Services and Research Support
The Pharmacology Core provides ongoing analytical support for translational and pharmacology research investigating factors influencing therapeutic response and inflammation in HIV infected patients and those co-infected with malaria or tuberculosis (TB) and continues to develop new methods as needed to support advances in the field and the research of CFAR investigators.
Core methodologies are based on high performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC tandem MS).
- The core recently finalized an LC tandem MS method for quantification of methotrexate and underwent DAIDS Clinical Pharmacology Quality Assurance (CPQA) review and approval. Additionally, a method for tenofovir was also developed. Both of these assays are used to support a novel study assessing the use of methotrexate for inflammation in HIV infected patients in collaboration with Drs. S. Deeks and P. Hsue (also A5314).
- An LC tandem MS method for piperaquine (PQ), an antimalarial drug, in plasma underwent full validation and was used to support studies for Drs. G Dorsey and M. Feeney. Additional work has been done to optimize a DBS assay for PQ to improve field investigations. This work also involves correlating DBS and plasma results as plasma results are ~2-3 times higher than DBS results.
- A LC tandem MS method to measure atazanavir was developed as was an improved method for lopinavir/ritonavir using deuterated internal standards to support CFAR and ACTG studies.
- Development of novel method for kynurenine and tryptophan are currently under development to support the work of Dr. P. Hunt.
Collaborative and Translational Research
- Investigation of the interplay of ART and antimalarials is a high priority area of research of this Core and it continues to use its expertise to support related CFAR projects in drug quantitation and data analysis. Multiple HIV-malaria projects have been supported including PROMOTE I Project 1 in HIV infected children (Havlir, Dorsey), PROMOTE I Project 2 in HIV infected pregnant women and their infants (Havlir, Cohan, Gandhi), PROMOTE I Project 3 in HIV uninfected children (Dorsey) and now the recently funded PROMOTE II (Novel Strategies to Prevent Malaria and Improve Maternal-Child Health in Africa). In addition, the Core supports research for antimalarials with colleagues in Nigeria and ART for colleagues in Zimbabwe.
- The Core collaborates with CFAR scientists and members of industry to bring new TB treatments into the field and thus has been a leader in developing novel assay methods for measuring these drugs including PA-824, TMC207 (bedaquiline) and it’s M2, M3 metabolites. Projects are done in collaboration with CFAR investigators including Annie Luetkemeyer. The Core works to assure inclusion of critical PK/PD study components in clinical trial designs (e.g. ACTG protocols A5221, A5267, A5289, A5306). Current work includes providing expertise for A5289 which involves PK/PD assessment of sutezolid, under development.
- The Core supports leading CFAR investigators in developing innovative interventional studies aimed at reversing HIV-associated inflammation and accelerating decay of viral reservoirs.
- The Core studies the physiological differences related to gender, pregnancy, and childhood development, specifically investigating PK and treatment responses in these subjects in order to determine specific dosing guidelines.