Infectious Disease Faculty Heavily Involved in HIV Clinical Research
In addition to the wealth of bench research done by the Division of Infectious Diseases, MCW faculty are engaged in a variety of HIV clinical research trials. The research trials are conducted at the Froedtert Hospital Infectious Diseases clinic and at the AIDS Resource Center of Wisconsin medical clinic.
Under the leadership of Dr. Michael Frank, MCW is an affiliated research site with INSIGHT- (International Network for Strategic Initiatives in Global HIV Trials). INSIGHT is one of six HIV/AIDS clinical trials networks funded in 2006 by the National Institute of Allergy and Infectious Diseases, a division of the National Institutes of Health. MCW has been chosen as a site for the START trial (Strategic Timing of Antiretroviral Treatment). The purpose of this randomized study is to determine the optimal timing of initiation of antiretroviral therapy (ART) with regard to morbidity and mortality among HIV-1 infected patients who are naïve to ART and have CD4 + cell counts greater than 500 cells/mm3. This study will randomize participants to two study arms: (1) immediate initiation of ART; and, (2) deferred ART until the participant’s CD4+ cell count decreases to less than 350 cells/mm3. This study will answer an important and controversial question regarding the optimal time to initiate antiretroviral therapy. Current guidelines reflect the uncertainty of when to initiate therapy and no randomized-control trials have been done yet to address this important question.
MCW also participated in INSIGHT’s SMART (Strategies for the Management of Antiretroviral Therapy) trial. This was a pivotal trial which investigated whether episodic treatment based on CD4+count was preferable to continuous therapy, previously a controversial topic in HIV care. Importantly, and contrary to results of multiple observational cohort studies, this trial proved the superior outcomes of individuals who are treated with ART continuously.
Dr. Andrew Petroll currently serves as the Principal Investigator for three trials through Gilead Sciences. Two trials involve investigational combination pills which co-formulate an entire HIV-regimen into one pill that can be taken once a day. These regimens are much more potent, convenient and well-tolerated in comparison to some of the early treatments for HIV. Currently there is only one approved one-pill once-a-day antiretroviral regimen; however, it cannot be used in women of childbearing potential or patients with certain mental illnesses, and it is not effective in patients with certain HIV resistance mutations.
These pills may expand the options for one-pill-once a day treatment options for people living with HIV. A third trial is examining a new pharmacologic boosting agent that will allow for more convenient dosing of other antiretroviral medications and provide an alternative to the one boosting agent that is currently available. Dr. Petroll also serves as the Principal Investigator for trials through the Community Research Initiative (CRI), which MCW recently became affiliated with. CRI concentrates on investigating innovative strategies for ART use with a small network of clinical trial sites.
Other trials with investigational agents are carried out by Dr. Iram Nadeem. Dr. Nadeem serves as the Principal Investigator of the ECHO trial. The ECHO trial introduces a Non-Nucleoside Reverse transcriptase inhibitor which has activity against the K103N mutation. Currently, HIV strains with this mutation are resistant to all drugs in this class. Dr. Nadeem will also serve as the investigator for an upcoming trial with a brand new class of HIV drugs – an attachment inhibitor being developed by Bristol-Myers Squibb.
Dr. John Fangman, who is also the medical director of ARCW and a sub-Investigator of all trials carried out jointly with ARCW, serves as PI for several studies. One study he is involved with is “HIV elite controllers” – the 1% of individuals infected with HIV that can control the virus without antiretroviral medications. This study is done in collaboration with colleagues at the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University. Researchers there are trying to gain a better understanding of the immune response in these elite controllers with the hopes of improving treatments or developing a vaccine. Dr. Fangman also heads up a Healthier Wisconsin project involving HIV testing among individuals in high-risk social networks. Social networks testing (SNT) involves identification, recruitment and training of individuals presenting for HIV testing who can subsequently recruit untested, high-risk individuals from their social networks for testing. Targeted strategies such as SNT increase the proportion of high-risk persons tested for HIV compared to standard testing and may prove to be a more cost effective approach to finding those infected with HIV, and decreasing the spread of new infections.
Article written by Mandy Kastner, Program Coordinator III - Division of Infectious Diseases