California Collaborative Treatment Group (CCTG)

Richard Haubrich, UC-San Diego
California Collaborative HIV/AIDS Research Centers

Since 1986, the California Collaborative Treatment Group (CCTG) has been conducting high impact multi-centered, investigator- initiated clinical trials that address the primary theme of our application: Emerging Problems in the Management of HIV Infection. The group has over 140 publications and has a proven record of accomplishments that include: providing access to research opportunities for under represented populations, addressing research questions of importance to HIV infected patients in California, collaborating with diverse disciplines to expand the scope and depth of our research projects, mentoring junior investigators to become the next generation of California clinical investigators, and leveraging funding from additional sources, to build on core funding from the UARP.

The CCTG is a fi ve-center, academic affi liated clinical trials group. The CCTG represents a true partnership between the fi ve sites. All site principal investigators contribute equally to the group leadership process in directing not only the administrative and fi scal matters, but in contributing to the science and management of our studies. Our successful partnership for 18 years is a testament to the collegial, cooperative spirit of the CCTG which is greatly facilitated by monthly face to face meetings in Irvine. At these meetings, we present new concepts, work on existing protocols and discuss new data. Junior investigators are encouraged to lead these discussions which adds to the mentoring process.

The aims and designs of the three proposed studies, addressing emerging HIV management issues, form the core of this application.

Project 1: CCTG 584- Viral dynamics and pharmacokinetics of tenofovir (TDF) and abacavir (ABC). The goal of this study is to determine the pathogenesis of the poor virologic response to TDF + ABC containing regimens. By studying the interaction between TDF and ABC, we can explore the mechanism and determine the viability of this combination. The hypothesis is that the dual NRTI combination will be less potent than either drug used alone and that the difference can be explained in part by an intracellular interaction (reduced levels of intracellular active phosphoralated compounds). The specifi c primary aims are: to evaluate the relative potencies of TDF or ABC given alone for 7 days compared to TDF + ABC as assessed by the short-term HIV RNA response; and to compare the plasma and intracellular pharmacokinetic data of monotherapy vs. the dual NRTI regimen.

Project 2: CCTG 585- A comparison of once daily Lopinavir/ritonavir (LPV/r) given as liquid versus capsules. The goal of this study is to determine if we can simplify antiretroviral therapy with LPV by evaluating two once daily LPV regimens. Although LPV has been shown to be effective in once daily dosing, diarrhea limits its utility. The hypotheses for this study is that once daily LPV/r liquid will be better tolerated than once daily LPV/r capsules. The primary objective of the study is to compare the tolerability of once daily LPV/r (800/200 mg) given as 10 ml liquid vs. 6 capsules.

Project 3: CCTG 587- Pathogenesis of community-acquired MRSA among HIV + MSM. An important emerging new problem for HIV infected patients is infection with methicillin resistant Staphylococcus aureus. Understanding the epidemiology, risk factors and host defenses of this infection will be important to designing strategies to treat and prevent the infections. The objectives of this study are: 1) to prospectively determine the prevalence, incidence, persistence, and risk factors for asymptomatic MRSA colonization among HIV infected MSM and control groups; 2) to compare colonizing MRSA strains with MRSA strains causing clinical infection and to quantify the persistence of strain colonization; and 3) to identify factors in host defenses and host-defense interactions that may prevent S. aureus infections.

hese studies will address research questions of importance to HIV infected patients in California and will allow the CCTG to continue with our ancillary missions of providing research access to minority patients, mentoring junior investigators and expanding collaborations with diverse disciplines.