Antiviral Therapy

Researchers are looking for new medicines to prevent HIV-1 (Human Immunodeficiency Virus Type 1) infection. The goals of this study are to learn: * If taking MK-8527 once a month works to prevent HIV-1 infection as well as or better than a standard (usual) pre-exposure prophylaxis (PrEP) taken once a day * About the safety of MK-8527 and if people tolerate it

U.S. epidemiological data indicates that Black women are a high-risk HIV disparity group, yet initiation of novel prevention strategies like pre-exposure prophylaxis (PrEP) among this group is stagnant. Socio-structural challenges like intimate partner violence and gendered racism can constrain PrEP access among Black women, but few implementation studies have mitigated these challenges to improve PrEP initiation. The proposed research aims to implement and assess the effectiveness, implementation, and sustainability of a multilevel intervention to increase PrEP initiation among Black women with and without intimate partner violence in Baltimore.

Researchers are looking for new medicines to prevent HIV-1 (Human Immunodeficiency Virus Type 1) infection. The goals of this study are to learn: * If taking MK-8527 once a month works to prevent HIV-1 infection better than a standard (usual) pre-exposure prophylaxis (PrEP) taken once a day * About the safety of MK-8527 and if people tolerate it

Post mastectomy pain syndrome (PMPS) is considered one of the most common types of CPSP with incidence ranging between 20% - 50%. Pregabalin is one of the drugs that can reduce the excitability of the dorsal horn neurons. It is a γ-aminobutyric acid analogue that binds to α2-δ subunits of the voltage-gated calcium channels in the central nervous system. Duloxetine is an SNRI that increases serotonin and norepinephrine levels in the central nervous system, which helps modulate pain pathways. Originally developed for depression and anxiety, it is also used for chronic pain conditions such as fibromyalgia, diabetic neuropathy, and chronic musculoskeletal pain. Amantadine is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors. These receptors play a significant role in the development of central sensitization, acute opioid tolerance, and opioid-induced hyperalgesia.

Objective To compare the safety and efficacy of Apixaban vs. placebo in the prevention of LV thrombus formation in patients with acute anterior myocardial and severe LV dysfunction following primary PCI in an open label, randomized controlled trial. Methods: Inclusion Criteria .Patients aged 18-65 years, presenting with acute anterior STEMI and severe LV dysfunction (EF\<35%) with antero-apical akinesis, dyskinesis, or aneurysm. Exclusion Criteria * Patients with previous myocardial infarction or revascularization procedures. * Patients with cardiogenic shock * Patients with advanced CKD (Cr \< 2 and those on hemodialysis) * Recent ICH or major bleed requiring transfusion, low platelet counts\<100,000 * History of CVA * Patients with atrial fibrillation or other indications for chronic anticoagulation * Pregnant patients and those with hematological disorders Eligible patients will be enrolled after informed consent. Randomization will be undertaken once post PCI echocardiography is done and LV function is recorded. Patients randomized to the treatment arm will be given Apixaban 2.5 mg twice daily and DAPT for two weeks in addition to other guideline directed medical therapy (GDMT). After two weeks of triple therapy (DOAC+DAPT), aspirin will be dropped in the study arm. The control arm will be of standard care. After 4 weeks, treatment group will be switched to DAPT. Follow up The primary endpoint will be the incidence of LV thrombus formation recorded at 4-week follow-up echocardiography. Patients' clinical status, side effects, and medication compliance will be recorded. At 2-week: patients will be contacted via phone call to assess their clinical status, ensure drug compliance, discuss any necessary changes in drug regimen for those in the treatment group already prescribed on discharge, and inquire about any side effects. At 4-week: patients will undergo an in-person follow-up where echocardiography will be conducted alongside a comprehensive assessment In case of any cardiac complaints, patients will be advised to visit the hospital or cardiologist promptly to complete a comprehensive clinical and laboratory workup. Primary endpoint . Incidence of LV thrombus formation in the treatment arm vs. placebo at 4 week follow up echocardiography. Secondary endpoints * composite of death, recurrent myocardial infarction, stent thrombosis, and heart failure hospitalization in experimental arm vs. control group. * Major and minor bleeding in experimental arm vs. control group * Discontinuation of the drug due to side effects in experimental arm vs. control group A clinical events committee whose members are unaware of study-group assignments will independently adjudicate all potential endpoints.

The purpose of this research is to test the impact of dyadic, focused case management on financial well-being, access to food, linkage to and retention in care outcomes for individuals living with or vulnerable to HIV. The study population is men who have sex with men (MSM) or same-sex attraction, gender-diverse persons, and cis-gender women living with or at increased vulnerability to HIV. The study team will be testing the hypotheses that dyadic case management that is focused on financial wellness, will have better outcomes for folks living with or vulnerable to HIV. Analyses will be used to assess the efficacy of the intervention as an emerging practice.

Poverty is an important contributor to poor short- and long-term HIV outcomes for pregnant women with HIV. This problem is salient in Botswana, where antenatal HIV prevalence is \>20%. Poverty has been reported as a major barrier to sustained engagement in ART among pregnant women with HIV, and extreme poverty affects 15-20% of people in Botswana. Recent research in behavioral economics has shown that poverty can result in worse health outcomes by taxing mental bandwidth, resulting in a heightened focus on immediate needs and less attention to future-oriented decisions. Mental bandwidth is likely further taxed by the added burdens of HIV and the perinatal period. Consequently, anti-poverty interventions targeting pregnant women with HIV, such as cash transfers, may be particularly effective at improving health outcomes. However, equipoise remains about the role of cash transfers in HIV, with prior studies showing mixed results (e.g., HPTN068 showing no reduction in HIV incidence among school-aged girls receiving cash transfers in South Africa). In addition, there is a policy relevant question of whether and to what extent a pregnancy support grant could help improve outcomes. In this study, we will conduct a pilot Hybrid Type 2 effectiveness-implementation trial of an unconditional cash transfer intervention for pregnant women with HIV. This research will be conducted at antenatal clinics managed by the District Health Management Teams in Gaborone (e.g., Old Naledi, Mafitlakgosi) and Mogoditsane-Thamaga District (e.g., Lesirane). It will be a collaboration between the University of Botswana and the University of Pennsylvania, through the Botswana-Upenn-Partnership. The study population will be comprised of pregnant women with HIV receiving antenatal care. We will enroll a total of 100 participants in their second trimester - 50 assigned to the usual care arm (standard social support), and 50 assigned to the intervention arm (the addition of 1000 BWP per month through 6 months post partum). All participants will complete study visits at baseline (Visit 1), late pregnancy prior to delivery (Visit 2), and 3-6 months post-partum (Visit 3). Data collected at study visits will include survey questionnaires, bandwidth assessments, and clinical data from the electronic health record database. During the final study visit, we will recruit 20 participants (15 intervention, 5 control; randomly selected) for individual qualitative interviews. Primary outcomes will include mental bandwidth and ART adherence (effectiveness outcomes), and feasibility and acceptability of the intervention (implementation outcomes). These findings will be used as the basis for an NIH R01 proposal to conduct a larger trial of an unconditional cash transfer powered for clinical outcomes (e.g., postpartum viral suppression).

The goal of this clinical trial is to determine the efficacy of a client-center care coordination intervention (C4) in improving pre-exposure prophylaxis (PrEP) adherence in Black men who have sex with men (MSM). The main aims of the study are: 1. Determine the efficacy of C4 for increasing PrEP adherence among Black MSM. 2. Identify the optimal dose of C4 implementation for maximizing its effect on PrEP adherence. 3. Describe the acceptability and feasibility of C4 implementation in community settings. Participants in the clinical trial will be randomized to receive the intervention or standard of care for PrEP in two sites. Researchers will compare administration of C4 to standard of care to see if C4 improves adherence to PrEP. C4 is a longitudinal intervention which provides individualized client-centered HIV prevention and support services designed to address health and psychosocial needs that impact the success of PrEP use and adherence (i.e., co-morbidities, substance use, mental health, housing, etc.). The intervention pulls from the Centers for Disease Control and Prevention (CDC) Comprehensive Risk Counseling and Services (CRCS) and Self-Determination Theory (SDT) to support client-identified HIV prevention goals to promote, adopt, and maintain PrEP use. CRCS is a public health strategy to assist persons in developing behavioral goals to reduce HIV acquisition and transmission. In this intervention, the HIV prevention plan element of CRCS will be the foundation of the C4 intervention. After the initial prevention plan is developed, elements of SDT will be used to implement a client-centered care approach to assist in addressing issues which many arise which impede successful PrEP adherence.

Approval of the study was obtained from the hospital's ethical committee. The study design and methodology followed the tenets of Declaration of Helsinki. All patients were provided with written informed consent and received a thorough explanation of the use of 2% Ganciclovir Eye Drops, its potential risks and benefits. This is a monocencer, single arm, prospective study. The experimental group is: 2% Ganciclovir Eye Drops therapy group. Administration method and dose adjustment: 2% ganciclovir eye drops, 10 times / day for two weeks, 8 times/day for two weeks, 6 times/day for two weeks, 4 times/day for more than six weeks. According to best corrected visual acuity (BCVA), intraocular pressure, corneal abrasion, anterior chamber and vitreous inflammation, optical coherence tomography (OCT), Ultra wide angle fundus image and so on. The investigators evaluate the effects of 2% Ganciclovir Eye Drops in treatment of cytomegalovirus retinitis.

Intersectional stigma is a pervasive barrier to care that disproportionately affects people living with HIV (PLWH) and leads to poor clinical outcomes. While the understanding of intersectional stigma is still evolving, it is based on intersectionality, a long-standing understanding that oppressive forces intersect to create and maintain inequity. A major challenge in achieving the 2025 UNAIDS 95-95-95 goals is the persistent intersectional stigma faced by PLWH who are marginalized and minoritized because of mental health (MH) problems, sexual and gender minority (SGM) status, race, and/or other dimensions. The relationship between these dimensions, intersectional stigma, and health outcomes is complex. Globally, key populations, who often face intersectional stigma, are more likely to become infected with HIV and less likely to initiate ART and achieve viral suppression. A 2021 systematic review found the prevalence of MH problems among PLWH to be 28-62%. Marginalized populations, who often face minority stress, are even more likely to report MH problems, which are associated with further (layered or intersecting) stigma and poor health outcomes. Therefore, addressing intersectional stigma is crucial for improving HIV outcomes and quality of life for PLWH. The Nepali government's 2023 HIV report estimated there are 30,000 PLWH, 93% of whom are aware of their status, and 77% of those who were tested had initiated ART. However, only 54% of PLWH receiving ART had achieved viral load (VL) suppression, and this rate was low before the COVID pandemic as well: 47% in 2018 and 45% in 2019. These data highlight the importance of increasing HIV care engagement in Nepal. Although there is a lack of studies directly assessing intersectional stigma in Nepal, there is a high prevalence of stigma in the relevant dimensions of HIV, MH, SGM, and Dalit minoritized caste in Nepal. In a nationally representative 2022 study (N=927), stigma was highlighted as an important driver of poor care engagement and quality of life among Nepali PLWH. Prevalence of stigma and discrimination was high among SGMs (22-30%), with 19% reporting that health care workers (HCWs) were the source. Among PLWH who had interrupted ART in the last 12 months, 49% reported stigma as the main reason (e.g., fear of others finding out and poor treatment from HCWs). We have described the role of SGM stigma in worsening HIV outcomes in Nepal. The pervasiveness of MH stigma is well-documented in Nepal, including by our team, showing that HCWs have virtually no formal MH training and are often dismissive of people with MH problems. The importance of MH is further elevated because of the high rates of MH problems among PLWH both globally and in Nepal. Furthermore, because only 10% of people with MH problems receive any treatment at all, this allows MH problems to persist. As such, consistent with the goals of this study, there is an urgent need to develop and test interventions that address stigma from HIV, MH, and other dimensions among PLWH in low- and middle-income countries (LMICs) such as Nepal to achieve the goals of improved HIV outcomes. As the field of intersectional stigma grows, there are three major challenges that we seek to address with our intervention. There are multiple challenges in assessing intersectional stigma. There may not be a standard approach to measure something as complex as intersectional stigma, and several recommendations have emerged. First, assessments need to be multidimensional by capturing dynamic contributions from HIV, MH, and other dimensions such as SGM status and/or race (in Nepal, caste). Second, both quantitative and qualitative methods are necessary to capture the complex experiences of PLWH while also tracking trends at a systems-level. Third, assessments should be used routinely within regular clinical practice, both for long-term sustainability and to address the lack of routine stigma data from clinical settings. While assessments need to be multi-level (intrapersonal, interpersonal, organizational, and higher levels), they must incorporate the experiences of PLWH. Finally, assessments should be actionable by directly leading to stigma reduction interventions, and they need to be feasible to use within regular clinical practice. Many interventions have been developed to address stigma, but they often focus on specific conditions (e.g., positive contact with a person with MH problems) and/or at a certain driver (e.g., HCW training to improve comfort and competency in working with SGM), and work at a specific level (e.g., client-level intervention to facilitate access to peers). However, because multidimensional intersectional stigma is driven by multiple drivers working at multiple levels, a major challenge is that stigma-reduction interventions are rarely tailored and customized to the stigma drivers, dimensions, and levels that affect individual clients. As an example, from our consultations in Nepal, if a racially minoritized transgender PLWH is feeling guilty about her decision to take hormones because they are exacerbating her anxiety and she is worried about being stigmatized and stereotyped for not having her emotions under control, this experience may worsen her internalized intersectional stigma from HIV, minority stress, SGM status, and having MH problems. In such a situation, implementing a clinic-wide policy aimed at just one dimension (e.g., developing SGM-friendly registration forms) or HCW training targeting one driver (e.g., dismantling negative SGM stereotypes) is unlikely to increase her engagement in care because these activities, while potentially helpful, are not tailored to her experience. Stigma-reduction activities are often sporadic and are rarely directly linked to specific concerns and experiences of PLWH. As such, there is a large gap in developing and testing interventions that can directly link PLWH concerns with the appropriate stigma-reduction activities. A 2018 review of stigma-reduction activities for HIV, MH problems, and physical disabilities found that 99% of interventions were at intrapersonal or interpersonal levels rather than at organizational/structural levels. This is consistent with other reviews and recent calls for multi-level interventions. Because oppressive structural forces sustain intersectional stigma, interventions need to be multi-level and expand beyond the intrapersonal or interpersonal levels. Digital health can facilitate novel approaches to address the aforementioned three challenges in assessing and addressing intersectional stigma using evidence-based, multi-level activities that are tailored to the dimensions and drivers that are most relevant to PLWH. We have developed a digital health tool INterseCtional stigma assessment and reduction at multiple Levels and mUltiple DimEnsions (INCLUDE) to improve HIV care in ART centers in Nepal. This tool was developed using a human-centered five-step design thinking approach, which is based on the principles of participatory co-design and can incorporate the perspectives of the end users and beneficiaries to develop tools that can help address the problems they face. This tool is designed to address the modifiable drivers of stigma and discrimination at multiple levels. At the organization-level, INCLUDE will routinely link stigma with poor HIV outcomes, enhancing its salience and importance. INCLUDE will provide ART centers with easily accessible stigma-reduction resources and strategies. At the HCW-level, it will facilitate positive contact with stigmatized individuals and deliver training targeting misconceptions and negative stereotypes. At the client level, INCLUDE will facilitate the identification of client-specific stigma drivers and provide a connection with peers who can provide support and acceptance. INCLUDE will provide access to evidence-based stress reduction strategies and referrals to providers who have been identified by local activists as being supportive and accepting of stigmatized individuals. By interrupting the pathways via which intersectional stigma reduces care engagement, we theorize that our multi-level intervention will improve HIV outcomes. The overall goal of this study is to test a digital health tool INterseCtional stigma assessment and reduction at multiple Levels and mUltiple DimEnsions (INCLUDE) to improve HIV care in ART centers in Nepal. The specific objective of this study is to assess the acceptability and feasibility of INCLUDE among clients, HCWs, and ART center leads in four ART centers. This pilot trial will use a single-arm design and will collect both quantitative and qualitative data to evaluate the tool's performance in real-world settings. Participants, including PLWH and HCWs, will be recruited from diverse ART centers, with a particular focus on ensuring representation from marginalized groups, such as Dalits and sexual and gender minorities (SGMs). The study will gather data through surveys, app usage analytics (paradata), in-depth interviews, and focus group discussions. This combination of data collection methods will provide a comprehensive understanding of how the tool is used and perceived, allowing for further refinement and potential scaling of INCLUDE.