Increases in multimorbidity and obesity have been noted in HIV infected populations in the current treatment era. Patterns of multimorbid disease clustering as well as the impact of obesity on multimorbidity are understudied in this population.
We examined obesity and multimorbidity patterns among 1844 HIV-infected patients in the UAB 1917 Clinic. Exploratory factor analysis (EFA) was used to identify the underlying factor structure responsible for clustering. Patterns among the resulting morbidity factors by body mass index (BMI) category were explored. Multivariable logistic regression models were fit to identify predictors of multimorbidity cluster patterns.
The prevalence of multimorbidity was 65% (1205/1844). Prevalence increased with progressive BMI categories from underweight (64%) to obese (79%). Three multimorbidity clusters were identified: “Metabolic” including hypertension (HTN), gout, diabetes mellitus, and chronic kidney disease (CKD) (range: 0.41 to 0.84; P<0.001); “Behavioral“ including mood disorders, dyslipidemia, chronic obstructive pulmonary disease (COPD), chronic ulcer disease, osteoarthritis, obstructive sleep apnea (OSA), and cardiac disorders (range: 0.32 to 0.57; P<0.001); “Substance Use” including alcohol abuse, substance abuse, tobacco abuse, and hepatitis C (range: 0.53 to 0.89; P<0.001). Obesity was associated with increased odds of multimorbidity (Obese vs. Normal BMI category: OR=1.52, 95%CI=1.15-2.00).
Three patterns of disease clustering were identified. Obesity was associated with a higher likelihood of multimorbidity. The management of multimorbidity and obesity will need to be addressed in future clinical practice guidelines to enhance long term outcomes of HIV-infected patients in the current treatment era.
Multimorbidity; Obesity; HIV; Factor Analysis; Tetrachoric
Aspirin for primary prevention of cardiovascular events is underutilized in human immunodeficiency virus (HIV)–infected patients. As these patients are at increased risk for events compared with HIV-negative persons, interventions are needed to increase HIV provider awareness of and adherence to existing guidelines.
Background. Individuals infected with human immunodeficiency virus (HIV) are at increased risk for cardiovascular disease (CVD) events compared with uninfected persons. However, little is known about HIV provider practices regarding aspirin (ASA) for primary prevention of CVD.
Methods. A cross-sectional study was conducted among patients attending the University of Alabama at Birmingham 1917 HIV Clinic during 2010 to determine the proportion receiving ASA for primary prevention of CVD and identify factors associated with ASA prescription. Ten-year risk for CVD events was calculated for men aged 45–79 and women aged 55–79. The 2009 US Preventive Services Task Force (USPSTF) guidelines were used to determine those qualifying for primary CVD prevention.
Results. Among 397 patients who qualified to receive ASA (mean age, 52.2 years, 94% male, 36% African American), only 66 (17%) were prescribed ASA. In multivariable logistic regression analysis, diabetes mellitus (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.28–5.27), hyperlipidemia (OR, 3.42; 95% CI, 1.55–7.56), and current smoking (OR, 1.87; 95% CI, 1.03–3.41) were significantly associated with ASA prescription. Odds of ASA prescription more than doubled for each additional CVD-related comorbidity present among hypertension, diabetes, hyperlipidemia, and smoking (OR, 2.13, 95% CI, 1.51–2.99).
Conclusions. In this HIV-infected cohort, fewer than 1 in 5 patients in need received ASA for primary CVD prevention. Escalating likelihood of ASA prescription with increasing CVD-related comorbidity count suggests that providers may be influenced more by co-occurrence of these diagnoses than by USPSTF guidelines. In the absence of HIV-specific guidelines, interventions to improve HIV provider awareness of and adherence to existing general population guidelines on CVD risk reduction are needed.
Co-occurring pain, mood disorders, and substance abuse are common in HIV-infected patients. Our objective was to investigate the relationship between pain, alone and in the context of mood disorders and substance abuse, on clinic utilization, antiretroviral therapy (ART) adherence, and virologic suppression.
Pain, mood disorders, and substance abuse were assessed at the first visit. No-show and urgent visits were measured over a one-year period. Models were adjusted for age, race, sex, insurance status, CD4+ T-lymphocyte count, and HIV risk factor.
Among 1521 participants, 509 (34%) reported pain, 239 (16%) had pain alone, 189 (13%) had pain and a mood disorder, and 30 (2%) had pain and substance abuse. In univariate models, participants with pain, mood disorders, and substance abuse had higher odds of a no-show visit than participants without these conditions [OR 1.4 (95% CI 1.1–1.8); OR 1.5 (95% CI 1.2–1.9); OR 2.0 (95% CI 1.4–2.8), respectively]. In the multivariable model, pain increased the odds of a no-show visit only in participants without substance abuse [OR 1.5 (95% CI 1.1–1.9)], and pain reduced the odds of a no-show visit in participants with substance abuse [OR 0.5 (95% CI 0.2–0.9), p for interaction=0.0022].
In this study, pain increased the odds of no-show visits, but only for participants without substance abuse. Because pain, mood disorders, and substance abuse are highly prevalent in HIV-infected patients, our findings have implications for HIV treatment success. Interventions that incorporate pain management may be important for improving health outcomes in patients living with HIV infection.
HIV; Pain; Psychiatric Illness; Substance Abuse; ART Adherence; Health Care Utilization
In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru.
Design And Methods
Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ≥1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ≥1 clinic visit.
Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables.
856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies.
Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99).
The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.
The success of antiretroviral therapy (ART) has led to dramatic changes in causes of morbidity and mortality in HIV-infected individuals. As chronic diseases rates have increased in HIV+ populations, modifiable risk factors such as obesity have increased in importance. Our objective was to evaluate factors associated with weight change among patients receiving ART.
ART-naïve patients initiating therapy at the University of Alabama - Birmingham 1917 HIV/AIDS Clinic from 2000– 2008 were included. Body Mass Index (BMI) was categorized as: underweight (<18.5), normal weight (18.5–24.9), overweight (25–29.9) and obese (≥30). Linear regression models were used to evaluate overall change in BMI and factors associated with increased BMI category 24 months following ART initiation.
Among 681 patients, the mean baseline BMI was 25.4 ± 6.1; 44% of patients were overweight/obese. At 24 months, 20% of patients moved from normal to overweight/obese or overweight to obese BMI categories. Greater increases in BMI were observed in patients with baseline CD4 count < 50 cells/μl (3.4 ± 4.1, P<0.01) and boosted protease inhibitor use (2.5±4.1 P=0.01), but did not account for all of the variation observed in weight change.
The findings that almost half of patients were overweight or obese at ART initiation, and 1 in 5 patients moved to a deleterious BMI category within 2 years of ART initiation are alarming. ART therapy provides only a modest contribution to weight gain in patients. Obesity represents a highly prevalent condition in patients with HIV infection and an important target for intervention.
obesity; HIV; body mass index
The AIDS Drug Assistance Program (ADAP) provides antiretroviral medications to low-income individuals with HIV infection.
A prospective cohort study of ADAP utilization, measured using medication possession ratio (MPR), was conducted during the 2008 calendar year at the University of Alabama at Birmingham 1917 HIV Clinic. Multivariable ordinal logistic regression evaluated factors associated with ADAP utilization.
Among 245 patients, MPR quartiles (Q) were the following: Q1<69 percent, Q2 = 69–83 percent, Q3 = 84–93 percent, Q4>93 percent. In ordinal logistic regression, younger age (OR = 0.59 per 10 years; 95 percent CI = 0.44–0.79), nonwhite males (2.18; 1.18–4.04), lower CD4 count (2.79 for <200 cells/mm3; 1.44–5.43), and a history of alcohol abuse (2.11; 1.02–4.37) were associated with poor ADAP utilization.
One quarter of ADAP enrollees had MPR below 69 percent, a level well below that associated with optimal HIV treatment outcomes, indicating a need for programmatic interventions to improve ADAP utilization.
HIV; adherence; public health
Following HIV diagnosis and linkage to care, achieving and sustaining viral load (VL) suppression has implications for patient outcomes and secondary HIV prevention. We evaluated factors associated with expeditious VL suppression and cumulative VL burden among patients establishing outpatient HIV care.
Patients initiating HIV medical care from January 2007-October 2010 at the University of Alabama at Birmingham and University of Washington were included. Multivariable Cox proportional hazards and linear regression models were used to evaluate factors associated with time to VL suppression (<50 copies/mL) and cumulative VL burden, respectively. Viremia copy-years (VCY), a novel area under the longitudinal VL curve measure, was used to estimate 2-year cumulative VL burden from clinic enrollment.
Among 676 patients, 63% achieved VL<50 copies/mL in a median 308 days. In multivariable analysis, patients with more time-updated “no show” visits experienced delayed VL suppression (HR=0.83 per “no show” visit, 95%CI=0.76,0.91). In multivariable linear regression, visit non-adherence was independently associated with greater cumulative VL burden (log10VCY) during the first two years in care (Beta coefficient=0.11 per 10% visit non-adherence, 95%CI=0.04-0.17). Across increasing visit adherence categories, lower cumulative VL burden was observed (mean ± standard deviation log10 copy × years/mL); 0-79% adherence: 4.6 ± 0.8; 80-99% adherence: 4.3 ± 0.7; and 100% adherence: 4.1 ± 0.8 log10 copy × years/mL, respectively (P<0.01).
Higher rates of early retention in HIV care are associated with achieving VL suppression and lower cumulative VL burden. These findings are germane for a test and treat approach to HIV prevention.
HIV; Viral load; Retention in care; Adherence; Engagement in care
Diagnoses of substance abuse and depression made using patient reported outcomes (PROs) correlate better with nonadherence to medication than do diagnoses captured in traditional electronic medical records. PROs are an important resource in HIV/AIDS clinics for research and clinical care.
Introduction. Computerized collection of standardized measures of patient reported outcomes (PROs) provides a novel paradigm for data capture at the point of clinical care. Comparisons between data from PROs and Electronic Health Records (EHR) are lacking. We compare EHR and PRO for capture of depression and substance abuse and their relationship to adherence to antiretroviral therapy (ART).
Methods. This retrospective study includes HIV-positive patients at an HIV clinic who completed an initial PRO assessment April 2008–July 2009. The questionnaire includes measures of depression (PHQ-9) and substance abuse (ASSIST). Self-reported ART adherence was modeled using separate logistic regression analyses (EHR vs PRO).
Results. The study included 782 participants. EHR vs PRO diagnosis of current substance abuse was 13% (n = 99) vs 6% (n = 45) (P < .0001), and current depression was 41% (n = 317) vs 12% (n = 97) (P < .0001). In the EHR model, neither substance abuse (OR = 1.25; 95% CI = 0.70–2.21) nor depression (OR = 0.93; 95% CI = 0.62–1.40) was significantly associated with poor ART adherence. Conversely, in the PRO model, current substance abuse (OR = 2.78; 95% CI = 1.33–5.81) and current depression (OR = 1.93; 95% CI = 1.12–3.33) were associated with poor ART adherence.
Discussions. The explanatory characteristics of the PRO model correlated best with factors known to be associated with poor ART adherence (substance abuse; depression). The computerized capture of PROs as a part of routine clinical care may prove to be a complementary and potentially transformative health informatics technology for research and patient care.
To examine long-term effects of antiretroviral therapy (ART) on kidney function, we evaluated the incidence and risk factors for chronic kidney disease (CKD) among ART-naive, HIV-infected adults and compared changes in estimated glomerular filtration rates (eGFR) before and after starting ART.
Multicenter observational cohort study of patients with at least one serum creatinine measurement before and after initiating ART. Cox proportional hazard models, and marginal structure models examined CKD risk factors; mixed-effects linear models examined eGFR slopes.
Three thousand, three hundred and twenty-nine patients met entry criteria, contributing 10 099 person-years of observation on ART. ART was associated with a significantly slower rate of eGFR decline (from −2.18 to −1.37 ml/min per 1.73 m2 per year; P = 0.02). The incidence of CKD defined by eGFR thresholds of 60, 45 and 30 ml/min per 1.73 m2 was 10.5, 3.4 and 1.6 per 1000 person-years, respectively. In adjusted analyses black race, hepatitis C coinfection, lower time-varying CD4 cell count and higher time-varying viral load on ART were associated with higher CKD risk, and the magnitude of these risks increased with more severe CKD. Tenofovir and a ritonavir-boosted protease inhibitor (rPI) was also associated with higher CKD risk [hazard odds ratio for an eGFR threshold <60 ml/min per 1.73 m2: 3.35 (95% confidence interval (CI) = 1.40–8.02)], which developed in 5.7% of patients after 4 years of exposure to this regimen-type.
ART was associated with reduced CKD risk in association with CD4 cell restoration and plasma viral load suppression, despite an increased CKD risk that was associated with initial regimens that included tenofovir and rPI.
antiretroviral therapy; chronic kidney disease; tenofovir
Little is known about the long-term effectiveness of albendazole in the medical therapy of non-complicated hepatic cystic echinococcosis (HCE) in resource-constrained settings. We performed a retrospective review of patients starting albendazole for HCE in Lima, Peru from January 1997 to December 2007. Patients successfully recontacted underwent chart abstraction and clinical and ultrasonographic reevaluation. Descriptive statistics were used to delineate patient characteristics and treatment effectiveness at the conclusion of albendazole and after reevaluation. Patients (N = 27) were primarily female, mean age was 51. Initial treatment success at albendazole conclusion was 26% (N = 7) per patient and 37.5% (N = 24) per cyst. After 3.8 ± 2.5 years, albendazole success was 34% (N = 9) per patient and 40% (N = 24) per cyst. We found a gap in the effectiveness of albendazole HCE therapy compared with the efficacy reported in clinical trials. This underscores the need for further investigation into alternate therapeutic strategies for this neglected disease.
Viremia copy-years predicted all-cause mortality independent of traditional, cross-sectional viral load measures and time-updated CD4+ T-lymphocyte count in antiretroviral therapy-treated patients suggesting cumulative human immunodeficiency virus replication causes harm independent of its effect on the degree of immunodeficiency.
Background. Cross-sectional plasma human immunodeficiency virus (HIV) viral load (VL) measures have proven invaluable for clinical and research purposes. However, cross-sectional VL measures fail to capture cumulative plasma HIV burden longitudinally. We evaluated the cumulative effect of exposure to HIV replication on mortality following initiation of combination antiretroviral therapy (ART).
Methods. We included treatment-naive HIV-infected patients starting ART from 2000 to 2008 at 8 Center for AIDS Research Network of Integrated Clinical Systems sites. Viremia copy-years, a time-varying measure of cumulative plasma HIV exposure, were determined for each patient using the area under the VL curve. Multivariable Cox models were used to evaluate the independent association of viremia copy-years for all-cause mortality.
Results. Among 2027 patients contributing 6579 person-years of follow-up, the median viremia copy-years was 5.3 log10 copy × y/mL (interquartile range: 4.9–6.3 log10 copy × y/mL), and 85 patients (4.2%) died. When evaluated separately, viremia copy-years (hazard ratio [HR] = 1.81 per log10 copy × y/mL; 95% confidence interval [CI], 1.51–2.18 per log10 copy × y/mL), 24-week VL (1.74 per log10 copies/mL; 95% CI, 1.48–2.04 per log10 copies/mL), and most recent VL (HR = 1.89 per log10 copies/mL; 95% CI: 1.63–2.20 per log10 copies/mL) were associated with increased mortality. When simultaneously evaluating VL measures and controlling for other covariates, viremia copy-years increased mortality risk (HR = 1.44 per log10 copy × y/mL; 95% CI, 1.07–1.94 per log10 copy × y/mL), whereas no cross-sectional VL measure was independently associated with mortality.
Conclusions. Viremia copy-years predicted all-cause mortality independent of traditional, cross-sectional VL measures and time-updated CD4+ T-lymphocyte count in ART-treated patients, suggesting cumulative HIV replication causes harm independent of its effect on the degree of immunodeficiency.
In an effort to evaluate factors associated with the development of antiretroviral (ARV) resistance, we assessed the prevalence of toxicity-related regimen changes and modeled its association to the subsequent development of ARV resistance in a cohort of treatment-naive individuals initiating ARV therapy (ART). A retrospective analysis of patients initiating ART was conducted at the UAB 1917 Clinic from 1 January 2000 to 30 September 2007. Cox proportional hazards models were fit to identify factors associated with the development of resistance to ≥1 ARV drug class. Among 462 eligible participants, 14% (n=64) developed ARV resistance. Individuals with ≥1 toxicity-related regimen change (HR=3.94, 95% CI=1.09–14.21), initiating ART containing ddI or d4T (4.12, 1.19–14.26), and from a minority race (2.91, 1.16–7.28) had increased risk of developing resistance. Achieving virologic suppression within 12 months of ART initiation (0.10, 0.05–0.20) and higher pretreatment CD4 count (0.85 per 50 cells/mm3, 0.75–0.96) were associated with decreased hazards of resistance. Changes in ART due to drug intolerance were associated with the subsequent development of ARV resistance. Understanding the role of ARV drug selection and other factors associated with the emergence of ARV resistance will help inform interventions to improve patient care and ensure long-term treatment success.
Many newly diagnosed patients present to outpatient care with advanced HIV infection. More timely HIV diagnosis and initiation of care has the potential to improve individual health outcomes and has public health implications.
To assess temporal trends in late presentation for outpatient HIV medial care as measured by CD4 count <200 cells/mm3 and the implications on short-term (1-year) mortality.
We conducted a cohort study nested in a prospective HIV clinical cohort including patients establishing initial outpatient HIV treatment between 2000–2010. Time series regression analysis evaluated temporal trends in late presentation for care measured by the proportion of patients with a CD4 count <200 cells/mm3 or an opportunistic infection at enrollment, and also evaluated trends in short-term mortality.
Patients establishing initial outpatient HIV treatment between 2000–2010 at an academic HIV clinic.
The proportion of patients with a CD4 count <200 cells/mm3 or an opportunistic infection at initial presentation and short-term (1-year) mortality following clinic enrollment.
Among 1121 patients, 41% had an initial CD4 count <200 cells/mm3, 25% had an opportunistic infection and 2.4% died within 1-year of their initial visit. Time series regression analysis demonstrated significant reductions in late presentation for HIV care and decreases in short-term mortality with temporal improvement preceding updated CDC HIV testing recommendations.
We observed a significant decline in the number of patients presenting for outpatient HIV care with advanced disease, particularly in 2006–2010. A significant trend in improved short-term survival among patients establishing HIV care was also observed, likely related to more timely presentation for outpatient care in more recent years.
HIV; HIV testing; mortality; disparity; health policy
The CDC released revised HIV testing guidelines in 2006 recommending routine, opt-out HIV testing in acute care settings including emergency departments (ED). Patient attitudes have been cited as a barrier to implementation of routine HIV testing in the ED. We assessed patients' perceptions of HIV testing in the ED through a contextual qualitative approach. The study was conducted during a 72-h period. All adults presenting to the ED without life-threatening trauma or psychiatric crisis completed a standardized questionnaire. The questionnaire explored HIV testing history, knowledge of testing resources, and qualitative items addressing participant perceptions about advantages and disadvantages to ED testing. After completion of the interview, participants were offered a free, confidential, rapid HIV test. Among 329 eligible individuals approached, 288 (87.5%) completed the initial interview. Participants overwhelmingly (n=247, 85.8%) reported support for testing and identified increased knowledge (41%), prevention (12.5%), convenience (11.8%), and treatment (4.9%) among the advantages. Fear and denial about one's HIV status, reported by <5% of patients, were identified as the most significant barriers to ED testing. Bivariate analysis determined race and ethnicity differences between individuals completing the interview and those who refused (p<0.05). Among individuals consenting for testing (n=186, 64.6%), no positives were detected. Most patients support HIV testing in the ED, noting knowledge of status, prevention, convenience, and linkage to early treatment as distinct advantages. These data are of particular benefit to decision makers considering the addition of routine HIV testing in EDs.
U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes.
We analyzed data from HIV-infected individuals who were clinically-eligible for ART between 2001 and 2009 (i.e., a first reported CD4+ <350 cells/uL or AIDS-defining illness) from 14 U.S. cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Using propensity score matching and Cox regression, we assessed ART initiation (within 6 months following eligibility) and virologic suppression (within 1 year) based on differences in two state ADAP features: the amount of state funding in annual ADAP budgets and the implementation of waiting lists. We performed an a priori subgroup analysis in persons with a history of injection drug use (IDU).
Among 8,874 persons, 56% initiated ART within six months following eligibility. Persons living in states with no additional state contribution to the ADAP budget initiated ART on a less timely basis (hazard ratio [HR] 0.73, 95% CI 0.60–0.88). Living in a state with an ADAP waiting list was not associated with less timely initiation (HR 1.12, 95% CI 0.87–1.45). Neither additional state contributions nor waiting lists were significantly associated with virologic suppression. Persons with an IDU history initiated ART on a less timely basis (HR 0.67, 95% CI 0.47–0.95).
We found that living in states that did not contribute additionally to the ADAP budget was associated with delayed ART initiation when treatment was clinically indicated. Given the changing healthcare environment, continued assessment of the role of ADAPs and their features that facilitate prompt treatment is needed.
This study compared the effectiveness and toxicity of different statins among 700 HIV-infected patients in routine clinical care. Findings suggest that atorvastatin and rosuvastatin are preferable to pravastatin leading to greater declines in lipid levels with similar low rates of toxicity.
Background. Dyslipidemia is common and is often treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins). Little is known about the comparative effectiveness of statins among human immunodeficiency virus (HIV)–infected patients. This study compared the effectiveness and toxicity of statins among HIV-infected patients in clinical care.
Methods. We conducted a retrospective cohort study of patients starting their initial statin medications at 2 large HIV clinics (N = 700). The primary observation was change in lipid levels during statin therapy. Secondary observations included whether individualized National Cholesterol Education Program (NCEP) goals for low density lipoprotein cholesterol (LDL-C) and non–high density lipoprotein cholesterol (non-HDL-C) levels were reached, and toxicity rates. We used linear regression to examine change in lipid levels, controlling for baseline lipid values and demographic and clinical characteristics. We conducted secondary analyses using propensity scores to address confounding by indication.
Results. The most commonly prescribed statins were atorvastatin (N = 303), pravastatin (N = 280), and rosuvastatin (N = 95). One year after starting a statin therapy, patients who received atorvastatin or rosuvastatin had significantly greater decreases in total cholesterol, LDL-C, and non-HDL-C than patients on pravastatin. The likelihood of reaching NCEP goals for LDL-C levels was higher with the use of rosuvastatin (OR 2.1; P = .03) and atorvastatin (odds ratio [OR], 2.1; P = .001) compared with that of pravastatin. The likelihood of reaching NCEP goals for non-HDL-C levels was higher for rosuvastatin (OR 2.3; P = .045) but not atorvastatin (OR, 1.5; P = .1) compared with pravastatin. Toxicity rates were similar for all 3 statins: 7.3% for atorvastatin, 6.1% for pravastatin, and 5.3% for rosuvastatin.
Conclusions. Our findings suggest that atorvastatin and rosuvastatin are preferable to pravastatin for treatment of HIV-infected patients with dyslipidemia, due to greater declines in total cholesterol, LDL-C, and non-HDL-C, with similar lower toxicity rates.
Several new antiretroviral (ARV) agents for treatment experienced HIV-infected patients have been approved since June 2006, including darunavir (DRV) and raltegravir (RAL). While efficacious in clinical trials, the effectiveness, durability, and tolerability of these new ARVs remains understudied in the context of routine clinical care. The Darunavir Outcomes Study is a prospective cohort study of three-class ARV-experienced patients changing regimens at the 1917 Clinic after 1/7/2006. All treatment decisions were at the discretion of primary providers. Multivariate (MV) logistic regression for 48 week VL <400c/ml and Cox models for regimen durability were completed. Propensity score methods controlled for sociodemographics. Among 108 patients, mean age of 46, 48% were white, 80% male, with prior exposure to a mean 10.5 ARVs. Overall, 64% of patients achieved 48-week VL <400 c/ml. In MV modeling DRV/rll (OR = 5.77;95%CI = 1.62–20.58) and RAL (OR = 3.84;95%CI = 1.23–11.95) use increased odds of 48-week suppression. Use of these agents exhibited a trend towards prolonged regimen durability in Cox models. Among those highly ARV-experienced, regimens containing DRV/r and/or RAL were more likely to achieve 48-week VL <400 c/ml and exhibited a trend towards prolonged durability. New agents have transformed the treatment landscape for ARV-experienced patients, with effectiveness in routine clinical care mirroring efficacy in clinical trials.
The implementation of routine computer-based screening for suicidal ideation and other psychosocial domains through standardized patient reported outcome instruments in two high volume urban HIV clinics is described. Factors associated with an increased risk of self-reported suicidal ideation were determined.
HIV/AIDS continues to be associated with an under-recognized risk for suicidal ideation, attempted as well as completed suicide. Suicidal ideation represents an important predictor for subsequent attempted and completed suicide. We sought to implement routine screening of suicidal ideation and associated conditions using computerized patient reported outcome (PRO) assessments.
Two geographically distinct academic HIV primary care clinics enrolled patients attending scheduled visits from 12/2005 to 2/2009. Touch-screen-based, computerized PRO assessments were implemented into routine clinical care. Substance abuse (ASSIST), alcohol consumption (AUDIT-C), depression (PHQ-9) and anxiety (PHQ-A) were assessed. The PHQ-9 assesses the frequency of suicidal ideation in the preceding two weeks. A response of “nearly every day” triggered an automated page to pre-determined clinic personnel who completed more detailed self-harm assessments.
Overall 1,216 (UAB= 740; UW= 476) patients completed initial PRO assessment during the study period. Patients were white (53%; n=646), predominantly males (79%; n=959) with a mean age of 44 (± 10). Among surveyed patients, 170 (14%) endorsed some level of suicidal ideation, while 33 (3%) admitted suicidal ideation nearly every day. In multivariable analysis, suicidal ideation risk was lower with advancing age (OR=0.74 per 10 years;95%CI=0.58-0.96) and was increased with current substance abuse (OR=1.88;95%CI=1.03-3.44) and more severe depression (OR=3.91 moderate;95%CI=2.12-7.22; OR=25.55 severe;95%CI=12.73-51.30).
Suicidal ideation was associated with current substance abuse and depression. The use of novel technologies to incorporate routine self-reported screening for suicidal ideation and other health domains allow for timely detection and intervention for this life threatening condition.
The generalizability of clinical trial findings (efficacy) to routine care (effectiveness) may be limited. The present study found similar first year virologic and CD4 outcomes among antiretroviral-naïve patients treated through routine care vs. those participating in clinical trials.
The generalizability of clinical trial findings (efficacy) to routine care (effectiveness) may be limited due to study eligibility criteria and volunteer bias. While well chronicled in many conditions, the efficacy vs. effectiveness of antiretroviral therapy (ART) remains understudied.
A retrospective study of the UAB 1917 Clinic Cohort evaluated naïve patients starting ART between 1/1/00–12/31/06. Patients received ART through clinical trials or routine care. Multivariable logistic and linear regression models were fit to evaluate factors associated with virologic failure (VF=VL>50 copies/mL) and change from baseline CD4 count 6 and 12 months after ART initiation. Sensitivity analyses evaluated the impact of missing data on outcomes.
Among 570 patients starting ART during the study period, 121 (21%) enrolled in clinical trials vs. 449 (79%) receiving ART via routine care. ART receipt through routine care was not associated with VF at either 6 (OR=1.00;95%CI=0.54–1.86) or 12 (OR=1.56;95%CI=0.80–3.05) months in primary analyses. No significant differences in CD4 count responses at 6 and 12 months were observed.
Though marked differences in efficacy vs. effectiveness have been observed in the therapeutic outcomes of other conditions, our analyses found no evidence of such divergence among our patients initiating antiretroviral therapy for HIV.
Efficacy; effectiveness; ART; HIV
Numerous antiretroviral therapy (ART) regimens are recommended for first-line and subsequent HIV care, but regimen selection for clinical use may not represent the full range of options. We hypothesized that despite an increase in available antiretrovirals, clinical trial data on regimen efficacy and fixed-dose combination options have lead to uniformity in initial ART. We evaluated regimen selection for ART-naïve patients at the University of Alabama at Birmingham (UAB) 1917 Clinic between January 2000 and December 2007. The annual number of unique initial regimens was quantified. Initial regimen variability was expressed as regimens per 100 patients. Subsequent ART regimens were characterized for complexity via regimen sequence trees detailing the first three generations of regimens for patients starting the two most common initial combinations. Four hundred eighty-two ART-naïve patients were treated with 39 unique initial regimens (8.0 regimens per 100 patients). Variability in initial regimen selection was highest in the first 6 years (14.9–24.4 regimens per 100 patients). A sharp decline was observed in 2006 (16.1 regimens per 100 patients) and 2007 (6.5 regimens per 100 patients). The most dramatic shift in drug selection involved an increase in emtricitabine plus tenofovir plus efavirenz, from 0% in 2003 to 85% in 2007. During the study period, 205 of 482 (43%) patients required a change in initial therapy. Of these, 156 of 205 (76%) had a unique sequence of regimens. A shift toward homogeneity of initial ART was observed (85% of patients received the same first-line regimen in 2007). In contrast, regimen sequencing beyond the first regimen remained complex. These shifts in ART prescribing patterns may have implications for collaborative HIV care.
Syphilis outbreaks in the United States have been reported since 2000 with highest rates in the South and many cases among HIV-infected individuals. We evaluated incident syphilis cases and concurrent gonorrhea and chlamydia screening at a southern HIV clinic. A retrospective cohort study included HIV-infected patients with at least one reactive plasma reagin (test for serum reagin antibodies to cardiolipin-cholesterol-lecithin antigen) and primary care visit from July 2004 to June 2007. Primary, secondary, and early latent syphilis cases were identified as incident syphilis and evaluation for gonorrhea and chlamydia within 1 month were described. Logistic regression was performed to determine factors associated with incident syphilis. Among 1544 patients, 40 incident syphilis cases were identified (5 primary, 29 secondary, and 6 early latent). The majority of patients were not virologically suppressed and only 25% had gonorrhea and chlamydia testing. In adjusted analyses, younger age (0.57 per 10 years, 95% confidence interval [CI] 0.41–0.80) and minority race (2.26, 95% CI 1.12–4.59) were associated with incident syphilis. Among 40 incident syphilis cases, only 1 in 4 were further tested for gonorrhea and chlamydia. These low rates are concerning as concurrent sexually transmitted infections (STIs) increase risk for HIV transmission. HIV care provider education with emphasis on STI testing in the setting of incident syphilis is key in prevention.
Following HIV diagnosis, linkage to outpatient treatment, antiretroviral initiation, and longitudinal retention in care represent the foundation for successful treatment. While prior studies have evaluated these processes in isolation, a systematic evaluation of successive steps in the same cohort of patients has not yet been performed. To ensure optimal long-term outcomes, a better understanding of the interplay of these processes is needed. Therefore, a retrospective cohort study of patients initiating outpatient care at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic between January 2000 and December 2005 was undertaken. Multivariable models determined factors associated with: late diagnosis/linkage to care (initial CD4 < 350 cells/mm3), timely antiretroviral initiation, and retention across the first two years of care. Delayed linkage was observed in two-thirds of the overall sample (n = 567) and was associated with older age (odds ratio [OR] 1.31 per 10 years; 95% confidence interval [CI] = 1.06-1.62) and African American race (OR = 2.45; 95% CI = 1.60-3.74). Attending all clinic visits (hazard ratio [HR] = 6.45; 95% CI = 4.47-9.31) and lower initial CD4 counts led to earlier antiretroviral initiation. Worse retention in the first 2 years was associated with younger age (OR = 0.68 per 10 years; 95% CI = 0.56-0.83), higher baseline CD4 count, and substance abuse (OR = 1.78; 95% CI = 1.16-2.73). Interventions to improve timely HIV diagnosis and linkage to care should focus on older patients and African Americans while efforts to improve retention should address younger patients, those with higher baseline CD4 counts, and substance abuse. Missed clinic visits represent an important obstacle to the timely initiation of antiretroviral therapy. These data inform development of interventions to improve linkage and retention in HIV care, an emerging area of growing importance.