Effects of Hydroxychloroquine on Immune Activation and Disease Progression Among HIV-Infected Patients Not Receiving Antiretroviral Therapy

Abstract

International HIV treatment guidelines recommend that antiretroviral therapy should be started when the CD4 cell count reaches 350 cells/μL,¹ but resource limitations prevent implementation of this recommendation in many countries. An inexpensive, safe, and well-tolerated intervention that slowed the rate of decline of CD4 cells (and thereby delayed the time of starting combination antiretroviral therapy) would therefore be attractive. One potential therapeutic target for such an intervention is immune activation, which is considered to play a central causative role in HIV-driven CD4 cell loss by rendering uninfected, resting CD4 and CD8 cells susceptible to spontaneous apoptosis.^2,3 In observational studies, the level of immune activation is independently associated with the subsequent rate of CD4 cell loss.^4-6 A second potential target might be HIV-associated activation of inflammatory and coagulation pathways (as shown by elevated levels of IL-6 and D-dimer, respectively), high levels of which have been shown to predict increased risk of death in both the short- and long-term.⁷ An intervention that decreased immune activation or inflammation or both in early HIV disease might therefore be of benefit.