Michael S. Saag

The Therapeutic Implications of Timely Linkage and Early Retention in HIV Care

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.

Distribution of Health Care Expenditures for HIV-Infected Patients

BACKGROUNDnHealth care expenditures for persons infected with human immunodeficiency virus (HIV) in the United State determined on the basis of actual health care use have not been reported in the era of highly active antiretroviral therapy.nnnMETHODSnPatients receiving primary care at the University of Alabama at Birmingham HIV clinic were included in the study. All encounters (except emergency room visits) that occurred within the University of Alabama at Birmingham Hospital System from 1 March 2000 to 1 March 2001 were analyzed. Medication expenditures were determined on the basis of 2001 average wholesale price. Hospitalization expenditures were determined on the basis of 2001 Medicare diagnostic related group reimbursement rates. Clinic expenditures were determined on the basis of 2001 Medicare current procedural terminology reimbursement rates.nnnRESULTSnAmong the 635 patients, total annual expenditures for patients with CD4+ cell counts <50 cells/microL (36,533 dollars per patient) were 2.6-times greater than total annual expenditures for patients with CD4+ cell counts > or =350 cells/microL (13,885 dollars per patient), primarily because of increased expenditures for nonantiretroviral medication and hospitalization. Expenditures for highly active antiretroviral therapy were relatively constant at approximately 10,500 dollars per patient per year across CD4+ cell count strata. Outpatient expenditures were 1558 dollars per patient per year; however, the clinic and physician component of these expenditures represented only 359 dollars per patient per year, or 2% of annual expenses. Health care expenditures for patients with HIV infection increased substantially for those with more-advanced disease and were driven predominantly by medication costs (which accounted for 71%-84% of annual expenses).nnnCONCLUSIONSnPhysician reimbursements, even with 100% billing and collections, are inadequate to support the activities of most clinics providing HIV care. These findings have important implications for the continued support of HIV treatment programs in the United States.

Trends in AIDS-Defining and Non—AIDS-Defining Malignancies among HIV-Infected Patients: 1989–2002

In a comparison of rates of acquired immunodeficiency syndrome (AIDS)-defining malignancies (ADMs) for 1989-1996 versus 1997-2002, we found a decrease in ADMs (rate ratio, 0.31; P<.0001) and a significant increase in non-AIDS-defining malignancies (non-ADMs; rate ratio, 10.87; P<.0002). The mean CD4 cell count was lower among patients with ADMs than among those with non-ADMs. A longer duration of survival during highly active antiretroviral therapy might explain the increasing incidence of non-ADMs.

Duration of Highly Active Antiretroviral Therapy Regimens

The median duration of highly active antiretroviral therapy (HAART) regimens was reported to be 11.8 months in one US study, but that study included both treatment-experienced and treatment-naive patients. The duration of initial HAART regimens for treatment-naive patients alone has not been reported. We selected 405 antiretroviral-naive patients who were seen at the University of Alabama at Birmingham HIV Outpatient Clinic from 1 January 1996 through 9 October 2001, and we assessed the duration of initial and successive HAART regimens in this group. Any antiretroviral medication change, excluding dosage changes, that lasted >or=14 days was considered to indicate the start of a new regimen. The median duration of regimens was determined by Kaplan-Meier analysis, and proportional hazards regression was used to identify factors associated with shorter duration of initial regimen. The median duration of initial regimens was 1.6 years, and medication toxicity-associated events were the cause of one-half of discontinuations. Only a history of opportunistic infection and injection drug use were significantly associated with shorter regimen duration.

Multimorbidity Patterns in HIV-Infected Patients: The Role of Obesity in Chronic Disease Clustering

Background:Increases in multimorbidity and obesity have been noted in HIV-infected populations in the current treatment era. Patterns of multimorbid disease clustering and the impact of obesity on multimorbidity are understudied in this population. Methods:We examined obesity and multimorbidity patterns among 1844 HIV-infected patients in the UAB 1917 Clinic. Exploratory factor analysis 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. Results: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, gout, diabetes mellitus, and chronic kidney disease (range, 0.41–0.84; P < 0.001); “Behavioral,” including mood disorders, dyslipidemia, chronic obstructive pulmonary disease, chronic ulcer disease, osteoarthritis, obstructive sleep apnea, and cardiac disorders (range, 0.32–0.57; P < 0.001); “Substance Use,” including alcohol abuse, substance abuse, tobacco abuse, and hepatitis C (range, 0.53–0.89; P < 0.001). Obesity was associated with increased odds of multimorbidity (obese vs. normal BMI category: OR = 1.52, 95% CI: 1.15 to 2.00). Conclusions: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.

HIV infection and obesity: Where did all the wasting go?

BACKGROUNDnThe 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.nnnMETHODSnART-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.nnnRESULTSnAmong 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.nnnCONCLUSIONSnThe 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.

Short-term discontinuation of HAART regimens more common in vulnerable patient populations

The durability of HAART regimens is often limited by antiretroviral toxicity and nonadherence, which lead to virologic failure. We sought to determine sociodemographic and psychosocial patient factors predictive of short-term discontinuation of HAART regimens overall and stratified by the reason for discontinuation. A retrospective cohort study of the UAB 1917 Clinic Cohort evaluated short-term HAART regimen discontinuation (within 12 months of regimen initiation) between 1/1995 and 8/2004 classified as (1) gastrointestinal (GI) toxicity, (2) non-GI toxicity, (3) virologic failure or nonadherence (VF/NA), (4) loss to follow-up, and (5) other. Multivariable multinomial logistic regression models accounting for dependent observations were fit to assess the relationship between patient factors and type-specific regimen discontinuation. Among the 738 study participants, 1026 of 1852 HAART regimens (55%) were discontinued within 12 months of initiation. In multivariable analysis, discontinuation for GI toxicity was more common in patients lacking private health insurance and those with a history of intravenous (IV) drug use, whereas non-GI toxicity was more common in younger patients and females. African-American patients and those with a history of IV drug use were more likely to stop a regimen due to VF/NA. Loss to follow-up was more common in younger patients, individuals who were uninsured, and those with a history of IV drug use. Short-term discontinuation of HAART regimens is more common in vulnerable populations that bear a disproportionate burden of the U.S. HIV/AIDS epidemic. More vigilant monitoring of patient populations at higher risk of toxicity and virologic failure may allow for improved HAART regimen durability.

Patient Reported Outcomes in Routine Care: Advancing Data Capture for HIV Cohort Research

INTRODUCTIONnComputerized 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).nnnMETHODSnThis 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).nnnRESULTSnThe 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.nnnDISCUSSIONSnThe 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.

Characteristics of an Ambulatory Palliative Care Clinic for HIV-Infected Patients

BACKGROUNDnMany HIV-infected patients in the current treatment era have substantial symptom burden, but few HIV palliative care clinics have been described. Our objective was to describe the University of Alabama at Birmingham (UAB) HIV palliative care clinic (HPCC) and compare it to the overall HIV clinic.nnnMETHODSnWe conducted a chart review of patients referred to the HPCC between April 2008 and June 2011. We evaluated the reason for referral and other issues addressed during palliative care visits. Patient Reported Outcome (PRO) data was used to assess depression (PHQ-9), anxiety (PHQ-A), and substance abuse (ASSIST).nnnRESULTSnAmong 124 patients, mean age was 44 (range 27-64), and median CD4 count was 352 cells/mm(3) (IQR 209-639). Depression (43, 35%), anxiety (40, 32%), and current 8 (7%) or prior 68 (56%) substance abuse occurred at higher rates than in the overall HIV clinic (p<0.05). Pain was the most common reason for referral (118, 95%); most was chronic (113, 90%) and included back pain (26, 21%) and neuropathic pain (15, 12%). Other problems commonly addressed by the palliative team included nonpain symptoms such as depression (39, 48%) and anxiety (17, 21%), insomnia (25, 30%), and constipation (26, 32%).nnnCONCLUSIONSnThis is the first description of a palliative care clinic embedded within an HIV primary care clinic in a developed country that sees patients at all stages of illness. Chronic pain and nonpain symptom management in patients with psychiatric and substance abuse comorbidities are important components of ambulatory palliative care for HIV-infected patients.

Immunologic and virologic consequences of temporary antiretroviral treatment interruption in clinical practice

To determine the long-term immunologic and virologic effects of antiretroviral treatment interruptions, a retrospective analysis of an ongoing observational database was performed at a university HIV clinic. All patients who began highly active antiretroviral therapy (HAART) after January 1, 1996 and (1) were HAART experienced for >/=90 days, (2) had a treatment interruption (TI) for >/=30 days, (3) resumed HAART for >/=30 days, and (4) had CD4(+) cell counts performed pre- and post-TI were included. Main outcome measures included the following: Immunologic success was defined as a post-TI CD4(+) cell count >90% of the pre-TI CD4(+) cell count (post-TI/pre-TI, >90%). Virologic success was defined as a post-TI viral load (VL) less or equal to twice the pre-TI VL (post-TI/pre-TI, </=2) or a post-TI VL of <1000 copies/ml. The pre-TI (baseline) value was the value at the start of the TI (range, -20 to +7 days); the post-TI value was the highest CD4(+) cell count and lowest VL copy achieved during the follow-up window (270 days). One thousand and eight patients were included in the analysis and 75 met the inclusion criteria. Forty-four of 75 patients (58.6%) achieved a successful immunologic outcome and 52 of 68 patients (76.5%; 7 patients did not have a VL determined within the specified periods) achieved a successful virologic outcome. No factors predicting success were identified. The median CD4(+) cell counts pre- and post-TI were 233 and 231 cells/microl, respectively; the median VLs pre- and post-TI were 11,456 and 404 copies/ml, respectively. We conclude that the majority of our patients in virologic failure who underwent a temporary TI recovered 90% of their baseline CD4(+) cell counts and returned to within 2-fold of their baseline VL when HAART was resumed.