Introduction We examine symptom variability in men and women with urological chronic pelvic pain syndrome (UCPPS). We describe symptom fluctuations as related to early symptom regression and its effect on estimated one-year symptom change. We then describe a method to quantify patient-specific symptom variability. Methods Symptoms were assessed biweekly in 424 UCPPS subjects over one year. Subjects were classified as ‘improved’, ‘no change’, or ‘worse’ according to their rate of change using 1) all data, 2) excluding week 0, and 3) excluding weeks 0 and 2 to evaluate the impact of early symptom regression. Patient-specific time-varying variability was calculated at each interval using a sliding window approach. Patients were classified as high, medium, or low variability at each time and ultimately as high or low variability overall based on their variability for the majority of contacts. Results Prior to excluding early weeks to adjust for early symptom regression 25–38% and 5–6% of patients were classified as improved and worse, respectively; after adjustment the percentage of patients improved or worse ranged from 15–25% and 6–9%. ‘High and ‘low’ variability phenotypes were each identified in 25–30% of participants. Conclusions Patients with UCPPS exhibit symptom variability. At enrollment, patients had, on average, worse symptoms, resulting in a regression effect that influenced the estimated proportion of improved or worse subjects. Prospective studies should include a run-in to account for regression to the mean and other causes of early symptom regression. Further, symptom variability may be quantified and used to characterize longitudinal UCPPS symptom profiles.

While it has long been appreciated that there is considerable variability in host containment of HIV/SIV replication, the determinants of that variability are not fully understood. Previous studies demonstrated that the degree of permissivity of a macaque's peripheral blood mononuclear cells (PBMC) for infection with simian immunodeficiency virus (SIV) in vitro predicted that animal's peak plasma virus RNA levels following SIV infection in vivo. The present study was conducted to define the mechanisms underlying the variable intrinsic susceptibility of rhesus monkey PBMC to SIVsmE660 infection. In a cohort of 15 unrelated Indian-origin rhesus monkeys, infectability of PBMC of individual animals with SIVsmE660, as defined by tissue culture infectious dose (TCID50), varied by more than 3 logs and was a stable phenotype over time. Susceptibility of a monkey's PBMC to wild type SIVsmE660 infection correlated with the susceptibility of that monkey's PBMC to infection with VSV-G pseudotyped SIVsm543-GFP. Moreover, the permissivity of an individual monkey's PBMC for infection with this construct correlated with the permissivity of a B-lymphoblastoid cell line (B-LCL) generated from PBMC of the same animal. We found that the degree of intrinsic resistance of monkey B-LCL correlated with the copy number of early reverse transcription (ERT) SIV DNA. The resistance of monkey B-LCL to SIVsmE660 replication could be abrogated by preincubation of cells with the SIV virus-like particles (VLPs) and SIV resistance phenotype could be transferred to a SIV susceptible B-LCL through cell fusion. Finally, we observed a positive correlation between susceptibility of monkey B-LCL to SIV infection with a VSV-G pseudotyped SIV-GFP construct in vitro and both the peak plasma virus RNA levels in vivo and time to death following wild type SIV infection. These findings suggest that a dominant early RT restricting factor that can be saturated by SIV capsid may contribute to the variable resistance to SIV infection in rhesus monkey B-LCL and that this differential intrinsic susceptibility contributes to the clinical outcome of an SIV infection.

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