Publications

The antiviral potency of the cytokine IFN-α has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-α-mediated suppression of HIV-1 replication in vitro. We sought to characterize the as-yet-undefined relationship between IFN-α treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated IFN-α/ribavirin (IFN-α/riba) combination therapy. IFN-α/riba therapy decreased HIV-1 viral load by -0.921 (±0.858) log(10) copies/mL in HIV/HCV-coinfected patients. APOBEC3G/3F and BST-2 mRNA expression was significantly elevated during IFN-α/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's ρ), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-α/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-α in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.

BACKGROUND

Breast cancer is frequently diagnosed after an abnormal mammography result. Language barriers can complicate communication of those results.

OBJECTIVES

We evaluated the association of non-English language with delay in follow-up.

METHODS

Retrospective cohort study of women at 3 mammography facilities participating in the San Francisco Mammography Registry with an abnormal mammogram result from 1997 to 2008. We measured median time from report of abnormal result to first follow-up test.

RESULTS

Of 13,014 women with 16,109 abnormal mammograms, 4027 (31%) had a non-English patient language. Clinical facilities differed in proportion of non-English speakers and in time to first follow-up test: facility A (38%; 25 d), facility B (18%; 14 d), and facility C (51%; 41 d). Most mammography examinations (67%) had breast imaging and reporting data system 0 (incomplete) assessment, requiring radiographic follow-up. At 30 days of follow-up, 67% of all English speakers with incomplete assessments had a follow-up examination compared with 50% of all non-English speakers (P<0.0001). The facility with the least delay and the lowest proportion of non-English speakers, had the biggest difference by language; compared with English speakers and adjusting for education, non-English speakers had twice the odds ratio of >30-day delay in follow-up (odds ratio=2.3; 95% confidence interval, 1.4-3.9).

CONCLUSIONS

There are considerable differences among facilities in delays in diagnostic follow-up of abnormal mammography results. More attention must be paid to understanding mammography facility factors, such as wait time to schedule diagnostic mammography and radiology workload, to improve rates of timely follow-up, particularly for those facilities disproportionately serving vulnerable non-English speaking patients.