HIV

Background: Human immunodeficiency virus (HIV) infection can affect areas of the brain that control thinking ability. These same areas of the brain also control the sense of smell. HIV infection is common in people with substance use disorder (SUD). SUD also affects thinking ability. Researchers want to learn more about the connection between the sense of smell and decision-making ability in people with HIV, SUD, or both. Objective: To test the sense of smell in people with HIV and/or SUD and how they make choices based on odors. Eligibility: People aged 18 to 65 years with any of these: (1) HIV, (2) SUD, (3) both HIV and SUD, or (4) neither SUD nor HIV. Design: Participants will have 2 visits. Each visit will last 3 to 5 hours. In visit 1, participants will have a blood draw and a saliva swab. They will answer questions about their health, sleep habits, food intake, and substance use. They will have smell tests: They will smell scented sticks and answer questions about them. They will be blindfolded for some tests. They will perform tasks on a computer. They will look at pictures and smell pleasant food odors, such as chocolate cake or pizza. Smells will be delivered using a nasal mask. Their sniffing and breathing will be measured. They may also be exposed to odor-free air. They will eat food that corresponds to one of the food odors they smelled. In visit 2, participants will do a saliva swab and a different computer task that involves odors. They will also have tests of their attention and memory. Participants may opt to have an imaging scan of the brain.

The goal of this clinical trial is to learn if depression treatment improves insulin resistance, or how the body uses insulin to lower blood sugar, in people with HIV on HIV treatment. Researchers will compare an internet-based (online) depression treatment program called cognitive behavioral therapy with depression education. In the online group, participants will undergo 9 weekly treatment sessions. The education group will receive learning materials about depression and will be monitored every month. All participants will have 4 study visits over 12 months.

Managing HIV well requires taking antiretroviral therapy (ART) every day, but many people living with HIV experience interruptions in their treatment. These pauses in medication can happen for many reasons, such as side effects, challenges with getting to the clinic, personal circumstances, stigma, or difficulties with everyday life. When HIV treatment is stopped, the viral load can increase, which may affect a person's health and make it easier for HIV to be passed on to others. Restarting treatment quickly after an interruption is important for both personal and public health. However, it can be difficult for people who miss doses to get back on treatment right away. There are often several steps and medical appointments required before restarting, such as waiting for lab results or reviewing medical history, which can cause further delays. These additional steps can make it even harder for people to re-engage and may discourage them from returning to care. The REINITIATE study is designed for people living with HIV who have not taken any antiretroviral medications for at least the last 12 weeks. The study will offer participants a way to restart their HIV therapy quickly, by beginning treatment with B/F/TAF on the same day that they return to care. B/F/TAF is a widely used, once-daily HIV regimen, and is recommended in national treatment guidelines. Researchers want to find out if this rapid restart approach is safe and effective, and whether it helps people regain control of HIV and remain in care. The study will also examine how many participants are able to keep the virus at a low level (viral suppression), stay engaged in their HIV care, and tolerate the medication after rapidly restarting treatment. In addition, the study will include interviews with some participants, to gain a better understanding of why they stopped taking their medications and what supported their return to treatment. These insights could help healthcare teams develop better ways to support people living with HIV in the future.

A modern and urgent challenge in fighting HIV infection is to achieve sustained HIV remission without the use of antiretrovirals. The investigators' preliminary data indicate that the use of combined strategies to mitigate the HIV proviral reservoir size among individuals with suppressive antiretroviral treatment achieved unprecedented results in the reduction of HIV DNA present in these cells and in the reduction of CD4 + and CD8 + T cell activation. Combined interventions include intensified antiretroviral treatment to mitigate residual HIV replication, use of a histone deacetylase inhibitor to interrupt viral latency, use of an anti-proliferative medication to reduce long-lived T cells that harbor HIV and a personalized dendritic cell therapy vaccine to eliminate cells with latent HIV infection or cells present in viral sanctuaries. Due to the good results obtained in the exploratory stage of the project, the investigators propose to expand it by recruiting a larger number of patients to confirm the previously obtained results and to generate new insights related to the mechanisms involved in viral latency, latency disruption and the effects of analytical treatment interruption of antiretrovirals among patients undergoing all above mentioned interventions.

Project SPACE is a micro-randomized trial evaluating the proximal effects theory-based text messages on alcohol use and sexual HIV risk behaviors among HIV-negative young adult men at the day-level. At baseline, all participants will complete GamePlan, an existing brief online sexual health program. During the subsequent 8-week intervention period, participants will complete a brief morning assessment of the preceding day and will be randomized each afternoon, with equal probability, to receive concrete ("how"), abstract ("why"), neutral control, or no afternoon intervention messages. Participants will also complete pre- and post-intervention measures. The effects of GamePlan are not being separately evaluated in this study.

All patients will be enrolled in Mozambique and Brazil. They will provide informed consent to use their cervical biopsy and/or LEEP specimens for imaging with DeepDOF prior to sending for standard of care processing and interpretation.

This study will collect white blood cells and plasma for research on how the immune system controls HIV infection. The immune system of a very small group of people with HIV, called non-progressors, has been able to control HIV for long periods without antiretroviral therapy. Some immune system-related genes important for this control have been identified in these patients. People living with HIV who are 18 years of age and older, documented or suspected long-term nonprogressors in generally good health may be eligible to screen for the study. Participants will undergo apheresis (a method for collecting larger quantities of certain blood components than can safely be collected through a simple blood draw) if venous access is adequate once yearly. Some may be asked to return every six months. * Automated apheresis - Blood is drawn through a needle placed in an arm vein and spun in a machine, separating the blood components. The white cells are extracted and the red cells, with or without plasma (liquid part of the blood), are re-infused into the donor through a needle in the other arm. An anticoagulant (medication to prevent blood from clotting) is usually added to the blood while in the machine to prevent it from clotting during processing. * Blood draw - a needle placed in an arm vein for large volume (approx 75ml) blood draw if veins considered inadequate for apheresis procedure. Some of the blood collected through apheresis may be stored for future studies of HIV disease and immune function and for HLA testing, a genetic test of markers of the immune system. ...

We are studying virologic and/or immunologic parameters of HIV infection and other infectious or non-infectious immune deficiency diseases in order to better understand the pathogenesis of HIV. Because of the lack of an adequate animal model it is generally necessary to utilize human peripheral blood cells for studying aspects of either in vivo or in vitro HIV infection. We wish to be able to continue to elucidate many pathogenic aspects of HIV infection in relation to other infectious or non-infectious immune regulation and dysregulation using human peripheral blood mononuclear cells as a model....

This study is being done to test whether a drug called baricitinib, which blocks specific causes of inflammation, affects HIV-1 viral rebound and viral load levels after HIV treatment is discontinued. Researchers will test the effects of continuing baricitinib in people with HIV before and after discontinuing their antiretroviral therapy. This drug is approved by the Food and Drug Administration (FDA) for other diseases; it is not approved for the treatment of HIV-1. The study team will also investigate any side effects associated with the drug.

Background: People living with HIV(PLWH) are at a higher risk for cancers that may be curable with a bone marrow transplant. HIV infection itself is no longer a reason to not get a transplant, for patients who otherwise have a standard reason to need transplant. Objective: This study is being done to see if a new combination of drugs (cyclophosphamide, maraviroc, and bortezomib) is both safe and effective at protecting against graft-versus-host disease after bone marrow transplant. The study will also test the transplant s impact on your survival and control of your cancer. Eligibility: People aged 18 years and older living with HIV and a blood cancer that is eligible for a transplant. Healthy family members aged 12 or older who are half matched to transplant recipients are also needed to donate bone marrow. Design: The study will be done in 2 phases. The first phase will be to see if we can safely use a new combination of drugs to prevent GVHD. If the combination is safe in the first phase, the study will proceed to the second phase. In the second phase, we will see if this new combination can better protect against GVHD after transplant. Participants will be screened. Their diagnoses, organ function and eligibility will be confirmed. Participants will have a catheter inserted into a vein in their chest or neck. Medications and transfusions will be given through the catheter; blood will be drawn from it. Participants will be in the hospital for 6 weeks or longer. They will receive various drugs for 2 weeks to prep their body for the transplant. The transplant cells will be administered through the catheter. Participants will continue to receive drug treatments after the transplant. Blood transfusions may also be needed. Participants will return 1-2 times per week for follow-up visits for 3 months after discharge. Participants will have visits 6, 12, 18, 24 months after transplant, then once a year for 5 years.

There is evidence that early and aggressive treatment with antiretroviral drugs can prevent the loss of immune cell function that accompanies HIV infection. This study will use leukapheresis (drawing blood, separating out the white cells and returning the blood to the patient) to obtain blood cells from HIV-infected patients in either the acute or chronic stage of infection who are being treated with early highly active antiretroviral therapy (HAART). Leukapheresis is necessary to obtain enough cells to delineate the response of B cells to CD4+ T cell help, the CD8 factors associated with suppression of viral replication and normalization of immune function, and natural killer function relative to HIV disease. Study participants will be adult (older than 18 years) HIV primary or acutely affected patients (those with a history of exposure to HIV but not yet showing chronic symptoms of HIV disease) and HIV chronically infected patients (those infected with HIV for longer than 12 months or showing other symptoms of HIV disease) who are not receiving HAART at the beginning of the study. The study seeks to enroll 30 primary and 30 chronic patients. Pregnant women will not be enrolled in the study; women who become pregnant will be dropped from the study. Leukapheresis will be performed on each patient before HAART therapy begins and then three times a year. Each session will take between 1 and 3 hours. This longitudinal study will enable researchers to examine the function of certain B cells, natural killer cells, and CD8+ T cells in people who do not have chronic HIV disease and in those who do have the disease and are treated with HAART.

This phase 1 study will evaluate the safety, tolerability, and immune responses of two experimental mRNA HIV vaccines in adults living with HIV who are in overall good health. The study will enroll about 42 participants at multiple study sites. Researchers will assess whether these vaccines can start or strengthen antibody responses against HIV. The study will also evaluate how a closely monitored planned pause in antiretroviral therapy affects these immune responses.

The goal of this study is to learn if STEP-UP (Streamlining Telehealth for Expanded PrEP Utilization through community Partnerships) works to expand access to PrEP for people who could benefit from HIV prevention tools. STEP-UP is an innovative model for PrEP delivery that positions community-based organizations (CBOs) as hubs for PrEP access. STEP-UP builds on the established trust, community expertise, and comprehensive services of CBOs serving individuals who could benefit from HIV prevention tools, integrating telehealth PrEP delivery into their existing infrastructure through partnership with a local telehealth PrEP program. By enabling CBOs to offer telePrEP navigation within their array of health and social services, STEP-UP creates accessible, comprehensive care centers that address barriers to PrEP access faced by individuals who could benefit from HIV prevention tools. The main questions it aims to answer are: 1. Is STEP-UP acceptable and feasible to implement in community settings? 2. Does STEP-UP increase PrEP prescription rates compared to the existing direct-to-consumer telehealth model? Researchers will compare people who receive telehealth PrEP services through STEP-UP at community-based organizations to those who access telehealth PrEP through the existing direct-to-consumer telehealth model. Some participants will: 1. Complete surveys about their experiences with the program 2. Participate in an interview to share their perspectives and feedback about the program.

Background: Human immunodeficiency virus (HIV) infects CD4 T cells. There is no cure for HIV. People with HIV need to take daily medications called antiretroviral therapy (ART) to control their infection. ART stops HIV from infecting cells, but HIV does not go away. Some infected cells remain. If ART is stopped, then HIV levels will rise and infect more cells. Objective: To compare changes in the amount of virus in blood and lymph nodes after a short treatment interruption. Eligibility: Adults aged 18 years or older who are undergoing ART for HIV infection. Design: Participants will be screened with a physical exam, including blood tests. They will be assigned to 1 of 2 groups: One group will stay on ART. They will have 2 study visits: the first 45 days after screening, and the second 12 to 16 weeks later. They will have a PET/CT scan at each visit. A substance called a tracer will be injected into their arm. They will lie still on a table that moves through a doughnut-shaped machine. This process takes up to 2 hours. The other group will stop ART for no more than 90 days. This group will have 3 PET/CT scans over 8 months. Once they stop ART, they will visit the clinic weekly for blood tests. After restarting ART, they will continue to visit the clinic weekly until their HIV level is safe. All participants will have small samples of tissue taken from lymph nodes. They may also opt to provide semen samples or vaginal fluid. They may have samples taken of bone marrow or the fluid inside their spinal column.

The goal of this clinical trial is to learn if a program called Kupambana can improve mental health and HIV care outcomes in young people with HIV in Zambia by combining stigma-reduction support with financial and job-skills training. The main questions it aims to answer are whether Kupambana is feasible and acceptable to young people with HIV and whether it improves mental health, reduces stigma, and improves progress along the HIV care continuum, such as staying in care and taking HIV medicine as prescribed. Researchers will compare young people who participate in Kupambana with those who receive a one-time financial literacy training session (usual care) to determine whether Kupambana leads to greater improvements in stigma, mental health, and HIV care outcomes. Participants will complete a baseline questionnaire and then be randomly assigned to either the Kupambana program or the one-time financial literacy training. Those assigned to Kupambana will attend eight weekly peer-led support group sessions focused on reducing HIV- and poverty-related stigma, receive a voucher for technical and vocational education and training, and attend a one-time financial literacy session. Those assigned to the comparison group will attend only the one-time financial literacy session. All participants will complete follow-up surveys at the end of the program and again 3 and 6 months later.

This clinical trial is designed to test the effects of alendronate (ALN) on people living with HIV who are already receiving antiretroviral therapy (ART). Participants are randomly assigned in a 2:1 ratio to either receive alendronate or a placebo, and neither the participants nor the researchers know who is receiving the actual treatment. The goal is to see if alendronate can reduce the size and activity of the HIV-1 reservoir in these individuals.

The goal of this research study is to test how well an automated text messaging smoking treatment program helps smokers with HIV quit smoking.

There are \~38 million people living with HIV (PLH), with the majority in low-and middle-income countries (LMICs), where the UNAIDS 95-95-95 HIV targets are at risk of not being achieved. Data show that incident infections are concentrated in sub-Saharan Africa and focused in difficult to reach populations. These harder to reach persons frequently also have higher-risk profiles for HIV, making them essential target populations to receive HIV Testing Services (HTS). Among target populations, men, adolescents and young adults (AYAs) aged 15-24 years, and persons from key populations (KPs) represent crucial groups to be reached. In Africa, Emergency Departments (ED) provide care to large numbers of persons that often do not otherwise access health services. Data from Africa show that those seeking emergency care have high burdens of HIV, and desire ED-HTS. As in higher-income countries, EDs in LMICs provide a strategic opportunity to deliver evidence-based HTS interventions to higher-risk persons. In Kenya one in five PLH are unaware of their status, less than half of men are reached for HIV testing at appropriate frequencies, AYAs account for 42% of new infections and KPs contribute to hyper-endemic transmission. To address this, Kenya national strategy calls for utilizing facilities-based care to deliver HTS for difficult to reach populations. However, while the guidelines include EDs as service delivery points, HTS during emergency care in Kenya is still evolving and the evidence-base on best practices is in early development. The HIV Enhanced Access Testing in Emergency Department (HEATED) program in Kenya was developed by a collaborative team led by PI Aluisio (K23AI145411). The HEATED program was derived using the Capability-Opportunity-Motivation Behavioral model to enhance delivery of HTS, through locally appropriate and pragmatic systems initiatives. HEATED program implementation significantly improved HIV testing for the overall ED population by 31%, while also significantly increasing testing for men, AYA and KP and was found to be acceptable by stakeholders. Although pilot evaluation of the HEATED program demonstrated improved HTS for target populations, more robust understanding of optimal implementation strategies in ED settings, impacts on linkage to HIV care outcomes, costing and maintenance data are needed to inform development of ED-HTS programming in Kenya. To address this, the current proposal will build upon the HEATED program by evaluating use of the Systems Analysis and Improvement Approach (SAIA) implementation strategy (HEATED-SAIA) to improve HTS in a cluster randomized trial in all Ministry of Health EDs in Kilifi, Mombasa and Kwale Counties of the Coast Region of Kenya. The Reach, Effectiveness, Adoption, Implementation and Maintenance framework with quantitative and qualitative data will be used in trial assessment. Building on the K23 pilot data and leveraging SAIA, the HEATED-SAIA program has substantial potential to improve HTS delivery by strategically and pragmatically engaging difficult to reach populations already interfacing with emergency health systems, while being acceptable and cost-effective.

Older gay and bisexual men living with HIV (OGBMLH) are more likely to experience depression and loneliness, which can lead to negative health outcomes. This mixed-methods research study will assess the feasibility and acceptability of the Bridge to Belonging (B2B) intervention. B2B is a peer-delivered, manualized program designed to increase engagement in LGBTQ+-affirming elder services and thereby reduce loneliness and depression among OGBMLH. The program utilizes a) cognitive behavioral therapy-based Friendship Enrichment Program (FEP) to build social skills; b) Peer Mentoring (PM) to model and support engagement in community services; and c) connecting participants to affirming elder services such as meal programs, bereavement groups, social activities, etc. Interventions like B2B are essential to the NIH's goal of improving access to behavioral interventions through advances in HIV/AIDS research.

Sexual minority men (SMM) in Jamaica face many challenges that affect their health and well-being. Although they make up a relatively small part of the population, they are much more likely to be living with HIV than the general public. Many also experience discrimination because of their sexual orientation, HIV-related stigma, violence, poverty, unstable housing, limited educational opportunities, and barriers created by laws and social attitudes. These experiences can have a serious impact on mental health, leading to problems such as depression, anxiety, trauma, and thoughts of suicide. Many people also face barriers to getting mental health care because of stigma or a lack of services that are welcoming and appropriate for their needs. These challenges can make it difficult for people living with HIV to stay connected to medical care and take their HIV medications consistently. Missing appointments or stopping treatment can make it harder to keep the virus under control and can lead to poorer health over time. While researchers know that stigma, discrimination, and violence affect health, we still do not fully understand how these experiences work together to influence HIV care among sexual minority men in Jamaica. To help address these challenges, we developed the Gwan Enjoy Life program, a culturally relevant program designed specifically for sexual minority men living with HIV in Jamaica. The program combines practical coping skills, emotional support, and strategies for managing the effects of trauma and stress. It is led by trained peer mentors who are also living with HIV, allowing participants to learn from people who understand their experiences. The six-session program gives participants the option of meeting one-on-one with a peer mentor or participating in a small group, depending on what they find most comfortable. The program will be tested in partnership with Jamaica AIDS Support for Life (JASL), one of Jamaica's leading HIV service organizations. Sixty participants from JASL clinics in Kingston and St. Andrew, St. James, and St. Ann will take part in the intervention. Participants will be randomly assigned to either receive the Gwan Enjoy Life program or continue with their usual care, and they will be followed for one year. Researchers will examine whether the program improves mental health, strengthens social support, helps participants stay engaged in HIV care, and improves medication adherence. The goal of the intervention is to determine whether the Gwan Enjoy Life intervention is a practical and effective program that can be expanded to reach more people across Jamaica. The findings will help researchers, healthcare providers, and policymakers better understand how stigma, violence, and mental health affect HIV care and will support the development of programs that improve the health and well-being of sexual minority men living with HIV.

Mentor Mothers (MMs) are peer supporters who help pregnant and postpartum women living with HIV (WLHIV) as they receive prevention of mother-to-child transmission of HIV (PMTCT) services in resource-limited settings like Kenya. Differentiated service delivery (DSD) is a care model that tailors services based on clients' needs, helping to improve both the quality and efficiency of care. This hybrid implementation-effectiveness study will test whether an enhanced MM strategy that uses DSD can be successfully carried out and improve health outcomes for mothers and infants. The study will take place at Burnt Forest Sub-District Hospital (BFSDH) in Kenya. Researchers will ask: * Can the enhanced MM strategy be delivered as planned and accepted by patients and staff? * Does the strategy improve clinical outcomes like keeping mothers in PMTCT care, achieving HIV viral suppression, completing infant HIV testing, and preventing HIV transmission to infants? Researchers will compare health outcomes before and after the strategy is introduced at BFSDH, and also compare outcomes at other similar clinics that continue with standard MM services. Women who choose to participate will meet with a MM during their routine antenatal and postnatal clinic visits. They will be offered the enhanced MM support, but can choose to receive standard care if they prefer.

The study will adapt and test a combination peer navigation and mHealth approach, Intensive Combination Approach to Rollback the Epidemic in Nigeria (iCARE Nigeria), to improve HIV treatment engagement, medication adherence and viral suppression among YMSM and YTW, ages 15-29.

This is a single site, randomized exercise trial with individuals at least 50 years of age living with HIV who experience suboptimal cognition. The overall goals of this proposal are to determine whether 16 weeks of structured high-intensity interval training (HIIT) can overcome vascular and cognitive impairments (Aim 1) to a greater extent than continuous moderate exercise. Additionally, investigator will seek to identify barriers to engagement in exercise and the participants' perceptions of the study and exercise interventions (Aim 2). This study will enroll 60 participants in Birmingham, Alabama. Data collection will occur at each visit, with baseline data collected at the initial visit with a 3-month follow-up occurring following completion of the intervention.

BACKGROUND: * A number of important scientific advances can be made through the study of blood, bone marrow, tumor, or other tissue samples from patients with HIV infection, infection with Kaposi s sarcoma associated herpesvirus (KSHV), infection with other oncogenic viruses, or cancer. * This protocol provides a mechanism to affect a variety of such studies. OBJECTIVES: -Acquisition of serum, circulating cells, bone marrow, and tumor or normal tissue samples from participants with HIV infection, KSHV infection, or with cancer. ELIGIBILITY: -Eligibility criteria include age 18 years or older and at least one of the following: Exposure risk to HIV, KSHV, or HPV; HIV seropositive; KSHV seropositive; EBV seropositive; HTLV-1 seropositive; malignancy, Castleman s disease, or skin lesions with appearance of Kaposi s sarcoma; or cervical or anal intraepithelial lesion. DESIGN: * Up to 999 subjects will be enrolled in this study. * Blood samples may be collected at the initial visit, and at follow-up visits. * Other fluids/excretions may be collected (such as urine, saliva, semen, and stool). * Tumor samples may be obtained by fine needle aspirate, by removal of pleural or peritoneal fluid, by skin punch biopsy, or by excisional biopsy, providing the tumor is accessible with minimal risk to the participants. * Specific risks will be described in a separate consent to be obtained at the time of the biopsy. * Samples will be studied in the HIV and AIDS Malignancy Branch, CCR, NCI; laboratories in NCI-Frederick; or those of collaborating investigators.

This is a study to determine the effect of the human immunodeficiency virus (HIV) on lymphoid tissues (e.g., lymph nodes) as compared to peripheral white blood cells. We have shown in previous studies that the lymph node is a major site of accumulation of HIV in the body, as well as being a site where much of the viral replication occurs which leads to the destruction of the body's immune system. To better understand the role of the lymph node in HIV infection and destruction of one s immunity, we wish to examine both the virus itself as well as the effects it is having on various types of white cells (called lymphocytes) obtained simultaneously from both peripheral blood and lymph nodes of people living with HIV (PLWH). We also need to look at cells derived from blood and lymph nodes from people who do not have HIV to serve as a control for experiments. We may also use your lymph node tissue and blood cells to attempt to make new T-cells, or rebuild the immune cells, in the laboratory by adding various factors or other substances released by different cells in the body. If you are living with HIV, you may be asked to undergo a second biopsy six weeks to 12 months after the first biopsy. Because of the ability of aspirin to interfere with blood clotting, you must have refrained from the use of aspirin for one week (7 days) prior to the biopsy date. You also cannot use non-aspirin containing, non-steroidal, anti-inflammatory medications (e.g., ibuprofen, naproxen, and similar drugs) one week (7 days) prior to the biopsy. In addition, pregnancy testing will be performed on all females at the time of admission and a positive test will exclude you from participation. No participant will undergo more than six biopsies while participating in this study unless a particular research requires it.