Clinical Research Directory

Therapy Adapted for High Risk and Low Risk HIV-Associated Anal Cancer

This phase II trial studies the side effects of chemotherapy and intensity modulated radiation therapy in treating patients with low-risk HIV-associated anal cancer, and nivolumab after standard of care chemotherapy and radiation therapy in treating patients with high-risk HIV-associated anal cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as mitomycin, fluorouracil, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab after standard of care chemotherapy and radiation therapy may help reduce the risk of the tumor coming back.

Menopausal HT for Women Living With HIV (HoT)

Women living with HIV have been shown to experience more frequent and severe hot flashes and night sweats (collectively known as vasomotor symptoms) as compared to women living without HIV. This correlates with disturbed sleep, increased depressive symptoms, increased anxiety, worse mental function, interference with activities of daily living including work, and worse overall quality of life. Hormone therapy is considered to be the most effective therapy for hot flashes and night sweats and the most appropriate choice to prevent bone loss at the time of menopause for women without HIV. However, the usefulness of hormone therapy has not been specifically studied in women living with HIV. This trial is being done to see if: * There is evidence to support the use of hormone therapy (estradiol with or without progesterone) for the treatment of hot flashes and night sweats in women living with HIV * Hormone therapy improves mental function, mood, sleep, quality of life, bone health, heart health, and inflammation in women living with HIV * Hormone therapy is safe and tolerable for women living with HIV

the ANRS CO21 " Extreme " Cohort (CODEX)

A consortium of research teams has studied the immunovirological characteristics of these patients: The ANRS CO15 ALT cohort The ANRS CO18 HIV Controller cohort the ANRS EP47 VISCONTI study

Very Early Intensive Treatment of Infants Living With HIV to Achieve HIV Remission

The study will explore the effects of early intensive antiretroviral therapy (ART) with or without a broadly neutralizing antibody (bNAb) on achieving HIV remission (HIV RNA below the limit of detection of the assay) among infants living with HIV.

Surgery in Treating Patients With Early Stage Anal Canal or Perianal Cancer and HIV Infection

This phase II trial studies surgery in treating patients with anal canal or perianal cancer that is small and has not spread deeply into the tissues and human immunodeficiency virus (HIV) infection. Local surgery may be a safer treatment with fewer side effects than bigger surgery or radiation and chemotherapy.

MK-4646 Multiple Dose Trial in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) (MK-4646-003)

This study will examine if at least one dose level of MK-4646 can lower HIV-1 viral load in a person's blood by a certain amount. The goals of this study are to learn about the safety of MK-4646 and if people tolerate it; and how HIV-1 viral load may decrease after starting to take MK-4646.

Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV

This phase I trial investigates the side effects of cabozantinib and nivolumab in treating patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and who are undergoing treatment for human immunodeficiency virus (HIV). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and nivolumab may shrink or stabilize cancer in patients undergoing treatment for HIV.

#AWARE.HIV Europe: Supporting Healthcare Professionals to Find Undiagnosed HIV in European Hospitals: An Effectiveness-implementation Trial.

The #aware.hiv Europe study is a real-world, multicenter, stepped-wedge cluster randomized, effectiveness-implementation trial designed to evaluate whether the introduction of dedicated HIV teams in hospitals can improve HIV testing rates among patients presenting with HIV indicator conditions across ten European countries. Study Design: The study employs a stepped-wedge design, whereby clusters of hospitals transition sequentially from a control phase (routine care) to an intervention phase. All patient data are collected retrospectively from routine care, while prospective data are gathered at the healthcare professional level. The project spans four years and involves hospitals from the Netherlands, Belgium, United Kingdom, Germany, Spain, France, Italy, Romania, Poland, and Ukraine. This design allows for comparison of HIV testing rates and related outcomes before and after the implementation across different settings and time points. Intervention: The core intervention involves the establishment of hospital-based HIV teams. Each team is led by an HIV specialist and supported by nurses and data collectors. Their responsibilities include: Identification and Surveillance: Screening routine electronic health records for HIV indicator conditions using predefined ICD-10 codes and verifying cases that warrant HIV testing. Audit \& Feedback: Providing targeted recommendations to treating physicians when an HIV test is indicated but has not been performed, thereby prompting action. Education \& Training: Delivering training sessions to healthcare professionals to improve their knowledge and attitudes towards HIV testing, prevention, and care. Enabling Environment: Implementing digital solutions and other support mechanisms to streamline testing processes, reduce stigma, and enhance overall guideline adherence. Linkage to prevention: Improving linkage to the locally available preventive services. The intervention is intended to integrate seamlessly into routine hospital care, thereby reinforcing existing guidelines while addressing the current diagnostic testing gap. Endpoints and Outcome Measures: Primary Endpoint: The change in HIV testing rate among patients diagnosed with HIV indicator conditions before and after the implementation of HIV teams. Key Secondary Endpoints: The change in the incidence of new HIV diagnoses among patients with HIV indicator conditions. Variations in HIV testing rates across different countries, medical specialties, and types of indicator conditions, as well as over time. Assessment of the cascade of HIV diagnosis, including the proportion of patients identified with an indicator condition, the offer and acceptance of HIV testing, and documented reasons for non-testing. Evaluation of the cascade of HIV care and prevention, including linkage to HIV care, achievement of viral suppression, and referral and uptake of preventive services. Changes in healthcare professionals' knowledge, attitudes, and levels of stigma towards HIV. Implementation outcomes such as fidelity of HIV team activities, resource utilization, cost-effectiveness, and sustainability of the intervention. Analysis of contextual factors, barriers, and facilitators impacting the implementation process, using established frameworks like CFIR and RE-AIM. Impact: By introducing HIV teams and systematically monitoring their effect on HIV testing practices, the study aims to enhance early HIV diagnosis and improve patient outcomes. The findings will contribute to evidence-based guidelines and may promote the adoption of similar interventions across European healthcare settings, ultimately reducing HIV-associated morbidity, mortality, and transmission rates. This project not only addresses a critical diagnostic gap in HIV care but also provides valuable insights into the effective implementation of complex interventions in routine clinical practice.

Baricitinib Curative Repression of HIV-1

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.

"Pregnancy and Viral Infections: Impact on Pregnant Women and Their Children. French Prospective Cohort"

The VIROPREG study is a French prospective multicenter cohort study that aims to assess the impact of viral infections and antiviral treatments received during pregnancy on maternal and child health. The study focuses on both chronic viral infections: human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV)\] and on arbovirus infections. This study aims at investigating the following research questions: * What is the rate of mother-to-child transmission for each virus? * What are the effects of maternal infection on (i) pregnancy outcomes, (ii) the mother's physical and psychological health, and (iii) the fetus' health and development, with a focus on long-term psychomotor development in children born to women living with HIV? * What is the impact of antiretroviral and/or antiviral prophylactic and/or therapeutic treatments administered during pregnancy on maternal and fetal health? Mother-child pairs will be followed from pregnancy through delivery and from birth until the child reaches 7 years of age. Each mother-child pair will be enrolled into one of four cohort groups based on the maternal infection. HIV Cohort: Pregnant women living with HIV who participate in the research will: * Be followed according to the routine care schedule from enrollment to post-natal visit usually scheduled in maternity after delivery (6-8 weeks post-partum) * Participate in additional follow-up by phone call or videoconference at 4- and 7-years post-partum for research purposes * Complete questionnaires at inclusion, delivery, 4- and 7- years postpartum * In case of breastfeeding, receive follow-up care aligned with routine schedules for up to 2 years postpartum, including 2 additional visits specifically for research at 2- and 3- months postpartum. * In selected cases: provide blood, umbilical cord blood, colostrum and breast milk samples during follow-up visits for research purposes (pharmacological and virological analyses). Children born to mothers living with HIV and who participate in the research will: * Be followed according to the routine care schedule from birth until 2 years of age * Participate in additional follow-up by phone call or videoconference, addressed to mothers, at 4- and 7- years of age for research purposes. HBV Cohort: Pregnant HBV-infected women who participate in the research will: * Be followed according to the routine care schedule from enrollment to post-natal visit usually scheduled in maternity after delivery (6- 8 weeks post-partum) * Complete questionnaires at inclusion and delivery * Provide blood samples during follow-up visits for research purposes. Children born to HBV-infected mothers and who participate in the research will: * Be followed according to the routine care schedule from birth to 2 years of age * Participate in additional follow-up for research purposes at 3 months and 18-24 months of age. HCV Cohort: Pregnant HCV-infected women who participate in the research will: * Be followed according to the routine care schedule from enrollment to post-natal visit usually scheduled in maternity after delivery (6 - 8 weeks post-partum) * Complete questionnaires at inclusion and delivery * Provide blood samples during follow-up visits for research purposes. Children born to HCV-infected mothers and who participate in the research will: * Be followed according to the routine care schedule from birth until 2 years of age * Attend additional follow-up visits scheduled at 3 and 9 months of age for research purposes. Arbovirus Cohort: Pregnant women infected with arbovirus who participate in the research will: * Be followed according to the routine care schedule from enrollment to delivery * Participate in additional follow-up for research purposes at 4 years after delivery. * In case of breastfeeding, women will be monitored for research purposes at Day 7 and Day 30 postpartum * Complete questionnaires at inclusion, Day 7-10 from the inclusion, delivery and 4 years after delivery * Provide blood, amniotic fluid, placenta, umbilical cord blood, colostrum and breast milk samples during follow-up visits for research purposes. Children born to mothers infected with arbovirus and who participate in the research will: * Be followed according to the routine care schedule from birth until 2 years of age. * Participate in additional follow-up for research purposes at inclusion, Day 7 and Day 30 after inclusion * Participate in additional follow-up by phone call or videoconference, addressed to mothers, at 4- and 7- years of age for research purposes.

Immune Cell Therapy (CAR-T) for the Treatment of Patients With HIV and B-Cell Non-Hodgkin Lymphoma

This phase I trial evaluates the side effects and usefulness of axicabtagene clioleucel (a CAR-T therapy) and find out what effect, if any, it has on treating patients with HIV-associated aggressive B-cell non-Hodgkin lymphoma that has come back (relapsed) or not responded to treatment (refractory). T cells are infection fighting blood cells that can kill tumor cells. Axicabtagene ciloleucel consists of genetically modified T cells, modified to recognize CD-19, a protein on the surface of cancer cells. These CD-19-specific T cells may help the body's immune system identify and kill CD-19-positive B-cell non-Hodgkin lymphoma cells.

Integrating Vaccination Into Hospital Care Pathways for Vulnerable Patients

AMBU-VAX is a prospective, single-center observational study designed to develop and implement an organizational model for delivering recommended vaccinations within a hospital setting. The study targets adult and elderly patients with chronic diseases or immunocompromising conditions who are eligible for vaccination according to national immunization guidelines. Vaccination is actively proposed during outpatient visits, hospital admissions, or at discharge and, when accepted, administered within the hospital or coordinated with local public health vaccination services. The study aims to evaluate the feasibility, uptake, and completion of hospital-based vaccination pathways and to support integration between hospital and territorial prevention services for vulnerable populations.

Multiplo Tp/HIV Self-Test

To help reach the undiagnosed living with HIV and/or syphilis in Canada, self-tests for HIV and Syphilis may have substantial utility for increased identification of infected individuals through their relative ease of use and portability, as well as their ability to deliver rapid, actionable results while the care provider still has access to the patient. MedMira Laboratories Inc. (Halifax, Nova Scotia, Canada) has developed a point-of-care (POC) test to detect HIV and Syphilis antibodies in fingerstick blood samples that is under final review by Health Canada for use by trained Healthcare professionals. A self-test version of this test, with simplified instructions for use has been developed for investigational studies. The goal of the following study sponsored by REACH Nexus is to provide evidence that untrained lay persons / intended users can perform the Multiplo Tp/HIV Self-Test without any increased risk of obtaining erroneous results.

Impact of Behavior Modification Interventions and Lung Cancer Screening on Smoking Cessation in People Living With HIV: A Feasibility Study

This clinical trial evaluates the usefulness of using a smartphone-based HIV-specific smoking cessation intervention at the time of lung cancer screening in helping people living with HIV quit smoking. Positively Smoke Free - Mobile may help patients with HIV quit smoking.

HIV+ Deceased Donor Heart Transplant Study for HIV+ Recipients

This will be a prospective single-center interventional trial to compare the outcomes of HIV-positive heart transplant recipients by the HIV status of the donor; HIV-positive vs. HIV-negative and learn whether heart organ transplantation from HIV+ deceased donors is as safe and effective in HIV+ recipients as transplants from HIV- deceased donors. Patient will undergo standard evaluation for eligibility of transplantation by the primary heart transplant team. If patient meets eligibility criteria, they will be informed about the study and consent will be obtained. Informed consent will be obtained in a private clinic or inpatient hospital room in a confidential setting. HIV-positive or HIV-negative offers will be made by Organ Procurement and Transplantation Network (OPTN) (serving as a means of "natural randomization" and this information will also be collected, along with the information regarding any information for primary offer declines from the patients as well as other clinical indications to decline an organ offer. As a result of this, there will be two main groups in the study participants that will undergo analysis: 1. patients/recipients that are HIV+ who receive an organ from an HIV+ donor (HIV D+/R+ group) 2. patients/recipients that are HIV+ who receive an organ from an HIV negative donor (HIV D-/R+ group) Only study participants will be able to receive organ offers from both HIV-positive and HIV-negative organ donors whichever is available first regardless of HIV status. This is the only study intervention. Baseline visit parameters will be obtained during a routine heart transplant visit. There will be no additional procedures or blood collection after the baseline study visit. Study data will be collected from chart review of routine post-transplant follow-up visits at weeks 52 (1 year), 104 (2 years), and 152 (3 years) after the transplant.

MAPS PrEP Van Study

For this study the investigators aim to see if giving participants an oral HIV prevention medication on a medical van, is a good option of care for individuals who inject drugs and/or are sexually active and therefore at a higher risk of contracting HIV.

Enhancing Cervical Cancer Screening and Treatment in Women Living With HIV in Kenya, the ENHANCE LINKAge Trial

Background In sub-Saharan Africa (SSA), human papillomavirus (HPV) and HIV create a dual burden of disease that causes significant morbidity and mortality in the form of cervical cancer (CC). Women living with HIV (WLWH) have a six-fold higher risk of developing precancerous lesions that persist and progress to CC, which is the leading cause of cancer mortality among women in Kenya. Significant support from the Go Further campaign, represented by donors such as the President's Emergency Plan for AIDS Relief (PEPFAR), the George W. Bush Institute, UNAIDS, Merck, and Roche, to integrate CC screening into HIV clinics represents an exceptional opportunity to scale CC impact across SSA, but only if implementation science evidence is available to inform strategy. Currently, the impact of Go Further has been undermined by fractured linkages to care and insensitive screening methods; in Kenya, less than 2% of WLWH screened have received appropriate treatment. Implementation science studies are needed to better understand and surmount barriers to integrated care in publicly funded HIV clinics. Broad objective This study seeks to explore and innovate strategies to overcome patient-, provider-, and system-level barriers to implementing CC screening and referral guidelines, link WLWH who require further diagnostic testing and/or treatment with effective and accessible care, and document services for accountability and quality improvement. In this proposal, our team will apply our extensive implementation science expertise and partnerships with Kenya Ministry of Health (MOH) to adapt and test evidence-based strategies (e.g., HPV self-testing, care navigators, and the WEMA mHealth app \[tested and scaled in Tanzania\]) that address key multi-level barriers identified through a formative, stakeholder-engaged research phase. Methodology Using the EPIS framework to guide our project, we will: Aim 1a), Explore (engage a multi-disciplinary stakeholder advisory board to co-design the intervention package and prioritize implementation strategies that align with local capacity, opportunities, and motivations; Aim 1b), Prepare (develop tools and strengthen capacity at clinics to implement the strategies; Aim 2), Implement and evaluate the package of implementation strategies via a cluster-randomized stepped wedge trial in 9 clinics (assessing implementation \[provision of CC screening with HPV self-testing\] and effectiveness \[proportion of HPVpositive WLWH who receive subsequent diagnostic triage and/or treatment\] over months 0-12; and Aim 3), assess Sustainability (costs, cost-effectiveness, and transfer of delivery from study to local staff over months 13-18. Significance of the study The overall goal of this study is to employ rigorous empirical methods to adapt and test implementation strategies that expand the scope of HIV care to screen for and treat early precancerous CC lesions in a sustainable, scalable way. Through partnering with Kenya's MOH, this project will have critical institutional support and dissemination capability, and will directly inform public health practice and policy.

A Study of Doravirine/Islatravir (DOR/ISL, MK-8591A) for the Treatment of Human Immunodeficiency Virus 1 (HIV-1) Infection in Participants Who Previously Received DOR/ISL (MK-8591A-054)

The purpose of this study is to evaluate the safety and tolerability of DOR/ISL in adult participants with HIV-1 who had been previously treated with DOR/ISL in earlier clinical studies. There are no formal hypotheses to be tested in this study.

Gene Therapy After Frontline Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma

This pilot clinical trial studies gene therapy after frontline chemotherapy in treating patients with acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). Placing genes for anti-human immunodeficiency virus (HIV) ribonucleic acid (RNA) into stem/progenitor cells may make the body build an immune response to AIDS. Giving the chemotherapy drug busulfan before gene therapy can help gene-modified cells engraft and work better.

Screening Algorithms for Cervical and Anal High-Grade Squamous Intraepithelial Lesions in People With HIV in Mexico and Puerto Rico

This clinical trial aims to find what different tests work best to find high-grade squamous intraepithelial lesions (HSIL) in the cervix or anus in patients living with human immunodeficiency virus (HIV). Patients with HIV are at high risk of becoming infected with human papillomavirus (HPV) in the cervix or anus where it can turn into cancer over several years. HPV causes changes to the cervix and anus, known as HSIL. This means that there is an area of abnormal tissue on the top layers of the cervix or anus. It is considered cervical or anal cancer if the abnormality spreads down into the layers of tissue below the top. If found early, many cases of HSIL can be treated before turning into cancer. Screening for cervical or anal cancer detection or HSIL associated with HPV may result in earlier treatment, if necessary, for patients living with HIV.

Gene Therapy and Combination Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma

This pilot clinical trial studies gene therapy following combination chemotherapy in treating patients with acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma. Placing genes that have been shown in the laboratory to inhibit the growth and spread of the immunodeficiency virus (HIV) into the patient's peripheral blood stem cells may improve the body's ability to fight HIV. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving gene therapy after combination chemotherapy may improve the body's ability to fight HIV and AIDS-related non-Hodgkin lymphoma.

Establishing Optimal Number of Doses for HPV Vaccination in Children and Adolescents Living With HIV, OPTIMO Trial

This phase IV trial compares 3 different dosing schedules to find the optimal number of doses for HPV vaccination in children and adolescents living with HIV. Comparing 3 different dosing schedules may help researchers determine whether a single dose of HPV vaccine could be effective in preventing HPV in children and adolescents living with HIV.

Cardiovascular Risk in Children With Chronic Conditions Study

Children living with chronic health conditions face a higher risk of developing cardiovascular diseases than their peers, largely due to the accelerated aging of the heart and blood vessels. Although experts recognize this elevated risk and recommend close monitoring and early intervention, the underlying mechanisms driving this phenomenon remain poorly understood. At present, no effective interventions specifically target its root causes. Recent research shows that both large blood vessels (such as the carotid artery) and small vessels (such as those in the retina) can display early signs of damage decades before clinically apparent heart or vascular disease emerges. This accelerated vascular aging can result from multiple factors - including disease-related processes such as persistent inflammation and metabolic disturbances, treatment-related effects such as chemotherapy or long-term steroid use, and lifestyle changes associated with chronic illness, such as reduced physical activity and altered eating habits. However, it is still unclear how these factors influence the development and progression of vascular changes in children as they grow. Importantly, these changes can be monitored through non-invasive methods, offering a unique opportunity to study at-risk patients many years before overt cardiovascular disease develops. Identifying these early changes may enable us to detect and track individuals at heightened risk well in advance of clinical disease. This study aims to deepen our understanding of the causes of increased cardiovascular risk in children with chronic conditions and to lay the groundwork for earlier, more targeted prevention strategies.

Anal Cytology Collection Procedures in Predicting High-Grade Anal Dysplasia in Men Who Have Sex With Men

This clinical trial compares three anal cytology collection procedures (collected at a single visit) in men who have sex with men (MSM). It also compares two different tests for human papilloma virus, the virus that causes high grade anal dysplasia, which is thought to occur before anal cancer. This study may help doctors develop better screening for high-grade anal dysplasia in MSM in order to identify those who need to return for additional screening and treatment.