Stressful and traumatic life events as disruptors to antiretroviral therapy adherence

Stressful and traumatic life events (STLEs) are common among HIV-infected individuals and may affect health behaviors such as adherence to antiretroviral (ARV) therapy, with important implications for treatment outcomes. We examined the association between STLEs and ARV adherence among 289 US-based participants enrolled between 7/1/2010 and 9/1/2013 in a study of depression treatment for HIV-infected patients. Participants received monthly telephone calls to assess STLEs and pill count-based ARV adherence. Inverse probability of observation weighting was combined with multiple imputation to address missing data. Participants were mostly male (71%) and black (63%), with a median age of 45 years. Median monthly adherence was 96% (interquartile range (IQR): 85–100%). Participants experienced a mean of 2.48 STLEs (range: 0–14) in the previous month. The presence of ≥2 STLEs was associated with a mean change in adherence of −3.67% (95% confidence interval (CI): −7.12%, −0.21%) and decreased likelihood of achieving ≥95% adherence (risk ratio (95% CI) = 0.82 (0.71, 0.95)). For each additional STLE, the mean adherence change was −0.90% (95% CI: −1.79%, 0.00%). STLEs were associated with poorer ARV adherence, including decreased likelihood of adhering to ≥95% of ARV doses. This level of adherence has a critical role in regimen effectiveness and prevention of resistance

The Impact of Cumulative Depression Along the HIV Care Continuum in Women Living with HIV during the Era of Universal Antiretroviral Treatment

Background: Data are limited on cumulative impacts of depression on engagement in care and HIV outcomes in women living with HIV (WLWH) during the era of universal antiretroviral therapy (ART). Understanding the relationship of accumulated depression with HIV disease management may help identify benefits of interventions to reduce severity and duration of depressive episodes. Setting: A cohort of WLWH (N = 1491) from the Women's Interagency HIV Study at 9 sites across the US.Methods:This longitudinal observational cohort study (2013-2017) followed WLWH for a maximum of 9 semiannual visits. Depression was quantified as a time-updated measure of percent of days depressed (PDD) created from repeated assessments using the Center for Epidemiologic Studies Depression scale. Marginal structural Poisson regression models were used to estimate the effects of PDD on the risks of missing an HIV care appointment, <95% ART adherence, and virological failure (≥200 copies/mL). Results: The risk of missing an HIV care appointment [risk ratio (RR) = 1.16, 95% confidence interval = 0.93 to 1.45; risk difference (RD) = 0.01, -0.01 to 0.03], being <95% ART adherent (RR = 1.27, 1.06-1.52; RD = 0.04, -0.01 to 0.07), and virological failure (RR = 1.09, 1.01-1.18; RD = 0.01, -0.01 to 0.03) increased monotonically with increasing PDD (comparing those with 25 to those with 0 PDD). The total effect of PDD on virological failure was fully (%100) mediated by being <95% ART adherent. Conclusions: Time spent depressed increases the risk of virological failure through ART adherence, even in the era of universal ART regimes forgiving of imperfect adherence

Impact of Medicare Part D on mental health treatment and outcomes for dual eligible beneficiaries with HIV

Depression is common among women with HIV and untreated depression can result in poor quality of life and worsen HIV outcomes. Women with HIV who are dually enrolled in Medicaid and Medicare faced a potential disruption in medication access when Medicare Part D was implemented in 2006. The goal of this study was to estimate the effects of Medicare Part D implementation on antidepressant use, depressive symptoms, and hospitalization in Medicaid-Medicare dual eligible women with HIV. This study used 2003–2008 data from the Women's Interagency HIV Study. The effects of Medicare Part D were estimated using a difference-in-differences approach, adjusting for temporal trends using a matched control group of Medicaid-only enrollees. Before Medicare Part D implementation, dual eligibles differed from Medicaid-only enrollees in antidepressant use and hospitalization, despite having identical prescription drug coverage through Medicaid. For dual enrollees, the transition to Medicare Part D was not associated with changes in antidepressant use, depressive symptoms, or hospitalization. We did not find disruptive effects on antidepressant use and related outcomes among dual eligibles in this study. Stable antidepressant use may be due to better access to medical care for dual eligibles through Medicare both before and after Medicare Part D implementation, which may have eclipsed any effects of the transition. It may also signal that classification of antidepressants as a protected drug class under Medicare Part D was effective in preventing psychiatric medication disruption

Associations between Medicare Part D and Out-of-Pocket Spending, HIV Viral Load, Adherence, and ADAP Use in Dual Eligibles with HIV

Background: The implementation of Medicare part D on January 1, 2006 required all adults who were dually enrolled in Medicaid and Medicare (dual eligibles) to transition prescription drug coverage from Medicaid to Medicare part D. Changes in payment systems and utilization management along with the loss of Medicaid protections had the potential to disrupt medication access, with uncertain consequences for dual eligibles with human immunodeficiency virus (HIV) who rely on consistent prescription coverage to suppress their HIV viral load (VL). Objective: To estimate the effect of Medicare part D on self-reported out-of-pocket prescription drug spending, AIDS Drug Assistance Program (ADAP) use, antiretroviral adherence, and HIV VL suppression among dual eligibles with HIV. Methods: Using 2003–2008 data from the Women’s Interagency HIV Study, we created a propensity score–matched cohort and used a difference-in-differences approach to compare dual eligibles’ outcomes pre-Medicare and post-Medicare part D to those enrolled in Medicaid alone. Results: Transition to Medicare part D was associated with a sharp increase in the proportion of dual eligibles with self-reported out-of-pocket prescription drug costs, followed by an increase in ADAP use. Despite the increase in out-of-pocket costs, both adherence and HIV VL suppression remained stable. Conclusions: Medicare part D was associated with increased out-of-pocket spending, although the increased spending did not seem to compromise antiretroviral therapy adherence or HIV VL suppression. It is possible that increased ADAP use mitigated the increase in out-of-pocket spending, suggesting successful coordination between Medicare part D and ADAP as well as the vital role of ADAP during insurance transitions

Premature and early menopause among US women with or at risk for HIV

Objective:Little is known about the prevalence and treatment of premature and early menopause among people with HIV. We described premature and early menopause and subsequent hormonal treatment in a longitudinal cohort of women living with or at risk for HIV in the US.Methods:Data from the Women's Interagency HIV Study between 2008 and 2020 were analyzed to describe premature and early menopause among cohort participants under the age of 51.Results:Of 3,059 eligible women during the study period, 1% (n=35) underwent premature menopause before age 41, 3% (n=101) underwent menopause between ages 41 and 46, and 21% (n=442) underwent menopause between ages 46 and 50, inclusive. Of participants who experienced menopause before age 41, between age 41 and 45, and between ages 46 and 50, 51%, 24%, and 7% (respectively) received either menopausal hormone therapy or hormonal contraception.Conclusion:These findings suggest that disparities in receipt of recommended hormone therapy for premature and early menopause may contribute, in part, to evident health disparities, such as cardiovascular disease, osteoporosis, and overall mortality. They also suggest a substantial need for education among people experiencing early menopause and their providers, with the goal of improving access to hormone therapy based on guidelines to address health disparities and minimize future health consequences

Cumulative burden of depression and all-cause mortality in women living with human immunodeficiency virus

Background Research linking depression to mortality among people living with human immunodeficiency virus (PLWH) has largely focused on binary "always vs never" characterizations of depression. However, depression is chronic and is likely to have cumulative effects on mortality over time. Quantifying depression as a cumulative exposure may provide a better indication of the clinical benefit of enhanced depression treatment protocols delivered in HIV care settings. Methods Women living with HIV (WLWH), naive to antiretroviral therapy, from the Women's Interagency HIV Study were followed from their first visit in or after 1998 for up to 10 semiannual visits (5 years). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. An area-under-the-curve approach was used to translate CES-D scores into a time-updated measure of cumulative days with depression (CDWD). We estimated the effect of CDWD on all-cause mortality using marginal structural Cox proportional hazards models. Results Overall, 818 women contributed 3292 woman-years over a median of 4.8 years of follow-up, during which the median (interquartile range) CDWD was 366 (97-853). Ninety-four women died during follow-up (2.9 deaths/100 woman-years). A dose-response relationship was observed between CDWD and mortality. Each additional 365 days spent with depression increased mortality risk by 72% (hazard ratio, 1.72; 95% confidence interval, 1.34-2.20). Conclusions In this sample of WLWH, increased CDWD elevated mortality rates in a dose-response fashion. More frequent monitoring and enhanced depression treatment protocols designed to reduce CDWD may interrupt the accumulation of mortality risk among WLWH

Structure and Function of the Hair Cell Ribbon Synapse

Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1 ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. While the electron microscopy hallmark of the hair cell afferent synapse — the electron-dense synaptic ribbon or synaptic body — has been recognized for decades, dissection of the synapse’s molecular make-up has only just begun. Recent cell physiology studies have added important insights into the synaptic mechanisms underlying fidelity and reliability of sound coding. The presence of the synaptic ribbon links afferent synapses of cochlear and vestibular hair cells to photoreceptors and bipolar neurons of the retina. This review focuses on major advances in understanding the hair cell afferent synapse molecular anatomy and function that have been achieved during the past years

Mortality under plausible interventions on antiretroviral treatment and depression in HIV-infected women: an application of the parametric g-formula

Purpose Among HIV-infected persons, antiretroviral therapy (ART) and depression are strongly associated with mortality. We estimated reductions in 5-year mortality in Women's Interagency HIV Study participants under plausible hypothetical increases in ART initiation and reductions in depression (CES-D score≥16). Methods We followed 885 ART-naïve Women's Interagency HIV Study participants for 5 years from their first study visit after April 1998 to death or censoring. We used the parametric extended g-formula to estimate cumulative mortality under the natural course (NC) and alternative exposure distributions. Results Baseline prevalence of depression was 52% and 62% initiated ART by 5 years. Compared with mortality under NC (13.2%), immediate ART and elimination of 36% or 67% of depressive episodes were associated with risk differences (RDs) of −5.2% (95% CI: −7.7%, −2.6%) and −5.7 (95% CI: −8.7, −2.7). Compared with immediate ART and NC for depression, additionally eliminating 67% of the depressive episodes was associated with RD = −1.6 (95% CI: −3.9, 0.8). Compared with 5-year mortality under NC for ART and elimination of 67% of depression, also initiating ART immediately was associated with RD = -2.6 (95% CI: -5.0, -0.3). Conclusions Increasing ART initiation and reducing depression were associated with moderate reductions in 5-year mortality among HIV-infected women

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd