g received any investigational drug 30 days prior to the start of the study; chronic active viral hepatitis B or hepatitis C, current or previous pancreatitis; pregnancy; history of, or currently receiving, interferon therapy; presence of didanosine-associated resistance mutations; current or recent use of immunomodulatory agents; current or recent use of ribavarin; and known allergy to the active or inactive components of VS411. Study Monitoring, Data Collection, Analysis and Statistical Methods The study was monitored by an independent CRO, IATEC, who also provided data management. Data were described by means and standard deviations or median and interquartile ranges. The changes from baseline in log-transformed plasma HIV-1 RNA levels and immunological parameters were analyzed by a repeated measurements procedure using a generalized linear model. The incidence of adverse events and laboratory abnormalities were tabulated and compared between study arms using the chi-square test. All tests of hypotheses were two-sided and used a 5% level of significance. The described Butein site analyses were performed on a modified Intent-to-treat population, the On-Treatment population. Data presented in this paper reflect the mITT population. Two sub-populations were also studied to document changes in immunological parameters. Pre- and post-treatment time points were selected for these analyses due to the short nature of the study. These analyses were intended to be conducted only on a subset of the total population due to the logistical complexity of adequately collecting, processing and shipping viable cells at multiple time points. Analyses of the panel of four biomarkers were performed upon viable cells obtained from 38 subjects from sites that had the capacity to properly collect, store, and ship viable cell samples per the protocol. An analysis of changes in HIV-1-specific immune responses was performed in a subset of 22 of those 38 subjects with a sufficient number of viable cells remaining after the biomarker analyses. Comparisons of each sub-population to the mITT population showed them to be statistically similar in terms of response to study therapy and baseline demographics. The baseline demographics for the two sub-studies are available as supporting information; see Sub-Study Demographics S1. HIV-1 RNA Eurofins Medinet B.V. provided the Central Laboratory services. The plasma HIV-1 RNA levels were determined using the commercial “RT-PCR Cobas AmpliprepCobas Amplicor” assay with a lower limit of quantification of 50 copies/mL. Genotypic Resistance HIV Genosure, an HIV genotyping assay, was employed to examine the viral genetic sequence to identify resistance-associated mutations. Both the reverse transcriptase and the protease genes were examined. Viral RNA was isolated from plasma samples at baseline and at Day 29, reverse transcribed and the relevant genome segment amplified and sequenced using Applied Biosystems Incorporated technology. Subject-derived viral sequences were compared to wild type to identify specific mutations associated with current antivirals. Dosing Arm ddI a VS411-A VS411-B VS411-C VS411-D b Collection and Processing of Peripheral 
Blood Mononuclear Cells Selected sites were recruited to provide subject blood samples for the two immunology sub-studies flow cytometry analysis of immune activation markers in 32 subjects and analysis of HIV-1specific immune responses by ELISPOT assay in 22 subjects. At these sites, 30 mL of bl