Abstract
Initiating combination antiretroviral therapy (ART) during acute HIV infection has been correlated with decreased viral set point and improved lymphocyte function. However, the long term effects of single-agent therapy administered only during the acute stage of infection (interrupted treatment) remain largely uncharacterized. In this study we provide longitudinal data using the feline immunodeficiency virus (FIV) model for HIV infection. Infected cats were treated with a prophylactic single-agent therapy, Fozivudine tidoxil (FZD), for six weeks, starting one day before infection. The initial acute infection study, reported elsewhere, demonstrated a decrease in plasma- and cell-associated viremia at two weeks post-infection (PI) in FZD-treated cats as compared to placebo-treated cats. We hypothesized that this early alteration in plasma- and cell-associated viremia would alter the virus set point and ultimately affect the outcome of chronic infection. Here we provide data at one, two and three years PI for plasma- and/or cell-associated viremia, total lymphocyte counts and CD4:CD8 ratios. There was no difference in viremia or cell counts between treated and nontreated groups at all time points tested. Contrary to our hypothesis, these results suggest that treatment with a single agent anti-retroviral drug during acute lentivirus infection does not significantly alter viral load and immune function during the chronic, asymptomatic stage of infection.
Highlights
There is not uniform agreement on when to initiate early treatment of HIV patients with anti-retroviral therapy (ART), evidence suggests early therapy correlates to improved immune responses and reduced viral replication during the course of infection [1,2,3,4]
The protective effect of early drug therapy may be a result of decreased viral set point and delayed viremia, as several studies have demonstrated that high viremia during chronic infection can be indicative of more rapid disease progression when compared to patients which maintain a low viral set point [5,6,7]
The cats in the current study were initially part of a non-blinded, placebo controlled study to assess the effectiveness of a novel nucleoside analogue reverse transcriptase inhibitor (NRTI), Fozivudine tidoxil (FZD), during acute Feline Immunodeficiency virus (FIV) infection [9]
Summary
There is not uniform agreement on when (and if) to initiate early treatment of HIV patients with anti-retroviral therapy (ART), evidence suggests early therapy correlates to improved immune responses and reduced viral replication during the course of infection [1,2,3,4]. Delayed seroconversion with early ART treatment has been described [8] These studies use various combination therapies, typically administered over long periods of time with only short term disruptions in treatments [1,2,3,4,5,6,7]. Little is known regarding the long term effect of single therapeutic treatment, administered only during acute infection, on immune function and virus load during the later chronic stage. The lipid portion is removed following intracellular cleavage and the remaining ZDV monophosphate is phosphorylated into the active form of the drug [11,12] This requirement for intracellular processing decreases the potential for hematologic toxicity and reduces the concern for anemia in treating FIV infected cats [11]. CD4:CD8 ratios and hematocrit values were analyzed at two and three years PI
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