Owing to ongoing improvements in antiretroviral therapy, people with HIV (PWH) are achieving near-normal lifespans with many surviving into middle and old age. Despite this success, PWH have a higher ...than expected risk of developing non-AIDS comorbidities, multimorbidity, and functional decline at ages younger than those without HIV.
As part of the Inter-CFAR (Center for AIDS Research) Symposium, HIV and Aging in the era of Antiretroviral Therapy and COVID-19, we presented a research update from HIV clinical cohorts and specifically described 3 lessons learned from the Centers for AIDS Research Network of Integrated Clinical Systems cohort that are important for HIV and aging research moving forward.
Adjudicated outcomes are particularly beneficial for less common comorbidities such as myocardial infarction. Multiple ascertainment approaches increase sensitivity over using diagnoses alone (89% vs. 44%). Adjudication eliminates false-positive events and allows myocardial infarction types to be identified. Comorbidity research has often relied on composite outcomes, such as all cardiovascular diseases, often to increase power. Mechanistic differences across outcomes demonstrate the importance of moving away from many composite outcomes. Timely data are needed to ensure findings are relevant to improve care or outcomes for the population of PWH who are currently aging.
A better understanding of the causes, mechanisms, prevention and treatment of functional decline, comorbidities, and multimorbidities is a crucial research focus as PWH are aging. Clinical cohorts with timely, comprehensive harmonized clinical data and carefully adjudicated outcomes are ideally positioned to improve understanding of these questions.
Health care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost ...importance to patients, clinicians, and health-care planners. We examined changes in 3 year survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013.
We analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between 1996 and 2010 and had at least 3 years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause-specific mortality hazard ratios (HRs) for the first year after ART initiation and the second and third years after ART initiation in four calendar periods (1996–99, 2000–03 comparator, 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART.
88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second or third year of ART. Patients starting ART in 2008–10 had lower all-cause mortality in the first year after ART initiation than did patients starting ART in 2000–03 (adjusted HR 0·71, 95% CI 0·61–0·83). All-cause mortality in the second and third years after initiation of ART was also lower in patients who started ART in 2008–10 than in those who started in 2000–03 (0·57, 0·49–0·67); this decrease was not fully explained by viral load and CD4 cell count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART in 2008–10 (vs 2000–03) in the first year (0·48, 0·34–0·67) and second and third years (0·29, 0·21–0·40) after initiation of ART. Between 1996 and 2010, life expectancy in 20-year-old patients starting ART increased by about 9 years in women and 10 years in men.
Even in the late ART era, survival during the first 3 years of ART continues to improve, which probably reflects transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity. Prognostic models and life expectancy estimates should be updated to account for these improvements.
UK Medical Research Council, UK Department for International Development, EU EDCTP2 programme.
Medication adherence plays an important role in optimizing the outcomes of many treatment and preventive regimens in chronic illness. Self-report is the most common method for assessing adherence ...behavior in research and clinical care, but there are questions about its validity and precision. The NIH Adherence Network assembled a panel of adherence research experts working across various chronic illnesses to review self-report medication adherence measures and research on their validity. Self-report medication adherence measures vary substantially in their question phrasing, recall periods, and response items. Self-reports tend to overestimate adherence behavior compared with other assessment methods and generally have high specificity but low sensitivity. Most evidence indicates that self-report adherence measures show moderate correspondence to other adherence measures and can significantly predict clinical outcomes. The quality of self-report adherence measures may be enhanced through efforts to use validated scales, assess the proper construct, improve estimation, facilitate recall, reduce social desirability bias, and employ technologic delivery. Self-report medication adherence measures can provide actionable information despite their limitations. They are preferred when speed, efficiency, and low-cost measures are required, as is often the case in clinical care.
BACKGROUND:Patient-reported outcomes (PROs) are gaining recognition as key measures for improving the quality of patient care in clinical care settings. Three factors have made the implementation of ...PROs in clinical care more feasibleincreased use of modern measurement methods in PRO design and validation, rapid progression of technology (eg, touchscreen tablets, Internet accessibility, and electronic health records), and greater demand for measurement and monitoring of PROs by regulators, payers, accreditors, and professional organizations. As electronic PRO collection and reporting capabilities have improved, the challenges of collecting PRO data have changed.
OBJECTIVES:To update information on PRO adoption considerations in clinical care, highlighting electronic and technical advances with respect to measure selection, clinical workflow, data infrastructure, and outcomes reporting.
METHODS:Five practical case studies across diverse health care settings and patient populations are used to explore how implementation barriers were addressed to promote the successful integration of PRO collection into the clinical workflow. The case studies address selecting and reporting of relevant content, workflow integration, previsit screening, effective evaluation, and electronic health record integration.
CONCLUSIONS:These case studies exemplify elements of well-designed electronic systems, including response automation, tailoring of item selection and reporting algorithms, flexibility of collection location, and integration with patient health care data elements. They also highlight emerging logistical barriers in this area, such as the need for specialized technological and methodological expertise, and design limitations of current electronic data capture systems.
High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between ...settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.
Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 South Africa, 29,727 Europe, and 7,160 North America), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.
After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary.
Research on patient engagement in health care shows that better health outcomes and lower healthcare costs are observed among highly engaged patients. Similar to other illnesses, high levels of ...patient engagement in HIV care are considered essential to maintaining optimal health, and patients who are on treatment and retained in HIV care are known to have better health outcomes. In this article, we draw on focus group discussion data with patients living with HIV in order to explain tacit expectations associated with engagement in care. The main objective of our research was to elicit an explanatory model of engagement in HIV care from the patients' perspective. We conducted focus group discussions with a sample of two distinct types of patients: those who regularly attended medical appointments and those who did not. In total, we conducted six focus group discussions (n = 43) across in three cities in the US; these included two focus group discussions with a well-engaged and less-well-engaged group in each location. Both types of patients assigned a moral dimension to engagement in care, in that well-engaged patients were considered to be 'good' patients. Aspiring to become a 'good' patient provided a meaningful goal for some and deepened vulnerabilities among patients that struggled to achieve this status. More vulnerable patients may feel less secure in health care interactions and these feelings may be amplified if patients have an unreasonable impression of what constitutes a 'good' patient; thereby leading to disengagement in care. Our findings can inform the development of patient-centered, tailored messages to better serve patients struggling to stay engaged in HIV care.
To describe disparities along the depression treatment cascade, from indication for antidepressant treatment to effective treatment, in HIV-infected individuals by gender and race/ethnicity.
The ...Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) cohort includes 31,000 HIV-infected adults in routine clinical care at 8 sites. Individuals were included in the analysis if they had a depressive symptoms measure within one month of establishing HIV care at a CNICS site. Depressive symptoms were measured using the validated Patient Health Questionnaire-9 (PHQ-9). Indication for antidepressant treatment was defined as PHQ-9 ≥ 10 or a current antidepressant prescription. Antidepressant treatment was defined as a current antidepressant prescription. Evidence-based antidepressant treatment was considered treatment changes based on a person's most recent PHQ-9, in accordance with clinical guidelines. We calculated the cumulative probability of moving through the depression treatment cascade within 24 months of entering CNICS HIV care. We used multivariable Cox proportional hazards models to estimate associations between gender, race/ethnicity, and a range of depression outcomes.
In our cohort of HIV-infected adults in routine care, 47% had an indication for antidepressant treatment. Significant drop-offs along the depression treatment cascade were seen for the entire study sample. However, important disparities existed. Women were more likely to have an indication for antidepressant treatment (HR 1.54; 95% CI 1.34, 1.78), receive antidepressant treatment (HR 2.03; 95% CI 1.53, 2.69) and receive evidence-based antidepressant treatment (HR 1.67; 95% CI 1.03, 2.74), even after accounting for race/ethnicity. Black non-Hispanics (HR 0.47, 95% CI 0.35, 0.65), Hispanics (HR 0.63, 95% CI 0.44, 0.89) and other race/ethnicities (HR 0.35, 95% CI 0.17, 0.73) were less likely to initiate antidepressant treatment, compared to white non-Hispanics.
In our cohort of HIV-infected adults depressive symptoms were common. Important disparities in the prevalence of depressive symptoms and receipt of antidepressant treatment existed by gender and race/ethnicity.
Background. Some human immunodeficiency virus (HIV)–infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. ...We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/μL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. Methods. We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/μL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/μL) and Cox regression to identify associations with mortality. Results. Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/μL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/μL. Individuals with CD4 ≤200 cells/μL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86–3.61) compared with those who achieved CD4 count >200 cells/μL. The increased mortality was seen across different patient groups and for all causes of death. Conclusions. Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/μL have substantially increased long-term mortality.
Traditional cardiovascular disease risk factors (CVDRFs) increase the risk of acute myocardial infarction (AMI) among HIV-infected (HIV+) participants. We assessed the association between HIV and ...incident AMI within CVDRF strata.
Cohort-81,322 participants (33% HIV+) without prevalent CVD from the Veterans Aging Cohort Study Virtual Cohort (prospective study of HIV+ and matched HIV- veterans) participated in this study. Veterans were followed from first clinical encounter on/after April 1, 2003, until AMI/death/last follow-up date (December 31, 2009). Predictors-HIV, CVDRFs (total cholesterol, cholesterol-lowering agents, blood pressure, blood pressure medication, smoking, diabetes) used to create 6 mutually exclusive profiles: all CVDRFs optimal, 1+ nonoptimal CVDRFs, 1+ elevated CVDRFs, and 1, 2, 3+ major CVDRFs. Outcome-Incident AMI defined using enzyme, electrocardiogram (EKG) clinical data, 410 inpatient ICD-9 (Medicare), and/or death certificates. Statistics-Cox models adjusted for demographics, comorbidity, and substance use.
Of note, 858 AMIs (42% HIV+) occurred over 5.9 years (median). Prevalence of optimal cardiac health was <2%. Optimal CVDRF profile was associated with the lowest adjusted AMI rates. Compared with HIV- veterans, AMI rates among HIV+ veterans with similar CVDRF profiles were higher. Compared with HIV- veterans without major CVDRFs, HIV+ veterans without major CVDRFs had a 2-fold increased risk of AMI (HR: 2.0; 95% confidence interval: 1.0 to 3.9; P = 0.044).
The prevalence of optimal cardiac health is low in this cohort. Among those without major CVDRFs, HIV+ veterans have twice the AMI risk. Compared with HIV- veterans with high CVDRF burden, AMI rates were still higher in HIV+ veterans. Preventing/reducing CVDRF burden may reduce excess AMI risk among HIV+ people.
Transgender women (TW) are disproportionately affected by both HIV and cardiovascular disease (CVD).
We aim to quantify prevalence of elevated predicted CVD risk for TW compared to cisgender women ...(CW) and cisgender men (CM) in HIV care and describe the impact of multiple operationalizations of CVD risk score calculations for TW.
We conducted a cross-sectional analysis of patients engaged in HIV care between October 2014 and February 2018.
The Centers for AIDS Research Network of Integrated Clinical Systems, a collaboration of 8 HIV clinical sites in the United States contributed data for this analysis.
221 TW, 2983 CW, and 13467 CM.
The measure of interest is prevalence of elevated 10-year cardiovascular disease risk based on ACC/AHA Pooled Cohort Risk Assessment equations (PCE) and the Framingham Risk Score (FRS), calculated for TW by: birth-assigned sex (male); history of exogenous sex hormone use (female/male); and current gender (female).
Using birth-assigned sex, the adjusted prevalence ratio (aPR) was 2.52 (95% CI: 1.08,5.86) and 2.58 (95% CI: 1.71,3.89) comparing TW to CW, by PCE and FRS, respectively. It was 1.25 (95% CI: 0.54,2.87) and 1.25 (95% CI: 0.84,1.86) comparing TW to CM, by PCE and FRS, respectively. If TW were classified according to current gender versus birth-assigned sex, their predicted CVD risk scores were lower.
PCE and FRS have not been validated in TW with HIV. Few adjudicated CVD events in the data set precluded analyses based on clinical outcomes.
After adjustment for demographics and history of HIV care, prevalence of elevated CVD risk in TW was similar to CM and equal to or higher than in CW, depending operationalization of the sex variable. Future studies with CVD outcomes are needed to help clinicians accurately estimate CVD risk among TW with HIV.
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