HIV epidemic among key populations in Nigeria: results of the integrated biological and behavioural surveillance survey (IBBSS), 2020-2021.

INTRODUCTION: Nigeria has the fastest-growing HIV epidemic in West and Central Africa and key populations (KPs) bear a higher burden of HIV. This integrated biological and behavioural surveillance survey was conducted among female sex workers (FSW), men who have sex with men (MSM), people who inject drugs (PWID) and transgender (TG) populations to understand the changing dynamics of HIV to improve HIV prevention efforts in Nigeria. METHODS: Using a cross-sectional design, data were collected between October and November 2020 in 12 states, from randomly selected KP members using multistage probability sampling. Behavioural data were collected using a structured questionnaire followed by three rapid HIV tests. The study was approved by ethical review boards in Nigeria and Canada and all ethical considerations including maintaining the privacy and confidentiality of all study subjects were followed. RESULTS: A total number of 17 975 KP members were interviewed, with a response rate of over 98.0%. A weighted HIV prevalence of 28.8% (95% CI 27.4% to 30.2%), 25.0% (95% CI 23.7% to 26.3%), 15.5% (95% CI 14.3% to 16.4%) and 10.9% (95% CI 9.9% to 11.8%) was found among TGs, MSMs, FSWs and PWIDs respectively. A high number of sex partners and consistent condom use were low for all types of KPs, especially with regular partners. Both MSM and TGs reported high rates of unprotected receptive anal intercourse ranging between 71.2% and 85.0%. Nearly 60.0% of PWID shared their used syringe with another PWID. Overall, 90.2% FSWs, 77.2% MSM, 81.9% TGs and 84.3% PWID were ever tested for HIV. CONCLUSION: This study highlights the progressing trends of HIV prevalence among all KPs in Nigeria. A focused prevention approach is needed to control the emerging epidemic among KPs who constitute the epicentre of the HIV epidemic in Nigeria.

Describing the effect of COVID-19 on sexual and healthcare-seeking behaviours of men who have sex with men in three counties in Kenya: a cross-sectional study.

BACKGROUND: While the COVID-19 pandemic disrupted HIV preventative services in sub-Saharan Africa, little is known about the specific impacts the pandemic has had on men who have sex with men (MSM) in Kenya. METHODS: Data were from an HIV self-testing intervention implemented in Kisumu, Mombasa and Kiambu counties in Kenya. Baseline data collection took place from May to July 2019, and endline in August-October 2020, coinciding with the lifting of some COVID-19 mitigation measures. Using endline data, this study characterised the impact the pandemic had on participants' risk behaviours, experience of violence and behaviours related to HIV. Logistic regression was used to understand factors related to changes in risk behaviours and experiences of violence; adjusted AORs (AORs) and 95% CIs are reported. RESULTS: Median age was 24 years (IQR: 21-27). Most respondents (93.9%) reported no change or a decrease in the number of sexual partners (median number of male sexual partners: 2, IQR: 2-4). Some participants reported an increase in alcohol (10%) and drug (16%) consumption, while 40% and 28% reported decreases in alcohol and drug consumption, respectively. Approximately 3% and 10% reported an increase in violence from intimate partners and police/authorities, respectively. Compared with those with primary education, those with post-secondary education were 60% less likely to report an increase in the number of male sexual partners per week (AOR: 0.4, 95% CI: 0.2 to 0.9), while those who were HIV positive were at twofold the odds of reporting an increase or sustained levels of violence from intimate partners (AOR: 2.0, 95% CI: 1.1 to 4.0). CONCLUSION: The results of this study demonstrate heterogeneity in participants' access to preventative HIV and clinical care services in Kenya after the onset of the COVID-19 epidemic. These results indicate the importance of responding to specific needs of MSM and adapting programmes during times of crisis.

Geographic and socioeconomic inequalities in the coverage of contraception in Uttar Pradesh, India.

BACKGROUND: Uttar Pradesh (UP) is the most populous state in India, with a historically lower level of family planning coverage than the national average. In recent decades, family planning coverage in UP has significantly increased, yet there are considerable geographic and socio-economic inequalities. METHODS: The data used for the study is derived from a cross-sectional quantitative survey of 12,200 currently married women conducted during December 2020-February 2021 in UP by the Technical Support Unit. Univariate and bivariate analyses were performed and equiplots were used to make visualizing inequalities easy. RESULTS: The findings of the study reveal significant variation in family planning coverage indicators amongst currently married women in reproductive ages by administrative divisions in UP. For instance, in the Jhansi division, it was 72.4%, while in Faizabad, it was 39.3%. Jhansi division experienced the highest modern contraceptive coverage with the lowest inequity compared to other divisions. However, the range of coverage within the division by Accredited Social Health Activist (ASHA) areas is 25% to 75%. In fact, for some ASHA areas in the Jhansi division, the family planning demand satisfied for modern contraception ranged from more than 85% to less than 22%. On the other hand, the Gonda division with the lowest coverage and lowest inequity for demand satisfied for modern contraception has some ASHA areas with less than 5% and some with more than 36%. The study also revealed intersectionality of education, wealth, place of residence and geographic divisions in identifying inequity patterns. For instance, in case of Mirzapur and Varanasi, the demand satisfied among the illiterates was 69% and the corresponding percentage for literates was 49%. With respect to place of residence, Basti division, where the coverage for modern contraception is extremely low, demand satisfied for modern contraceptive methods is 16.3% among rural residents compared to 57.9% in the case of urban residents. CONCLUSIONS: The findings showed inequality in the modern family planning methods coverage in UP in both best and worst performing divisions. The inequalities exist even in extremely small geographies such as ASHA areas. Within the geographies as well, the socio-economic inequalities persisted. These inequalities at multiple levels are important to consider for effective resource allocation and utilization.

A cross-sectional survey exploring HIV and HCV prevalence among men who purchase sex in Dnipro, Ukraine.

BACKGROUND: HIV programming in Ukraine largely targets "key population" groups. Men who purchase sex are not directly reached. The aim of our study was to explore the prevalence of sexually transmitted and blood-borne infections (STBBIs) among men who purchase sex from female sex workers. METHODS: Following geographic mapping and population size estimation at each "hotspot", we conducted a cross-sectional bio-behavioural survey with men who purchase sex between September 2017 and March 2018 in Dnipro, Ukraine. Eligibility criteria included purchasing sex services at a "hotspot" and being ≥ 18 years. Participants completed a structured questionnaire, followed by HIV/HCV rapid testing and a dried blood spot (DBS) sample collection for confirmatory serology. RESULTS: The study enrolled 370 participants. The median age was 32 (interquartile range [IQR] = 27-38) and the median age of first purchase of sexual services was 22 (IQR = 19-27). Over half (56%) of participants reported ever testing for HIV; four participants (2%, N = 206) reported having tested positive for HIV, with three out of the four reporting being on ART. Forty percent of participants had ever tested for HCV, with three (2%, N = 142) having ever tested positive for HCV. In DBS testing, nine participants (2.4%) tested positive for HIV and 24 (6.5%) tested positive for ever having an HCV infection. CONCLUSION: Prevalence of HIV and HCV in this population was high. Given high rates of study enrolment and testing, efforts should be made to reach men who purchase sex with expanded STBBI programming.

Quantifying the contribution of Fc-mediated effector functions to the antiviral activity of anti-HIV-1 IgG1 antibodies in vivo.

In combating viral infections, the Fab portion of an antibody could mediate virus neutralization, whereas Fc engagement of Fc-γ receptors (FcγRs) could mediate an array of effector functions. Evidence abounds that effector functions are important in controlling infections by influenza, Ebola, or HIV-1 in animal models. However, the relative contribution of virus neutralization versus effector functions to the overall antiviral activity of an antibody remains unknown. To address this fundamental question in immunology, we utilized our knowledge of HIV-1 dynamics to compare the kinetics of the viral load decline (ΔVL) in infected animals given a wild-type (WT) anti-HIV-1 immunoglobulin G1 (IgG1) versus those given a Fc-Null variant of the same antibody. In three independent experiments in HIV-1-infected humanized mice and one pivotal experiment in simian-human immunodeficiency virus (SHIV)-infected rhesus macaques, an earlier and sharper decline in viral load was consistently detected for the WT antibody. Quantifications of the observed differences indicate that Fc-mediated effector functions accounted for 25-45% of the total antiviral activity in these separate experiments. In this study, Fc-mediated effector functions have been quantified in vivo relative to the contribution of virus neutralization mediated by the Fab.

Understanding the rise in traditional contraceptive methods use in Uttar Pradesh, India.

BACKGROUND: The sustainable development goals (SDG) aim at satisfying three-fourths of family planning needs through modern contraceptive methods by 2030. However, the traditional methods (TM) of family planning use are on the rise, along with modern contraception in Uttar Pradesh (UP), the most populous Indian state. This study attempts to explore the dynamics of rising TM use in the state. METHODS: We used a state representative cross-sectional survey conducted among 12,200 Currently Married Women (CMW) aged 15-49 years during December 2020-February 2021 in UP. Using a multistage sampling technique, 508 primary sampling units (PSU) were selected. These PSU were ASHA areas in rural settings and Census Enumeration Blocks in urban settings. About 27 households from each PSU were randomly selected. All the eligible women within the selected households were interviewed. The survey also included the nearest public health facilities to understand the availability of family planning methods. Univariate and bivariate analyses were conducted. Appropriate sampling weights were applied. RESULTS: Overall, 33.9% of CMW were using any modern methods and 23.7% any TM (Rhythm and withdrawal) at the time of survey. The results show that while the modern method use has increased by 2.2 percentage points, the TM use increased by 9.9 percentage points compared to NFHS-4 (2015-16). The use of TM was almost same across women of different socio-demographic characteristics. Of 2921 current TM users, 80.7% started with TM and 78.3% expressed to continue with the same in future. No side effects (56.9%), easy to use (41.7%) and no cost incurred (38.0%) were the main reasons for the continuation of TM. TM use increased despite a significant increase (66.1 to 81.3%) in the availability of modern reversible methods and consistent availability of limiting methods (84.0%) in the nearest public health facilities. CONCLUSION: Initial contraceptive method was found to have significant implications for current contraceptive method choice and future preferences. Program should reach young and zero-parity women with modern method choices by leveraging front-line workers in rural UP. Community and facility platforms can also be engaged in providing modern method choices to women of other parities to increase modern contraceptive use further to achieve the SDG goals.

In Uttar Pradesh, the use of traditional methods of contraception is on the rise, observed similarly in many other Indian states in recent times. The emphasis on modern contraceptive methods and the rise and high prevalence of traditional method use in the state call for a systematic assessment to understand the dynamics such as patterns, prevalence and reasons for traditional method use for better family planning programming. Using a state representative cross-sectional survey data from Uttar Pradesh, we attempted to understand the dynamics of increasing traditional methods use. We found no significant variations in use of traditional methods by their socio-demographic characteristics. Not only that, most current traditional method users reported that their first method was a traditional method and an overwhelming proportion of women (4/5 traditional methods users) expressed to continue with the same method in future. Also the findings reveal that more than half of the traditional method users used the method consistently over the three-years calendar period. Among those who had unmet need at the time of survey, a considerable proportion of them intend to use traditional methods in future. This emphasized the importance of initial contraceptive method choice on current contraceptive use and future preference. Traditional methods use increased in the state despite a significant increase (66.1 to 81.3% during 2018 to 2021) in availability of modern reversible methods and consistent availability of limiting method (84.0%) in public health facilities.

Declining fertility and increasing use of traditional methods of family planning: a paradox in Uttar Pradesh, India?

Uttar Pradesh (UP), with more than 220 million people, is the most populous state in India. Despite a high unmet need for modern family planning methods, the state has experienced a substantial decline in fertility. India has also seen a decline during this period which can be attributed to the increased prevalence of modern methods of family planning, particularly female sterilisation, but in UP, the corresponding increase was marginal. At the same time, Traditional Family Planning Methods (TMs) increased significantly in UP in contrast to India, where it was marginal. The trends in UP raise questions about the drivers in fertility decline and question the conventional wisdom that fertility declines are driven by modern methods, and the paper aims to understand this paradox. Fertility trends and family planning practices in UP were analysed using data from different rounds of National Family Health Surveys (NFHS) and the two UP Family Planning Surveys conducted by the UP Technical Support Unit to understand whether the use of TMs played a role in the fertility decline. As per NFHS-4, the prevalence of TM in India (6%) was less than half that of UP (13%). The UP Family Planning Survey in 25 High Priority Districts estimated that 22% of women used TMs. The analysis also suggested that availability and accessibiility of modern contraceptives might have played a role in the increased use of TMs in UP. If there are still couples who make a choice in favour of TMs, they should be well informed about the risks associated with the use of traditional methods as higher failure rate is observed among TMs users.

Advancing Sexual Harassment Prevention and Elimination in the Sciences: "Every ... Health Organization Must Do Something Similar".

BACKGROUND: Sexual harassment is pervasive in science. A 2018 report found that the prevalence of sexual harassment in academia in the United States is 58%. An activity held at an international scientific congress was designed to advance sexual harassment prevention and elimination and empower binary and nonbinary persons at risk for harassment, discrimination, and violence. The objective is to describe the activity and outcomes to provide a promising model for other scientific communities. METHODS: A description of the plenary and key components as well as the data collection and analysis of selected outcomes are provided. RESULTS: Among 1338 congress participants from 61 countries, 526 (39%) attended the #MeToo plenary, and the majority engaged in some way during the plenary session. Engagement included standing for the pledge (~85%), participating in the question and answer session (n = 5), seeking counseling (n = 3), and/or providing written post-it comments (n = 96). Respondents to a postcongress survey (n = 388 [24% of all attendees]) ranked the plenary as number 1 among 14 congressional plenaries. In postanalysis, the written post-it comments were sorted into 14 themes within 6 domains, including: (1) emotional responses, (2) barriers to speaking out, (3) public health priorities, (4) reframing narratives about the issue, (5) allyship, and (6) moving the issue forward. CONCLUSIONS: Scientific organizations, agencies, and institutions have an important role to play in setting norms and changing enabling policies toward a zero-tolerance culture of sexual harassment. The activity presented offers a promising model for scientific communities with similar goals. The outcomes suggest that the plenary successfully engaged participants and had a measurable impact on the participants.

Delayed vaginal SHIV infection in VRC01 and anti-α4ß7 treated rhesus macaques.

VRC01 protects macaques from vaginal SHIV infection after a single high-dose challenge. Infusion of a simianized anti-α4ß7 mAb (Rh-α4ß7) just prior to, and during repeated vaginal exposures to SIVmac251 partially protected macaques from vaginal SIV infection and rescued CD4+ T cells. To investigate the impact of combining VRC01 and Rh-α4ß7 on SHIV infection, 3 groups of macaques were treated with a suboptimal dosing of VRC01 alone or in combination with Rh-α4ß7 or with control antibodies prior to the initiation of weekly vaginal exposures to a high dose (1000 TCID50) of SHIVAD8-EO. The combination Rh-α4ß7-VRC01 significantly delayed SHIVAD8-EO vaginal infection. Following infection, VRC01-Rh-α4ß7-treated macaques maintained higher CD4+ T cell counts and exhibited lower rectal SIV-DNA loads compared to controls. Interestingly, VRC01-Rh-α4ß7-treated macaques had fewer IL-17-producing cells in the blood and the gut during the acute phase of infection. Moreover, higher T cell responses to the V2-loop of the SHIVAD8-EO envelope in the VRC01-Rh-α4ß7 group inversely correlated with set point viremia. The combination of suboptimal amounts of VRC01 and Rh-α4ß7 delayed infection, altered antiviral immune responses and minimized CD4+ T cell loss. Further exploration of the effect of combining bNAbs with Rh-α4ß7 on SIV/HIV infection and antiviral immune responses is warranted and may lead to novel preventive and therapeutic strategies.

Programmatic mapping and size estimation of female sex workers, transgender sex workers and men who have sex with men in Istanbul and Ankara, Turkey.

OBJECTIVES: Despite a growing HIV threat, there is no definition and characterisation of key populations (KPs), who could be the major drivers of the epidemic in Turkey. We used programmatic mapping to identify locations where KPs congregate, estimate their numbers and understand their operational dynamics to develop appropriate HIV programme implementation strategies. METHODS: Female and transgender sex workers (FSWs and TGSWs), and men who have sex with men (MSM) were studied in Istanbul and Ankara. Within each district, hot spots were identified by interviewing key informants and a crude spot list in each district was developed. The spot validation process was led by KP members who facilitated spot access and interviews of KPs associated with that spot. Final estimates were derived by aggregating the estimated number of KPs at all spots, which was adjusted for the proportion of KPs who visit multiple spots, and for the proportion of KPs who do not visit spots. RESULTS: FSWs were the largest KP identified in Istanbul with an estimate of 30 447 (5.8/1000 women), followed by 15 780 TGSWs (2.9/1000 men) and 11 656 MSM (2.1/1000). The corresponding numbers in Ankara were 9945 FSWs (5.2/1000 women), 1770 TGSWs (1/1000 men) and 5018 MSM (2.5/1000 men). Each KP had unique typologies based on the way they find and interact with sex partners. MSM were mostly hidden and a higher proportion operated through internet and phone-based applications. Night time was the peak time with Friday, Saturday and Sunday being the peak days of activity in both Istanbul and Ankara. CONCLUSIONS: This study has highlighted the presence of a substantial number of FSWs, TGSW and MSM in Istanbul and Ankara. The information obtained from this study can be used to set priorities for resource allocation and provide HIV prevention services where coverage could be the highest.

Comparing the Ecological Niches of Chlamydial and Gonococcal Infections in Winnipeg, Canada: 2007-2016.

BACKGROUND: Previous studies have shown substantial differences in geographic clustering of sexually transmitted infections (STI), such as chlamydia (CT) and gonorrhea (NG), conditional on epidemic phase. Chlamydia and NG have recently shown resurgent epidemiology in the northern hemisphere. This study describes the recent epidemiology of CT and NG in Winnipeg, Canada, combining traditional surveillance tools with place-based analyses, and comparing the ecological niches of CT and NG, in the context of their evolving epidemiology. METHODS: Data were collected as part of routine public health surveillance between 2007 and 2016. Secular trends for CT and NG, and CT/NG coinfection were examined. Gini coefficients and population attributable fractions explored the distribution, and concentration of infections over time and space. RESULTS: Rates of CT increased from 394.9/100,000 population to 476.2/100,000 population from 2007 to 2016. Gonorrhea rates increased from 78.0/100,000 population to 143.5/100,000 population during the same period. Each pathogen had its own ecological niche: CT was widespread geographically and socio-demographically, while NG was clustered in Winnipeg's inner-core. CT/NG co-infections had the narrowest space and age distribution. NG was shown to be undergoing a growth phase, with clear signs of geographic dispersion. The expansion of NG resembled the geographic distribution of CT. CONCLUSIONS: We demonstrated that NG was experiencing a growth phase, confirming theoretical predictions of geographic dispersion during a growth phase. During this phase, NG occupied similar geographic spaces as CT. Knowledge of different ecological niches could lead to better targeting of resources for subpopulations vulnerable to STIs.

Suicidality among gender minorities in Karnataka, South India.

BACKGROUND: It is argued that Indian gender minorities displayed differential mental health problems and suicide attempts. Hence, the study was intended to understand the prevalence of anxiety, depression and suicidality among this group, specifically those living in a metropolitan city in South India. METHODS: The data was generated from a cross-sectional study that employed a structured questionnaire to collect information about experiences of anxiety, depression and suicidal behavior among gender-diverse individuals in Bangalore, the capital city of Karnataka state. The study used stratified simple random sampling of eligible individuals who were 18 years of age and older and who were enrolled in an HIV prevention program implemented for gender-diverse individuals run by the Karnataka Health Promotion Trust and the University of Manitoba at the time of the study (2012). Bivariate and multivariate analyses were used to assess the relative contribution of various factors that affect suicide ideation or actual attempts among the gender diverse participants. RESULTS: Results showed that 62% whose main source of income was Basti (socially sanctioned practice of begging), 52% of Hijras, 56% who lived with their Gurus, 58% who were not happy with their physical appearance, 55% who consumed alcohol daily, and 63% who experienced high depression had ever thought of or attempted suicide in the month prior to the survey. However, multivariate analysis showed that respondents who were not happy with their physical appearance and thought of changing it had significantly higher odds (AOR = 2.861; CI 1.468,5.576; p = 0.002) of either having thoughts that it was better being dead or wished they died. Similarly, those who experienced high depression, their odds of either having had thoughts of or having attempted suicide increased by three times (AOR = 3.997; CI 1.976, 8.071; p < 0.000). CONCLUSIONS: It is observed that a high percentage of gender minorities had attempted suicide or thought of suicide during the month preceding the data collection. The findings bring new insights on the proximate determinant of physical appearance on the suicidality of gender minorities assigned male at birth and appropriate to account for this while addressing the mental health issues.

Association of identification of facility and transportation for childbirth with institutional delivery in high priority districts of Uttar Pradesh, India.

BACKGROUND: Timely and skilled care is key to reducing maternal and neonatal mortality. Birth preparedness involves preparation for safe childbirth during the antenatal period to reach the appropriate health facility for ensuring safe delivery. Hence, understanding the factors associated with birth preparedness and its significance for safe delivery is essential. This paper aims to assess the levels of birth preparedness, its determinants and association with institutional deliveries in High Priority Districts of Uttar Pradesh, India. METHODS: A community-based cross-sectional survey was conducted between June-October 2018 in the rural areas of 25 high priority districts of Uttar Pradesh, India. Simple random sampling was used to select 40 blocks among 294 blocks in 25 districts and 2646 primary sampling units within the selected blocks. The survey interviewed 9458 women who had a delivery 2 months prior to the survey. Descriptive statistics were included to characterize the study population. Multivariable logistic regression analyses were performed to identify the determinants of birth preparedness and to examine the association of birth preparedness with institutional delivery. RESULTS: Among the 9458 respondents, 61.8% had birth preparedness (both facility and transportation identified) and 79.1% delivered in a health facility. Women in other caste category (aOR = 1.24, CI 1.06-1.45) and those with 10 or more years of education (aOR = 1.68, CI 1.46-1.92) were more likely to have birth preparedness. Antenatal care (ANC) service uptake related factors like early registration for ANC (aOR = 1.14, CI 1.04-1.25) and three or more front line worker contacts (aOR = 1.61, CI 1.46-1.79) were also found to be significantly associated with birth preparedness. The adjusted multivariate model showed that those who identified both facility and transport were seven times more likely to undergo delivery in a health facility (aOR = 7.00, CI 6.07-8.08). CONCLUSION: The results indicate the need for focussing on marginalized groups for improving birth preparedness. Increasing ANC registration in the first trimester of pregnancy, improving frontline worker contact, and optimum utilization of antenatal care check-ups for effective counselling on birth preparedness along with system level improvements could improve birth preparedness and consequently institutional delivery rates in Uttar Pradesh, India.

Leaving no one behind? An equity analysis of the HIV care cascade among a cohort of people living with HIV in Manitoba, Canada.

BACKGROUND: Manitoba is a central Canadian province with annual rates of new HIV infections consistently higher than the Canadian average. National surveillance statistics and data from the provincial HIV care program suggest that epidemiological heterogeneity exists across Manitoba. New HIV cases are disproportionately reported among females, Indigenous-identifying individuals, and those with a history of injection drug use. Given the heterogeneity in acquisition, it is of interest to understand whether this translates into inequalities in HIV care across Manitoba. METHODS: A sample of 703 participants from a clinical cohort of people living with HIV in Manitoba, with data current to the end of 2017, was used to conduct cross-sectional, disaggregated analyses of the HIV care cascade to identify heterogeneity in service coverage and clinical outcomes among different groups receiving HIV care in Manitoba. Equiplots are used to identify and visualize inequalities across the cascade. Exploratory multivariable logistic regression models quantify associations between equity variables (age, sex, geography, ethnicity, immigration status, exposure category) and progression along the cascade. Adjusted odds ratios (AOR) and 95% confidence intervals (95%CI) are reported. RESULTS: Equity analyses highlight inequalities in engagement in and coverage of HIV-related health services among cohort participants. Equiplots illustrate that the proportion of participants in each cascade step is greater for those who are older, white, non-immigrants, and report no history of injection drug use. Compared to those living in Winnipeg, participants in eastern Manitoba have greater odds of achieving virologic suppression (AOR[95%CI] = 3.8[1.3-11.2]). The odds of Indigenous participants being virologically suppressed is half that of white participants (AOR[95%CI] = 0.5[0.3-0.7]), whereas African/Caribbean/Black participants are significantly less likely than white participants to be in care and retained in care (AOR[95%CI] = 0.3[0.2-0.7] and 0.4[0.2-0.9], respectively). CONCLUSIONS: Inequalities exist across the cascade for different groups of Manitobans living with HIV; equiplots are an innovative method for visualizing these inequalities. Alongside future research aiming to understand why inequalities exist across the cascade in Manitoba, our equity analyses can generate hypotheses and provide evidence to inform patient-centred care plans that meet the needs of diverse client subgroups and advocate for policy changes that facilitate more equitable HIV care across the province.

Establishing evidence-based decision-making mechanism in a health eco-system and its linkages with health service coverage in 25 high-priority districts of Uttar Pradesh, India.

BACKGROUND: Achievement of successful health outcomes depends on evidence-based programming and implementation of effective health interventions. Routine Health Management Information System is one of the most valuable data sets to support evidence-based programming, however, evidence on systemic use of routine monitoring data for problem-solving and improving health outcomes remain negligible. We attempt to understand the effects of systematic evidence-based review mechanism on improving health outcomes in Uttar Pradesh, India. METHODS: Data comes from decision-tracking system and routine health management information system for period Nov-2017 to Mar-2019 covering 6963 health facilities across 25 high-priority districts of the state. Decision-tracking data captured pattern of decisions taken, actions planned and completed, while the latter one provided information on service coverage outcomes over time. Three service coverage indicators, namely, pregnant women receiving 4 or more times ANC and haemoglobin testing during pregnancy, delivered at the health facility, and receive post-partum care within 48 h of delivery were used as outcomes. Univariate and bivariate analyses were conducted. RESULTS: Total 412 decisions were taken during the study reference period and a majority were related to ante-natal care services (31%) followed by delivery (16%) and post-natal services (16%). About 21% decisions-taken were focused on improving data quality. By 1 year, 67% of actions planned based on these decisions were completed, 26% were in progress, and the remaining 7% were not completed. We found that, over a year, districts witnessing > 20 percentage-point increase in outcomes were also the districts with significantly higher action completion rates (> 80%) compared to the districts with < 10 percentage-point increase in outcomes having completion of action plans around 50-70%. CONCLUSIONS: Findings revealed a significantly higher improvement in coverage outcomes among the districts which used routine health management data to conduct monthly review meetings and had high actions completion rates. A data-based review-mechanisms could specifically identify programmatic gaps in service delivery leading to strategic decision making by district authorities to bridge the programmatic gaps. Going forward, establishing systematic evidence-based review platforms can be an important strategy to improve health outcomes and promote the use of routine health monitoring system data in any setting.

In vivo inhibition of tryptophan catabolism reorganizes the tuberculoma and augments immune-mediated control of Mycobacterium tuberculosis.

Mycobacterium tuberculosis continues to cause devastating levels of mortality due to tuberculosis (TB). The failure to control TB stems from an incomplete understanding of the highly specialized strategies that M. tuberculosis utilizes to modulate host immunity and thereby persist in host lungs. Here, we show that M. tuberculosis induced the expression of indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan catabolism, in macrophages and in the lungs of animals (mice and macaque) with active disease. In a macaque model of inhalation TB, suppression of IDO activity reduced bacterial burden, pathology, and clinical signs of TB disease, leading to increased host survival. This increased protection was accompanied by increased lung T cell proliferation, induction of inducible bronchus-associated lymphoid tissue and correlates of bacterial killing, reduced checkpoint signaling, and the relocation of effector T cells to the center of the granulomata. The enhanced killing of M. tuberculosis in macrophages in vivo by CD4+ T cells was also replicated in vitro, in cocultures of macaque macrophages and CD4+ T cells. Collectively, these results suggest that there exists a potential for using IDO inhibition as an effective and clinically relevant host-directed therapy for TB.

Once-Weekly Oral Dosing of MK-8591 Protects Male Rhesus Macaques From Intrarectal Challenge With SHIV109CP3.

BACKGROUND: MK-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine [EFdA]) is a novel reverse transcriptase-translocation inhibitor. METHODS: We assessed MK-8591 as preexposure prophylaxis in the rhesus macaque model of intrarectal challenge with simian/human immunodeficiency virus (SHIV). In study 1, 8 rhesus macaques received 3.9 mg/kg of MK-8591 orally on day 0 and once weekly for the next 14 weeks. Eight controls were treated with vehicle. All rhesus macaques were challenged with SHIV109CP3 on day 6 and weekly for up to 12 challenges or until infection was confirmed. The dose of MK-8591 was reduced to 1.3 and 0.43 mg/kg/week in study 2 and further to 0.1 and 0.025 mg/kg/week in study 3. In studies 2 and 3, each dose was given up to 6 times once weekly, and animals were challenged 4 times once weekly with SHIV109CP3. RESULTS: Control macaques were infected after a median of 1 challenge (range, 1-4 challenges). All treated animals in studies 1 and 2 were protected, consistent with a 41.5-fold lower risk of infection (P < .0001, by the log-rank test). In study 3, at a 0.1-mg/kg dose, 2 rhesus macaques became infected, consistent with a 7.2-fold lower risk of infection (P = .0003, by the log-rank test). The 0.025-mg/kg dose offered no protection. CONCLUSIONS: These data support MK-8591's potential as a preexposure prophylaxis agent.

Nanoscale Probing of Liposome Encapsulating Drug Nanocrystal Using Atomic Force Microscopy-Infrared Spectroscopy.

Use of liposomes encapsulating drug nanocrystals for the treatment of diseases like cancer and pulmonary infections is gaining attention. The potential therapeutic benefit of these engineered formulations relies on maintaining the physical integrity of the liposomes and the stability of the encapsulated drug. With the significant advancement in the microscopic and analytical techniques, analysis of the size and size distribution of these nanosized vesicles is possible. However, due to the limited spatial resolution of conventional vibrational spectroscopy techniques, the chemical composition of individual nanosized liposome cannot be resolved. To address this limitation, we applied atomic force microscopy infrared spectroscopy (AFM-IR) to assess the chemical composition of individual liposomes encapsulating ciprofloxacin in dissolved and nanocrystalline form. Spatially resolved AFM-IR spectra acquired from individual liposomes confirmed the presence of peaks related to N-H bending vibration, C-N stretching and symmetric, and asymmetric vibration of the carboxyl group present in the ciprofloxacin. Our results further demonstrated the effectiveness of AFM-IR in differentiating the liposome containing ciprofloxacin in dissolved or nanocrystalline form. Spectra acquired from dissolved ciprofloxacin had peaks related to the ionised carboxyl group, i.e., at 1576 and 1392 cm-1, which were either absent or far weaker in intensity in the spectra of liposomal sample containing ciprofloxacin nanocrystals. These findings are highly significant for pharmaceutical scientists to ascertain the stability and physicochemical composition of individual liposomes and will facilitate the design and development of liposomes with greater therapeutic benefits.

Trio housing of adult male rhesus macaques (Macaca mulatta): Methodology and outcome predictors.

BACKGROUND: This study evaluated the feasibility of trio housing caged adult male rhesus macaques and attempted to identify outcome predictors for trio housing formation and its intermediary introduction steps. METHODS: Subjects were familiarized consecutively to each potential group member via protected contact prior to introduction into the trio. Seven trios were attempted, involving 18 males, with three males attempted in two different trios. RESULTS: One group was deemed successful, with a tenure of 51 days. Five were disbanded within minutes, and one was deemed unsuccessful the following morning. Two males sustained wounds requiring veterinary care over the course of the study. Outcome of the protected contact phase was predicted by age and temperament disparities as well as initial behavior. CONCLUSIONS: While outcomes were poor, it suggests that attempts can be made relatively safely, and alternative introduction strategies should be explored to increase the feasibility of trio housing for adult males.

Integrin α4ß7 Blockade Preferentially Impacts CCR6+ Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques.

Infusion of a simianized anti-α4ß7 mAb (Rh-α4ß7) just before and following SIV infection protected rhesus macaques from developing AIDS and partially from vaginal SIV acquisition. Recently, short-term treatment with Rh-α4ß7 in combination with cART was found to lead to prolonged viral suppression after withdrawal of all therapeutic interventions. The humanized form of Rh-α4ß7, vedolizumab, is a highly effective treatment for inflammatory bowel disease. To clarify the mechanism of action of Rh-α4ß7, naive macaques were infused with Rh-α4ß7 and sampled in blood and tissues before and after treatment to monitor several immune cell subsets. In blood, Rh-α4ß7 increased the CD4+ and CD8+ T cell counts, but not B cell counts, and preferentially increased CCR6+ subsets while decreasing CD103+ and CD69+ lymphocytes. In mucosal tissues, surprisingly, Rh-α4ß7 did not impact integrin α4+ cells, but decreased the frequencies of CCR6+ and CD69+ CD4+ T cells and, in the gut, Rh-α4ß7 transiently decreased the frequency of memory and IgA+ B cells. In summary, even in the absence of inflammation, Rh-α4ß7 impacted selected immune cell subsets in different tissues. These data provide new insights into the mechanisms by which Rh-α4ß7 may mediate its effect in SIV-infected macaques with implications for understanding the effect of treatment with vedolizumab in patients with inflammatory bowel disease.