Effectiveness of a mindfulness and acceptance-based intervention for improving the mental health of adolescents with HIV in Uganda: An open-label trial.

Adolescents with HIV (AWH) face the double burden of dealing with challenges presented by their developmental phase while coping with stigma related to HIV, affecting their mental health. Poor mental health complicates adherence to daily treatment regimens, requiring innovative psychosocial support strategies for use with adolescents. We assessed the effectiveness of a mindfulness and acceptance-based intervention on the mental health of AWH in Uganda. One hundred and twenty-two AWH, mean age 17 ±1.59 (range 15 to 19 years), 57% female, receiving care at a public health facility in Kampala were enrolled in an open-label randomized trial (ClinicalTrials.gov: NCT05010317) with assessments at pre-and post-intervention. The mindfulness and acceptance-based intervention involved weekly 90-minute group sessions for four consecutive weeks facilitated by two experienced trainers. Sessions involved clarifying values, skillfully relating to thoughts, allowing and becoming aware of experiences non-judgmentally, and exploring life through trial and error. The control group received the current standard of care. Three mental health domains (depression, anxiety, and internalized stigma) were compared between the intervention and control groups. A linear mixed effects regression was used to analyze the effect of the intervention across the two time points. Results showed that the intervention was associated with a statistically significant reduction in symptoms of depression (ß = -10.72, 95%CI: 6.25, -15.20; p < .0001), anxiety (ß = -7.55, 95%CI: 2.66, -12.43; p = .0003) and stigma (ß = -1.40, 95%CI: 0.66 to -2.15; p = .0004) over time. Results suggest that mindfulness and acceptance-based interventions have the potential to improve the mental health of AWH.

Generation of Anti-HIV CAR-T Cells for Preclinical Research.

The inability of people living with HIV (PLWH) to eradicate human immunodeficiency virus (HIV) infection is due in part to the inadequate HIV-specific cellular immune response. The antiviral function of cytotoxic CD8+ T cells, which are crucial for HIV control, is impaired during chronic viral infection because of viral escape mutations, immune exhaustion, HIV antigen downregulation, inflammation, and apoptosis. In addition, some HIV-infected cells either localize to tissue sanctuaries inaccessible to CD8+ T cells or are intrinsically resistant to CD8+ T cell killing. The novel design of synthetic chimeric antigen receptors (CARs) that enable T cells to target specific antigens has led to the development of potent and effective CAR-T cell therapies. While initial clinical trials using anti-HIV CAR-T cells performed over 20 years ago showed limited anti-HIV effects, the improved CAR-T cell design, which enabled its success in treating cancer, has reinstated CAR-T cell therapy as a strategy for HIV cure with notable progress being made in the recent decade.Effective CAR-T cell therapy against HIV infection requires the generation of anti-HIV CAR-T cells with potent in vivo activity against HIV-infected cells. Preclinical evaluation of anti-HIV efficacy of CAR-T cells and their safety is fundamental for supporting the initiation of subsequent clinical trials in PLWH. For these preclinical studies, we developed a novel humanized mouse model supporting in vivo HIV infection, the development of viremia, and the evaluation of novel HIV therapeutics. Preclinical assessment of anti-HIV CAR-T cells using this mouse model involves a multistep process including peripheral blood mononuclear cells (PBMCs) harvested from human donors, T cell purification, ex vivo T cell activation, transduction with lentiviral vectors encoding an anti-HIV CAR, CAR-T cell expansion and infusion in mice intrasplenically injected with autologous PBMCs followed by the determination of CAR-T cell capacity for HIV suppression. Each of the steps described in the following protocol were optimized in the lab to maximize the quantity and quality of the final anti-HIV CAR-T cell products.

Patient and clinician preferences for diabetes management among older adults with co-morbid HIV: A qualitative exploration.

BACKGROUND: Older adults with HIV are at increased risk of developing certain chronic health conditions including type 2 diabetes mellitus (T2DM). As the number and complexity of conditions increases, so do treatment and health care needs. We explored patient and clinician preferences for HIV+T2DM care and perceived solutions to improving care. METHODS: We conducted an exploratory qualitative study comprised of individual in-depth interviews. Participants included English-speaking patients aged 50 and older living with HIV and T2DM and infectious disease (ID) and primary care (PC) clinicians from a large academic health center in Chicago. Thematic analysis drew from the Framework Method. RESULTS: A total of 19 patient and 10 clinician participants were interviewed. Many patients reported seeking HIV and T2DM care from the same clinician; they valued rapport and a 'one-stop-shop'. Others reported having separate clinicians; they valued perceived expertise and specialty care. Nearly all clinicians reported comfort screening for T2DM and initiating first line oral therapy; ID clinicians reported placing referrals for newer, complex therapies. Patients would like educational support for T2DM management; clinicians would like to learn more about newer therapies and easier referral processes. CONCLUSIONS: Patient-centered care includes managing T2DM from a variety of clinical settings for individuals with HIV, yet strategies are needed to better support clinicians. Future research should examine how best to implement these strategies.

Person-centred interventions to improve patient-provider relationships for HIV services in low- and middle-income countries: a systematic review.

INTRODUCTION: Person-centred care (PCC) has been recognized as a critical element in delivering quality and responsive health services. The patient-provider relationship, conceptualized at the core of PCC in multiple models, remains largely unexamined in HIV care. We conducted a systematic review to better understand the types of PCC interventions implemented to improve patient-provider interactions and how these interventions have improved HIV care continuum outcomes and person-reported outcomes (PROs) among people living with HIV in low- and middle-income countries. METHODS: We searched databases, conference proceedings and conducted manual targeted searches to identify randomized trials and observational studies published up to January 2023. The PCC search terms were guided by the Integrative Model of Patient-Centeredness by Scholl. We included person-centred interventions aiming to enhance the patient-provider interactions. We included HIV care continuum outcomes and PROs. RESULTS: We included 28 unique studies: 18 (64.3%) were quantitative, eight (28.6.%) were mixed methods and two (7.1%) were qualitative. Within PCC patient-provider interventions, we inductively identified five categories of PCC interventions: (1) providing friendly and welcoming services; (2) patient empowerment and improved communication skills (e.g. supporting patient-led skills such as health literacy and approaches when communicating with a provider); (3) improved individualized counselling and patient-centred communication (e.g. supporting provider skills such as training on motivational interviewing); (4) audit and feedback; and (5) provider sensitisation to patient experiences and identities. Among the included studies with a comparison arm and effect size reported, 62.5% reported a significant positive effect of the intervention on at least one HIV care continuum outcome, and 100% reported a positive effect of the intervention on at least one of the included PROs. DISCUSSION: Among published HIV PCC interventions, there is heterogeneity in the components of PCC addressed, the actors involved and the expected outcomes. While results are also heterogeneous across clinical and PROs, there is more evidence for significant improvement in PROs. Further research is necessary to better understand the clinical implications of PCC, with fewer studies measuring linkage or long-term retention or viral suppression. CONCLUSIONS: Improved understanding of PCC domains, mechanisms and consistency of measurement will advance PCC research and implementation.

CRISPR/Cas9 genome editing of CCR5 combined with C46 HIV-1 fusion inhibitor for cellular resistant to R5 and X4 tropic HIV-1.

Hematopoietic stem-cell (HSC) transplantation using a donor with a homozygous mutation in the HIV co-receptor CCR5 (CCR5Δ32/Δ32) holds great promise as a cure for HIV-1. Previously, there were three patients that had been reported to be completely cured from HIV infection by this approach. However, finding a naturally suitable Human Leukocyte Antigen (HLA)-matched homozygous CCR5Δ32 donor is very difficult. The prevalence of this allele is only 1% in the Caucasian population. Therefore, additional sources of CCR5Δ32/Δ32 HSCs are required. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) system is one method to mediate CCR5 knockout in HSCs that has been successfully employed as a gene editing tool in clinical trials. Additional anti-HIV-1 strategies are still required for broad-spectrum inhibition of HIV-1 replication. Here in this study, we combined an additional anti-HIV-1 therapy, which is C46, a cell membrane-anchored HIV-1 fusion inhibitor with the CRISPR/Cas9 mediated knockout CCR5. The combined HIV-1 therapeutic genes were investigated for the potential prevention of both CCR5 (R5)- and CXCR4 (X4)-tropic HIV-1 infections in the MT4CCR5 cell line. The combinatorial CRISPR/Cas9 therapies were superior compared to single method therapy for achieving the HIV-1 cure strategy and shows potential for future applications.

Developing an mHealth program to improve HIV care continuum outcomes among young Black gay and bisexual men.

BACKGROUND: Young Black gay and bisexual men (YBGBM) in the United States face significant disparities in HIV care outcomes. Mobile health (mHealth) interventions have shown promise with improving outcomes for YBGBM across the HIV care continuum. METHODS: We developed an mHealth application using human-centered design (HCD) from 2019-2021 in collaboration with YBGBM living with HIV and with HIV service providers. Our HCD process began with six focus groups with 50 YBGBM and interviews with 12 providers. These insights were used to inform rapid prototyping, which involved iterative testing and refining of program features and content, with 31 YBGBM and 12 providers. We then collected user feedback via an online survey with 200 YBGBM nationwide and usability testing of a functional prototype with 21 YBGBM. RESULTS: Focus groups and interviews illuminated challenges faced by YBGBM living with HIV, including coping with an HIV diagnosis, stigma, need for social support, and a dearth of suitable information sources. YBGBM desired a holistic approach that could meet the needs of those newly diagnosed as well as those who have been living with HIV for many years. Program preferences included video-based content where users could learn from peers and experts, a range of topics, a community of people living with HIV, and tools to support their health and well-being. Providers expressed enthusiasm for an mHealth program to improve HIV care outcomes and help them serve clients. Rapid prototyping resulted in a list of content topics, resources, video characteristics, community features, and mHealth tools to support adherence, retention, goal setting, and laboratory results tracking, as well as tools to help organization staff to support clients. Online survey and usability testing confirmed the feasibility, acceptability, and usability of the content, tools, and features. CONCLUSIONS: This study demonstrates the potential of a video-based mHealth program to address the unique needs of YBGBM living with HIV, offering support and comprehensive information through a user-friendly interface and videos of peers living with HIV and of experts. The HCD approach allowed for continuous improvements to the concept to maximize cultural appropriateness, utility, and potential effectiveness for both YBGBM and HIV service organizations.

The importance of self-management for better treatment outcomes for HIV patients in a low-income setting: perspectives of HIV experts and service providers.

BACKGROUND: Self-management is the most important strategy to improve quality of life in patients with a chronic disease. Despite the increasing number of people living with HIV (PLWH) in low-income countries, very little research on self-management is conducted in this setting. The aim of this research is to understand the perspectives of service providers and experts on the importance of self-management for PLWH. METHODS: A systematizing expert interview type of qualitative methodology was used to gain the perspectives of experts and service providers. The study participants had experience in researching, managing, or providing HIV service in east and southern African (ESA) countries. All the interviews were audio recorded, transcribed, and translated to English. The quality of the transcripts was ensured by randomly checking the texts against the audio record. A thematic analysis approach supported by Atlas TI version 9 software. RESULT: PLWH face a variety of multi-dimensional problems thematized under contextual and process dimensions. The problems identified under the contextual dimension include disease-specific, facility-related, and social environment-related. Problems with individual origin, such as ignorance, outweighing beliefs over scientific issues, low self-esteem, and a lack of social support, were mostly highlighted under the process dimensions. Those problems have a deleterious impact on self-management, treatment outcomes, and the quality of life of PLWH. Low self-management is also a result of professional-centered service delivery in healthcare facilities and health service providers' incapacity to comprehend a patient's need beyond the medical concerns. Participants in the study asserted that patients have a significant stake in enhancing treatment results and quality of life through enhancing self-management. CONCLUSION AND RECOMMENDATION: HIV patients face multifaceted problems beyond their medical issues. The success of medical treatment for HIV is strongly contingent upon patients' self-management practices and the supportive roles of their family, society, and health service providers. The development and integration of self-management practices into clinical care will benefit patients, their families, and the health system.

"I am still human and worth a life:" a qualitative study of the impacts of a community based, peer-led, treatment support model for young adults living with HIV in Zimbabwe.

Background: A persistent treatment gap remains between children and adults living with HIV. The Zvandiri program, developed by Africaid, is one of the few models of differentiated service delivery for children, adolescents, and youth that has been shown to improve outcomes along the HIV care continuum, employing Community Adolescent Treatment Supporters (CATS) to offer peer counseling and patient navigation. Our qualitative study provides an in-depth analysis of the feelings and experiences Zimbabwean youth had following an HIV diagnosis, and the ways that CATS facilitated linkage and retention in care. Methods: We conducted in-depth interviews in Shona with adolescents and young adults who were recently diagnosed with HIV in Zimbabwe. Interviews were audio-recorded, transcribed, and then translated to English. Interviews were coded in Dedoose using a structured a priori codebook. We wrote semi-structured summary memos for each interview. We co-conducted thematic analysis, guided by interpretive phenomenology with a team of Zimbabwean and American experienced qualitative researchers and community partners. We co-developed memos to elaborate and understand key themes across interviews. Results: Most of our interview participants recounted an immediate sense of loss upon testing HIV positive and a fear that "there was no hope for the future." CATS played a pivotal role for youth, providing emotional, educational, and logistical support to facilitate treatment initiation, adherence, and persistence in care. The CATS program supported youth through multiple approaches: group sessions, individual meetings, and via text or phone. While CATS offered counseling and comfort to participants, they emphasized the long-term importance of identifying at least one other person in participants' lives who could know their status and support them around HIV. Conclusion: Our findings delineate some of the key concerns that face youth after receiving an HIV diagnosis and the ways that a community-based adherence peer navigation program supported participants to navigate both their feelings and the health care system. Results can inform practice at community-based agencies that are implementing or considering peer youth navigation programs and garner support for policy to fund interventions for youth.

Evaluation of an HIV homecare program for lost-to-follow-up populations: a mixed methods study in Detroit, Michigan.

BACKGROUND: Maintaining people living with HIV (PLWHIV) in clinical care is a global priority. In the Metro Detroit area of Michigan, approximately 30% of PLWHIV are out of care. To re-engage lost-to-follow-up patients, Wayne Health Infectious Disease clinic launched an innovative Homecare program in 2017. In addition to home healthcare delivery, the program included links to community resources and quarterly community meetings. We aimed to evaluate Homecare's impact on participants' ability to stay engaged in HIV care and reach viral suppression. We included data from PLWHIV and their healthcare workers. METHODS: We used a convergent mixed-methods design, including first year program record review, semi-structured interviews, and a validated Likert scale questionnaire rating illness perception before and after Homecare. Interview data were collected from 15 PLWHIV in Metro Detroit and two healthcare workers responsible for program delivery. Semi-structured interviews focused on obstacles to clinic-based care, support networks, and illness perceptions. Interview data were transcribed and analyzed using a thematic approach. A fully coded analysis was used to create a conceptual framework of factors contributing to Homecare's success. Means in eight categories of the Brief Illness Perception (IPQ) were compared using paired T-tests. RESULTS: In the first year of Homecare, 28 of 34 participants (82%) became virally suppressed at least once. The program offered (1) social support and stigma reduction through strong relationships with healthcare workers, (2) removal of physical and resource barriers such as transportation, and (3) positive changes in illness perceptions. PLWHIV worked towards functional coping strategies, including improvements in emotional regulation, acceptance of their diagnosis, and more positive perspectives of control. Brief-IPQ showed significant changes in six domains before and after Homecare. CONCLUSION: Homecare offers an innovative system for successfully re-engaging and maintaining lost-to-follow-up PLWHIV in care. These findings have implications for HIV control efforts and could inform the development of future programs for difficult to reach populations.

The Need to Widen the Concept of Health and to Include the Spiritual Dimension.

For many, the World Health Organization's (WHO) definition of health does not reflect their own understanding of health, because it lacks aspects such as spiritual wellbeing. Responding to these concerns, the WHO called in 2023 for a vision of health that integrates physical, mental, psychological, emotional, spiritual, and social wellbeing. To date, medical practitioners are often reluctant to consider spiritual aspects, because of a perceived lack of statistical evidence about the strength of relations. Research on this topic is emerging. A recent study among 800 young people living with HIV in Zimbabwe showed how study participants navigated three parallel, at times contradicting health systems (religious, traditional, medical). Conflicting approaches led to multifaceted dilemmas (= spiritual struggles), which were significantly related to poorer mental and physical health. This illustrates the need for inclusion of spiritual aspects for health and wellbeing in research, and of increased collaboration between all stakeholders in healthcare.

A simultaneous knockout knockin genome editing strategy in HSPCs potently inhibits CCR5- and CXCR4-tropic HIV-1 infection.

Allogeneic hematopoietic stem and progenitor cell transplant (HSCT) of CCR5 null (CCR5Δ32) cells can be curative for HIV-1-infected patients. However, because allogeneic HSCT poses significant risk, CCR5Δ32 matched bone marrow donors are rare, and CCR5Δ32 transplant does not confer resistance to the CXCR4-tropic virus, it is not a viable option for most patients. We describe a targeted Cas9/AAV6-based genome editing strategy for autologous HSCT resulting in both CCR5- and CXCR4-tropic HIV-1 resistance. Edited human hematopoietic stem and progenitor cells (HSPCs) maintain multi-lineage repopulation capacity in vivo, and edited primary human T cells potently inhibit infection by both CCR5-tropic and CXCR4-tropic HIV-1. Modification rates facilitated complete loss of CCR5-tropic replication and up to a 2,000-fold decrease in CXCR4-tropic replication without CXCR4 locus disruption. This multi-factor editing strategy in HSPCs could provide a broad approach for autologous HSCT as a functional cure for both CCR5-tropic and CXCR4-tropic HIV-1 infections.

Linkage to HIV care and early retention in HIV care among men in the 'universal test-and-treat' era in a high HIV-burdened district, KwaZulu-Natal, South Africa.

INTRODUCTION: Despite the numerous efforts and initiatives, males with HIV are still less likely than women to receive HIV treatment. Across Sub-Saharan Africa, men are tested, linked, and retained in HIV care at lower rates than women, and South Africa is no exception. This is despite the introduction of the universal test-and-treat (UTT) prevention strategy anticipated to improve the uptake of HIV services. The aim of this study was to investigate linkage to and retention in care rates of an HIV-positive cohort of men in a high HIV prevalence rural district in KwaZulu-Natal province, South Africa. METHODS: From January 2018 to July 2019, we conducted an observational cohort study in 18 primary health care institutions in the uThukela district. Patient-level survey and clinical data were collected at baseline, 4-months and 12-months, using isiZulu and English REDCap-based questionnaires. We verified data through TIER.Net, Rapid mortality survey (RMS), and the National Health Laboratory Service (NHLS) databases. Data were analyzed using STATA version 15.1, with confidence intervals and p-value of ≤0.05 considered statistically significant. RESULTS: The study sample consisted of 343 male participants diagnosed with HIV and who reside in uThukela District. The median age was 33 years (interquartile range (IQR): 29-40), and more than half (56%; n = 193) were aged 18-34 years. Almost all participants (99.7%; n = 342) were Black African, with 84.5% (n = 290) being in a romantic relationship. The majority of participants (85%; n = 292) were linked to care within three months of follow-up. Short-term retention in care (≤ 12 months) was 46% (n = 132) among men who were linked to care within three months. CONCLUSION: While the implementation of the UTT strategy has had positive influence on improving linkage to care, men's access of HIV treatment remains inconsistent and may require additional innovative strategies.

Which Features of Telehealth in HIV Care Are Most Important? A Mixed-Methods Study With HIV Care Providers and People Living With HIV in South Carolina.

ABSTRACT: Telehealth was rapidly implemented in HIV care during COVID-19 yet remains understudied. To assess the importance of telehealth features, we conducted a mixed-methods study with HIV care providers and people living with HIV. Qualitative interviews and ranking exercises revealed heterogeneity in preference-relevant features of telehealth in HIV care.

Experiences and resultant care gaps among women with HIV in Canada: concept mapping the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) findings.

OBJECTIVES: The community-based, longitudinal, Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) explored the experiences of women with HIV in Canada over the past decade. CHIWOS' high-impact publications document significant gaps in the provision of healthcare to women with HIV. We used concept mapping to analyse and present a summary of CHIWOS findings on women's experiences navigating these gaps. DESIGN: Concept mapping procedures were performed in two steps between June 2019 and March 2021. First, two reviewers (AY and PM) independently reviewed CHIWOS manuscripts and conference abstracts written before 1 August 2019 to identify main themes and generate individual concept maps. Next, the preliminary results were presented to national experts, including women with HIV, to consolidate findings into visuals summarising the experiences and care gaps of women with HIV in CHIWOS. SETTING: British Columbia, Ontario and Quebec, Canada. PARTICIPANTS: A total of 18 individual CHIWOS team members participated in this study including six lead investigators of CHIWOS and 12 community researchers. RESULTS: Overall, a total of 60 peer-reviewed manuscripts and conference abstracts met the inclusion criteria. Using concept mapping, themes were generated and structured through online meetings. In total, six composite concept maps were co-developed: quality of life, HIV care, psychosocial and mental health, sexual health, reproductive health, and trans women's health. Two summary diagrams were created encompassing the concept map themes, one for all women and one specific to trans women with HIV. Through our analysis, resilience, social support, positive healthy actions and women-centred HIV care were highlighted as strengths leading to well-being for women with HIV. CONCLUSIONS: Concept mapping resulted in a composite summary of 60 peer-reviewed CHIWOS publications. This activity allows for priority setting to optimise care and well-being for women with HIV.

The CRISPR-Cas9 induced CCR5 Δ32 mutation as a potent gene therapy methodology for resistance to HIV-1 variant: a review.

Human Immunodeficiency Virus (HIV) has continuously been the greatest epidemic for humanity over a period spanning almost five decades. With no specific cure or treatment available to date despite extensive research, the C-C Chemokine Receptor 5, Delta 32 (CCR5 Δ32) allele genetic point mutation plays an imperative role in the prevention of acquired immunodeficiency syndrome (AIDS). This comprehensive study aims to review the induction of the homozygous recessive deletion genotype using the Clustered Regularly Interspaced Short Palindromic Repeats, Cas 9 Enzyme (CRISPR-Cas9), and hematopoietic stem cell transplantation under positive selection pressure for active immunity in seropositive patients' populations as the phenotype. A methodology is proposed to trigger a significant increase in the expression of Delta 32 beneficial mutant alleles within controlled modern healthcare facilities utilizing totipotent stem cells through somatic gene therapy. It acts upon two dysfunctional CCR5 genes, translating mutant G protein-coupled co-receptors, whose primary function is similar to that of C-X-C Motif Chemokine receptor 4 (CXCR4), by blocking the entry of viral RNA into the CD4+ T helper lymphocytes, halting infection and seizing viral life cycle. This modification is endemic in Northern Europe, where it naturally pertains to the Caucasian descent population samples in the form of polymorphism, p (X=0.01), where X is the probability of frequency of complete immunity against HIV-1 in population samples. The epigenetics of the single nucleotide polymorphism (SNP) are analyzed as they play a significant role in immunity distribution. Furthermore, a comparative analysis within the ethical boundaries of CRISPR-Cas9 is conducted to discuss the practical aspects and challenges of the presented methodologies and treatment alternatives. Additionally, the study assembles all available data and summarizes preexisting research while providing a promising solution to this ethical dilemma. Finally, a methodology is devised to answer the question of whether the variant-specific epidemic of AIDS caused by HIV-1 can be cured via artificially inducing immunity by CRISPR-Cas9.

Barriers to accessing care for cardiometabolic disorders in Malawi: partners as a source of resilience for people living with HIV.

BACKGROUND: People living with HIV (PLWH) are at increased risk of cardiometabolic disorders (CMD). Adequate access to care for both HIV and CMD is crucial to improving health outcomes; however, there is limited research that have examined couples' experiences accessing such care in resource-constrained settings. We aimed to identify barriers to accessing CMD care among PLWH in Malawi and the role of partners in mitigating these barriers. METHODS: We conducted a qualitative investigation of barriers to CMD care among 25 couples in Malawi. Couples were eligible if at least one partner was living with HIV and had hypertension or diabetes (i.e., the index patient). Index patients were recruited from HIV care clinics in the Zomba district, and their partners were enrolled thereafter. Interviews were conducted separately with both partners to determine barriers to CMD care access and how partners were involved in care. RESULTS: Participants framed their experiences with CMD care by making comparisons to HIV treatment, which was free and consistently available. The main barriers to accessing CMD care included shortage of medications, cost of tests and treatments, high cost of transportation to health facilities, lengthy wait times at health facilities, faulty or unavailable medical equipment and supplies, inadequate monitoring of patients' health conditions, some cultural beliefs about causes of illness, use of herbal therapies as an alternative to prescribed medicine, and inadequate knowledge about CMD treatments. Partners provided support through decision-making on accessing medical care, assisting partners in navigating the healthcare system, and providing financial assistance with transportation and treatment expenses. Partners also helped manage care for CMD, including communicating health information to their partners, providing appointment reminders, supporting medication adherence, and supporting recommended lifestyle behaviors. CONCLUSIONS: Couples identified many barriers to CMD care access, which were perceived as greater challenges than HIV care. Partners provided critical forms of support in navigating these barriers. With the rise of CMD among PLWH, improving access to CMD care should be prioritized, using lessons learned from HIV and integrated care approaches. Partner involvement in CMD care may help mitigate most barriers to CMD care.

The Evidence Project: Protocol for Systematic Reviews of Behavioral Interventions and Behavioral Aspects of Biomedical Interventions for HIV Prevention, Treatment, and Health Service Delivery in Low- and Middle-Income Countries.

The Evidence Project conducts systematic reviews and meta-analyses of HIV behavioral interventions, behavioral aspects of biomedical interventions, combination prevention strategies, modes of service delivery, and integrated programs in low- and middle-income countries. Here, we present the overall protocol for our reviews. For each topic, we conduct a comprehensive search of five online databases, complemented by secondary reference searching. Articles are included if they are published in peer-reviewed journals and present pre/post or multi-arm data on outcomes of interest. Data are extracted from each included article by two trained coders working independently using standardized coding forms, with differences resolved by consensus. Risk of bias is assessed with the Evidence Project tool. Data are synthesized descriptively, and meta-analysis is conducted when there are similarly measured outcomes across studies. For over 20 years, this approach has allowed us to synthesize literature on the effectiveness of interventions and contribute to the global HIV response.

Program Director Reports of COVID-19 Lockdown-Driven Service Changes in Community-Based STI Clinics and Syringe Services Programs in the Southeastern U.S.

The COVID-19 pandemic strained the U.S. health care system, posing logistical challenges for community-based programs. This study surveyed 11 program directors in sexually transmitted infection (STI) clinics and syringe services programs (SSPs) that served people who use substances and are at risk for HIV in five southeastern U.S. states. Brief survey questions asked about programs' use of in-person and telehealth services. Results indicated widespread reduction of in-person services and concomitant adoption of telehealth services. In STI clinics, telehealth replaced in-person visits for all but urgent treatment of active symptoms. In SSPs, in-person contact continued or increased from pre-pandemic volumes. In both programs, the most salient telehealth use barrier was limited device or internet access and limited technological ease. Services were sustained through innovative adaptations. This snapshot of response to the early COVID-19 lockdown phase offers actionable guidance about service preparedness for future public health catastrophes in community-based programs serving vulnerable populations.

Factors influencing integration of mental health screening and treatment at HIV clinic settings in Cameroon: a qualitative study of health providers' perspectives.

BACKGROUND: Mental disorders are common among people with HIV (PWH) and are associated with poor HIV outcomes. Despite high unmet mental health needs among PWH, use of evidence-based mental health screening and treatment protocols remains limited at HIV treatment facilities across low-resource settings. Integrating mental health services into HIV care can reduce this gap. This study's objective was to explore factors that influence integration of mental health screening and treatment into HIV clinics in Cameroon. METHODS: We analyzed 14 in-depth interviews with clinic staff supporting PWH at three urban HIV treatment clinics in Cameroon. Interviews focused on current processes, barriers and facilitators, and types of support needed to integrate mental health care into HIV care. Interviews were recorded and transcribed. French transcripts were translated into English. We used thematic analysis to identify factors that influence integration of mental health screening and treatment into HIV care in these settings. Ethical review boards in the United States and Cameroon approved this study. RESULTS: Respondents discussed a lack of standardized mental health screening processes in HIV treatment facilities and generally felt ill-equipped to conduct mental health screening. Low community awareness about mental disorders, mental health-related stigma, limited physical space, and high clinic volume affected providers' ability to screen clients for mental disorders. Providers indicated that better coordination and communication were needed to support client referral to mental health care. Despite these barriers, providers were motivated to screen clients for mental disorders and believed that mental health service provision could improve quality of HIV care and treatment outcomes. All providers interviewed said they would feel more confident screening for mental disorders with additional training and resources. Providers recommended community sensitization, training or hiring additional staff, improved coordination to manage referrals, and leadership buy-in at multiple levels of the health system to support sustainable integration of mental health screening and treatment into HIV clinics in Cameroon. CONCLUSIONS: Providers reported enthusiasm to integrate mental health services into HIV care but need more support and training to do so in an effective and sustainable manner.

Anti-PD-1 chimeric antigen receptor T cells efficiently target SIV-infected CD4+ T cells in germinal centers.

Programmed cell death protein 1 (PD-1) is an immune checkpoint marker commonly expressed on memory T cells and enriched in latently HIV-infected CD4+ T cells. We engineered an anti-PD-1 chimeric antigen receptor (CAR) to assess the impact of PD-1 depletion on viral reservoirs and rebound dynamics in SIVmac239-infected rhesus macaques (RMs). Adoptive transfer of anti-PD-1 CAR T cells was done in 2 SIV-naive and 4 SIV-infected RMs on antiretroviral therapy (ART). In 3 of 6 RMs, anti-PD-1 CAR T cells expanded and persisted for up to 100 days concomitant with the depletion of PD-1+ memory T cells in blood and tissues, including lymph node CD4+ follicular helper T (TFH) cells. Loss of TFH cells was associated with depletion of detectable SIV RNA from the germinal center (GC). However, following CAR T infusion and ART interruption, there was a marked increase in SIV replication in extrafollicular portions of lymph nodes, a 2-log higher plasma viremia relative to controls, and accelerated disease progression associated with the depletion of CD8+ memory T cells. These data indicate anti-PD-1 CAR T cells depleted PD-1+ T cells, including GC TFH cells, and eradicated SIV from this immunological sanctuary.