Caregivers' experiences of accessing HIV Early Infant Diagnosis (EID) services and its barriers and facilitators, India.

BACKGROUND: India has rolled out Early Infant Diagnosis (EID) program for HIV infection in all states. EID program consists of testing of Infants exposed to HIV periodically over 18 months of age which is a multi-step complex testing cascade. Caregivers represent the primary beneficiary of EID program i.e., infants exposed to HIV and face multiple challenges to access EID services. As part of national EID program outcome assessment study, this study narrates caregivers' perspectives on barriers and facilitators to access and utilize EID services. METHODS: The study was conducted in 31 integrated counselling and testing centres (ICTCs) located in 11 high burden HIV states. A total of 66 in-depth interviews were conducted with caregivers' of infants enrolled in EID program. Thematic analysis was carried out to help identify themes underlying barriers and facilitators to access EID services and utilization from caregivers' perspectives. RESULTS: The stigma and discrimination prevalent in society about HIV remains a key demand side (caregiver-level) barrier. Non-disclosure or selective disclosure of HIV status led to missed or delayed EID tests and delayed HIV diagnosis and initiation of Anti-Retroviral Therapy (ART) for infants exposed to HIV. On supply side (health system-level), accessibility of healthcare facility with EID services was reported as a key barrier. The distance, time and cost were key concerns. Many caregivers faced difficulties to remember the details of complex EID test schedule and relied on a phone call from ICTC counsellor for next due EID test. Delayed EID test results and lack of communication of test results to caregiver were reported as primary barriers for completing the EID test cascade. DISCUSSION: The study reports caregiver-level and health system-level barriers and facilitators for access to EID services from the caregivers' perspectives. While, decentralisation and single window approaches can improve the access, timely communication of test results to the caregiver also need to be built in with appropriate use of technology. A holistic intervention including PLHIV support networks and the peer-led support mechanisms would be useful to address societal factors. CONCLUSION: The study findings have high significance for developing program implementation strategies to improve access and to build right-based and patient-centred EID services.

Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy.

BACKGROUND: Opportunities for adjunct therapies with cooling in neonatal encephalopathy are imminent; however, robust biomarkers of early assessment are lacking. Using an optical platform of broadband near-infrared spectroscopy and diffuse correlation spectroscopy to directly measure mitochondrial metabolism (oxCCO), oxygenation (HbD), cerebral blood flow (CBF), we hypothesised optical indices early (1-h post insult) after hypoxia-ischaemia (HI) predicts insult severity and outcome. METHODS: Nineteen newborn large white piglets underwent continuous neuromonitoring as controls or following moderate or severe HI. Optical indices were expressed as mean semblance (phase difference) and coherence (spectral similarity) between signals using wavelet analysis. Outcome markers included the lactate/N-acetyl aspartate (Lac/NAA) ratio at 6 h on proton MRS and TUNEL cell count. RESULTS: CBF-HbD semblance (cerebrovascular dysfunction) correlated with BGT and white matter (WM) Lac/NAA (r2 = 0.46, p = 0.004, r2 = 0.45, p = 0.004, respectively), TUNEL cell count (r2 = 0.34, p = 0.02) and predicted both initial insult (r2 = 0.62, p = 0.002) and outcome group (r2 = 0.65 p = 0.003). oxCCO-HbD semblance (cerebral metabolic dysfunction) correlated with BGT and WM Lac/NAA (r2 = 0.34, p = 0.01 and r2 = 0.46, p = 0.002, respectively) and differentiated between outcome groups (r2 = 0.43, p = 0.01). CONCLUSION: Optical markers of both cerebral metabolic and vascular dysfunction 1 h after HI predicted injury severity and subsequent outcome in a pre-clinical model. IMPACT: This study highlights the possibility of using non-invasive optical biomarkers for early assessment of injury severity following neonatal encephalopathy, relating to the outcome. Continuous cot-side monitoring of these optical markers can be useful for disease stratification in the clinical population and for identifying infants who might benefit from future adjunct neuroprotective therapies beyond cooling.

Impact of COVID-19 Pandemic on HIV Testing Uptake Among Key Populations Enrolled in Targeted Intervention Program in Maharashtra, India.

The COVID-19 pandemic posed unprecedented challenges to HIV services globally. We evaluated the impact of the COVID-19 pandemic on the uptake of HIV testing in the Targeted Intervention (TI) program in Maharashtra-a high HIV burden state in India. Annual HIV testing was sustained during the pandemic year (2020-2021), at levels similar to the pre-pandemic year (2019-2020), among Female Sex Workers (FSW), Men having Sex with Men (MSM), Transgender (TG), and Truckers; but not among Migrants and Intravenous Drug Users (IDU). There was an acute decline during the lockdown across all typologies. Sharp recovery was seen among FSW, MSM, and TG during the early months of the un-lockdown. The community-based screening (CBS) approach primarily contributed to this recovery. Among migrants and truckers, recovery was delayed. There was an overall reduction of 58% in annual HIV-positive registrations. The community-based networks, participatory structures, and processes of HIV programs played an essential role in reaching the community during the pandemic.

The Extracellular Vesicle Citrullinome and Signature in a Piglet Model of Neonatal Seizures.

Neonatal seizures are commonly associated with acute perinatal brain injury, while understanding regarding the downstream molecular pathways related to seizures remains unclear. Furthermore, effective treatment and reliable biomarkers are still lacking. Post-translational modifications can contribute to changes in protein function, and post-translational citrullination, which is caused by modification of arginine to citrulline via the calcium-mediated activation of the peptidylarginine deiminase (PAD) enzyme family, is being increasingly linked to neurological injury. Extracellular vesicles (EVs) are lipid-bilayer structures released from cells; they can be isolated from most body fluids and act as potential liquid biomarkers for disease conditions and response to treatment. As EVs carry a range of genetic and protein cargo that can be characteristic of pathological processes, the current study assessed modified citrullinated protein cargo in EVs isolated from plasma and CSF in a piglet neonatal seizure model, also following phenobarbitone treatment. Our findings provide novel insights into roles for PAD-mediated changes on EV signatures in neonatal seizures and highlight the potential of plasma- and CSF-EVs to monitor responses to treatment.

Assessment of levels and trends of HIV infections among different subgroup populations of Gujarat State - Prioritization of the districts.

Background: In India, HIV prevalence varies by region and high-risk groups. General population rates have decreased in high prevalence states through HIV Sentinel Surveillance among pregnant women, while low-moderate prevalence states show variable trends. Gujarat, in western India, has mixed HIV prevalence according to 2017 Sentinel Surveillance data. Objectives: To study the level and trend of HIV positivity among pregnant women and high-risk groups (HRGs) across different districts of the state of Gujarat from year 2012-13 to 2016-17. To review the possible determinants of the HIV epidemic across the selected districts in the state of Gujarat. Materials and Methods: Data from the National AIDS Control Organization (NACO) spanning 2012-17 was analyzed for HIV trends in Gujarat. This included combined HIV testing data from pregnant women at Integrated and Counseling Testing Centers, blood unit testing data from selected districts, and HIV testing among high-risk populations through Targeted Intervention sites. Results: HIV cases in Kheda district declined post-2013-14 among pregnant women (0.38% to 0.21% in 2016-17), and in general ICTC clients (5.53% to 0.264% in 2017-18). MSM seropositivity dropped from 1.15% (2014-15) to 0.74% (2016-17), FSWs from 0.7% (2014-15) to 0.29% (2015-16). Contrastingly, blood donors exhibited an increasing trend, rising from 0.15% (2012-13) to 0.24% (2016-17). In Mehsana, ANC mother seropositivity rose to 0.6% (2013-14), fell to 0.32% (2015-16), and rose again to 0.48% (2016-17). General ICTC clients declined from 1.2% (2012-13) to 0.53% (2016-17). FSWs had 0.25% seropositivity (2015-16), while MSM saw a drop from 0.44% (2014-15) to 0.23% (2016-17). Blood donors' trend was inconsistent. Sabarkantha's pregnant women seropositivity dipped from 0.59% (2012-13) to 0.20% (2014-15), rising to 0.25% (2017-18). General ICTC client seropositivity decreased from 5.34% (2012-13) to 1.17% (2017-18). Conclusion: While declines in HIV prevalence are evident among certain groups such as pregnant women and general ICTC clients, there are fluctuations in seropositivity among high-risk populations like MSM, FSWs, and blood donors. These insights emphasize the need for targeted interventions and ongoing monitoring to effectively address the evolving HIV landscape in these districts.

Comparison of prevention of parent-to-child HIV transmission programme & national biennial HIV sentinel surveillance data for tracking HIV epidemic in India.

Background & objectives: HIV sentinel surveillance (HSS) among antenatal women in India has been used to track the epidemic for many years. However, reliable tracking at the local level is not possible as ANC sentinel sites are limited in number and cover a smaller sample size at each site. Prevention of parent-to-child-transmission (PPTCT) programme data has a potential advantage due to better geographical coverage, which could provide more precise HIV case estimates; therefore, we compared HSS ANC data with PPTCT programme data for HIV tracking. Methods: Out of the 499 surveillance sites, where HSS and PPTCT programme was being conducted in 2015, 210 sites (140 urban and 70 rural) were selected using a stratified random sampling method. HSS (n=72,981) and PPTCT (n=112,832) data records were linked confidentially. The sociodemographic characteristics of HSS and PPTCT attendees were compared. HIV prevalence from HSS ANC was compared with the PPTCT programme data using Chi-square test. State- and site-level correlation of HIV prevalence was also done. Concordance between HSS and PPTCT HIV positivity was estimated using kappa statistics. Results: The age distribution of HSS and PPTCT attendees was similar (range: 23 to 27 yr); however, HSS ANC participants were better educated, whereas PPTCT recorded a higher proportion of homemakers. The correlation of HIV prevalence between HSS and PPTCT was high (r=0.9) at the State level and moderate at the site level (r=0.7). The HIV positivity agreement between HSS ANC and PPTCT was good (kappa=0.633). A similar prevalence was reported across 26 States, whereas PPTCT had a significantly lower prevalence than HSS in three States where PPTCT coverage was low. Overall HIV prevalence was 0.31 per cent in HSS and 0.22 per cent in PPTCT (P<0.001). Interpretation & conclusions: High-quality PPTCT programme data can provide reliable HIV trends in India. An operational framework for PPTCT-based surveillance should be pilot-tested in a phased manner before replacing HSS with PPTCT.

Loss to follow-up of HIV-exposed infants for confirmatory HIV test under Early Infant Diagnosis program in India: analysis of national-level data from reference laboratories.

BACKGROUND: Early Infant Diagnosis was launched in India in 2010 and its effect on the diagnosis of HIV-exposed infants needs to be assessed. The present study was done to find out the median age at DBS sample collection for early infant diagnosis and its trend over years, the median age at diagnosis of HIV among the HIV-exposed infants with DNA PCR tests, and the proportion of infants who completed testing cascades after detection of HIV-1 in a sample. METHODS: DNA PCR data (from 2013 to 2017) maintained at all regional reference laboratories in India was collated with each infant identified by a unique code. Cohort analysis of the infant data was used to find the median age at sample collection and diagnosis. The outcomes of testing in each cascade and the overall outcomes of testing for infants were prepared. RESULTS: The median age at sample collection for the four years combined at all India level was 60 days (48-110 days). The median age at diagnosis of HIV was 285 days (174-418 days). HIV-1 was detected in samples of 1897 (6.3%) infants out of 30,216 infants who had a DNA PCR test, out of whom 1070 (56.4%) completed the testing cascade and the rest were lost to follow-up. CONCLUSION: The data highlights delay in diagnosis; both due to delay in sample collection and turn-around-times. Loss to follow-up of HIV-exposed infants with virus detection is a significant concern to the Early Infant Diagnosis and tracking systems need to be strengthened.

Integrating HCV testing with HIV programs improves hepatitis C outcomes in people who inject drugs: A cluster-randomized trial.

BACKGROUND & AIMS: There have been calls to integrate HCV testing into existing services, including harm reduction and HIV prevention and treatment, but there are few empirical trials to date. We evaluated the impact of integrating HCV testing/education into integrated care centers (ICCs) delivering HIV services to people who inject drugs (PWID) across India, using a cluster-randomized trial. METHODS: We compared ICCs with usual care in the PWID stratum (12 sites) of a 22-site cluster-randomized trial. In 6 sites, ICCs delivering HIV testing, harm reduction, other preventive services and linkage to HIV treatment were scaled from opioid agonist therapy centers and operated for 2 years. On-site rapid HCV antibody testing was integrated after 1 year. To assess impact, we conducted baseline and evaluation surveys using respondent-driven sampling (RDS) across the 12 sites (n = 11,993 recruited at baseline; n = 11,721 recruited at evaluation). The primary outcome was population-level self-reported HCV testing history. RESULTS: At evaluation, HCV antibody prevalence ranged from 7.2-76.6%. Across 6 ICCs, 5,263 ICC clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were 4-fold more likely to report being tested for HCV than in usual care clusters, adjusting for baseline testing (adjusted prevalence ratio [aPR] 3.69; 95% CI 1.34-10.2). PWID in ICC clusters were also 7-fold more likely to be aware of their HCV status (aPR 7.11; 95% CI 1.14-44.3) and significantly more likely to initiate treatment (aPR 9.86; 95% CI 1.52-63.8). CONCLUSIONS: We provide among the first empirical data supporting the integration of HCV testing into HIV/harm reduction services. To achieve elimination targets, programs will need to scale-up such venues to deliver comprehensive HCV services. CLINICALTRIALS. GOV IDENTIFIER: NCT01686750. LAY SUMMARY: Delivering hepatitis C virus (HCV) testing to people who inject drugs (PWID) in places where they also have access to HIV prevention and treatment services is an effective way to improve uptake of HCV testing among communities of PWID. To achieve the World Health Organization's ambitious elimination targets, integrated programs will need to be scaled up to deliver comprehensive HCV services.

High IL-5 levels possibly contributing to HIV viremia in virologic non-responders at one year after initiation of anti-retroviral therapy.

Lack of viral monitoring in HIV infected patients on anti-retroviral therapy in low income countries may result in missing virologic non-responders (VNR) who show immunologic recovery in spite of unsuppressed viral replication. Biomarkers and drug resistance patterns in these discordant patients in comparison to the concordant treatment failure group need to be studied to understand possible risk factors associated with this condition. HIV infected patients on anti-retroviral therapy for one year were enrolled under three categories namely VNRs (n = 25), treatment failures (n = 18) and treatment responders (n = 40). They were assessed for HIV drug resistance by sequencing, plasma cytokines by luminex assay, T cell activation status by flow cytometry and total IgE levels by ELISA. VNR and failure patients had significantly lower median baseline CD4 counts than the responders. VNRs had significantly higher CD4 counts but lower viral load than treatment failures at one year of ART. VNRs had the highest eosinophil counts and the highest IL-5 levels among all the groups. IL-5 levels in them correlated with their viral load values. Frequency of Treg cells was also highest among the VNR group participants. More than 60% of the viremic patients irrespective of their groups harboured multiple HIV drug resistance mutations and mutation pattern did not differ between the groups. Low baseline CD4 counts and presence of multiple drug resistance mutations in the viremic groups highlighted the importance of early ART initiation and viral load monitoring irrespective of presence of immunologic failure. High IL-5 levels in VNR group indicated a need for investigating causal relationship between IL-5 and viral replication to devise therapeutic strategies to control viremia.

Possible role of plasma Galectin-9 levels as a surrogate marker of viremia in HIV infected patients on antiretroviral therapy in resource-limited settings.

BACKGROUND: Early detection of viremia in HIV infected patients on anti-retroviral therapy (ART) is important to prevent disease progression as well as accumulation of drug resistance mutations. This makes HIV viral load (VL) monitoring indispensable in HIV infected patients on ART. However VL, being an expensive test, results in heavy financial burden on health services. Hence, cheaper surrogate markers of viremia are desired to reduce overall cost of management of HIV infected patients. METHODS: We enrolled aviremic (n = 63, M:F = 31:32) and viremic (n = 43, M:F = 21:22) HIV infected patients at 1 year after ART initiation. Viremic individuals were identified as those having a plasma VL of more than 1000 copies/µl and aviremic individuals as less than 40 copies/µl. The study participants also included immuno-virologically discordant patients as they demonstrate differential degrees of immune-reconstitution and are likely to harbour concomitant infections influencing levels of immune-activation markers screened as the surrogate markers. Immune activation markers viz. plasma hs-CRP, soluble-CD14 and Galectin-9 levels were estimated by ELISA, IL-6 by luminex assay and percentages of CD38+ CD8+ cells were determined by flow cytometry. The levels were compared between viremic and aviremic patients and correlated with plasma viral load. Receiver operated curve (ROC) analysis was done for plasma Galectin-9 levels. RESULTS: Viremic patients had significantly higher levels of Galectin-9 and %CD38+ CD8+ cells (p values < 0.0001) than aviremic patients. Levels of the other activation markers did not differ between viremic and aviremic individuals. Galectin-9 levels (r = 0.76) and %CD38+ CD8+ cells (r = 0.39) correlated positively with VL. Area under curve for Galectin-9 levels for distinguishing between viremic and aviremic individuals was 0.98. Youden index, sensitivity, specificity, positive predictive value and negative predictive value for Galectin-9 levels were 0.87, 0.97, 0.90, 0.87 and 0.98, respectively, at the cut-off value of 5.79 ng/ml. CONCLUSIONS: Plasma Galectin-9 levels could identify viremic individuals with sensitivity and specificity of more than 90%. Thus, they showed a potential to serve as a surrogate marker of viremia in HIV infected patients on ART and would have cost implications on HIV management especially in resource-limited settings. However, the findings need to be confirmed in the patients on ART for different durations of time.

Evaluation of key survey components of bio-behavioral surveillance among HIV high-risk subpopulation in Western India.

BACKGROUND: High-quality data are of prime importance in any health survey because survey data are considered as a gold standard for nationally representative data. The quality of data collection largely depends on the design of the questionnaire, training, and skills of the interviewer. OBJECTIVES: In the present study, we tried to evaluate three key components, such as questionnaire design, human resource and training of the field staff for Integrated Biological and Behavioural Surveillance carried out among the HIV high-risk subpopulation. METHODS: A mixed-methods approach was used. Qualitative and quantitative data collection was carried out in the year 2015 with cross-sectional survey design in western states of India. The in-depth interviews of 10 stakeholders, structured interviews of the survey respondents (n = 560), and field investigators (n = 71) were conducted. Data triangulation was used to find out the concurrence of the qualitative and quantitative data. RESULTS: Comprehensive and standardized survey questionnaire, structured training agenda, and strategic preparation for recruiting human resources were the overall strengths of the survey. However, during the implementation of the survey, there were some difficulties reported in data collection process. Overall, the respondents and investigators felt that the questionnaire was long and exhaustive. Difficulties were faced while collecting data on sexual history. The field staffs were not adequately experienced to work with sensitive population. CONCLUSIONS: In order to have accurate, reliable data, especially on sexual behavior; emphasis should be given on simple questionnaire with the use of community-friendly language, skilled and experienced interviewers for data collection, and extensive field training.

Sustained progress, but no room for complacency: Results of 2015 HIV estimations in India.

BACKGROUND & OBJECTIVES: Evidence-based planning has been the cornerstone of India's response to HIV/AIDS. Here we describe the process, method and tools used for generating the 2015 HIV estimates and provide a summary of the main results. METHODS: Spectrum software supported by the UNAIDS was used to produce HIV estimates for India as a whole and its States/Union Territories. This tool takes into consideration the size and HIV prevalence of defined population groups and programme data to estimate HIV prevalence, incidence and mortality over time as well as treatment needs. RESULTS: India's national adult prevalence of HIV was 0.26 per cent in 2015. Of the 2.1 million people living with HIV/AIDS, the largest numbers were in Andhra Pradesh, Maharashtra and Karnataka. New HIV infections were an estimated 86,000 in 2015, reflecting a decline by around 32 per cent from 2007. The declining trend in incidence was mirrored in most States, though an increasing trend was detected in Assam, Chandigarh, Chhattisgarh, Gujarat, Sikkim, Tripura and Uttar Pradesh. AIDS-related deaths were estimated to be 67,600 in 2015, reflecting a 54 per cent decline from 2007. There were variations in the rate and trend of decline across India for this indicator also. INTERPRETATION & CONCLUSIONS: While key indicators measured through Spectrum modelling confirm success of the National AIDS Control Programme, there is no room for complacency as rising incidence trends in some geographical areas and population pockets remain the cause of concern. Progress achieved so far in responding to HIV/AIDS needs to be sustained to end the HIV epidemic.

Incorporating omics-based tools into endophytic fungal research.

Fungal endophytes are valuable sources of bioactive compounds with diverse applications. The exploration of these compounds not only contributes to our understanding of ecological interactions but also holds promise for the development of novel products with agricultural, medicinal, and industrial significance. Continued exploration of fungal endophyte diversity and understanding the ecological roles of bioactive compounds present opportunities for new discoveries and applications. Omics techniques, which include genomics, transcriptomics, proteomics, and metabolomics, contribute to the discovery of novel bioactive compounds produced by fungal endophytes with their potential applications. The omics techniques play a critical role in unraveling the complex interactions between fungal endophytes and their host plants, providing valuable insights into the molecular mechanisms and potential applications of these relationships. This review provides an overview of how omics techniques contribute to the study of fungal endophytes.

Voucher incentives to improve viral suppression among HIV-positive people who inject drugs and men who have sex with men in India: a cluster randomised trial.

BACKGROUND: Progress on HIV treatment outcomes for people who inject drugs and men who have sex with men in India has been slow compared with that in other populations. We assessed whether HIV treatment incentives would improve outcomes among these groups. METHODS: We did a matched-pair, cluster randomised trial in 16 sites (eight for people who inject drugs and eight for men who have sex with men) across 15 cities in India. We recruited cohorts of HIV-positive people who inject drugs or men who have sex with men who were antiretroviral therapy (ART)-naive or had less than 12 months of ART exposure. We randomised sites to provide incentives or usual care. At intervention sites, we provided incentive vouchers, which could be exchanged for food or household goods, for attending motivational interviewing sessions and timely appointments at government ART clinics. An ART-naive participant meeting all targets could earn the equivalent to 14 days' wages over 12 months. The primary outcome was survival with viral suppression at 12 months. We used an intention-to-treat analytic approach appropriate for matched-pair cluster randomised trials, adjusting for baseline viral suppression. This study was registered with ClinicalTrials.gov, NCT02969915, and is complete. FINDINGS: Between Oct 30, 2017, and Oct 12, 2018, we recruited 1200 people who inject drugs and 1114 men who have sex with men living with HIV. Among people who inject drugs, 154 (12·8%) identified as female gender and 1046 (87·2%) as male. The site median percentage of participants earning one or more incentives was 96·1% (IQR 93·7-98·1). At 12 months, HIV viral suppression was 31·9% (n=383) among people who inject drugs and 52·1% (n=580) among men who have sex with men. The incentive intervention was not associated with significantly improved survival with viral suppression compared with usual care (adjusted prevalence difference 9·6 percentage points, 95% CI -4·4 to 23·7). INTERPRETATION: Despite high intervention engagement, incentives did not improve survival with viral suppression among people who inject drugs and men who have sex with men living with HIV in India. The poor outcomes overall underscore the need for innovative, multilevel approaches to engage marginalised people living with HIV in low-income and middle-income settings. FUNDING: US National Institutes of Health, Elton John AIDS Foundation.

Acceptability, usability, and willingness to pay for HIV self-test kits distributed through community-based, PLHIV network-led and private practitioners models in India: Results from the STAR III Initiative.

INTRODUCTION: HIV self-testing (HIVST) has been shown to increase the uptake of HIV testing and help achieve the UNAIDS 95-95-95 targets. This study assessed the acceptability, usability (ease of use and result interpretation) and the willingness to pay for HIVST kits distributed through three distribution models, namely the community-based, PLHIV network-led and private practitioners models, in India. METHODS: This cross-sectional study was implemented across 14 states in India between September 2021 and June 2022. All participants could choose between blood-based or oral-fluid-based test kits. Participants were shown a test-kit usage demonstration video, and pre- and post-test counselling was provided for all. Participants were followed-up after testing, and if reported reactive, were further supported for linkage to confirmatory testing and antiretroviral therapy (ART) initiation. RESULTS: Among the 90,605 participants found eligible, 88,080 (97%) accepted an HIVST kit. Among the 87,976 who reported using an HIVST kit, 45,207 (51%) preferred a blood-based kit, and 42,120 (48%) reported testing for the first time. For future testing, 77,064 (88%) reported preferring HIVST over other HIV testing methods. Among those who used the kit, 83,308 (95%) found the kit easy to use, and 83,237 (95%) reported that the test results were easy to interpret. Among those who preferred HIVST for future use, 52,136 (69%) were willing to pay for the kit, with 35,854 (69%) of those willing to pay less than US$ 1.20. Only one instance of social harm was reported, with a participant reporting suicidal tendencies due to discord with their partner. Out of 328 participants (0.4%) who tested reactive with HIVST, 291 (89%) were linked to confirmatory testing; of these, 254 were confirmed HIV positive, and 216 (85%) successfully initiated ART. CONCLUSIONS: Overall, we report that nearly all participants were willing to accept HIVST, found the test kits easy to use and interpret, and about two-thirds were willing to pay for HIVST. Given the high levels of acceptance and the ability to reach a large proportion of first-time testers, HIVST in India could contribute to achieving the UNAIDS first 95 and ending the HIV epidemic.

Bioengineering of fungal endophytes through the CRISPR/Cas9 system.

The CRISPR/Cas9 system is a genome-editing tool that allows for precise and efficient modifications to the DNA of a cell. This technology can be used in endophytic fungi, which live within plants and can have beneficial effects on their host, making them important for agriculture. Using CRISPR/Cas9, researchers can introduce specific genetic changes into endophytic fungal genomes, allowing them to study the function of genes, improve their plant-growth-promoting properties, and create new, more beneficial endophytes. This system works by using the Cas9 protein, which acts as a pair of molecular scissors, to cut DNA at specific locations determined by a guide RNA. Once the DNA is cut, the cell's natural repair mechanisms can be used to insert or delete specific genes, allowing for precise editing of the fungal genome. This article discusses the mechanism and applications of CRISPR/Cas9 to fungal endophytes.

Industrial applications of fungal lipases: a review.

Fungal lipases (triacylglycerol acyl hydrolases EC 3.1.1.3) are significant industrial enzymes and have several applications in a number of industries and fields. Fungal lipases are found in several species of fungi and yeast. These enzymes are carboxylic acid esterases, categorized under the serine hydrolase family, and do not require any cofactor during the catalyzing of the reactions. It was also noticed that processes including the extraction and purification of lipases from fungi are comparatively easier and cheaper than other sources of lipases. In addition, fungal lipases have been classified into three chief classes, namely, GX, GGGX, and Y. Fungal lipases have applications not only in the hydrolysis of fats and oils (triglycerides) but are also involved in synthetic reactions such as esterification, acidolysis, alcoholysis, interesterification, and aminolysis. The production and activity of fungal lipases are highly affected by the carbon source, nitrogen source, temperature, pH, metal ions, surfactants, and moisture content. Therefore, fungal lipases have several industrial and biotechnological applications in many fields such as biodiesel production, ester synthesis, production of biodegradable biopolymers, formulations of cosmetics and personal care products, detergent manufacturing, degreasing of leather, pulp and paper production, textile industry, biosensor development, and drug formulations and as a diagnostic tool in the medical sector, biodegradation of esters, and bioremediation of wastewater. The immobilization of fungal lipases onto different carriers also helps in improving the catalytic activities and efficiencies of lipases by increasing thermal and ionic stability (in organic solvents, high pH, and temperature), being easy to recycle, and inducing the volume-specific loading of the enzyme onto the support, and thus, these features have proved to be appropriate for use as biocatalysts in different sectors.

Determinants of Turn-Around-Time for Early Infant Diagnosis of HIV Testing: Retrospective Analysis of National Level PCR Testing Data.

India has been implementing one of the biggest Early Infant Diagnosis (EID) of HIV intervention globally. The turn-around-time (TAT) for EID test is one of the major factors for success of the program. This study was to assess the turnaround time and its determinants. It is a mixed methods study with quantitative analysis of retrospective data (2013-2016) collected from all the 7 Early Infant Diagnosis testing laboratories (called as regional reference laboratories or RRLs) in India and qualitative component that can help explain the determinants of turn-around-time. The retrospective national level data available from the RRLs was analyzed to measure the turn-around-time from the receipt of samples to the dispatch of results and to understand the determinants for the same. The 3 components transport time, testing time, and dispatch time were also calculated. Transport time was analyzed state-wise and the testing time RRL wise to understand disparities, if any. Qualitative interviews with the RRL officials were conducted to understand the underlying determinants of TAT. The Median turn-around-time ranged between 29 and 53 days over the 4 years. Transport time was significantly higher for states without RRL (42 days) than those with RRL (27 days). Testing time varied from RRL to RRL and was associated with incomplete forms, inadequate samples, kits logistics, staff turnover, staff training, and instrument related issues. The TAT is high and can be potentially reduced with interventions, such as decentralization of RRLs; courier systems for sample transport; and ensuring adequate resources at the RRL level.

ExoDx prostate test as a predictor of outcomes of high-grade prostate cancer - an interim analysis.

BACKGROUND: Patient outcomes were assessed based on a pre-biopsy ExoDx Prostate (EPI) score at 2.5 years of the 5-year follow-up of ongoing prostate biopsy Decision Impact Trial of the ExoDx Prostate (IntelliScore). METHODS: Prospective, blinded, randomized, multisite clinical utility study was conducted from June 2017 to May 2018 (NCT03235687). Urine samples were collected from 1049 men (≥50 years old) with a PSA 2-10 ng/mL being considered for a prostate biopsy. Patients were randomized to EPI vs. standard of care (SOC). All had an EPI test, but only EPI arm received results during biopsy decision process. Clinical outcomes, time to biopsy and pathology were assessed among low (<15.6) or high (≥15.6) EPI scores. RESULTS: At 2.5 years, 833 patients had follow-up data. In the EPI arm, biopsy rates remained lower for low-risk EPI scores than high-risk EPI scores (44.6% vs 79.0%, p < 0.001), whereas biopsy rates were identical in SOC arm regardless of EPI score (59.6% vs 58.8%, p = 0.99). Also in the EPI arm, the average time from EPI testing to first biopsy was longer for low-risk EPI scores compared to high-risk EPI scores (216 vs. 69 days; p < 0.001). Similarly, the time to first biopsy was longer with EPI low-risk scores in EPI arm compared to EPI low-risk scores in SOC arm (216 vs 80 days; p < 0.001). At 2.5 years, patients with low-risk EPI scores from both arms had less HGPC than high-risk EPI score patients (7.9% vs 26.8%, p < 0.001) and the EPI arm found 21.8% more HGPC than the SOC arm. CONCLUSIONS: This follow-up analysis captures subsequent biopsy outcomes and demonstrates that men receiving EPI low-risk scores (<15.6) significantly defer the time to first biopsy and remain at a very low pathologic risk by 2.5-years after the initial study. The EPI test risk stratification identified low-risk patients that were not found with the SOC.

A protocol for feasibility of plasma based GeneXpert platform and Dried Blood Spot (DBS) based Abbott platform for HIV-1 viral load testing among the people living with HIV attending ART centers in India.

BACKGROUND: HIV-1 Viral load (VL) measures efficiency of the antiretroviral therapy (ART) after treatment initiation and helps to diagnose virological failures at an early stage. Current VL assays require sophisticated laboratory facilities. As well as there are other challenges pertaining to insufficient laboratory access, cold-chain management and sample transportation. Hence the number of HIV-1 VL testing laboratories is inadequate in the resource limited settings. The revised national tuberculosis elimination programme (NTEP) in India has developed a vast network of point of care (PoC) testing facilities for diagnosis of tuberculosis and several GeneXpert platforms are functional under this programme. Both the GeneXpert HIV-1 assay and HIV-1 Abbott real time assay are comparable and GeneXpert HIV-1 assay can be used as PoC for HIV-1 Viral load testing. Also, the dried blood spot (DBS) as a sample type has been considered as a good option for HIV-1 VL testing in hard to reach areas. This protocol is therefore developed to assess the feasibility of integrating HIV-1 VL testing among people living with HIV (PLHIV) attending ART centres using the two public health models under the current programme: 1. HIV-1 VL testing using GeneXpert platform and plasma as a sample type, and 2. HIV-1 VL testing using Abbott m2000 platform and DBS as a sample type. METHODS: This ethically approved feasibility study will be implemented at two moderate to high burden ART centres where VL testing facility is not available in the town. Under Model-1, arrangements will be made to carry out VL testing on the adjacent GeneXpert facility and under Model-2, DBS will be prepared on site and couriered to identified viral load testing laboratories. In order to assess the feasibility, data will be collected on pretested questionnaire pertaining to number of samples tested for VL testing, number of samples tested for tuberculosis (TB) diagnosis and the turnaround time (TAT). In-depth interviews will be conducted among the service providers at ART centre and different laboratories for addressing any issues regarding the model implementation. RESULTS: The proportion of PLHIV tested for VL at ART centres, total TAT for both models including TAT for sample transportation, sample testing and receipt of results as well as proportion of sample rejections and reasons for the same, correlation coefficient between DBS based and plasma based VL testing will be estimated using various statistical tools. CONCLUSION: If found promising, these public health approaches will be helpful for the policy makers and program implementation in scaling up HIV-1 viral load testing within India.