÉSULTATS: L'utilisation du bloc à quatre points a entraîné une modification de la pression requise pour déclencher le retrait (valeur F 17,7; P < 0,0001) ainsi que du temps de retrait (valeur F 20,4; P < 0,0001), pour les membres affectées par rapport au membres témoins. Les scores de boiterie ont diminué après le bloc (statistique de Signed-rank 85,5; P < 0,0001). CONCLUSION PRINCIPALE: Le bloc nerveux en quatre points a entraîné une anesthésie du membre distal chez le mouton dans ce modèle clinique.(Traduit par Dr Serge Messier).

Diagnostic Accuracy of Assays Using Point-of-Care Testing or Dried Blood Spot Samples for the Determination of Hepatitis C Virus RNA: A Systematic Review.

BACKGROUND: Finger-stick point-of-care and dried blood spot (DBS) hepatitis C virus (HCV) RNA testing increases testing uptake and linkage to care. This systematic review evaluated the diagnostic accuracy of point-of-care testing and DBS to detect HCV RNA. METHODS: Bibliographic databases and conference presentations were searched for eligible studies. Meta-analysis was used to pool estimates. RESULTS: Of 359 articles identified, 43 studies were eligible and included. When comparing the Xpert HCV Viral Load Fingerstick assay to venous blood samples (7 studies with 987 samples), the sensitivity and specificity for HCV RNA detection was 99% (95% confidence interval [CI], 97%-99%) and 99% (95% CI, 94%-100%) and for HCV RNA quantification was 100% (95% CI, 93%-100%) and 100% (95% CI, 94%-100%). The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing was 6% (95% CI, 3%-11%). When comparing DBS to venous blood samples (28 studies with 3988 samples) the sensitivity and specificity for HCV RNA detection was 97% (95% CI, 95%-98%) and 100% (95% CI, 98%-100%) and for HCV RNA quantification was 98% (95% CI, 96%-99%) and 100% (95% CI, 95%-100%). CONCLUSIONS: Excellent diagnostic accuracy was observed across assays for detection of HCV RNA from finger-stick and DBS samples. The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing highlights the importance of operator training and quality assurance programs.

Supply-side readiness to deliver HIV testing and treatment services in Indonesia: Going the last mile to eliminate mother-to-child transmission of HIV.

INTRODUCTION: Despite national efforts to integrate Prevention of Mother-to-Child Transmission (PMTCT) of HIV services into antenatal care in Indonesia, the rate of mother-to-child transmission of HIV remains the highest in the world. A range of barriers to uptake and long-term engagement in care have been identified, but far less is known about health system preparedness to deliver PMTCT of HIV services. This study explored supply-side barriers to the delivery of PMTCT services in Indonesia and whether these factors are associated with the uptake of antenatal HIV testing. MATERIALS AND METHODS: An ecological analysis was undertaken, linking data from the World Bank Quality Service and Delivery Survey (2016) with routine data from Indonesia's HIV and AIDS case surveillance system and district health profile reports (2016). Supply-side readiness scores-generated from a readiness index that measures overall structural capacity and is often used as proxy for quality of care-were adapted from the WHO Service Availability and Readiness Assessment and presented by sector and geographic area. Univariate and multivariate regression analysis was used to explore factors associated with the uptake of antenatal HIV testing in public facilities. RESULTS: In general, public facilities scored more highly in most inputs compared to private facilities. Facilities located in urban areas also scored more highly in the majority of inputs compared to ones in rural areas. Readiness scores were lowest for PMTCT services compared to Antenatal Care and HIV Care and Support services, especially for the availability of medicines such as zidovudine and nevirapine. The national composite readiness score for PMTCT was only 0.13 (based on a maximum score of 1) with a composite score of 0.21 for public facilities and 0.06 for private facilities. The multivariate analysis shows that the proportion of pregnant women tested for HIV was more likely to be greater than or equal to 10% in facilities with a higher readiness score and a higher number of trained counsellors available, and less likely in facilities located outside of Java-Bali and in facilities supporting a higher number of village midwives. DISCUSSION: Despite targeted efforts by the Indonesian government and multinational agencies, significant gaps exist in the delivery of PMTCT that compromise the standard of care delivered in Indonesia. Future strategies should focus on improving the availability of tests and treatment, especially in the private sector and in rural areas.

Sustaining success: a qualitative study of gay and bisexual men's experiences and perceptions of HIV self-testing in a randomized controlled trial.

BACKGROUND: HIV self-testing was proved as an effective tool for increasing testing frequency in gay and bisexual men at high risk of infection. Questions remain about understanding why HIVST encouraged testing and how such success can be translated to programmatic implementation. METHODS: We conducted a qualitative investigation of how FORTH participants experienced and perceived HIVST. Stratified sampling was used to recruit gay and bisexual men participating in the FORTH HIVST intervention to take part in interviews, focusing on infrequent testers and those who had received inaccurate HIVST results. RESULTS: Our analysis identified several prominent themes organized into two overarching domains from the 15 interviews: (i) aspects of HIVST contributing to HIV testing frequency, and (ii) sustaining HIVST into the future. Participants also believed that their use of HIVST in the future would depend on the test kit's reliability, particularly when compared with highly reliable clinic-based testing. CONCLUSION: HIVST increases the frequency of HIV testing among gay and bisexual men due, in part, to the practical, psychological, and social benefits it offers. To capitalize fully on these benefits, however, strategies to ensure the availability of highly reliable HIVST are required to sustain benefits beyond the confines of a structured research study.

The longer-term effects of access to HIV self-tests on HIV testing frequency in high-risk gay and bisexual men: follow-up data from a randomised controlled trial.

BACKGROUND: A wait-list randomised controlled trial in Australia (FORTH) in high-risk gay and bisexual men (GBM) showed access to free HIV self-tests (HIVSTs) doubled the frequency of HIV testing in year 1 to reach guideline recommended levels of 4 tests per year, compared to two tests per year in the standard-care arm (facility-based testing). In year 2, men in both arms had access to HIVSTs. We assessed if the effect was maintained for a further 12 months. METHODS: Participants included GBM reporting condomless anal intercourse or > 5 male partners in the past 3 months. We included men who had completed at least one survey in both year 1 and 2 and calculated the mean tests per person, based on the validated self-report and clinic records. We used Poisson regression and random effects Poisson regression models to compare the overall testing frequency by study arm, year and testing modality (HIVST/facility-based test). FINDINGS: Overall, 362 men completed at least one survey in year 1 and 343 in year 2. Among men in the intervention arm (access to HIVSTs in both years), the mean number of HIV tests in year 2 (3⋅7 overall, 2⋅3 facility-based tests, 1⋅4 HIVSTs) was lower compared to year 1 (4⋅1 overall, 1⋅7 facility-based tests, 2⋅4 HIVSTs) (RR:0⋅84, 95% CI:0⋅75-0⋅95, p=0⋅002), but higher than the standard-care arm in year 1 (2⋅0 overall, RR:1⋅71, 95% CI:1⋅48-1.97, p<0⋅001). Findings were not different when stratified by sociodemographic characteristics or recent high risk sexual history. INTERPRETATION: In year 2, fewer HIVSTs were used on average compared to year 1, but access to free HIVSTs enabled more men to maintain higher HIV testing frequency, compared with facility-based testing only. HIV self-testing should be a key component of HIV testing and prevention strategies. FUNDING: This work was supported by grant 568971 from the National Health and Medical Research Council of Australia.

Brief Report: Case Comparison of Therapy With the Histone Deacetylase Inhibitor Vorinostat in a Neonatal Calf Model of Pulmonary Hypertension.

Pulmonary hypertension (PH) is an incurable condition in humans; driven by pulmonary vascular remodeling partially mediated by epigenetic mechanisms; and leading to right ventricular hypertrophy, failure, and death. We hypothesized that targeting chromatin-modifying histone deacetylases may provide benefit. In this Brief Report we describe case comparison studies using the histone deacetylase inhibitor vorinostat (suberanilohydroxamic acid, 5 mg/kg/day for the first 5 study days) in an established model of severe neonatal bovine PH induced by 14 days of environmental hypoxia. Echocardiographic, hemodynamic, and pharmacokinetic data were obtained in hypoxia-exposed (one each, vorinostat-treated vs. untreated) and normoxic vorinostat-treated control animals (n = 2). Echocardiography detected PH changes by day 4 and severe PH over 14 days of continued hypoxic exposure. RV dysfunction at day 4 was less severe in vorinostat-treated compared to untreated hypoxic calves. Cardioprotective effects were partially maintained following cessation of treatment through the duration of hypoxic exposure, accompanied by hemodynamic evidence suggestive of reduced pulmonary vascular stiffening, and modulated expression of HDAC1 protein and genes involved in RV and pulmonary vascular remodeling and pathological RV hypertrophy. Control calves did not develop PH, nor show adverse cardiac or clinical effects. These results provide novel translation of epigenetic-directed therapy to a large animal severe PH model that recapitulates important features of human disease.

Evaluation of Hepatitis C Virus Core Antigen Assay in a Resource-Limited Setting in Pakistan.

The diagnosis of Hepatitis C virus (HCV) infection can be challenging due to its cost and a lack of access to centralized testing. There is an urgent need to develop simplified HCV testing algorithms. The aim of this study was to evaluate the performance characteristics of a Hepatitis C core antigen (HCVcAg) assay in a decentralized, resource-limited setting. This is a descriptive cross-sectional study from a highly endemic area of Karachi, Pakistan. Between October 2019 and July 2020, subjects aged 12 years and above who screened positive for HCV antibodies were simultaneously tested for HCV RNA (Xpert HCV Viral Load, GeneXpert® IV, Cepheid, France) and HCVcAg (ARCHITECT HCV Ag assay, Abbott® Diagnostics) to confirm active HCV infection. An Abbott ARCHITECT® i1000SR Immunoassay Analyser was installed at a local district hospital as a point-of-care (POC) facility for HCVcAg testing, while samples for HCV RNA were tested in a central lab. Two hundred individuals (mean age 46.4 ± 14.5 years, 71.5% females), who screened positive for HCV antibody, were included in the study. HCV RNA was detected in 128 (64.0%) while HCVcAg was reactive in 119 (59.5%) cases. Performance of the Immunoassay Analyser was excellent with a higher throughput and quicker readout value compared to the GeneXpert System. The sensitivity and specificity of HCVcAg (≥10 fmol/L) at HCV RNA thresholds of ≥12 was 99.1% (95% CI: 95-100%) and 87.6% (95%CI: 78.4-94%). A strong agreement was observed between the HCVcAg assay and HCV RNA. The ARCHITECT HCV Ag assay showed high sensitivity and specificity compared to HCV RNA in a decentralized, resource-limited setting. It can therefore be used as a confirmatory test in HCV elimination programs, particularly for low-income countries such as Pakistan.

Sofosbuvir/velpatasvir for 12 vs. 6 weeks for the treatment of recently acquired hepatitis C infection.

BACKGROUND & AIMS: Shortened duration therapy for acute and recent HCV infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens; however, large randomised studies are lacking. METHODS: REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early. RESULTS: The primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n = 93), standard arm (n = 95). Ninety-seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4-89.0) in the short arm and 86/95, 90.5% (95% CI 82.7-95.6) in the standard arm. The difference between the arms was -8.8 (95% CI -18.6 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss to follow-up), SVR12 was 76/85, 89.4% (95% CI 80.8-95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0-99.7; difference -8.3%, p = 0.025). CONCLUSIONS: In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy. LAY SUMMARY: In this randomised trial, 188 people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. CLINICALTRIALS. GOV IDENTIFIER: NCT02625909.

The costs of scaling up HIV and syphilis testing in low- and middle-income countries: a systematic review.

Around two-thirds of all new HIV infections and 90% of syphilis cases occur in low- and middle-income countries (LMICs). Testing is a key strategy for the prevention and treatment of HIV and syphilis. Decision-makers in LMICs face considerable uncertainties about the costs of scaling up HIV and syphilis testing. This paper synthesizes economic evidence on the costs of scaling up HIV and syphilis testing interventions in LMICs and evidence on how costs change with the scale of delivery. We systematically searched multiple databases (Medline, Econlit, Embase, EMCARE, CINAHL, Global Health and the NHS Economic Evaluation Database) for peer-reviewed studies examining the costs of scaling up HIV and syphilis testing in LMICs. Thirty-five eligible studies were identified from 4869 unique citations. Most studies were conducted in Sub-Saharan Africa (N = 17) and most explored the costs of rapid HIV in facilities targeted the general population (N = 19). Only two studies focused on syphilis testing. Seventeen studies were cost analyses, 17 were cost-effectiveness analyses and 1 was cost-benefit analysis of HIV or syphilis testing. Most studies took a modelling approach (N = 25) and assumed costs increased linearly with scale. Ten studies examined cost efficiencies associated with scale, most reporting short-run economies of scale. Important drivers of the costs of scaling up included testing uptake and the price of test kits. The 'true' cost of scaling up testing is likely to be masked by the use of short-term decision frameworks, linear unit-cost projections (i.e. multiplying an average cost by a factor reflecting activity at a larger scale) and availability of health system capacity and infrastructure to supervise and support scale up. Cost data need to be routinely collected alongside other monitoring indicators as HIV and syphilis testing continues to be scaled up in LMICs.