Clinical Research Directory

REINItiation of Antiretroviral Therapy Using Oral bicTegravir, emtrIcitAbine and Tenofovir alafenamidE

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 Clinical Trial Investigating the Safety and Biological Activity of the Antibody BNT351 in Adults Living Without and With HIV

This study will test the safety and blood levels of the antibody BNT351 in people living without and with human immunodeficiency virus (HIV). This study will also test the anti-viral activity of BNT351 in people living with HIV (PLWH) with detectable virus levels. The main goals of this study are: * To learn about the safety of BNT351 and check for side effects. * To measure the amount of BNT351 antibody in blood over time. * To test the amount of HIV in the blood at different times after treatment with BNT351 in people living with HIV.

Early Neutralizing Antibodies in Infants Living With HIV to Enhance Their Life (2)

The goal of this clinical trial is to learn if subcutaneous ePGT121v1-LS and VRC07-523-LS added to standard antiretroviral therapy (ART) is safe and helps improve HIV viral suppression in infants living with HIV in Mozambique and Cameroon. The study will also learn how the body processes ePGT121v1-LS and VRC07-523-LS and whether caregivers and health workers find this treatment approach acceptable. The main questions it aims to answer are: * Are ePGT121v1-LS and and VRC07-523-LS safe and well tolerated in infants living with HIV? * Does adding ePGT121v1-LS and VRC07-523-LS to standard ART increase the number of infants who achieve HIV viral suppression by week 48? * How long does it take participants receiving ePGT121v1-LS and VRC07-523-LS to achieve viral suppression compared with standard treatment alone? * How does ePGT121v1-LS and VRC07-523-LS behave in the body after repeated subcutaneous injections? Researchers will compare infants receiving ePGT121v1-LS and VRC07-523-LS plus ART to infants receiving standard ART plus placebo (saline) to see if ePGT121v1-LS improves HIV viral suppression. Participants will: * Continue taking standard oral ART. * Receive 4 subcutaneous injections of ePGT121v1-LS and VRC07-523-LS or placebo every 12 weeks. * Attend regular clinic visits for safety checks, blood tests, and HIV viral load monitoring. * Have follow-up visits for 48 weeks. * Participate in evaluations of treatment adherence and acceptability from the perspective of caregivers and health workers.

Impacts of HIV Treatment Regimens on Archived Drug Resistance

The study aims to determine the prevalence of drug resistance mutation (DRM) in virally suppressed HIV infection, and the impacts of regimen change and the presence of low level viremia. Adults living with HIV infection on antiretroviral therapy (ART) with full viral suppression would be recruited. Cases are patients planning for regimen switch, while controls are those with and without low level viraemia (LLV) not planned for switch. Blood samples would be collected before and after switch. Sequencing would be performed to identify DRM present in HIV-1 proviral DNA.

Resistance Profile to Antiretroviral Medications in Individuals Living With HIV Who Failed a First-Line Regimen With Tenofovir / Lamivudina and Dolutegravir in Brasil

The goal of this study is to understand the profile of individuals who demonstrate transmitted drug resistance to Dolutegravir (DTG) among PLHIV in Brazil in terms of the subtypes of virus and other individual characteristics after 24 weeks of treatment with a regimen of DTG, Tenofovir, and Lamivudine (TL+D). The study also seeks to determine what alterations occur in the 3'-PPT region of the HIV virus in patients with failing the TL+D regimen. The test group will be compared to a control group of individuals randomly selected whose viral control remains below detection limit (50 copies/mL) for 24 weeks after the initiation of treatment. The study uses clinics in cities in each of the five regions of Brazil: South region (Porto Alegre, Viamão), Southeast region (São Paulo, Santos, Guarujá), Northeast region (Salvador), Center West region (Brasília), and the North region (Manaus). Porto Alegre and Viamão are of interest because of the strong presence of subtype C in the South region. Salvador is a focus for subtype F of HIV. Finally, in Santos there is a strong presence of recombinant forms of subtypes F and B. These non-B subtypes are important to the study as they are typical of other medium and low income countries. The plan for the study includes 200 cases who will receive the TL+D medication for 24 weeks (50 in each region) and 400 controls again spread among the regions on a 1 (case): 2(control ratio.

Cabotegravir & Rilpivirine Antiretroviral Therapy in Pregnancy

Phase IV, multi-site, open-label, non-randomized study of the pharmacokinetics (PK) of long-acting injectable cabotegravir and rilpivirine (CAB LA + RPV LA) during pregnancy and postpartum.

HIV-1 Virologic Suppression With TMB-365 and TMB-380 Antibodies Study

TMB-365 is a monoclonal antibody that binds to the CD4 receptor. TMB-380, aka VRC07-523LS is a monoclonal antibody that binds to HIV. Both interfere with HIV entry. This study is designed to test the combination of the antibodies as maintenance therapy in HIV infected suppressed individuals discontinuing oral cART for 48 weeks. Researchers will compare TMB-365/TMB-380 given IV every 8 weeks to continuation of daily oral cART to see if TMB-365/TMB-380 can also maintain viral suppression. Participants will: 1. Receive TMB-365/TMB-380 infusion or take oral cART as scheduled for 48 weeks 2. Visit the clinic as schedule for checkups and tests

Short-term Effects of Methamphetamine on Residual Latent HIV Disease Study

The most commonly used illicit stimulant in people with HIV (PWH) is methamphetamine (MA). Prior studies demonstrate strong evidence that MA promotes increased HIV transcription as well as immune dysregulation. A challenge in achieving worldwide HIV eradication is targeting specific marginalized populations who are most likely to benefit from an HIV cure but possess poorer immune responses. For this study, N = \~20 PWH virally-suppressed on antiretroviral therapy (ART) with no prior history of MA use disorder will be administered oral methamphetamine to determine the effects of short-term MA exposure on residual virus production, gene expression, and inflammation. Measures of MA exposure in urine and serum will then be associated with residual virus production, gene expression, cell surface immune marker protein expression, and systemic markers of inflammation. Thus, the proposed work will leverage a unique clinical trial design to generate advanced gene expression and immunologic data to identify potential novel targets for reversing HIV latency, reducing inflammation, and personalizing future therapies in PWH who use MA.

Combining Latency Reversing Agents to Address the HIV Reservoir

The PLUTO trial aims to contribute to the worldwide search for a functional cure of HIV. One the strategies ("shock and kill' strategy) aims to reverse the HIV-reservoir from latency by increasing cell-associated HIV-RNA, which will lead to increased antigen presentation, trigger immune recognition, and facilitate the elimination of reservoir cells. Participants of the trial are adults with HIV with undetectable viral load that are able to give informed consent to participate in the trial, in total 30 patients will be recruited. The investigational medical compounds in this trial are topiramate, lenalidomide and pyrimethamine, which will be combined. These are all licensed drugs for other conditions. The study consists of two phases. In phase I participants will receive a single dose of the IMPs, as combination therapy. Sampling will be performed before, during and after medical treatment to evaluate latency reversal and safety endpoints. In phase II, participants will receive the combination of IMPs which is the most potent and within safety limits selected from phase I during a four-week treatment. Sampling will take place on a weekly basis to assess latency reversal, reservoir reduction and safety. Participants will be recruited from the Erasmus MC, Amsterdam university Medical Center, Radboud University Medical Center and the University Medical Center Utrecht.

Safety Study of MucoCept-CVN

MucoCept-CVN uses a Lactobacillus strain native to the human vagina that is modified into a live biotherapeutic product (LBP) that continuously expresses a potent anti-HIV drug. If research shows that MucoCept-CVN is safe and effective, it could become a self-renewing, female-initiated prevention product for women that promotes vaginal health and provides protection from HIV. The goal of this first-in-human Phase 1 dose-ranging, randomized, placebo-controlled study of MucoCept-CVN is to collect data on safety, colonization, changes to the vaginal microbiota and clearance of the strain with antibiotics. Twelve healthy women will be enrolled and take either one or three doses of MucoCept-CVN or placebo, and a week later will receive antibiotics to clear the Lactobacillus strain. If research shows that MucoCept-CVN is safe and effective, it could become a self-renewing, long-acting, female-initiated prevention product for women that promotes vaginal health and provides protection from HIV.

Prevention ICONA Dedicated Ensemble

Despite significant advances in HIV treatment, transmission remains a public health concern. In 2022, there were 1.3 million new HIV infections worldwide and 1,888 new diagnoses in Italy, with sexual transmission being the predominant route. Many individuals are still diagnosed late, and a portion of people living with HIV are unaware of their status. Pre-Exposure Prophylaxis (PrEP) has emerged as an effective biomedical strategy to prevent new infections, especially when integrated into comprehensive prevention efforts. Study Objectives The primary objective of this observational study is to establish a large prospective cohort of individuals using PrEP in Italy. The study aims to assess PrEP's effectiveness, tolerability, adherence, and barriers to long-term use in a real-world setting. These data will be instrumental in guiding future strategic interventions to optimize PrEP management and move toward the goal of zero new HIV infections in Italy. Primary Objective * To assess the incidence of new HIV infections among PrEP users in Italy. Secondary Objectives * Incidence of other sexually transmitted infections (STIs); * Tolerability of PrEP; * Psychological and behavioral aspects related to PrEP use; * Adherence and persistence in care; * Use of therapies and prophylaxis for STIs during PrEP use. Study Design and Coordination This is a prospective observational study, promoted by Fondazione ICONA in collaboration with clinical centers and community-based organizations. The coordinating enrolling center is INMI "L. Spallanzani" IRCCS in Rome. Participating Centers: * 49 university and hospital-based centers across Italy; * 4 non-clinical checkpoints offering PrEP screening, prescription, and follow-up. Study Population Adults (≥18 years) who are HIV-negative, sexually active, and considered eligible for PrEP per national or international guidelines, including both new and current PrEP users. Inclusion Criteria * Age ≥18 years; * Negative HIV test at enrollment; * Willingness to initiate or continue PrEP; * Informed consent provided. Exclusion Criteria * HIV infection or strong suspicion of infection; * Contraindications to PrEP medications; Known allergy to PrEP components; Refusal to comply with study procedures.

PERSON-CENTERED APPROACHES TO VIREMIA: CONNECTION, RAPPORT, AND ENGAGEMENT STUDY

The study aims to increase the reach of the person-centred interpersonal practices by developing and accessing a tailored, scalable, and sustainable approach that meets the distinctive needs of populations identified as most disproportionately affected by viremia in Zambia. The study population include pregnant and breastfeeding women, children, adolescents and adult that are more than thirty -30 days late for their next hospital appointments.The study will be implemented over a period of 36 months in 24 facilities in Lusaka and Central province, Zambia.

Establishment of a Database of HIV Subjects Initiating or Simplifying Dual Therapy With Dolutegravir/Lamivudine

The introduction of combination antiretroviral therapy (cART) has completely revolutionized the management of HIV-positive patients, drastically reducing HIV-associated mortality and morbidity. In fact, the course of HIV infection has transformed into a chronic disease. The availability of different classes of antiretroviral drugs, such as nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs, NNRTIs), protease inhibitors (PIs), integrase inhibitors (INSTIs) and viral entry inhibitors (IEs) that act in different phases of the HIV life cycle, together with careful patient management, has allowed us to obtain long-lasting therapeutic efficacy in the vast majority of Italian patients, making this infection a chronic disease.