Clinical Trials

The University of Miami has engaged in NIH-sponsored and industry sponsored clinical trials encompassing Phase 1, Phase II, and Phase III studies in HIV-infected adults, children including adolescents, and HIV infected pregnant women for prevention of mother to child transmission as well as trials conducted through the Drug Abuse Clinical Trials Network. In addition, investigator initiated clinical trials are also ongoing.

Description of Clinical Intervention Trials
The University of Miami has been a designated site for NIH-sponsored AIDS Clinical trials since the inception of the AIDS Clinical Trials Group (ACTG) in 1987, including both, the Adult and Pediatric AIDS Clinical Trials Units, (which includes perinatally infected children and adolescents as well as pregnant women) and the expansion of this effort through the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) in 1999. 

UM ACTUs have played pivotal roles in the development and optimization of therapies and prevention modalities for HIV/AIDS.  In addition, UM is a very active site for industry-sponsored trials.  Through the clinical trials, UM has contributed toward the approval of several antiretroviral drugs, numerous HIV treatment strategies including lower and alternative dosing schedules for all three major classes of antiretroviral agents, early treatment intervention, combination therapies with dual NRTIs, and triple/quadruple-drug therapy.

The Adult AIDS Clinical Trials Group, AACTG (Margaret A. Fischl, M.D.)
Studies conducted by the AACTG have produced dramatic improvements in the clinical care, quality of life, and survival of persons with HIV/AIDS. The AACTG developed, conducted, and published the majority of the ground-breaking randomized clinical trials that are the basis of the current national and international antiretroviral therapy and opportunistic infection treatment and prevention guidelines for the management of HIV-1-infected adults.

The Miami ACTU continues to actively participate in HIV Disease RAC efforts and provide expertise to address study treatment strategies for initial therapy, treatment options for virologic failure and utilization of phenotypic and genotypic assessments to direct subsequent therapy and treatment intensification. The Miami ACTU will also bring expertise in the areas of hepatitis B and C pathogenesis and treatment, metabolic complications of HIV-1 protease inhibitor pathogenesis and treatment, HIV dementia pathogenesis and treatment and peripheral neuropathy pain assessment, Kaposi sarcoma (KS) pathogenesis, intensive immunologic monitoring and definition, and validation of immunologic determinants of treatment response.

The Miami ACTU enrolls approximately 100 subjects per year across AACTG studies and 70 patients into AACTG sub studies, including complications, virology, viral dynamics, pharmaceuticals, metabolic, neurological, women's health and adherence and outcomes sub studies.

The Pediatric AIDS Clinical Trials Group, PACTG (Gwendolyn B. Scott, M.D.)
The PACTG has addressed critical questions related to the interruption of mother-to-child transmission (MTCT) of HIV and the treatment of HIV infection and its complications in pregnant women, infants, children, and youth.

This effort resulted in the first studies to define treatments that have reduced MTCT of HIV and the majority of the efficacy and safety data for antiretroviral therapy in infants, children, and pregnant women.

These efforts have also contributed to understanding the pathogenesis of HIV in the pediatric population, including neonatal HIV infection, co-receptor usage and pediatric-specific HIV disease markers used to assess the effectiveness of antiretroviral therapy.

Over the next several years, the Miami Unit will continue to contribute to the scientific agenda of the new network, IMPAACT (International Maternal, Pediatric, Adolescent Treatment Trials) by developing new protocols, participating in scientific committees, and assisting in the expansion of the scientific endeavors of the IMPAACT in the developing world.

The Adolescent Medicine Trials Network, ATN (Lawrence Friedman, M.D.)
The ATN has been involved in promising behavioral, microbicidal, prophylactic, and therapeutic studies for the adolescent population affected by HIV. ATN research has focused on antiretroviral strategies tailored to the adolescent population, the impact of metabolic complications of antiretroviral therapies in women, the typology of adherence in youth and the assessment and comparison of serum and salvia antibody testing for detuned assays to enhance the rapidity and ease of the recognition of HIV infection in youths.

The Special Adolescent Clinic (SAC), in which HIV-infected youth are seen, is intimately related to the Ryan White CARE Act Title IV family-centered efforts in the Departments of Pediatrics and Obstetrics and was the most active site of the NIH’s longitudinal 1994-2001 REACH Study research program for HIV-infected adolescents, enrolling the largest cohort.

The research effort continues and since 2001, this site is a part of the NIH’s current Adolescent Trials Network for HIV/AIDS Interventions. Miami has distinguishing itself by having the highest site performance score since inception, as well as great subject enrollment.

Clinical Research Unit: (Michael Kolber, M.D., Ph.D.)
The Infectious Diseases Research Unit (IDRU) at the University of Miami Miller School of Medicine was established seven years ago to provide a venue and research for physicians to perform clinical trials, and foster academic growth of physicians. 

In general, the focus of the Unit has been on the performance of industry sponsored HIV-related trials and has performed over 80 clinical trials from phase II to phase IV over the past 5 years. Routinely 20-30 clinical studies stemming from pharmaceutical and federally sponsored trials are performed involving approximately 200 subjects at any one time.  The Unit currently participates in two trials that have been folded into the INSIGHT network-ESPRIT (Dr. Kolber) and SMART (Dr. Rodriguez).

The Miami VAMC HIV/AIDS program (Gordon Dickinson, M.D. and Nancy Klimas, M.D.)
The VA HIV program was established as one of four national centers in 1987. Since that time we have cared for more than 3,000 HIV infected veterans. Currently this program is an outpatient-based multidisciplinary program with MD and ARNP specialists also providing primary care for HIV infected veterans.

The program also has designated nursing, social work, nutrition, and psychology staff in addition to research personnel. These patients are predominantly heterosexual, African-American, males, with almost 40% population older than 50 years of age, providing opportunities for study of HIV in aging, and HIV with atherosclerotic co-morbidities. This group has been conducting clinical trials and research studies funded by the CDC.

The AIDS Malignancy Consortium, AMC (William Harrington, Jr. M.D. (a component of research area #2, viral oncology)
This consortium has been involved in enhancing therapeutic options for patients with AIDS-associated malignancies, including Kaposi’s sarcoma, lymphoma, and human papillomavirus. The consortium has shifted focus to translational research/drug development, optimization of clinical management, and cancer prevention through primary studies or substudies to assess risk and cancer susceptibility in the HIV-positive population

The Drug Abuse Clinical Trials Network (Jose Szapocznik, M.D.)
This network has been involved in studies of behavioral, pharmacological, and integrated behavioral and has been in the forefront of pharmacological treatment interventions for drug abuse.

The Florida component of the Drug Abuse Clinical Trials Network has developed and published efficacious family-based treatment models and brings considerable strength in family-based interventions with drug abusing populations (adolescent drug abusers, drug addicted new mothers, HIV+ women using drugs intermittently) and with HIV+ populations (HIV transmission prevention, family ecological therapy to improve individual and family functioning).

HIV Complications Research
A large proportion of HIV infected patient population followed by UM physicians suffers from a co-morbidity including the cardiac, renal, hepatic, metabolic, osseous, and ocular or nervous system as well as co-infections such as TB and HCV.  Among these, the major NIH funding is for cardiovascular/metabolic/nutritional complications and neurological morbidity.

D-CFAR and Neuro-AIDS Research
The presence of a D-CFAR enhances and promotes Neuro-AIDS research, building on current faculty expertise and interest and in other fields of neuroscience that may be readily applicable to AIDS such as neuroimmunology, neurovirology, “neuropathogenesis,” and clinical neuromuscular disease.

The principal barrier to enhancing Neuro-AIDS research is the paucity of well-funded Neuro-AIDS-related basic scientists and clinical investigators.  Additional existing barriers to Neuro-AIDS research include lack of communication – research environments are not well linked – as well as the need for more human tissue substrates for laboratory-based Neuro-AIDS research.

To overcome these barriers, the D-CFAR permits established research centers at the Miller School of Medicine to coordinate expertise in immunology and histopathology (The Sylvester Comprehensive Cancer Center and its core facilities), neurobiology (The Miami Project to Cure Paralysis), and clinical neuromuscular disease (The Kessenich Family Center for ALS and the Division of Neuromuscular Disease, Department of Neurology).

One of the most important functions of the D-CFAR is to promote communication and education in order to develop and nurture the Neuro-AIDS research community.  This will be accomplished through seminar series or campus conferences on Neuro-AIDS sponsored by this D-CFAR.  The Department of Neurology has established funds to sponsor a Neuro-AIDS visiting professor annually, and this visit will be hosted by the D-CFAR.

Furthermore, the D-CFAR supports the formation of collaborative working groups of diverse investigators on the Miller School of Medicine campus, including funding for pilot proposals from investigators new to the area of Neuro-AIDS research.