CD4 T CELL ASSESSMENTS IN EVALUATION OF HIV THERAPEUTICS - Flow Cytometry in Drug Discovery and Development - page 165

CD4 T CELL ASSESSMENTS IN
EVALUATION OF HIV THERAPEUTICS

T HOMAS N. D ENNY ,R AUL L OUZAO ,J OHN W ONG , AND B ROOKE W ALKER

8.1 INTRODUCTION

Recent figures from the Joint United Nations Programme on HIV/AIDS (UNAIDS)
estimate that 33 million people are living with human immunodeficiency virus (HIV)
worldwide and an estimated 3million are on antiretroviral (ARV) therapy (Figures 8.1
and 8.2) [1]. As global efforts continue to make life-saving HIV therapeutics more
accessible and affordable to patients, there is a growing need to ensure that routine
monitoring of CD4 T cells is affordable and available for patients on ARV therapy.
CD4 has proven to be a fundamental immunological marker in HIV infection that can
indicate disease progression, drug adherence or resistance, and pathogen suscept-
ibility (e.g., opportunistic diseases such as Pneumocystis carinii pneumonia (PCP)).
The first clinical trials to assess the efficacy and safety of AZT validated CD4 as a
critical prognostic marker of the progression to AIDS and demonstrated its value to
accurately predict treatment success or failure. These findings led to the current use of
HIV-RNA levels and CD4 levels as end points for drug approval by the U.S. Food and
DrugAdministration (FDA) in clinical trials for antiretroviral drugs. International and
national clinical guidelines on ARV therapy and opportunistic infections (OIs) rely on
CD4 T cell counts to recommendwhen to initiate therapy and prophylaxis against OIs.
Timely monitoring of CD4 T cells in HIV-infected patients is critical to assess the
efficacy of any ARV drug regimen. It is, therefore, of vital importance that CD4
measurements are evaluated accurately and precisely to ensure that patients receive