His own research originally focused on infections, especially fungal infections, in patients with AIDS and cancer. More recently, he and his group have concentrated on the emerging toxicities of treatment of HIV, especially the metabolic complications seen in patients receiving effective therapy, including the development of diabetes, lipid abnormalities, and bone disease.

He is principal investigator for the Dublin HIV Cohort, a project funded through an HRB programme grant to establish a cohort of HIV infected patients in Dublin to study the natural history and complications of HIV in a diverse population of patients infected with the virus. This is a collaborative project involving investigators based at UCD, TCD and RCSI and the three major Dublin hospitals where HIV patients are seen - the Mater Misericordiae University Hospital, St. James Hospital and Beaumont Hospital. Because of the advances in HIV treatment, HIV/AIDS has changed dramatically from an inevitably fatal infection to one where many patients survive many years but require long-term, possibly lifelong treatment. A cohort study such as the Dublin HIV cohort is critically important in allowing investigators to evaluate new and emerging problems, perhaps relating to survival with a chronic infection or related to problems with long-term medications. The Dublin cohort is particularly pertinent because HIV infection in Dublin is essentially three separate epidemics - sexually transmitted disease in Irish patients (mainly homosexual men), infection in drug using patients and infection in the immigrant population. The cohort will allow investigators the opportunity to determine if there are differences in the natural history and complications of HIV in these diverse groups. To date over 700 patients have consented to participate in the study (which continues to enroll towards its target of 1500-200 patients). All patients are seen every 6 months and clinical and laboratory data recorded. In addition, viruses from the patients are stored at the NVRL and the majority of patients have also consented to DNA being saved and stored for potential future studies. Among the major goals of the study are proposals to examine whether different strains of HIV affect progression or response to treatment and to examine whether a patient's genetic make-up can predict side-effects of treatment.

One of the consequences of patients surviving with chronic HIV infection has been the emergence of long-term complications associated with HIV and its treatment. These included increased risk of increased cholesterol, diabetes and heart disease. Professor Powderly's group has had a long-standing interest in this and when he was based in Washington University in St. Louis, his group was the first to describe osteoporosis (loss of bone mineralization) as a long-term complication of chronic HIV infection. This is potentially important since osteoporosis in other populations leads to increased risk of bone fractures as time progresses. Currently, Professor Powderly's group at UCD and the Mater Misericordiae University Hospital are looking at the prevalence of this problem in the Irish HIV-infected population, examining the risk factors that might predict osteoporosis and studying different approaches to treating or prevention of the problem. In the laboratory, in collaboration with Dr. Peter Doran, director of the UCD-Mater GRU, his group is examining how HIV and drugs used in treatment affect the biology od osteoblasts (the major cells in the body involved in bone formation). They have shown that certain drugs (protease inhibitors) inhibit osteoblasts in culture and are exploring the mechanisms whereby this can occur, In addition, they have also shown that HIV proteins (from the virus itself) can affect osteoblasts in culture suggesting that both the virus and its treatment contribute to bone mineral loss. Identification of these mechanisms can lead to new avenues for treatment and or prevention of this important complication.

Prof. Powderly is widely published in the areas of HIV and AIDS with over 300 original articles or book chapters. Together with Prof. Jonathan Cohen, Dean of the School of Medicine at Brighton and Sussex in the UK, he has edited a major international textbook in Infectious Diseases.