Second Level Alignment of the PE Model 140

The Perkin Elmer Model 140 was investigated for second level alignment. Using a photolithographic evaluation mask, inspection of six wafers yielded overlay errors. The average x-translational error was -1.95 urn, the average y-translational error was -.4um, and the average rotational error was -.0005 uradians

Plasma host protein biomarkers correlating with increasing Mycobacterium tuberculosis infection activity prior to tuberculosis diagnosis in people living with HIV

BACKGROUND: Biomarkers correlating with Mycobacterium tuberculosis infection activity/burden in asymptomatic individuals are urgently needed to identify and treat those at highest risk for developing active tuberculosis (TB). Our main objective was to identify plasma host protein biomarkers that change over time prior to developing TB in people living with HIV (PLHIV). METHODS: Using multiplex MRM-MS, we investigated host protein expressions from 2 years before until time of TB diagnosis in longitudinally collected (every 3-6 months) and stored plasma from PLHIV with incident TB, identified within a South African (SA) and US cohort. We performed temporal trend and discriminant analyses for proteins, and, to assure clinical relevance, we further compared protein levels at TB diagnosis to interferon-gamma release assay (IGRA; SA) or tuberculin-skin test (TST; US) positive and negative cohort subjects without TB. SA and US exploratory data were analyzed separately. FINDINGS: We identified 15 proteins in the SA (n=30) and 10 in the US (n=24) incident TB subjects which both changed from 2 years prior until time of TB diagnosis after controlling for 10% false discovery rate, and were significantly different at time of TB diagnosis compared to non-TB subjects (p<0.01). Five proteins, CD14, A2GL, NID1, SCTM1, and A1AG1, overlapped between both cohorts. Furthermore, after cross-validation, panels of 5 – 12 proteins were able to predict TB up to two years before diagnosis. INTERPRETATION: Host proteins can be biomarkers for increasing Mycobacterium tuberculosis infection activity/burden, incipient TB, and predict TB development in PLHIV. FUNDING: NIH/NIAID AI117927, AI146329, and AI127173 to JMA

Dyslipidemia among HIV-infected Patients with Tuberculosis Taking Once-daily Nonnucleoside Reverse-Transcriptase Inhibitor–Based Antiretroviral Therapy in India

HIV-infected patients with tuberculosis who initiate nonnucleoside reverse-transcriptase-based anti-retroviral treatment in combination with rifampicin-based antituberculosis treatment demonstrate increases in total cholesterol, low-density cholesterol, and high-density cholesterol levels but no change in blood glucose level after 1 year. Cholesterol increases were more frequent among patients receiving efavirenz

Marginal Structural Models for Case-Cohort Study Designs to Estimate the Association of Antiretroviral Therapy Initiation With Incident AIDS or Death

To estimate the association of antiretroviral therapy initiation with incident acquired immunodeficiency syndrome (AIDS) or death while accounting for time-varying confounding in a cost-efficient manner, the authors combined a case-cohort study design with inverse probability-weighted estimation of a marginal structural Cox proportional hazards model. A total of 950 adults who were positive for human immunodeficiency virus type 1 were followed in 2 US cohort studies between 1995 and 2007. In the full cohort, 211 AIDS cases or deaths occurred during 4,456 person-years. In an illustrative 20% random subcohort of 190 participants, 41 AIDS cases or deaths occurred during 861 person-years. Accounting for measured confounders and determinants of dropout by inverse probability weighting, the full cohort hazard ratio was 0.41 (95% confidence interval: 0.26, 0.65) and the case-cohort hazard ratio was 0.47 (95% confidence interval: 0.26, 0.83). Standard multivariable-adjusted hazard ratios were closer to the null, regardless of study design. The precision lost with the case-cohort design was modest given the cost savings. Results from Monte Carlo simulations demonstrated that the proposed approach yields approximately unbiased estimates of the hazard ratio with appropriate confidence interval coverage. Marginal structural model analysis of case-cohort study designs provides a cost-efficient design coupled with an accurate analytic method for research settings in which there is time-varying confounding

Health Insurance Type and Control of Hypertension Among US Women Living With and Without HIV Infection in the Women’s Interagency HIV Study

BACKGROUND: Health care access is an important determinant of health. We assessed the effect of health insurance status and type on blood pressure control among US women living with (WLWH) and without HIV. METHODS: We used longitudinal cohort data from the Women's Interagency HIV Study (WIHS). WIHS participants were included at their first study visit since 2001 with incident uncontrolled blood pressure (BP) (i.e., BP ≥140/90 and at which BP at the prior visit was controlled (i.e., <135/85). We assessed time to regained BP control using inverse Kaplan-Meier curves and Cox proportional hazard models. Confounding and selection bias were accounted for using inverse probability-of-exposure-and-censoring weights. RESULTS: Most of the 1,130 WLWH and 422 HIV-uninfected WIHS participants who had an elevated systolic or diastolic measurement were insured via Medicaid, were African-American, and had a yearly income ≤$12,000. Among participants living with HIV, comparing the uninsured to those with Medicaid yielded an 18-month BP control risk difference of 0.16 (95% CI: 0.10, 0.23). This translates into a number-needed-to-treat (or insure) of 6; to reduce the caseload of WLWH with uncontrolled BP by one case, five individuals without insurance would need to be insured via Medicaid. Blood pressure control was similar among WLWH with private insurance and Medicaid. There were no differences observed by health insurance status on 18-month risk of BP control among the HIV-uninfected participants. CONCLUSIONS: These results underscore the importance of health insurance for hypertension control-especially for people living with HIV

Impact of Health Insurance, ADAP, and Income on HIV Viral Suppression Among US Women in the Womenʼs Interagency HIV Study, 2006–2009

Implementation of the Affordable Care Act motivates assessment of health insurance and supplementary programs, such as the AIDS Drug Assistance Program (ADAP) on health outcomes of HIV-infected people in the United States. We assessed the effects of health insurance, ADAP, and income on HIV viral load suppression

Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C

Since HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to Minimal Hepatic Encephalopathy (MHE) in the absence of cirrhosis

Cognitive changes during the menopausal transition: a longitudinal study in women with and without HIV

OBJECTIVE: To assess longitudinal changes in cognitive performance across menopause stages in a sample comprised primarily of low-income women of color, including women with HIV (WWH). METHODS: A total of 443 women (291 WWH; 69% African American; 18% Hispanic; median age = 42 y) from the Women's Interagency HIV Study completed tests of verbal learning and memory, attention/working memory, processing speed, verbal fluency, motor skills, and executive function first at an index premenopausal visit and thereafter once every 2 years for up to six visits (mean follow-up = 5.7 y). General linear-mixed effects regression models were run to estimate associations between menopause stages and cognition, in the overall sample and in WWH. We examined both continuous scores and categorical scores of cognitive impairment (yes/no >1 standard deviation below the mean). RESULTS: Adjusting for age and relevant covariates, the overall sample and WWH showed longitudinal declines in continuous measures of learning, memory, and attention/working memory domains from the premenopause to the early perimenopause and from the premenopause to the postmenopause, Ps < 0.05 to < 0.001. Effects on those same domains were also evident in categorical scores of cognitive impairment, with the increased odds of impairment ranging from 41% to 215%, Ps < 0.05 to < 0.001. The increase in predicted probability of impairment by menopausal stage (% affected) ranged from 4% to 13%. CONCLUSIONS: Menopause stage was a key determinant of cognition in a sample of low-income women of color, including WWH. Many of these changes reached a clinically significant level of cognitive impairment

Gone but Not Lost: Implications for Estimating HIV Care Outcomes When Loss to Clinic Is Not Loss to Care

Background: In some time-to-event analyses, it is unclear whether loss to follow up should be treated as a censoring event or competing event. Such ambiguity is particularly common in HIV research that uses routinely collected clinical data to report the timing of key milestones along the HIV care continuum. In this setting, loss to follow up may be viewed as a censoring event, under the assumption that patients who are "lost" from a study clinic immediately enroll in care elsewhere, or a competing event, under the assumption that people "lost" are out of care all together. Methods: We illustrate an approach to address this ambiguity when estimating the 2-year risk of antiretroviral treatment initiation among 19,506 people living with HIV who enrolled in the IeDEA Central Africa cohort between 2006 and 2017, along with published estimates from tracing studies in Africa. We also assessed the finite sample properties of the proposed approach using simulation experiments. Results: The estimated 2-year risk of treatment initiation was 69% if patients were censored at loss to follow up or 59% if losses to follow up were treated as competing events. Using the proposed approach, we estimated that the 2-year risk of antiretroviral therapy initiation was 62% (95% confidence interval: 61, 62). The proposed approach had little bias and appropriate confidence interval coverage under scenarios examined in the simulation experiments. Conclusions: The proposed approach relaxes the assumptions inherent in treating loss to follow up as a censoring or competing event in clinical HIV cohort studies