Engaging transgender women in HIV research in South Africa.

The Botshelo Ba Trans study was the first HIV bio-behavioral survey conducted with transgender women in South Africa. Engaging research with marginalized communities requires clear points of entry, reference points for understanding the internal culture, and establishing trust and understanding. The community-based participatory research approach guided the development and implementation of this study. We conducted a rapid qualitative and pre-surveillance formative assessment between August 2017 to January 2018 and a bio-behavioral survey between July 2018 and March 2019. At the start, a Steering Committee, comprising primarily of transgender women, was established and subsequently provided substantial input into the mixed methods study conducted in Buffalo City, Cape Town, and Johannesburg. Key to the study's success was building trust and establishing ownership of the survey by transgender women recognized as expert knowledge holders. Thus, a community-based participatory research-informed approach enhanced the validity of the data and ensured that we addressed relevant issues.

The HIV care continuum for sexually active transgender women in three metropolitan municipalities in South Africa: findings from a biobehavioural survey 2018-19.

BACKGROUND: Despite high HIV prevalence in transgender women in sub-Saharan Africa, to our knowledge no study presents data across the HIV care continuum for this population in the region. The aim of this study was to estimate HIV prevalence and present data to develop the HIV care continuum indicators for transgender women in three South African metropolitan municipalities. METHODS: Biobehavioural survey data were collected among sexually active transgender women in the metropolitan municipalities of Johannesburg, Buffalo City, and Cape Town, South Africa. Transgender women (aged ≥18 years, self-reporting consensual sex with a man in the 6 months before the survey) were recruited using respondent-driven sampling (RDS). An interviewer-administered questionnaire was used to determine awareness of HIV status; blood specimens were collected on dried blood spots to test for HIV antibodies, antiretroviral treatment (ART) exposure, and viral load suppression. Population-based estimates of HIV 95-95-95 cascade indicators were derived by use of individualised RDS weights with RDS Analyst software. Multivariate stepwise backward logistic regression modelling was used to determine factors associated with each cascade indicator. All eligible participants were included in the final analysis. FINDINGS: Between July 26, 2018, and March 15, 2019, we enrolled 887 sexually active transgender women: 323 in Johannesburg, 305 in Buffalo City, and 259 in Cape Town. HIV prevalence was highest in Johannesburg where 229 (74·1%) of 309 tests were positive (weighted prevalence estimate 63·3%, 95% CI 55·5-70·5), followed by Buffalo City where 121 (43·7%) of 277 were positive (46·1%, 38·7-53·6), and then Cape Town where 122 (48·4%) of 252 were positive (45·6%, 36·7-54·7). In Johannesburg, an estimated 54·2% (95% CI 45·8-62·4) of transgender women with HIV knew their positive status, in Cape Town this was 24·2% (15·4-35·8), and in Buffalo City this was 39·5% (27·1-53·4). Among those who knew their status, 82·1% (73·3-88·5) in Johannesburg, 78·2% (57·9-90·3) in Cape Town, and 64·7% (45·2-80·2) in Buffalo City were on ART. Of those on ART, 34·4% (27·2-42·4) in Johannesburg, 41·2% (30·7-52·6) in Cape Town, and 55·0% (40·7-68·4) in Buffalo City were virally suppressed. INTERPRETATION: Innovative strategies are needed to inform efforts to diagnose and to treat transgender women living with HIV promptly to achieve viral load suppression. Differentiated HIV services tailored to transgender women of race groups other than Black South African, and those with low education attainment and low outreach exposure, innovative testing, and adherence strategies should be developed to improve the HIV cascade for South African transgender women. FUNDING: The US President's Emergency Plan For AIDS Relief and US Centers for Disease Control and Prevention.

Core competencies in critical care for general medical practitioners in South Africa: A Delphi study.

Background: Despite a high burden of disease that requires critical care services, there are a limited number of intensivists in South Africa (SA). Medical practitioners at district and regional public sector hospitals frequently manage critically ill patients in the absence of intensivists, despite these medical practitioners having had minimal exposure to critical care during their undergraduate training. Objectives: To identify core competencies in critical care for medical practitioners who provide critical care services at public sector hospitals in SA where intensivists are not available to direct patient management. Methods: A preliminary list of core competencies in critical care was compiled. Thereafter, 13 national and international experts were requested to achieve consensus on a final list of core competencies that are required for critical care by medical practitioners, using a modified Delphi process. Results: A final list of 153 core competencies in critical care was identified. Conclusion: The core competencies identified by this study could assist in developing training programmes for medical practitioners to improve the quality of critical care services provided at district and regional hospitals in SA. Contribution of the study: The study provides consensus on a list of core competencies in critical care that non-intensivist medical practitioners managing critically ill patients in healthcare settings in South Africa, especially where intensivists are not readily available, should have. The list can form the core content of training programmes aimed at improving critical care competence of general medical practitioners, and in this way hopefully improve the overall outcomes of critically ill patients in South Africa.

Differentiated HIV services for transgender people in four South African districts: population characteristics and HIV care cascade.

INTRODUCTION: Transgender people in South Africa are disproportionately affected by HIV, discrimination and stigma. Access to healthcare and health outcomes are poor. Although integrating gender-affirming healthcare with differentiated HIV prevention, care and treatment services has shown improvement in HIV service uptake and health outcomes among transgender people, evidence is lacking on the implementation of differentiated service delivery models in southern Africa. This article describes a differentiated service delivery model across four South African sites and transgender individuals who access these services. We assess whether hormone therapy (HT) is associated with continued use of pre-exposure prophylaxis (PrEP) and viral load suppression. METHODS: In 2019, differentiated healthcare centres for transgender individuals opened in four South African districts, providing gender-affirming healthcare and HIV services at a primary healthcare level. Routine programme data were collected between October 2019 and June 2021. Descriptive statistics summarized patient characteristics and engagement with HIV prevention and treatment services. We conducted a multivariate logistic regression analysis to determine whether HT was associated with viral load suppression and PrEP continued use. RESULTS: In the review period, we reached 5636 transgender individuals through peer outreach services; 86% (4829/5636) of them accepted an HIV test and 62% (3535/5636) were linked to clinical services. Among these, 89% (3130/3535) were transgender women, 5% (192/3535) were transgender men and 6% (213/3535) were gender non-conforming individuals. Of those who received an HIV test, 14% (687/4829) tested positive and 91% of those initiated antiretroviral treatment. Viral load suppression was 75% in this cohort. PrEP was accepted by 28% (1165/4142) of those who tested negative. Five percent (161/3535) reported ever receiving HT through the public healthcare system. Service users who received HT were three-fold more likely to achieve viral load suppression. We did not find any association between HT and continued use of PrEP. CONCLUSIONS: A differentiated HIV and gender-affirming service delivery model at a primary healthcare level is feasible and can enhance service access in South Africa. HT can improve HIV clinical outcomes for transgender people. As trust is established between the providers and population, uptake of HIV testing and related services may increase further.

High-throughput nanofluidic real-time PCR to discriminate Pneumococcal Conjugate Vaccine (PCV)-associated serogroups 6, 18, and 22 to serotypes using modified oligonucleotides.

Current real-time high-throughput Polymerase Chain Reaction (qPCR) methods do not distinguish serotypes 6A from 6B, 18C from 18A/B and 22F from 22A. We established a nanofluidic real-time PCR (Fluidigm) for serotyping that included Dual-Priming-Oligonucleotides (DPO), a Locked-Nucleic-Acid (LNA) probe and TaqMan assay-sets for high-throughput serotyping. The designed assay-sets target capsular gene wciP in serogroup 6, wciX and wxcM in serogroup 18, and wcwA in serogroup 22. An algorithm combining results from published assay-sets (6A/B/C/D; 6C/D; 18A/B/C; 22A/F) and designed assay-sets for 6A/C; 18B/C/F; 18C/F, 18F and 22F was validated through blind analysis of 1973 archived clinical samples collected from South African children ≤ 5-years-old (2009-2011), previously serotyped with the culture-based Quellung method. All assay-sets were efficient (92-101%), had low variation between replicates (R2 > 0.98), and were able to detect targets at a limit of detection (LOD) of < 100 Colony-Forming-Units (CFU)/mL of sample. There was high concordance (Kappa = 0.73-0.92); sensitivity (85-100%) and specificity (96-100%) for Fluidigm compared with Quellung for serotyping 6A; 6B; 6C; 18C and 22F. Fluidigm distinguishes vaccine-serotypes 6A, 6B, 18C, next-generation PCV-serotype 22F and non-vaccine-serotypes 6C, 6D, 18A, 18B, 18F and 22A. Discriminating single serotypes is important for assessing serotype replacement and the impact of PCVs on vaccine- and non-vaccine serotypes.

Peer- and community-led responses to HIV: A scoping review.

INTRODUCTION: In June 2021, United Nations (UN) Member States committed to ambitious targets for scaling up community-led responses by 2025 toward meeting the goals of ending the AIDS epidemic by 2030. These targets build on UN Member States 2016 commitments to ensure that 30% of HIV testing and treatment programmes are community-led by 2030. At its current pace, the world is not likely to meet these nor other global HIV targets, as evidenced by current epidemiologic trends. The COVID-19 pandemic threatens to further slow momentum made to date. The purpose of this paper is to review available evidence on the comparative advantages of community-led HIV responses that can better inform policy making towards getting the world back on track. METHODS: We conducted a scoping review to gather available evidence on peer- and community-led HIV responses. Using UNAIDS' definition of 'community-led' and following PRISMA guidelines, we searched peer-reviewed literature published from January 1982 through September 2020. We limited our search to articles reporting findings from randomized controlled trials as well as from quasi-experimental, prospective, pre/post-test evaluation, and cross-sectional study designs. The overall goals of this scoping review were to gather available evidence on community-led responses and their impact on HIV outcomes, and to identify key concepts that can be used to quickly inform policy, practice, and research. FINDINGS: Our initial search yielded 279 records. After screening for relevance and conducting cross-validation, 48 articles were selected. Most studies took place in the global south (n = 27) and a third (n = 17) involved youth. Sixty-five percent of articles (n = 31) described the comparative advantage of peer- and community-led direct services, e.g., prevention and education (n = 23) testing, care, and treatment programs (n = 8). We identified more than 40 beneficial outcomes linked to a range of peer- and community-led HIV activities. They include improved HIV-related knowledge, attitudes, intentions, self-efficacy, risk behaviours, risk appraisals, health literacy, adherence, and viral suppression. Ten studies reported improvements in HIV service access, quality, linkage, utilization, and retention resulting from peer- or community-led programs or initiatives. Three studies reported structural level changes, including positive influences on clinic wait times, treatment stockouts, service coverage, and exclusionary practices. CONCLUSIONS AND RECOMMENDATIONS: Findings from our scoping review underscore the comparative advantage of peer- and community-led HIV responses. Specifically, the evidence from the published literature leads us to recommend, where possible, that prevention programs, especially those intended for people living with and disproportionately affected by HIV, be peer- and community-led. In addition, treatment services should strive to integrate specific peer- and community-led components informed by differentiated care models. Future research is needed and should focus on generating additional quantitative evidence on cost effectiveness and on the synergistic effects of bundling two or more peer- and community-led interventions.

Self-administration of gender-affirming hormones: a systematic review of effectiveness, cost, and values and preferences of end-users and health workers.

Self-administration of quality gender-affirming hormones is one approach to expanding access to hormone therapy for individuals seeking secondary sex characteristics more aligned with their gender identity or expression and can be empowering when provided within safe, supportive health systems. To inform World Health Organization guidelines on self-care interventions, we systematically reviewed the evidence for self-administration compared to health worker-administration of gender-affirming hormones. We conducted a comprehensive search for peer-reviewed articles and conference abstracts that addressed effectiveness, values and preferences, and cost considerations. Data were extracted in duplicate using standardised forms. Of 3792 unique references, five values and preferences articles were included; no studies met the criteria for the effectiveness or cost reviews. All values and preferences studies focused on self-administration of unprescribed hormones, not prescribed hormones within a supportive health system. Four studies from the U.S. (N = 2), Brazil (N = 1), and the U.K. (N = 1) found that individuals seeking gender-affirming hormone therapy may self-manage due to challenges finding knowledgeable and non-stigmatising health workers, lack of access to appropriate services, exclusion, and discomfort with health workers, cost, and desire for a faster transition. One study from Thailand found health worker perspectives were shaped by restrictive legislation, few transgender-specific services or guidelines, inappropriate communication with health workers, and medical knowledge gaps. There is limited literature on self-administration of gender-affirming hormone therapy. Principles of gender equality and human rights in the delivery of quality gender-affirming hormones are critical to expand access to this important intervention and reduce discrimination based on gender identity.

A new protocol for monitoring operational outcomes of environmental management in commercial forestry plantations.

Environmental degradation is a global phenomenon with a high likelihood of influencing human quality of life. Effective management responses are needed to achieve societal goals of sustainability. We develop here a new monitoring protocol (Management Check: MATCH) that comprehensively evaluates management outcomes at the operational level. Using the Driver-Pressure-State-Impact-Response (DPSIR) framework, we identified pressures influencing ecosystem integrity inside conservation corridors and commercial compartments of a timber production landscape mosaic. They were 1) domestic livestock grazing (the only exogenous pressure), 2) fire management, 3) invasive alien plants (IAPs), and potential soil erosion from two sources: 4) roads, and 5) harvested timber compartments. We assessed the effects of these on wetland and stream buffers. Environmental incidents accounted for more serious management issues (e.g. oil spills). Management responses were systematically unpacked into point-form questions, which formed the building blocks of our monitoring protocol. We assessed management in twelve plantations in KwaZulu-Natal, South Africa. Answers were compared with Best Operational Practice (BOP), and reworked into a Weighted Index of Compliance (WIC) per section. We found that there was poor management of livestock grazing, but good management of IAPs, roads, and timber compartments. Management of wetland and stream buffers was very good. Fire management presented problems linked to lack of direct effects, measurable at the spatial and temporal scales of operations. We discuss operational outcomes within their respective legislative frameworks, and suggest ways of improving management operations, where needed. MATCH is the first monitoring protocol to comprehensively assess environmental management of commercial forestry at the operational level, and to clearly translate operational activities into measurable progress towards strategic goals. In doing so, MATCH breaks down silos and builds bridges for efficient environmental management in dynamic socio-ecological systems. Moreover, the principles developed here can be applied to build tools that help manage major risks in other economic sectors too. Overall, MATCH strengthened strategic and informed action, which is necessary at multiple levels of an organization, to combat major societal risks, such as environmental degradation.

PrEP awareness and engagement among transgender women in South Africa: a cross-sectional, mixed methods study.

BACKGROUND: The South African national HIV plan recommends pre-exposure prophylaxis (PrEP) for transgender women, whose HIV prevalence estimates are as high as 25% in sub-Saharan Africa. The aim of this study was to explore PrEP awareness, uptake, and willingness, as well as associated barriers and facilitators, in order to inform PrEP implementation efforts with transgender women in South Africa. METHODS: Using a community-engaged, convergent parallel mixed methods design, trained local transgender women data collectors recruited 213 transgender women participants (aged >18 years, assigned male sex at birth, and identifying as a gender different from male), via network referral and word-of-mouth in Cape Town, East London, and Johannesburg. A subset of 36 transgender women also participated in qualitative in-depth interviews. Quantitative analyses included descriptive statistics and negative binomial regression models to assess correlates of PrEP willingness. Qualitative interviews were audio-recorded, transcribed verbatim, and coded. Thematic content analysis was used to identify key themes. Quantitative and qualitative data were integrated for interpretation. FINDINGS: Participants were recruited between June 1 and Nov 30, 2018. 57 (45%) of 127 HIV-negative participants were PrEP-aware and only 14 (11%) of 129 were currently taking PrEP. HIV-negative participants experiencing social (eg, violence, poverty) and interpersonal (eg, discrimination, low transgender women community connectedness) hardship reported PrEP awareness more frequently than HIV-negative transgender women who did not. Willingness to take PrEP was low, at 56 (55%) of 102, among HIV-negative participants who were not currently taking PrEP, and negatively associated with transgender women community connectedness (multivariable prevalence ratio 0·87; 95% CI 0·77-0·99). Barriers to PrEP included taking a daily pill, side-effects, and cost. Participants urged greater education and engagement of transgender women in PrEP implementation. INTERPRETATION: South Africa is poised to scale up PrEP services for transgender women. Dedicated transgender clinics are planned to provide comprehensive care, including PrEP, for transgender women. It is critical to ensure transgender women are aware of and have accurate information about PrEP, and that health-care sites are prepared to provide quality care for transgender women. FUNDING: Gilead Sciences.

Well-managed grassland heterogeneity promotes butterfly conservation in a corridor network.

Habitat degradation is a major concern in transformed landscapes, as it reduces complexity by removing species, interactions, and ultimately biodiversity. Degradation is also of concern for ecological networks (ENs) composed of an interconnected system of conservation corridors among South Africa's commercial forestry compartments. These corridors are predominantly grasslands, and used as rangeland, so managed to optimize grazing conditions. Yet, how this management approach influences biodiversity remains unknown. Here, we studied how butterfly assemblages respond to local differences in rangeland quality (low, high and reference sites), and how this effect compared to that of local environmental variables (e.g. rockiness and bare ground), meso environmental gradients (e.g. topographic position and aspect), and landscape composition (i.e. proportion of different land cover types in the surrounding matrix). We calculated species richness and composition, Shannon's diversity index (H'), and the Butterfly Conservation Index (BCIn) representing the proportion of sensitive and range-restricted butterfly species per site. Rangeland quality was considered less important for butterflies than other environmental variables, but it was also significantly confounded with other environmental variables. At the landscape scale, proportion of grassland in the landscape matrix influenced butterfly assemblage composition, while proportion of thicket had a significant positive effect on BCIn. Moreover, the effect of elevation on assemblage composition emphasizes the value of maintaining environmental gradients within these conservation corridors. At the meso spatial scale, butterfly species richness and diversity (H') declined with increased dominance by a single plant species, which usually occurs late in a normal fire cycle. This suggests a reliance by butterflies on recurring natural disturbances for long-term persistence. We recommend moderate patch burning and grazing, as well as occasional hot burns to reduce thicket in Afromontane grassland. This approach would improve local scale vegetation patterns, and increase heterogeneity across the landscape for conserving these butterflies into the future.

A pilot study to profile salivary angiogenic factors to detect head and neck cancers.

BACKGROUND: Early diagnosis of head and neck squamous cell carcinoma (HNSCCs) is an appealing way to increase survival rates in these patients as well as to improve quality of life post-surgery. Angiogenesis is a hallmark of tumor initiation and progression. We have investigated a panel of angiogenic factors in saliva samples collected from HNSCC patients and controls using the Bio-Plex ProTM assays. METHODS: We have identified a panel of five angiogenic proteins (sEGFR, HGF, sHER2, sIL-6Ra and PECAM-1) to be elevated in the saliva samples collected from HNSCC patients (n = 58) compared to a control cohort (n = 8 smokers and n = 30 non-smokers). RESULTS: High positive correlations were observed between the following sets of salivary proteins; sEGFR:sHER2, sEGFR:HGF, sEGFR:sIL-6Rα, sHER2:HGF and sHER2:sIL6Ra. A moderate positive correlation was seen between FGF-basic and sEGFR. CONCLUSION: We have shown that angiogenic factor levels in saliva can be used as a potential diagnostic biomarker panel in HNSCC.

Keeping our core values ALIV[H]E. Holistic, community-led, participatory and rights-based approaches to addressing the links between violence against women and girls, and HIV.

There is increasing recognition that violence against women is a barrier to sexual and reproductive health and rights, and a cause and consequence of HIV. In this viewpoint, we describe the recently published Action Linking Initiatives on Violence Against Women and HIV Everywhere (ALIV[H]E) framework [1]. The potential of this framework is explored in terms of it contributing to paradigm change to achieve the sexual and reproductive health rights of women experiencing, or living in contexts of, violence and/or HIV. We go on to suggest that a holistic approach to research and evaluation is vital to strengthen learning and expand the evidence base on violence against women and HIV.

HIV prevalence and behavioral and psychosocial factors among transgender women and cisgender men who have sex with men in 8 African countries: A cross-sectional analysis.

INTRODUCTION: Sub-Saharan Africa bears more than two-thirds of the worldwide burden of HIV; however, data among transgender women from the region are sparse. Transgender women across the world face significant vulnerability to HIV. This analysis aimed to assess HIV prevalence as well as psychosocial and behavioral drivers of HIV infection among transgender women compared with cisgender (non-transgender) men who have sex with men (cis-MSM) in 8 sub-Saharan African countries. METHODS AND FINDINGS: Respondent-driven sampling targeted cis-MSM for enrollment. Data collection took place at 14 sites across 8 countries: Burkina Faso (January-August 2013), Côte d'Ivoire (March 2015-February 2016), The Gambia (July-December 2011), Lesotho (February-September 2014), Malawi (July 2011-March 2012), Senegal (February-November 2015), Swaziland (August-December 2011), and Togo (January-June 2013). Surveys gathered information on sexual orientation, gender identity, stigma, mental health, sexual behavior, and HIV testing. Rapid tests for HIV were conducted. Data were merged, and mixed effects logistic regression models were used to estimate relationships between gender identity and HIV infection. Among 4,586 participants assigned male sex at birth, 937 (20%) identified as transgender or female, and 3,649 were cis-MSM. The mean age of study participants was approximately 24 years, with no difference between transgender participants and cis-MSM. Compared to cis-MSM participants, transgender women were more likely to experience family exclusion (odds ratio [OR] 1.75, 95% CI 1.42-2.16, p < 0.001), rape (OR 1.95, 95% CI 1.63-2.36, p < 0.001), and depressive symptoms (OR 1.30, 95% CI 1.12-1.52, p < 0.001). Transgender women were more likely to report condomless receptive anal sex in the prior 12 months (OR 2.44, 95% CI 2.05-2.90, p < 0.001) and to be currently living with HIV (OR 1.81, 95% CI 1.49-2.19, p < 0.001). Overall HIV prevalence was 25% (235/926) in transgender women and 14% (505/3,594) in cis-MSM. When adjusted for age, condomless receptive anal sex, depression, interpersonal stigma, law enforcement stigma, and violence, and the interaction of gender with condomless receptive anal sex, the odds of HIV infection for transgender women were 2.2 times greater than the odds for cis-MSM (95% CI 1.65-2.87, p < 0.001). Limitations of the study included sampling strategies tailored for cis-MSM and merging of datasets with non-identical survey instruments. CONCLUSIONS: In this study in sub-Saharan Africa, we found that HIV burden and stigma differed between transgender women and cis-MSM, indicating a need to address gender diversity within HIV research and programs.

MYBPH acts as modifier of cardiac hypertrophy in hypertrophic cardiomyopathy (HCM) patients.

Left ventricular hypertrophy is a risk factor for cardiovascular morbidity and mortality. Hypertrophic cardiomyopathy (HCM) is considered a model disease to study causal molecular factors underlying isolated cardiac hypertrophy. However, HCM manifests with various clinical symptoms, even in families bearing the same genetic defects, suggesting that additional factors contribute to hypertrophy. The gene encoding the cardiac myosin binding protein C (cMYBPC) is one of the most frequently implicated genes in HCM. Recently another myosin binding protein, myosin binding protein H (MYBPH) was shown to function in concert with cMYBPC in regulating cardiomyocyte contraction. Given the similarity in sequence, structure and the critical role MYBPH plays in sarcomere contraction, we proposed that MYBPH may be involved in HCM pathogenesis. Family-based genetic association analysis was employed to investigate the contribution of MYBPH in modifying hypertrophy. Seven single nucleotide polymorphisms and haplotypes in MYBPH were investigated for hypertrophy modifying effects in 388 individuals (27 families), in which three unique South African HCM-causing founder mutations (p.R403W and pA797T in ß-myosin heavy chain gene (MYH7) and p.R92W in the cardiac troponin T gene (TNNT2)) segregate. We observed a significant association between rs2250509 and hypertrophy traits in the p.A797T MYH7 mutation group. Additionally, haplotype GGTACTT significantly affected hypertrophy within the same mutation group. MYBPH was for the first time assessed as a candidate hypertrophy modifying gene. We identified a novel association between MYBPH and hypertrophy traits in HCM patients carrying the p.A797T MYH7 mutation, suggesting that variation in MYBPH can modulate the severity of hypertrophy in HCM.