Investigating the effects of cytokine biomarkers on HIV incidence: a case study for individuals randomized to pre-exposure prophylaxis vs. control.

Introduction: Understanding and identifying the immunological markers and clinical information linked with HIV acquisition is crucial for effectively implementing Pre-Exposure Prophylaxis (PrEP) to prevent HIV acquisition. Prior analysis on HIV incidence outcomes have predominantly employed proportional hazards (PH) models, adjusting solely for baseline covariates. Therefore, models that integrate cytokine biomarkers, particularly as time-varying covariates, are sorely needed. Methods: We built a simple model using the Cox PH to investigate the impact of specific cytokine profiles in predicting the overall HIV incidence. Further, Kaplan-Meier curves were used to compare HIV incidence rates between the treatment and placebo groups while assessing the overall treatment effectiveness. Utilizing stepwise regression, we developed a series of Cox PH models to analyze 48 longitudinally measured cytokine profiles. We considered three kinds of effects in the cytokine profile measurements: average, difference, and time-dependent covariate. These effects were combined with baseline covariates to explore their influence on predictors of HIV incidence. Results: Comparing the predictive performance of the Cox PH models developed using the AIC metric, model 4 (Cox PH model with time-dependent cytokine) outperformed the others. The results indicated that the cytokines, interleukin (IL-2, IL-3, IL-5, IL-10, IL-16, IL-12P70, and IL-17 alpha), stem cell factor (SCF), beta nerve growth factor (B-NGF), tumor necrosis factor alpha (TNF-A), interferon (IFN) alpha-2, serum stem cell growth factor (SCG)-beta, platelet-derived growth factor (PDGF)-BB, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and cutaneous T-cell-attracting chemokine (CTACK) were significantly associated with HIV incidence. Baseline predictors significantly associated with HIV incidence when considering cytokine effects included: age of oldest sex partner, age at enrollment, salary, years with a stable partner, sex partner having any other sex partner, husband's income, other income source, age at debut, years lived in Durban, and sex in the last 30 days. Discussion: Overall, the inclusion of cytokine effects enhanced the predictive performance of the models, and the PrEP group exhibited reduced HIV incidences compared to the placebo group.

Diagnostic performance of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in bronchoalveolar lavage fluid for pulmonary tuberculosis in HIV-infected patients.

Introduction: Pulmonary tuberculosis (PTB) remains a significant health concern, particularly in individuals infected with human immunodeficiency virus (HIV) who are more susceptible to developing active TB disease. Early and accurate diagnosis of TB is crucial for effective treatment and prevention of transmission. This study aims to evaluate the potential of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) analysis of bronchoalveolar lavage fluid (BALF) for diagnosis of suspected PTB in HIV-infected patients. Methods: This retrospective study recruited 60 HIV-infected patients with suspected PTB presenting with respiratory symptoms and abnormal chest radiographs between January 2022 and June 2023. BALF samples were collected and subjected to analysis using MALDI-TOF MS, GeneXpert, acid-fast bacilli (AFB) smear and culture. And their diagnostic performance was compared. Results: The sensitivity of MALDI⁃TOFMS for diagnosing PTB was 83.3 %, which was better than that of smear 11.9 %, culture 40.5 % or Xpert38.1 % (all p < 0.01). The area under the curve (AUC) value of MALDI⁃TOFMS was 0.889, which was better than that of smear 0.532, culture 0.675 or Xpert 0.690 (all p < 0.01). The katG315 and rpoB-RRDR 511 mutations were detected by the MALDI⁃TOFMS in two patients. Conclusion: Nucleotide MALDI-TOFMS has a good clinical performance for rapid diagnosis of PTB from BALF samples in HIV infected patients, and detects mutations of TB simultaneously.

Prevention method preferences and factors influencing hypothetical choice among women in South Africa: a survey exploring opportunities for a multipurpose prevention technology implant.

Introduction: South African women bear an intersecting burden of HIV, sexually transmitted infections (STIs) and unintended pregnancy. Multipurpose prevention technologies (MPTs) are a class of products that address multiple needs and have the potential to improve uptake and use of prevention products. Methods: Analysing survey data from 703 HIV-negative women 18-40 years in three provinces in South Africa, collected between July and November 2022, this study explores their preferences for prevention methods and factors influencing choice of hypothetical prevention methods, including MPTs. Descriptive statistics and multinomial regression analyses were conducted to determine prevention method preferences and factors associated with choosing a pill, injectable or MPT-implant type prevention method. Results: Most women wanted to prevent HIV, STIs and pregnancy. The most important factors when choosing a prevention product were whether it provided dual and long-term protection and if side effects were manageable. If choosing only one method, half of women would choose any MPT-implant and a quarter each would choose a pill or an injectable method, with method choices differing by population group. Discussion: Prevention method choices were influenced by sexual-behavioural factors and current and prior contraceptive method use. Providing a choice of prevention methods and a population specific approach to new method development and introduction with access to accurate information could enhance their ability to fill a gap in prevention needs.

Lower Prevalence Countries Outside of South-Eastern Africa Now Have the Fastest Growing HIV Epidemic.

The United Nations Program on HIV/AIDS (UNAIDS) targets aim to reduce new HIV infections below 370 000 annually by 2025. However, there were 1.3 million new HIV infections worldwide in 2022. We collected and analyzed data for key variables of the HIV epidemic from UNAIDS and supplemented by PUBMED/EMBASE searches and national reports. A total of 53% of the HIV infections worldwide were in 14 high-prevalence countries in Southern/East Africa-where most of the funding for treatment and prevention is allocated-versus 47% in 54 low-prevalence countries. In 2022, there were more new HIV infections (770 000 vs 468 000), more HIV-related deaths (383 000 vs 225 000), higher rates of mother-to-child transmissions (16% vs 9%) and lower antiretroviral therapy coverage (67% vs 83%) in low-prevalence countries versus high-prevalence countries. To achieve UNAIDS annual new infections target for 2025, ART coverage needs to be optimized worldwide, and preexposure prophylaxis coverage expanded to 74 million people, versus 2.5 million currently treated.

Long-acting HIV Treatments: Study Design, Logistics, and Access.

New long-acting HIV treatment products have the potential to change the HIV epidemic in the United States and globally. Phase 3 clinical trials of HIV treatments tend to underrepresent populations bearing a disproportionate burden of the HIV epidemic-including women, racial minorities, trans and gender-diverse people, older adults, the unhoused, people who inject drugs, those in rural areas, individuals with mental illness, and other marginalized groups. These populations commonly face significant challenges in adhering to daily HIV treatment regimens. Conducting clinical trials of long-acting treatment targeting specific unmet medical needs of these populations can improve understanding of optimal care approaches, broaden the indication for use of long-acting products, and inform treatment guidelines, all of which can influence reimbursement and access policies. Innovative trial designs and programmatic implementation can improve inclusivity for long-acting therapy. This article summarizes discussions of a multistakeholder workshop on study designs for long-acting HIV treatments.

Community dialogue to enhance understanding of beliefs, behaviours and barriers to care for people living with liver disease and HBV infection in KwaZulu Natal, South Africa.

Introduction: The World Health Organisation (WHO) has set targets for the elimination of Hepatitis B virus (HBV), which include preventing new infections and reducing deaths. We explored beliefs, behaviours and barriers to diagnosis, prevention and treatment for people living with HBV infection (PLWHB) and those with liver disease in a rural South African population in KwaZulu-Natal, to gather information to inform research and support the development of improved clinical and public health services. Methods: Using an interdisciplinary approach (combining public engagement, social science, clinical and laboratory team members) we conducted a community dialogue with members of the Africa Health Research Institute (AHRI) Community Advisory Board (CAB). Notes from the discussions were used to write up an account from which themes were identified during a team debrief session for data analysis. Results: There was a lack of knowledge and awareness of HBV infection and transmission and prevention amongst CAB members, also reported among community members and healthcare workers. The participants recognised liver disease symptoms. Perceived causes of liver disease reported by the CAB were alcohol and non-adherence to HIV treatment. Barriers to care included stigma, poverty, and delays in referrals for HBV diagnosis and management. Conclusion: Understanding barriers to care is important to shape future services for diagnosis, treatment and prevention of HBV and liver disease which are accessible, affordable and acceptable to the local population. Education, awareness and advocacy for improved liver health care pathways are required to make them effective for local communities.

Impact of in-utero exposure to HIV and latent TB on infant humoral responses.

Introduction: Latent tuberculosis infection (LTBI) is a common coinfection in people living with HIV (PWH). How LTBI and HIV exposure in utero influence the development of infant humoral immunity is not well characterized. To address this question, we assessed the relationship between maternal humoral responses in pregnant women with HIV or with HIV/LTBI on humoral responses in infants to BCG vaccination and TB acquisition. Methods: Plasma samples were obtained from mother infant pairs during pregnancy (14-34 wks gestation) and in infants at 12 and 44 wks of age from the IMPAACT P1078 clinical trial. LTBI was established by Interferon gamma release assay (IGRA). Progression to active TB (ATB) disease was observed in 5 women at various times after giving birth. All infants were BCG vaccinated at birth and tested for IGRA at 44 weeks. Mtb (PPD, ESAT6/CFP10, Ag85A, LAM), HIV (GP120), and Influenza (HA) specific IgG, IgM, and IgA were measured in plasma samples using a bead based Luminex assay with Flexmap 3D. Results: In maternal plasma there were no differences in Mtb-specific antibodies or viral antibodies in relation to maternal IGRA status. ATB progressors showed increases in Mtb-specific antibodies at diagnosis compared to study entry. However, when compared to the non-progressors at entry, progressors had higher levels of Ag85A IgG and reduced ESAT6/CFP10 IgG and LAM IgG, IgM, and IgA1. All infants showed a decrease in IgG to viral antigens (HIV GP120 and HA) from 12 to 44 weeks attributed to waning of maternally transferred antibody titers. However, Mtb-specific (PPD, ESAT6/CFP10, Ag85A, and LAM) IgG and IgM increased from 12 to 44 weeks. HIV and HA IgG levels in maternal and 12-week infant plasma were highly correlated, and ESAT6/CFP10 IgG and LAM IgG showed a relationship between maternal and infant Abs. Finally, in the subset of infants that tested IGRA positive at 44 weeks, we observed a trend for lower LAM IgM compared to IGRA- infants at 44 weeks. Discussion: The results from our study raise the possibility that antibodies to LAM are associated with protection from progression to ATB and support further research into the development of humoral immunity against TB through infection or vaccination.

HIV Subtypes and Drug-resistance-associated Mutations in US Blood Donors, 2015-2020.

Background: Monitoring genotypes of HIV infections in blood donors may provide insights into infection trends in the general population. Methods: HIV RNA was extracted from plasma samples of blood donors confirmed as HIV positive by blood screening nucleic acid and antibody tests. HIV genome target regions were amplified using nested real time-polymerase chain reaction followed by next-generation sequencing. Sequences were compared to those in the Los Alamos National Laboratory (LANL) database. Sequences were also assessed for drug resistance mutations (DRM) using the Stanford HIV DRM Database. Results: From available HIV-positive donations collected between 1 September 2015 and 31 December 2020, 563 of 743 (75.8%) were successfully sequenced; 4 were subtype A, 543 subtype B, 5 subtype C, 1 subtype G, 5 circulating recombinant forms (CRF), and 2 were subtype B and D recombinants. Overall, no significant differences between blood donor and available LANL genotypes were found, and the genotypes of newly acquired versus prevalent HIV infections in donors were similar. The proportion of non-B subtypes and CRF remained a small fraction, with no other subtype or CRF representing more than 1% of the total. DRM were identified in 122 (21.6%) samples with protease inhibitor, nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor DRMs identified in 4.9%, 4.6% and 14.0% of samples, respectively. Conclusions: HIV genetic diversity and DRM in blood donors appear representative of circulating HIV infections in the US general population and may provide more information on infection diversity than sequences reported to LANL, particularly for recently transmitted infections.

Prevalence and associated risk factors for men being paid for sex in Ethiopia: a multilevel analysis of 2016 Ethiopian demographic health survey data.

Paying for sex is considered a high-risk sexual behavior, especially among men. Men who pay for sex are perceived to be a bridge group for sexually transmitted illnesses. In sub-Saharan Africa, the prevalence of paid sex among men is approximately 4.3%. Men paid for sex are not studied in Ethiopia. Therefore, the objective of this study was to identify factors associated with men paying for sex in Ethiopia. We analyzed data from the 2016 Ethiopian Demographic Health Survey. In the analysis, 9070 men were included. To identify factors associated with paid-for sex among men, we used a multilevel logistic regression model. A p value less than 0.05 was considered to indicate statistical significance at the 95% confidence interval (CI). In this study, 509 (5.6%) men were ever paid for sex. Men who paid for sex were significantly more likely to be rich [Adjusted Odds Ratio (AOR) = 1.70; 95% CI 1.287, 2.246], widowed or separated (AOR = 1.97; 95% CI 1.142, 3.396), had more sexual partners [AOR = 1.03; 95% CI 1.005, 1.063], had ever been tested for human immunodeficiency virus (HIV) (AOR = 1.50; 95% CI 1.173, 1.916), drank alcohol (AOR = 4.15; 95% CI 3.086, 5.576), and chewing khat (AOR = 2.28; 95% CI 1.822, 2.85); men who had ever paid for sex were significantly less likely to have higher education (AOR = .63; 95% CI .438, .898) and the lowest age at first sex (AOR = .90; 95% CI .870, .924). In conclusion, educational level, wealth status, province, marital status, age at first sexual intercourse, number of sexual partners, HIV status, alcohol consumption status, and chewing khat were significantly associated with men's paid-for sex. From a public and sexual health perspective, more education is needed for illiterate, widowed, separated, and rich men. Additionally, preventive measures should be taken against men's behavior through the use of alcohol or khat, having many sexual partners, and having young men.

Perception of couples' on multipurpose prevention technology attribute choice: the case of MTN 045.

BACKGROUND: Multipurpose prevention technologies (MPTs) are products capable of simultaneously addressing multiple sexual and reproductive health needs such as unwanted pregnancy, STIs including HIV-1, and other reproductive tract infections. MPTs are urgently needed to address the double burden of unplanned pregnancy and HIV. While condoms are currently the only accessible MPTs, they are not solely under a woman's control, and female condoms face limitations due to poor acceptability and high cost. METHODS: We conducted a sub-analysis of qualitative data from 39 couples participating in the MTN 045 study to examine the perception of couples on choice and acceptability of a "2 in 1" MPT that combines HIV and pregnancy prevention. RESULTS: Couples recognized the benefits of MPTs for HIV and pregnancy prevention but perceptions tied to each indication and a novel prevention technology tool raised important concerns relevant to use of future MPTs. In the study, participants' perceptions of MPT use were influenced by pregnancy planning. When the timing was less critical, they prioritized HIV prevention. Misinformation about family planning methods, including MPTs, affected decision-making with potential to hinder uptake of future MPTs. Concerns about side effects, such as weight gain and hormonal imbalances, influenced willingness to use MPTs. CONCLUSION: Addressing the myths and misconceptions surrounding the use of contraceptives is crucial in promoting their acceptance and ultimate use. Strategies for addressing the drawbacks women might experience while using a particular product should be in place as new MPTs progress through the development pipeline and approach roll-out.

Challenges for novel antiretroviral development in an era of widespread TLD availability.

Over 80% of people living with HIV in low-and-middle-income countries (LMICs) take first-line TDF/XTC/DTG (TLD). Due to hard-fought activism, in >100 LMICs TLD now costs under $45pppy under Voluntary License. With final DTG patents expiring by 2029, generic TLD will soon be available globally. We identify seven critical benchmarks underpinning TLDs success which novel ART should now meet, and an eighth for which novel ART should aim. These are superior efficacy; a high genetic barrier to resistance; safety in hepatitis B coinfection; favourable drug-drug interaction profiles including with antimycobacterials; efficacy in HIV-2; safety in pregnancy, long-acting formulation availability and affordable pricing from the outset. We illustrate when generic TLD will become available worldwide and compare this with trial programmes and approval timelines for two case-study novel ART combinations: islatravir/doravirine and cabotegravir/rilpivirine. We demonstrate that currently these regimens and trial programmes will not meet key benchmarks required to compete with TLD.

Autoantibodies Neutralizing GM-CSF in HIV-Negative Colombian Patients Infected with Cryptococcus gattii and C. neoformans.

BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.

Using a Programme Science approach to substantially reduce the risk of HIV transmission and acquisition in sex transactions among female sex workers in Zimbabwe.

INTRODUCTION: We used a Programme Science platform, to generate evidence to support the implementation of programmes for sex workers in Africa. Female sex workers are estimated to make up 1.6% (1.3%-1.8%) of the population of women aged 15-49 years in Zimbabwe. We highlight how programme science can be used to help distinguish between when, where and with whom programmes need to be implemented and discuss two case studies that exemplify implementing better (Case study 1 (1 June 2019-30 June 2021) Optimizing implementation of a risk differentiated microplanning intervention) and implementing differently (Case study 2 (1 October 2016-30 September 2022) Reorientating implementation of DREAMS for young women selling sex). METHODS: Zimbabwe's nationally scaled programme for sex workers was established in 2009 in partnership with sex workers to provide comprehensive services for sex workers and generate evidence for programme design, implementation and scale up. Since inception, comprehensive data have been collected from all sex workers seeking services. As the scope of service provision has expanded so has the scope of data collection and analysis. At enrolment, sex workers are assigned an alphanumeric unique identifier which links consultations within and across programme sites. We conduct descriptive analyses of the Key Population (KP) programme data to guide programme implementation and redesign, embedding programmatic qualitative enquiry as required. RESULTS: Two case studies describing different approaches to programme optimization are presented. In the first, an optimization exercise was used to strengthen programme implementation ensuring that the KP programme got back on track after SARS-COV-2. In the second, an in-depth review of research and programme data led to a re-orientation of the DREAMS programme to ensure that young women at the highest risk of HIV acquisition were enrolled and had access to DREAMS social support interventions in turn strengthening their uptake of HIV prevention. CONCLUSIONS: Optimizing and sustaining HIV care and treatment programmes requires effective delivery with sufficient scale and intensity for population impact. Our programme science approach guided the scale up of the KP programme in Zimbabwe, providing evidence to support strategy, implementation and ongoing management, and importantly helping us distinguish between when we needed to just implement, implement better or implement differently.

Defining community-led monitoring and its role in programme-embedded learning: lessons from the Citizen Science Project in Malawi and South Africa.

INTRODUCTION: Programme Science (PS) and community-led monitoring (CLM) intersect in unexpected and promising ways. This commentary examines a CLM initiative in Malawi and South Africa to highlight the crucial role of CLM in bolstering the PS framework. By leveraging data sources often overlooked by conventional research and evaluation approaches, CLM emerges as a pivotal element in enhancing programme effectiveness. This paper delineates the fundamental principles of CLM, presents programme outcomes derived from CLM methodologies and contextualizes these findings within the broader framework of PS. DISCUSSION: The Citizen Science Project implements CLM continuously at 33 health facilities: 14 in Malawi (eight in Kasungu District and six in Dedza District), and 19 in South Africa (all in the West Rand District), representing a total catchment area of 989,848 people. Monitoring indicators are developed in an iterative process with community groups. The indicators are unique to each country, but both focus on the uptake of health services (quantitative) and barriers to access (qualitative). Monthly clinic records surveys capture 34 indicators in Malawi and 20 in South Africa and are supplemented by qualitative interviews with care recipients and healthcare workers. Qualitative interviews provide additional granularity and help confirm and explain the more macro trends in service coverage as described in quantitative data. The resulting data analysis reveals key themes that help stakeholders and decision-makers to solve problems collaboratively. Noteworthy outcomes include a substantial increase in multi-month dispensing of antiretroviral therapy (ART) during COVID-19 (from 6% to 31%) with a subsequent recovery surpassing of HIV service benchmarks in Malawi post-pandemic. CONCLUSIONS: While quantifying direct impact remains challenging due to the project's design, CLM proves to be a robust methodology that generates credible data and produces impactful outcomes. Its potential extends beyond the health sector, empowering community leadership and fostering interventions aligned with community needs. As CLM continues to evolve, its integration into PS promises to improve relevance, quality and impact across diverse disciplines.

Programme science methodologies and practices that address "FURRIE" challenges: examples from the field.

INTRODUCTION: "Programme science" deploys scientific methods to address questions that are a priority to support the impact of public health programmes. As such, programme science responds to the challenges of making such studies: (1) feasible to undertake, (2) useful, (3) rigorous, (4) real-world-relevant, (5) informative, and undertaken by (6) equitable partnerships. The acronym "FURRIE" is proposed to describe this set of six challenges. This paper discusses selected HIV/STI (sexually transmitted infection) programme science case studies to illustrate how programme science rises to the FURRIE challenges. DISCUSSION: One way in which programme science is made more feasible is through the analysis and interpretation of data collected through service delivery. For some questions, these data can be augmented through methods that reach potential clients of services who have not accessed services or been lost to follow-up. Process evaluation can enhance the usefulness of programme science by studying implementation processes, programme-client interactions and contextual factors. Ensuring rigour by limiting bias and confounding in the real-world context of programme science studies requires methodological innovation. Striving for scientific rigour can also have the unintended consequence of creating a gap between what happens in a study, and what happens in the "real-world." Community-led monitoring is one approach to grounding data collection in the real-world experience of clients. Evaluating complex, context-specific strategies to strengthen health outcomes in a way that is informative for other settings requires clear specification of the intervention packages that are planned and delivered in practice. Programme science provides a model for equitable partnership through co-leadership between programmes, researchers and the communities they serve. CONCLUSIONS: Programme science addresses the FURRIE challenges, thereby improving programme impact and ultimately health outcomes and health equity. The adoption and adaptation of the types of novel programme science approaches showcased here should be promoted within and beyond the HIV/STI field.

Community contexts and knowledge: accountability, leadership and meaningful involvement of communities in Programme Science.

INTRODUCTION: A Programme Science approach that prioritizes populations who will benefit most and ensuring resources are allocated to programmes that meet the needs of those populations will bring an equity focus to research. Gay men and other men who have sex with men, people who use drugs, sex workers of all genders, and trans and gender-diverse people, defined by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) as key populations, have been disproportionately impacted since the start of the HIV pandemic. Through documenting community experiences from global key population-led networks, the authors explore the potential value and impact of community-led organizations and service delivery as critical components in effective HIV and Sexually Transmitted infections (STI) programmes. DISCUSSION: Through advocacy and research interventions, global key population networks have identified barriers against scaling up interventions for criminalized and marginalized communities, as well as highlighted solutions. The authors examine some of the current barriers to meaningful involvement of communities and the scaling up of community-led programmes that need to be addressed if Programme Science is to maintain an equity lens and the needs of key populations are to be met and highlight the need to make visible community engagement and participation in embedded research and Programme Science. CONCLUSIONS: The Programme Science approach provides an important opportunity to understand practical issues that will increase effective coverage in the implementation of public health and other interventions, which will require the prioritizing of key populations and their priorities in HIV and STI programmes. It will require extensive time and work to build relationships, increase capacity and share power. Where this has already happened, it has resulted in positive outcomes, including better health outcomes, reduced stigma, increased agency for key populations, and built community-led organizations and responses.

Advancing Programme Science approaches to understand gaps in HIV prevention programme coverage for key populations in 12 Nigerian states: findings from the 2020 Integrated Biological and Behavioural Surveillance Survey.

INTRODUCTION: Effective HIV prevention programme coverage is necessary to achieve Nigeria's goal of ending the epidemic by 2030. Recent evidence highlights gaps in service coverage and utilization across the country. The Effective Programme Coverage framework is a Programme Science tool to optimize a programme's population-level impact by examining gaps in programme coverage using data generated through programme-embedded research and learning. We apply the framework using Integrated Biological and Behavioural Surveillance Survey (IBBSS) data from Nigeria to examine coverage of four prevention interventions-condoms, HIV testing, and needle and syringe programmes (NSP)-among four key population groups-female sex workers (FSW), men who have sex with men (MSM), people who inject drugs (PWID) and transgender people. METHODS: Data from Nigeria's 2020 IBBSS, implemented in 12 states, were analysed to examine HIV prevention programme coverage among key populations. For each key population group and prevention intervention of interest, weighted IBBSS data were used to retrospectively generate coverage cascades that identify and quantify coverage gaps. Required coverage targets were informed by targets articulated in Nigeria's National HIV/AIDS Strategic Framework or, in their absence, by guidelines from policy normative bodies. Availability-, outreach- and utilization coverage proxy indicators were defined using variables from IBBSS data collection tools. Sankey diagrams are presented to visualize pathways followed by participants between coverage cascade steps. RESULTS: Required coverage targets were missed for HIV testing and NSP among all key population groups. Condom availability coverage surpassed required coverage targets among FSW and MSM, while utilization coverage only among FSW exceeded the 90% required coverage target. Outreach coverage was low for all key population groups, falling below all required coverage targets. CONCLUSIONS: Our findings identify critical gaps in HIV prevention programme coverage for key populations in Nigeria and demonstrate non-linear movement across coverage cascades, signalling the need for innovative solutions to optimize coverage of prevention services. Programme-embedded research is required to better understand how key population groups in Nigeria access and use different HIV prevention services so that programmes, policies and resource allocation decisions can be optimized to achieve effective programme coverage and population-level impact.

Recommendations from Black and Latinx sexual minority males to include pharmacists to increase greater accessibility and OnlyFans stars to promote uptake of injectable PrEP.

BACKGROUND: Pre-exposure Prophylaxis (PrEP) medication is the keystone of preventative measures to curtail the spread of HIV. However, oral PrEP, the pill intended to prevent HIV, has been slow to proliferate among men who have sex with men (MSM). This is of major concern as MSM account for the largest number of new HIV diagnoses in the U.S. More recently, the newest generation of PrEP in the form of a long-acting injectable (LAI) is to be administered every two months as an intramuscular injection and many MSM indicate preferring LAI-PrEP to the oral form of PrEP. However, uptake of PrEP, in all forms, remains low. Research is sparse that focuses on LAI-PrEP uptake among Black/African American and Latinx men who have sex with men (BLMSM). OBJECTIVE: To address this concern, this study explored the willingness to uptake LAI-PrEP, and recommendations for increasing awareness and encouraging uptake of LAI-PrEP among BLMSM. METHODS: Qualitative data were collected between February 2022 to December 2022 through focus groups via Zoom with BLMSM (N=30; Black=14, Latinx=16) aged 18 to 29 (Mean = 23, SD = 3) in Los Angeles County. RESULTS: Findings revealed that while 90% of BLMSM were aware of PrEP in oral form, only 10% were aware of LAI-PrEP. Findings from the qualitative analysis suggested to consider self-administration of LAI-PrEP, allow local community pharmacists to assess and administer it, and promote uptake of LAI-PrEP using high-profile male content creators and stars on OnlyFans social media platform. CONCLUSION: Increasing PrEP uptake, in all forms available, such as promoting awareness through popular social media stars, and engaging community pharmacists in feasible ways, is critical for addressing the disproportionate impact of HIV among the BLMSM community.

A Fluorescence Polarization Assay for High-Throughput Screening of Inhibitors against HIV-1 Nef-Mediated CD4 Downregulation.

Therapeutic inhibition of the viral protein Nef is an intriguing direction of antiretroviral drug discovery-it may revitalize immune mechanisms to target, and potentially clear, HIV-1-infected cells. Of the many cellular functions of Nef, the most conserved is the downregulation of surface CD4, which takes place through Nef hijacking the clathrin adaptor protein complex 2 (AP2)-dependent endocytosis. Our recent crystal structure has unraveled the molecular details of the CD4-Nef-AP2 interaction. Guided by the new structural knowledge, we have developed a fluorescence polarization-based assay for inhibitor screening against Nef's activity on CD4. In our assay, AP2 is included along with Nef to facilitate the proper formation of the CD4-binding pocket, and a fluorescently labeled CD4 cytoplasmic tail binds competently to the Nef-AP2 complex generating the desired polarization signal. The optimized assay has a good signal-to-noise ratio, excellent tolerance of DMSO and detergent, and the ability to detect competitive binding at the targeted Nef pocket, making it suitable for high-throughput screening.

A Fluorescence Polarization Assay for High-Throughput Screening of Inhibitors against HIV-1 Nef-Mediated MHC-I Downregulation.

The multifunctional, HIV-1 accessory protein Nef enables infected cells to evade host immunity and thus plays a key role in viral pathogenesis. One prominent function of Nef is the downregulation of major histocompatibility complex class I (MHC-I), which disrupts antigen presentation and thereby allows the infected cells to evade immune surveillance by the cytotoxic T cells. Therapeutic inhibition of this Nef function is a promising direction of antiretroviral drug discovery as it may revitalize cytotoxic T cells to identify, and potentially clear, hidden HIV-1 infections. Guided by the crystal structure of the protein complex formed between Nef, MHC-I, and the hijacked clathrin adaptor protein complex 1 (AP1), we have developed a fluorescence polarization-based assay for inhibitor screening against Nef's activity on MHC-I. The optimized assay has a good signal-to-noise ratio, substantial tolerance of DMSO, and excellent ability to detect competitive inhibition, indicating that it is suitable for high-throughput screening.