Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201).

OBJECTIVES: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. METHODS: Thirty-four participants with virologic suppression ≥ 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56+CD16+) cells and cell-associated markers (HLA-DR, CD\u27s 38/69/94/95/158/279). RESULTS: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) \u3e50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL \u3e50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels. CONCLUSIONS: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. TRIAL REGISTRATION: ClinicalTrials.gov NCT00084019

Nitrate from Drinking Water and Diet and Bladder Cancer among Postmenopausal Women in Iowa.

BACKGROUND: Nitrate is a drinking water contaminant arising from agricultural sources and a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens. OBJECTIVES: To investigate the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women. METHODS: We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) \u3e10 years (N=15,577), we estimated average nitrate (NO3-N) and total trihalomethanes (TTHM) levels and the number of years exceeding one-half the maximum contaminant level (NO3-N: 5mg/L, TTHM: 40µg/mL) from historical monitoring data. We computed hazard ratios (HR) and 95% confidence intervals (CI), and assessed nitrate interactions with TTHM and modifiers of NOC formation (smoking, vitamin C). RESULTS: We identified 258 bladder cancer cases, including 130 among women \u3e10 years at their PWS. In multivariable-adjusted models, we observed non-significant associations among women in the highest versus lowest quartile of average drinking water nitrate concentration (HR=1.48;CI=0.92,2.40;ptrend=0.11), and significant associations among those exposed ≥4 years to drinking water with \u3e5mg/L NO3-N (HR=1.62;CI=1.06,2.47;ptrend=0.03) compared to women with no years of comparable exposure. TTHM adjustment had little influence on associations, and we observed no modification by vitamin C intake. Relative to a common reference group of never smokers with the lowest nitrate exposures, associations were strongest for current smokers with the highest nitrate exposures (HR=3.67;95% CI=1.43,9.38 and HR=3.48; 95% CI=1.20,10.06 for average water NO3-N and ≥4 years \u3e5mg/L, respectively). Dietary nitrate and nitrite intakes were not associated with bladder cancer. CONCLUSIONS: Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women