Clinical Research Directory

Implementation Study of Lenacapavir Pre-exposure Prophylaxis for HIV Prevention

The goal of this observational study is to generate real-life information on the use of lenacapavir (LEN, YEZTUGO®, (YTG)) for pre-exposure prophylaxis (PrEP) across diverse clinical settings in the United States. The study will characterize how PrEP is initiated, used, and discontinued in routine clinical practice when LEN is added as PrEP option and will evaluate persistence on LEN PrEP. The primary objective of this study is to evaluate real-life persistence on LEN PrEP at Week 52 in diverse clinical settings in the United States.

Testing the WeCare Intervention to Address Mental Health and Medication Adherence Challenges Among MSM in South Africa

The goal of this clinical trial is to learn if the WeCare intervention-an adapted Friendship Bench program that integrates problem-solving therapy, minority-stress-informed content, and explicit PrEP/ART adherence skills-improves mental health and HIV medication adherence among men who have sex with men (MSM). It will also assess the safety, acceptability, and feasibility of delivering WeCare through trained lay coaches in community clinics. Main questions the trial aims to answer: * Does WeCare reduce symptoms of depression and anxiety among MSM? * Does WeCare improve PrEP and ART adherence and increase rates of viral suppression among participants on ART? * Is WeCare acceptable, feasible, and safe when delivered by lay coaches in POP INN clinics compared with usual care?

Task Shifting to Treat Depression and HIV Medication Nonadherence in Low Resource Settings

A hybrid effectiveness-efficacy trial to evaluate a stepped care task shifted intervention to treat depression and HIV medication nonadherence in low resource settings in rural Zimbabwe.

Supporting Sustained HIV Treatment Adherence After Initiation

The investigators will implement a 24-month fractional factorial design study (Aim 1). The investigators will recruit 510 patients initiating antiretroviral therapy (ART) at three City of Cape Town ART clinics. Each patient will have adherence monitored using the Wisepill® electronic adherence monitoring device (EAM). After eligibility has been confirmed, each participant will be randomized to one of 16 experimental conditions. Each condition includes a unique combination of five adherence intervention components. Three of these components focus on identifying individuals with poor adherence, with increasing degrees of sophistication, with immediate linkage to adherence support. Two components focus on supporting good adherence. They both supplement the existing adherence support program delivered at the study clinics operated by City of Cape Town (standard of care component). Based on Self-Determination Theory, the investigators postulate these intervention components will: 1) enhance feelings of autonomy support, social support, and knowledge; 2) improve motivation and self-competence; and 3) increase ART retention, adherence, and viral suppression. A subset of the participants, as well as clinic staff, will be invited to in-depth interviews to explore mediating factors (Aim 1) and the implementation process (Aim 2); and the data collected in Aims 1 and 2 will be used to explore cost effectiveness (Aim 3).

Study to Evaluate Pharmacokinetic (PK), Safety and Tolerability of Cabotegravir (CAB) 400 Milligrams Per Milliliter (mg/mL) Formulation in Healthy Adult Participants

This is an active control, randomized study to investigate the safety, tolerability and PK of repeat dose administration of long-acting CAB 400 mg/mL formulation intramuscular (IM) (gluteus medius and vastus lateralis) and subcutaneous (SC) (abdominal) injections in healthy adult participants.

The Tatelo Plus Study

The purpose of this study is to advance pediatric HIV treatment and cure research by evaluating the impact of a combination of three anti-HIV-1 broadly neutralizing antibodies (bNAbs) or analytic treatment interruption (ATI) on viral reservoir, immune function, and maintenance of HIV suppression in early-treated children.

Clinic vs Clinic+Community Outreach HPV Self-Collection to Increase Cervical Screening in Women With HIV

This Clinical Trials Network for Human Immunodeficiency Virus (HIV)-Associated Cervical Cancer Screening and Treatment Optimization (CASCADE) C3001-A trial aims to assess how the introduction of a community-health-worker-facilitated model, in addition to the existing static clinic-only model, influences the rates of cervical cancer screening uptake among women living with HIV (WLWH). This study involves offering human papillomavirus (HPV) self-collection for cervical cancer screening to eligible WLWH. The 'CASCADE' Network is a clinical trials network aimed at improving cervical cancer screening, management, and pre-cancer treatment for WLWH, in various healthcare settings. The network will conduct implementation trials to improve the triage of HPV-positive WLWH, as well as algorithms to optimize access to and options for effective treatment. Trials will be conducted using a mixed-methods approach aimed at assessing implementation strategies and outcomes and their potential to integrate into existing health systems. Further understanding of HPV-based community-based strategies to reach WLWH, and the acceptability, feasibility, appropriateness, and cost of these strategies will be valuable for cervical cancer screening programs serving WLWH. Inputs from various 'CASCADE' Clinical Sites (CS) regarding feasible screening outreach options available in their settings for WLWH have guided this study that focuses on evaluating a pragmatic HPV self-collection implementation model to improve access to screening. While it is clear that HPV self-collection is a highly acceptable and feasible screening option, creating opportunities to conduct self-collection in alternative venues outside the clinic premises, and with the guidance of and facilitation by trusted community healthcare workers is an important implementation strategy that needs to be evaluated and considered for its potential benefit. Studies have not yet evaluated a community-based approach for HPV self-collection kit distribution among WLWH - who may have different characteristics, preferences, and access to screening services than women not living with HIV. Providing WLWH with the option of receiving HPV self-collection kits in their own homes or other community-based settings ('community-based HPV self-collection') is a novel implementation strategy that could improve cervical cancer screening rates among eligible women. Therefore, this novel trial aims to evaluate the feasibility and effectiveness of implementing community-based HPV self-collection among WLWH.

Protocol RV 583 Multinational Observational Cohort of HIV and Other Infections

Multinational Observational Cohort of HIV and other Infections (MOCHI). This observational study is to gain information regarding the number of new HIV infections among people who engage in behaviors that make them vulnerable to acquiring HIV across multiple international sites.

The TAIL-PrEP Study

The goal of the TAIL-PrEP study is to understand how to support the safe discontinuation of injectable long-acting cabotegravir (cab-LA) and lenacapavir (LEN) while maximizing the public health impact of biomedical HIV prevention interventions. In Aim 1, the study will pilot test and assess the acceptability and feasibility of the TAIL-PrEP intervention: for participants discontinuing cab-LA, this will consist of monthly cabotegravir drug level monitoring to provide personalized HIV prevention coaching, for participants considering discontinuing cab-LA or LEN, this will consist of a one-time personalized HIV prevention coaching session. In Aim 2, the study will refine the TAIL-PrEP intervention and implementation strategy based on findings from the pilot study.

An Adaptive Randomized Controlled Trial

This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of 4 intervention arms on a combined endpoint in adults with confirmed MDR-TB HIV initiating Bedaquiline-containing MDR-TB treatment regimens and on ART (integrase strand transfer inhibitor (INSTI)-based fixed dose combination therapy) in KwaZulu-Natal, South Africa. Interventions arms include: enhanced standard of care; psychosocial support; mHealth using cellular-enabled electronic dose monitoring; combined mHealth psychosocial support. Level of support will be adjusted using a differentiated service delivery (DSD)- informed assessment of treatment support needs.

A Study to Evaluate the Efficacy, Safety, Participant Choice and Preference of an Oral Once-daily Regimen or a Long-acting Injectable Regimen Every Two Months for Treatment of Human Immunodeficiency Virus (HIV-1) in Adults Who Have Not Previously Taken Antiretroviral Therapy

This is a multicentre study carried out in participants living with human immunodeficiency virus type 1 (HIV-1) who have not previously been treated with any antiretroviral therapies. The study will investigate two 2-drug regimens for the treatment of HIV-1: a fixed-dose combination oral tablet of dolutegravir/lamivudine (DTG/3TC) and cabotegravir plus rilpivirine long-acting agents (CAB + RPV LA). All participants will initially receive DTG/3TC once daily, and once virologic suppression is attained (plasma HIV-1 \<50 c/mL), participants will be offered a choice to switch to CAB + RPV LA or to continue taking oral DTG/3TC. This study will provide important data on the efficacy, safety, implementation effectiveness, and patient-reported outcomes of these two regimens in a study where participants have the option to choose between them based on individual preference. The aim of the study is to evaluate the antiviral effectiveness at 11 months after switching to CAB+RPV LA following initial virologic suppression on DTG/3TC and to provide data on how long it takes participants to suppress their viral load on DTG/3TC.

Study of Limited Versus Continuous Isoniazid Tuberculosis Preventive Therapy in HIV-infected Persons in Botswana

This is a randomized, blinded, two-arm comparative trial of continued versus limited isoniazid (INH) tuberculosis (TB) preventive therapy in HIV-infected adults in Gaborone and Francistown, Botswana. Subjects will be accrued over two years and followed for a minimum of 36 months.

A Study to Evaluate the Effectiveness of Long-acting (LA) Cabotegravir (CAB) + Rilpivirine (RPV) LA When Given to Participants With Detectable HIV-1

This study will assess how effective, safe, and long-lasting a long-acting antiretroviral therapy (ART) using CAB LA + RPV LA is for people with HIV who still have detectable virus levels despite being on oral ART. The study will also consider feedback from patients on their experience with this treatment.

Study of Oral TLR8 Agonist Selgantolimod on HBsAg in Participants With Both Chronic Hepatitis B and HIV

The study aims to assess safety and tolerability of oral toll-like receptor (TLR) 8 agonist Selgantolimod (SLGN) administered for 24 weeks in participants with both CHB and HIV who have been receiving suppressive antiviral therapy for both viruses for ≥5 years and have qHBsAg level \>1000 (3 log10) IU/mL at screening. The study will also evaluate if TLR8 stimulation with SLGN will reduce hepatitis B surface antigen (HBsAg) titers in the blood.

A Setting Focus Overdose Prevention Intervention

A pilot injection-setting targeted peer-driven intervention to reduce HIV and hepatitis C virus transmission and overdose risk behaviors among people who inject drugs (PWID).

Tele-Harm Reduction

The purpose of this study is to test 2 different methods for offering medications that treat HIV, cure Hepatitis C Virus (HCV) (if applicable) and treat substance use disorder (if desired) to people who inject drugs.

Improving the Reach & Effectiveness of Smoking Cessation Services Targeted to Veterans Living With HIV

This project will compare the effectiveness of an HIV-specific comprehensive wellness intervention designed to have broad appeal to smokers living with HIV to the effectiveness of standard care services that include referral to the National VA Quitline and SmokefreeVET texting program. Participants in both arms will have access to pharmacotherapy available through their Veterans Affairs (VA) healthcare providers.

A Peer-Driven Intervention to Increase PrEP Uptake Among Minority MSM

The objective of this study is to develop an effective peer-driven intervention (PDI) approach and assess its feasibility and efficacy on pre-exposure prophylaxis (PrEP) uptake among men who have sex with men.

Intervention Development for Syndemics Among PWH in SA

In South Africa, the country with the highest HIV prevalence (19%), co-occurring problems such as depression, post-traumatic stress, and food insecurity interact to enhance one another (i.e., syndemic problems) and are associated with worse HIV outcomes such as worse antiretroviral therapy (ART) adherence and worse viral load. This study proposes to: 1) explore how syndemic problems work together to make health worse for people with HIV (PWH) and explore what people think about a potential treatment; 2) develop a treatment to address syndemic problems and improve ART adherence (CBT-SA); 3a) assess whether people are willing to receive the CBT-SA we it can actually be done; and 3b) identify factors that make it easier or more difficult to receive CBT-SA.

A Study to Investigate Cabotegravir for Neonates Exposed to HIV-1

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of cabotegravir in neonates exposed to human immunodeficiency virus (HIV)-1.

Treatment of Chronic Hepatitis C With PEG Interferon alfa2a and Ribavirin in HIV-infected Patients

Combination of PEG interferon and ribavirin is the standard treatment of chronic hepatitis C. Efficacy of this treatment has never been evaluated in HCV-HIV infected patients, who have previously been treated with a first line anti-HCV treatment. The purpose of the study is to evaluate the combination PEG interferon alfa2a-ribavirin in HIV-infected patients with chronic hepatitis C pretreated with interferon alone or interferon combined with ribavirin. The patients receive a dose of 180 µg of PEGASYS once a week and 800 to 1200 mg/day of ribavirin (according to weight) for 48 weeks. Primary outcome of the study is a sustained virological response, defined as an undetectable HCV RNA level 24 weeks after the end of anti-HCV treatment.

A Study to Evaluate Efficacy, Safety and Tolerability in Antiretroviral Therapy (ART)-Experienced Participants of at Least 50 Years of Age Living With Human Immunodeficiency Virus (HIV) With Virologic Suppression Who Switch to DTG/3TC FDC From BIC/FTC/TAF

The study aims at evaluating the maintenance of virologic suppression of dolutegravir/lamivudine (DTG/3TC) fixed dose combination (FDC) at Week 48 post-switch from bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in participants living with Human Immunodeficiency Virus Type 1 (HIV-1) who are of at least 50 years of age and above.

Substance Checking Outreach and Pre-Exposure Prophylaxis (PrEP) Engagement Study

Through the proposed Substance Checking Outreach and Pre-Exposure Prophylaxis (PrEP) Engagement (SCOPE) study, the investigators will design and evaluate an overdose prevention and HIV prevention study among people who use drugs (PWUD). Specifically, SCOPE will provide access to drug-checking services for PWUD to better understand the contents of the drug supply, in combination with PrEP for those who are HIV-, to both reduce overdose and HIV among PWUD in Baltimore City.

NOTRE: Optimizing Long-Acting Pre-Exposure Prophylaxis and Medications for Opioid Use Disorder Interventions in Carceral Settings

The investigators plan to conduct an R61/33 hybrid type 2 implementation-effectiveness trial that includes 1) a one-year exploratory R61 phase that will enable the development of the intervention protocol needed for the R33 trial phase including concrete R61 phase milestones; 2) a four-year R33 phase that will include a concurrent implementation evaluation and a randomized control trial.