Work in the Joel Blankson Lab explores the mechanism of control of HIV-1 replication in a cohort of patients known as elite controllers or elite suppressors. These patients are HIV-1 seropositive but maintain levels of viremia that are below the limit of detection of standard clinical assays. We feel that elite suppressors represent a potential model for a therapeutic HIV vaccine. Our central hypothesis is that many of these patients are infected with fully replication-competent HIV-1 isolates that are held in check by the immune system. To test this hypothesis, we are studying many different host and viral factors in these patients.

Research in the Jonathan Golub Lab focuses primarily on the epidemiology of tuberculosis (TB), specifically in patients infected with HIV. We work with the CDC to explore potential delays in TB diagnoses as well as the risk factors that contribute to death from TB in the United States. Our research also includes ongoing studies of HIV and TB patients in Brazil and South Africa.

Research in the Joseph Margolick Lab focuses on the many effects of HIV/AIDS on human health. We are particularly interested in the mechanisms of T-cell loss and preservation among people infected with HIV and the evaluation of human immune functions.

The Johns Hopkins NIMH Center is comprised of an interdisciplinary research team who has pooled their talents to study the nature of HIV-associated neurocognitive disorders (HAND). Their aim is to translate discoveries of the pathophysiological mechanisms into novel therapeutics for HAND.Our objectives are to integrate aspects of ongoing research in HAND and SIV encephalitis; to develop high-throughput and screening assays for identifying novel therapeutic compounds; to use proteomics and lipidomics approaches to indentifying surrogate markers of disease activity; to disseminate information and education about HAND through existing and new educational systems, including the JHU AIDS Education Training Center and the JHU Center for Global Clinical Education and to facilitate the entry of new investigators into neuro-AIDS research, and to catalyze new areas of research, particularly where relevant for drug discovery or the development of validated surrogate markers.

Work in the Christian Merlo Lab includes studies on pulmonary arteriovenous malformations, outcomes in lung transplantation and treatment of cystic fibrosis (CF), and HIV-related pulmonary disease. We have studied methods of diagnosing and managing pulmonary arteriovenous malformations as well as the outcomes of adult CF patients who are infected with multiple antibiotic-resistant Pseudomonas aeruginosa. Our recent research has also explored recipient and donor variables in the success or failure of lung transplants, and ways in which national healthcare delivery systems impact lung transplant outcomes for CF patients.

Dr. Christine Durand, assistant professor of medicine and oncology and member of the Johns Hopkins Kimmel Cancer Center, is involved in clinical and translational research focused on individuals infected with HIV and hepatitis C virus who require cancer and transplant therapies. Her current research efforts include looking at outcomes of hepatitis C treatment after solid organ transplant, the potential use of organs from HIV-infected donors for HIV-infected solid organ transplant candidates, and HIV cure strategies including bone marrow transplantation. Dr. Durand is supported by multiple grants: • R01 from the National Institute of Allergy and Infectious Diseases (NIAID) to study HIV-to-HIV organ transplantation in the US. • K23 from the National Cancer Institute (NCI) to study antiretroviral therapy during bone marrow transplant in HIV-1 infection. • U01 from the NIAID to study HIV-to-HIV deceased donor kidney transplantation. U01 from the NIAID to study HIV-to-HIV deceased donor liver transplantation.

Research in the Craig W. Hendrix Lab concentrates on the chemoprevention of HIV infection, clinical pharmacology of antiviral drugs, drug interactions, and oral, topical and injectable HIV microbicide development. Our lab conducts small, intensive sampling studies of PK and PD of drugs for HIV prevention with a focus on developing methods to better understand HIV and drug distribution in the male genital tract, female genital tract and lower gastrointestinal tract. We also support numerous HIV pre-exposure prophylaxis development studies from phase I to phase III, largely as leader of the Pharmacology Core Laboratory of both the Microbicide Trial Network and HIV Prevention Trials Network.

A. Laboratory activities include the use of accelerator mass spectrometry (AMS) techniques to measure intracellular drugs and drugs metabolites. AMS is a highly sensitive method for detecting tracer amounts of radio-labeled molecules in cells, tissues, and body fluids. We have been able to measure intracellular zidovudine triphosphate (the active anabolite of zidovudine) in peripheral blood mononuclear cells from healthy volunteers given small doses of 14C-zidovudine, and have directly compared the sensitivity of AMS to traditional LC/MS methods carried out in our laboratory. B. Clinical research activities investigate the clinical pharmacology of new anti-HIV therapies and drug combinations. Specific drug classes studied include HIV reverse transcriptase inhibitors, protease inhibitors, entry inhibitors (selective CCR5 and CXCR4 antagonists), and integrase inhibitors. Scientific objectives of clinical studies include characterization of early drug activity, toxicity, and pharmacokinetics. Additional objectives are characterization of pathways of drug metabolism, and identification of clinically significant harmful and beneficial drug interactions mediated by hepatic and intestinal cytochrome P450 isoforms.

The Clinical Laboratory and Biomarkers Cores will coordinate access to laboratory expertise, testing, training, specimen repositories and Good Clinical Laboratory Practices (GCLP). The goals of this core are to assure that all JHU HIV investigators have access to and utilize appropriate, validated and, where applicable, certified laboratory assays. The core will also maintain a biomarker specimen repository for storage cataloguing and utilization of biological specimens.

Research in the Chloe Thio lab focuses on several areas. First, HBV virology and immunology in HBV monoinfected and HIV-HBV co-infected individuals that will ultimately help develop a cure for HBV. Second, HCV infection in men who have sex with men. Third, non-alcoholic fatty liver disease with a focus on HIV-infected individuals. Fourth, host genetic determinants of spontaneous HBV recovery and HCV clearance.