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HIV RNA viral load (VL) is a pivotal outcome variable in studies of HIV infected persons. We propose and investigate two frameworks for analyzing VL: (1) a single-measure VL (SMVL) per participant and (2) repeated measures of VL (RMVL) per participant. We compared these frameworks using a cohort of 720 HIV patients in care (4,679 post-enrollment VL measurements). The SMVL framework analyzes a single VL per participant, generally captured within a "window" of time. We analyzed three SMVL methods where the VL binary outcome is defined as suppressed or not suppressed. The omit-participant method uses a 8-month "window" (-6/+2 months) around month 24 to select the participant's VL closest to month 24 and removes participants from the analysis without a VL in the "window". The set-to-failure method expands on the omit-participant method by including participants without a VL within the "window" and analyzes them as not suppressed. The closest-VL method analyzes each participant's VL measurement closest to month 24. We investigated two RMVL methods: (1) repeat-binary classifies each VL measurement as suppressed or not suppressed and estimates the proportion of participants suppressed at month 24, and (2) repeat-continuous analyzes VL as a continuous variable to estimate the change in VL across time, and geometric mean (GM) VL and proportion of participants virally suppressed at month 24. Results indicated the RMVL methods have more precision than the SMVL methods, as evidenced by narrower confidence intervals for estimates of proportion suppressed and risk ratios (RR) comparing demographic strata. The repeat-continuous method had the most precision and provides more information than other considered methods. We generally recommend using the RMVL framework when there are repeated VL measurements per participant because it utilizes all available VL data, provides additional information, has more statistical power, and avoids the subjectivity of defining a "window."

Modulation of chemokine CXCL12 and its receptor CXCR4 has been implicated in attenuation of bleomycin (BLM)-induced pulmonary fibrosis and carbon tetrachloride (CCl4)-induced hepatic injury. In pulmonary fibrosis, published reports suggest that collagen production in the injured lung is derived from fibrocytes recruited from the circulation in response to release of pulmonary CXCL12. Conversely, in hepatic fibrosis, resident hepatic stellate cells (HSC), the key cell type in progression of fibrosis, upregulate CXCR4 expression in response to activation. Further, CXCL12 induces HSC proliferation and subsequent production of collagen I. In the current study, we evaluated AMD070, an orally bioavailable inhibitor of CXCL12/CXCR4 in alleviating BLM-induced pulmonary and CCl4-induced hepatic fibrosis in mice. Similar to other CXCR4 antagonists, treatment with AMD070 significantly increased leukocyte mobilization. However, in these two models of fibrosis, AMD070 had a negligible impact on extracellular matrix deposition. Interestingly, our results indicated that CXCL12/CXCR4 signaling has a role in improving mortality associated with BLM induced pulmonary injury, likely through dampening an early inflammatory response and/or vascular leakage. Together, these findings indicate that the CXCL12-CXCR4 signaling axis is not an effective target for reducing fibrosis.