The Potential for Dipeptidyl Peptidase IV (DPPIV) Usage as a Surrogate Marker for Antiretroviral Therapy Efficacy in HIV Infected Populations

Abstract

The most commonly used markers for monitoring efficacy of anti-retroviral therapy in Human Immunodeficiency Virus (HIV) infected individuals are the viral load and CD4+ cell counts. Viral load monitoring is limited in resource limited countries due to its high cost, therefore leaving the use of CD4+ T cell counts as the only alternative for evaluating HIV infected individuals. CD4+ cell counts is an unreliable predictor of disease progression even though it is cheaper and most readily available in these settings. There is therefore a need to develop more sensitive and less costly alternative techniques for the detection of treatment failure which can be of utmost importance in these resource limited settings. This study sought to evaluate the feasibility of using Dipeptidyl peptidase IV (DPPIV) in plasma as a novel marker for the clinical evaluation of efficacy of treatment in young HIV infected individuals. DPPIV is an enzyme that cleaves N-terminal dipeptides next to an alanine or proline residues. Blood samples were collected from HIV positive young individuals (n=76) before and after initiation of ART, then assessed for HIV RNA (viral load), CD4+ T cell count and DPPIV levels. Roche Amplicor HIV-1 Monitor Test kit was used to analyse viral load levels while the BD FACS Calibur flowcytometer was used to analyse the levels of CD 4+ T cell counts with the Human DPPIV Quantikine ELISA kit (R&D Systems, Minneapolis MN) used to analyse DPPIV levels. The levels of plasma DPPIV increased significantly in study participants after ART initiation (p = 0.017), while the levels of viral load declined after ART initiation with an increase in CD4+ cell counts. There was a weak correlation (r=0.26) between the change in DPPIV after ART to the change in viral load after ART while there was a no correlation (r=0.14) between the change in DPPIV levels after ART to the the change in CD 4+ cell counts after ART. There was no statistically significant difference in DPPIV (p=0.7460), viral load (p=0.9875), and CD 4+ cell counts (p= 0.548) with gender. The findings further showed a significant inverse relationship between the DPPIV levels (p=0.0017 increase after ART) and HIV viral load levels (p=0.0001 decrease after ART) and the presence of a direct relationship of DPPIV levels (p=0.0017 increase after ART) to the CD4+ Cell counts levels (p=0.0001 increase after ART). The latter suggesting a potential for DPPIV use as a more cost effective and a sensitive alternate surrogate marker for the evaluation of HIV disease progression in young individuals on HIV treatment