Human Immunodeficiency Virus

Background: A person s genome is the collection of all their genes. A gene instructs individual cells to make proteins. Proteins are involved in all of our body s chemical processes. Genome sequencing allows researchers to find variations in genes. Some of these are normal and are not known to cause disease. Some variants are known to cause or affect diseases like cancer. Researchers want to study genetic variants in people with cancer who also have an immunologic disease like HIV. Objective: To study the biology of cancer in order to improve ways to prevent, detect, and treat it. Eligibility: Adults at least 18 years old with certain cancers and/or immunodeficiencies Design: Participants will be screened with medical history, physical exam, and lab tests. Participants will give samples of one or more tissue type. They may give blood or urine samples. Researchers may get samples of tissue when participants have surgery or when the participants are on other protocols in the NCI. Participants may have a procedure to have tissue samples removed. Researchers may collect data from participant medical records. Researchers will compare the genes in a participant s cancer tissue to their normal tissue. They may use the tissue cells to grow new cells in a lab. Participants may be contacted about the results. The samples will be stored for future research. No personal data will be kept with them. ...

Background: Antiretroviral viral therapy (ART) allows people with human immunodeficiency (HIV) to live long, healthy lives. But ART is not a cure. HIV can remain in the body, in infected cells called reservoirs. If a person stops taking ART, the HIV can rebound and reach high levels in their blood. Researchers want to find ways to reduce the size of HIV reservoirs in people taking ART. Objective: To test a drug (lenacapavir) in people with HIV who are on effective ART. Lenacapavir, also called Sunlenca, is already approved for use in people with HIV who cannot be treated with standard ART. Eligibility: People aged 18 to 75 years with HIV that has been suppressed for at least 3 years with ART. Design: Participants will have 13 clinic visits over 2 years. Participants will be screened. They will have a physical exam with blood tests. They will maintain their ART throughout the study. Participants will undergo leukapheresis up to 6 times. Blood will be drawn via a tube in an arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be returned to the body through a second tube. Two-thirds of participants will take lenacapavir in addition to their regular ART. They will receive the drug as an injection under the skin 3 times at 6-month intervals. They will also take lenacapavir as 2 pills swallowed by mouth on the first 2 days of the study. ...

Historically, the database on the HIV was organized within the framework of the medico-economic file of the human immunodeficiency (DMI-2), introduced jointly by the Direction of Hospitals (Mission AIDS) and the INSERM at the end of the 80s. Today this database is fed via the computerized medical record NADIS. Most part of the research works on the theme of the HIV take support on this database (DAD, EuroAIDS, Neuradapt).

Background: A person s genome is the collection of all their genes. A gene instructs individual cells to make proteins. Proteins are involved in all of our body s chemical processes. Genome sequencing allows researchers to find variations in genes. Some of these are normal and are not known to cause disease. Some variants are known to cause or affect diseases like cancer. Researchers want to study genetic variants in people with cancer who also have an immunologic disease like HIV. Objective: To study the biology of cancer in order to improve ways to prevent, detect, and treat it. Eligibility: Adults at least 18 years old with certain cancers and/or immunodeficiencies Design: Participants will be screened with medical history, physical exam, and lab tests. Participants will give samples of one or more tissue type. They may give blood or urine samples. Researchers may get samples of tissue when participants have surgery or when the participants are on other protocols in the NCI. Participants may have a procedure to have tissue samples removed. Researchers may collect data from participant medical records. Researchers will compare the genes in a participant s cancer tissue to their normal tissue. They may use the tissue cells to grow new cells in a lab. Participants may be contacted about the results. The samples will be stored for future research. No personal data will be kept with them. ...

This phase II trial studies how well donor cytotoxic T lymphocytes work in treating patients with malignancies with BK and/or JC virus. Cytotoxic T lymphocytes are made from donated blood cells that are grown in the laboratory and are designed to kill viruses that can cause infections in transplant patients and may be an effective treatment in patients with malignancies with BK and/or JC virus.

Alcohol use disorder (AUD) has been associated with high prevalence of inflammation-associated co-morbidities in people living with HIV even those receiving effective antiretroviral therapy (ART). Our preliminary data support a model in which the combined insult of AUD and HIV on the gut, specifically on the microbiota and intestinal barrier integrity, exacerbates inflammation. Our preliminary data using intestinal organoids also suggest a potential mechanism for AUD-mediated changes in the gut barrier function during HIV; the intestines of HIV+ individuals have low resilience to alcohol induced intestinal barrier disruption caused by high levels of oxidative stress. Finally, our preliminary data also suggest a potential approach to enhance the integrity of the intestinal barrier and reduce gut derived inflammation in people living with HIV with/without AUD- short chain fatty acid prebiotics. These prebiotics prevent alcohol mediated adverse effects on the intestinal barrier and inflammation by preventing oxidative stress. These prebiotics are safe and decrease gut inflammation in humans. 40 HIV+ ART+ (20 AUD- and 20 AUD +), will be recruited for a prebiotic intervention. This is a proof-of-concept intervention study to establish a causal link between microbiota-gut and HIV pathology during ART by asking whether modifying microbiota and gut milieu impacts intestinal barrier function, systemic inflammation, and brain pathology in HIV+ people. Participants will complete three in-person clinic visits and four virtual check-in visits during this 8 week study. This study uses a crossover design. At baseline, participants will be randomized to receive either a prebiotic or a placebo for the first intervention period. After completing this period, participants will cross over to receive the alternate study product for the second intervention period, allowing each participant to serve as their own control. These participants are part of the larger observation study (n=160), which will test the hypothesis that intestines from HIV+ individuals have lower resilience to alcohol mediated gut barrier disruption than intestines from HIV-negative controls. New participants will also be recruited. Blood, urine, and stool, will be collected from participants to compare intestinal barrier integrity, system and gut inflammation, immune activation, oxidative stress, microbiome/metabolome. and HIV reservois.

The goal of this study is to test the maximum tolerated dose of ACU-D1 in HIV-positive people with HPV-associated vulvar and perianal lesions. The main questions it aims to answer are: * The maximum tolerated dose of ACU-D1 * Safety and tolerability of topical ACU-D1 * Whether topical ACU-D1 induces p53 and p53-mediated downstream signaling (including p21 induction) in HPV-related lesions * Whether topical ACU-D1 enhances markers of immunity in HPV-infected HIV-positive individuals Participants will be asked * To apply ACU-D1 on the lesions twice daily for 4 weeks * 3 biopsies will be performed at the screening and 3 at the end of 4 weeks.

This study seeks to improve mental health, pregnancy, and HIV outcomes among pregnant and postpartum women living with HIV with common mental health disorders in Kenya. The investigators will tailor a collaborative care model for peripartum women with HIV experiencing mental health symptoms and evaluate its impact on participants' mental health, antenatal, and HIV care outcomes. The investigators will actively engage key stakeholders throughout the process and assess scalability and sustainability through multi-method approaches. This study will contribute to the overall goal of achieving optimal health outcomes for women living with HIV and their families in sub-Saharan Africa.

There is an urgent need to address HIV inequities and disparities in the US, particularly within vulnerable communities such as Hispanic/Latino gay, bisexual, and other men who have sex with men (HLMSM).

This study aims to evaluate the efficacy of cefixime compared to benzathine penicillin G in the treatment of syphilis.

People living with HIV (PLWH) who use drugs experience significant health disparities including lower rates of retention in HIV care and higher rates of unsuppressed viral load, resulting in secondary infections and increased mortality. The proposed study will used mixed methods to explore (a) the relationship between healthcare providers' attitudes towards working with PLWH who use drugs and providers' acceptance and practice of structural and relational harm reduction; (b) the degree to which relational harm reduction moderates the effect of intersectional stigma experienced in healthcare settings on patients' perceptions of their relationship with providers; (c) the degree to which structural HR moderates the relationship between the patient-provider relationship and clinical outcomes, and (d) whether patient-perceived HR approaches to care are directly associated with HIV clinical outcomes. The study will also use these findings to inform the development and pre-testing of an intervention to operationalize harm reduction in HIV clinical settings, using stakeholder-engaged and human-centered design approaches, presenting a novel path to reducing HIV health inequities for PLWH who use drugs.

The goal of this randomized clinical trial is to evaluate the safety and immunogenicity of the HIV Therapeutic DNA Vaccine (ICVAX) in participants with HIV-1 infection under antiretroviral therapy (ART). The study compares three delivery methods - Teresa -EPT I, PharmaJet Tropis, and PapiVax TriGrid EP - to induce antigen-specific T cell responses in the participants. The primary objectives are to evaluate the safety of ICVAX delivered using three different devices in the participants within the period Day 0-Day 336, and to evaluate the antigen-specific T cell responses induced by ICVAX in the participants within the period Day 0-Day 168. The participants will receive four injections of ICVAX administered at 4-week intervals. Following the final dose, participants will be monitored for 36 weeks.

The increased life expectancy of Patients Living With HIV/AIDS (PLWHA) has increased the need for therapies for chronic conditions, such as chronic pain. Pain in the HIV population is often refractory and ends up being treated with chronic opioids, which are associated with adverse effects, including hyperalgesia, constipation, and risk of overdose. Naltrexone is an opioid antagonist used in the treatment of alcohol and opioid use disorders. Low Dose Naltrexone (LDN), naltrexone at a much lower dose, is thought to be an immune modulator and has been associated with an increased CD4 count in PLWHA. Repurposing this medication is relatively inexpensive and has the potential to expand access to treatment for a painful condition experienced in PLWHA. While there are many case reports on the efficacy of LDN in symptom reduction, there are only a small number of clinical trials that specifically examine pain and symptom relief. This study will include patients who are not completely virologically controlled and will monitor the CD4 counts drawn as a part of routine care. If the CD4 count improves with LDN and with reduced symptoms, this could be a significant improvement in HIV therapy for symptom control. There have been studies showing cytokine reduction in fibromyalgia patients but they did not investigate the correlation with cytokines and pain relief. This study involves repurposing a drug used for substance use disorder to a medication with the potential to treat pain and improve symptoms for PLWHA.

There is still no cure for the human immunodeficiency virus (HIV). While combination antiretroviral therapy (cART) is effective in decreasing deaths from HIV, infected individuals face a lifetime of treatment and many potential complications including end organ diseases such as HIV-associated neurocognitive disorders. HIV infection is controllable with antiretroviral therapy (ART), but ART cannot eliminate HIV reservoirs. Thus, there is no available cure for HIV. There is a large and growing body of evidence that the central nervous system (CNS) is an HIV reservoir site and a barrier to HIV eradication. Our group has done extensive pre-clinical work with janus-kinase (JAK 1/2) inhibitors. This includes baricitinib, which is an orally available, FDA-approved drug for rheumatoid arthritis. Evidence suggests that this drug has activity against HIV in the central nervous system (CNS). In our recently completed pilot study, we showed that baricitinib crosses the blood brain barrier (BBB) and decreases HIV CNS persistence in the brain. Using bloodwork, neurocognitive testing, MRIs and lumbar punctures, we plan to evaluate the change in central nervous system HIV after treatment with baricitinib versus placebo. We will also evaluate changes in neuroimaging, inflammation in blood and cerebrospinal fluid (CSF), and neuropsychological performance after treatment with baricitinib versus placebo. Evidence shows that the central nervous system is one of the reservoir sites that enables the HIV virus to persist in the body even after years of treatment. In order to attack this reservoir and eventually find a cure, it is vital to learn if certain medications can suppress HIV in the CNS.

There are very little data on human papillomavirus (HPV) vaccination among the 18 million women living with HIV (WLWH) globally, who constitute a population most vulnerable to HPV and the resultant cervical cancer. Particularly, there are no data to date on reduced-dose schedules of nonavalent HPV (9vHPV) vaccination in WLWH and there are very little data on the 9vHPV vaccine in this population overall. It is critical to examine the 9vHPV vaccine in WLWH now because the quadrivalent HPV (4vHPV) vaccine has been discontinued. Additionally, in order to reach the World Health Organization's global goal of cervical cancer elimination, we must determine the role of various HPV prevention strategies in this important population including reduced vaccine dosing which can drastically increase the feasibility of HPV vaccination programs globally. This randomized clinical trial will enrol WLWH aged 18-45 from across Canada who have not previously received an HPV vaccine. Participants will be randomized 1:1 to receive 3 doses of 9vHPV vaccine at the routine vaccine schedule of 0/2/6 months or 2 doses at an expanded schedule of 0/6 months with a third dose at month 12 to adhere to current recommendations for WLWH. We will compare the immune response generated to two versus three doses of 9vHPV vaccine and will follow participants for 2 years to examine the immune response over time. This study, which builds upon our team's prior work on HPV vaccination in WLWH, will determine whether two doses of 9vHPV vaccine can be used in WLWH instead of three, and will examine additional aspects of HPV vaccination in WLWH including the immune response to three doses, vaccine safety and efficacy, and attitudes towards self-collected HPV samples in this population. These data will inform global public health policy and programming and will inform the global strategy for cervical cancer elimination.

The goal of this study is to determine how many patients with HIV or at high risk of getting HIV attend the Emergency Department (ED) in South Africa (SA). The investigators will integrate HIV assessment in the ED and see how many people who would be a candidate for a drug that prevents HIV (PrEP). Universal test and connect (UTC) is a strategy that universally tests all patients and connects patients to long-term care, whether HIV positive or negative, including referrals for PrEP. The investigator's goal is to use UTC across two busy 24-hr EDs in Cape Town, SA.

The goal of this clinical trial is to learn if the DSD model (SUSTAIN-DSD) is effective in improving participants HIV treatment adherence. The main questions it aims to answer are: * Does the SUSTAIN-DSD intervention significantly improve participants' treatment adherence and increase rates of viral suppression? * Does the SUSTAIN-DSD intervention help retain people in care? * Does SUSTAIN-DSD intervention help reduce the length of treatment interruptions? * for 24 months, Participants will either receive the SUSTAIN-DSD intervention (i.e. be enrolled in an adherence club where the participants will pick up 6-months of ART medication and have the option to use peer support and additional counseling), and or enhanced standard of care (i.e. visit the clinic for treatment and participate in optional counseling sessions). Blood will be drawn from the participants at the adherence club visits for viral load tests at baseline and every 12 months. \- Participants will take part in interviews to discuss the participants' experience with the SUSTAIN-DSD intervention.

This is a Phase I, randomized, double-blind, placebo-controlled clinical study to define the safety and immunogenicity resulting from a rapid dose-escalating vaccination schedule as compared to that of a co-administered, dose-consistent vaccination schedule. Participants randomized to receive vaccines will get either dose-consistent injections of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV or rapid, dose-escalating injections of CH505 TF chTrimer+ALFQ with an Ad26.Mos4.HIV prime, followed by dose-consistent injection of CH505 TF chTrimer+ALFQ co-administered with Ad26.Mos4.HIV

The U.S. Department of Health and Human Services (HHS), through the National Institutes of Health (NIH), published Final Human Immunodeficiency Virus (HIV) Organ Policy Equity (HOPE) Act Safeguards and Research Criteria for Transplantation of Organs Infected With HIV. All such transplants must occur under an institutional review board (IRB) approved research protocol that is compliant with federal regulations governing human subjects research. This is an investigator-initiated, observational prospective study of solid organ transplantation utilizing HIV-positive donors in HIV positive recipients. Stable HIV-infected adults in need of a solid organ transplant (kidney) who meet standard and study specified HIV criteria for organ transplantation will be offered enrollment in the study. Deceased donors (kidney) and living donors (kidney) will be utilized in this protocol. The goal of this research is to increase knowledge about the safety, efficacy, and effectiveness of solid organ transplantation (SOT) utilizing HIV-positive donors in HIV-positive recipients.

The goal of this research study is to test an intervention to help quit tobacco use in participants with Human Immunodeficiency Virus (HIV). The study interventions used in this research study are: * Positively Smoke Free - Mobile (PSF-M) (mobile behavioral program) * Varenicline (or Chantix, apovarenicline, Champix or Nocrav)

The overall objective is to evaluate the efficacy of educational text messages to reduce cardiovascular risk among persons living with HIV (PLWH).

The primary objective of this study is to determine the magnitude and breadth of the serum antibody response to the nonavalent HPV vaccine (Gardasil-9) in adults with well-controlled HIV infection. The secondary objectives of the study are to observe short term clinical outcomes of prevalent HPV genotype-specific anogenital infections in adults living with HIV who complete the three-dose Gardasil-9 vaccine series, and to determine the protection afforded by Gardasil vaccine over time in previously vaccinated adults living with HIV. The clinical hypothesis is that adults with virologically controlled HIV mount a serum antibody response to the nonavalent HPV vaccine that is comparable to HIV negative counterparts. We also postulate that HPV vaccination will provide short-term clinical benefit against HPV infections and disease associated with vaccine genotypes and continuing protection against vaccine genotypes of HPV over time.

This proof-of-concept study aims to investigate the potential impact of supplementing with Nicotinamide Mononucleotide (NMN), a direct precursor of NAD+ on CD4+ T cell recovery in virologically suppressed HIV patients experiencing immunological failure on ART. We hypothesize that NMN supplementation will increase intracellular NAD+ levels, thereby improving CD4+ T cell function and potentially reversing immunological failure. A small cohort of patients will be recruited to evaluate the primary outcome of change in CD4+ T cell count from baseline to the end of the study period after receiving NMN daily for 12 weeks. Secondary outcomes including safety and tolerability, impact on pro-inflammatory markers, increase in NAD+ levels, immune activation markers and change in quality of life questionnaire scores. Patients will participate in two in person visits including a baseline and end of study with two telephone encounters. Patients will take 1,000mg NMN daily for a total of 12 weeks during which they will keep a daily log of doses taken and any side effects experienced. At all visits labs and quality of life questionnaire will be completed with complete physical exam to be done at baseline and end of study visit.

This will be a multi-center, single arm observational cohort study with an assessment of patient-reported outcomes (PROs) and of clinical and virologic outcomes. Primary outcome • Evaluate patient perception of, and satisfaction with, long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) for the treatment of HIV Secondary outcomes • Description of the demographic, HIV-, and non-HIV-related characteristics of participants included in this analysis

WHO: 24 participants with cognitive deficits due to a Human Immunodeficiency Virus (HIV) infection, able to engage in moderate physical activity. WHY: The Human Immunodeficiency Virus is known to cause deficits in cognitive function, even under effective pharmacological viral load suppression. Cognitive dysfunction in patients with HIV is frequent and has a detrimental impact on their everyday personal and professional life. The purpose of this study is to evaluate two sets of computerized exercises combining cognitive and physical effort to see if they can improve executive function in patients with an HIV infection. WHAT: Study participants first undergo cognitive and physical assessments. Additional questionnaires will assess mood, everyday life cognition, function and quality. This will be followed by a 6 week training period with 2 training sessions a week. The effect of the physical and cognitive training will be measured in a post-training evaluation session. Six months after completion of the training, the study will evaluate cognitive and physical abilities of participants to study long-term effects of the respective training program. WHERE: Both the evaluation and the training sessions will be conducted on the premises of the Lausanne University Hospital (Rue du Bugnon 46, 1005 Lausanne, Switzerland)