Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials.

BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints. RESULTS: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression.

Virologic Outcomes Among ART-Naïve Individuals Initiating Dolutegravir, Elvitegravir, Raltegravir or Darunavir: An Observational Study.

INTRODUCTION: Dolutegravir (DTG), Elvitegravir (EVG), Raltegravir (RAL) and Darunavir (DRV) are commonly prescribed core agents for antiretroviral therapy (ART), and a need exists to compare their clinical effectiveness, as defined by virologic failure risks in real-world settings. METHODS: This observational analysis of a US clinical cohort consisted of ART-naïve people living with HIV (PLWH) in the OPERA database initiating DTG-, EVG-, RAL- or DRV-based regimens between August 2013 and July 2016, with follow-up to July 2017. PLWH were observed from first core agent initiation until core agent discontinuation, clinical activity cessation, death, or study end. Key outcomes included viral suppression (HIV RNA < 50 copies/mL) and confirmed virologic failure (two consecutive viral loads > 200 copies/mL or a viral load > 200 copies/mL followed by discontinuation). Association between core agent and time to virologic failure was assessed with multivariate Cox proportional hazards models. RESULTS: Overall, 4049 ART-naïve PLWH initiated EVG (47.4%), DTG (34.7%), DRV (14.6%), or RAL (3.2%). DTG and EVG initiators had generally similar baseline demographics and clinical characteristics, including race, risk of infection, baseline viral load, and baseline CD4 levels. RAL and DRV initiators were older and generally sicker than DTG initiators. During follow-up, more DTG initiators achieved virologic suppression (78.7%) compared with EVG (73.6%; p < 0.05), RAL (51.9%; p < 0.0001) and DRV (48.6%; p < 0.0001) initiators. Compared to DTG, both RAL and DRV were associated with higher rates of virologic failure, with adjusted hazard ratios (95% confidence interval) of 4.70 (3.03, 7.30) and 2.38 (1.72, 3.29), respectively. No difference was observed between EVG and DTG with an adjusted hazard ratio of 1.24 (0.94, 1.64). CONCLUSION: In this large cohort representative of PLWH in care in the US, ART-naïve PLWH prescribed DTG had better virologic outcomes than RAL and DRV, but had virologic failure risks comparable to EVG, although RAL and DRV were preferentially prescribed to sicker individuals. FUNDING: ViiV Healthcare.

The costs of full suppression of plasma HIV RNA in highly antiretroviral-experienced patients.

The aim of antiretroviral treatment is long-term suppression of plasma HIV RNA<50 copies/ml. The DUET, BENCHMRK, and MOTIVATE trials evaluated the efficacy of etravirine, raltegravir, and maraviroc, respectively, versus placebo, each given with an optimized background regimen of nucleoside reverse transcriptase inhibitors, protease inhibitors, and/or enfuvirtide. These trials were conducted in treatment-experienced patients, where complex and expensive drug combinations are typically required. Rates of plasma HIV RNA suppression<50 copies in different treatment groups by week 48 were combined with drug costs to calculate the costs per patient with undetectable viremia. These results were compared with two recent pilot studies of novel triple combination treatment. The average annual per patient cost of antiretrovirals for the active plus optimized background regimen arm versus placebo plus optimized background regimen was US$ 47,324 vs. 38,267 in the DUET Trials, US$ 45,484 vs. 34,585 in BENCHMRK, and US$ 46,633 vs. 36,404 in MOTIVATE. In the three trials, the highest treatment costs were from nucleoside analogs (29-30% of total costs) and enfuvirtide (22-25% of total costs). In the two pilot studies, the total cost of raltegravir/etravirine/darunavir/ritonavir was US$ 32,208, while use of raltegravir/etravirine/maraviroc cost US$ 30,952 per patient-year. The mean cost per patient with HIV RNA<50 copies/ml at week 48 ranged from US$ 62,268 in the etravirine plus optimized background regimen arm of DUET, to US$ 214,141 in the placebo arm of MOTIVATE. In the pilot studies, the cost per patient with HIV RNA<50 copies/ml was US$ 33,204 for raltegravir/etravirine/darunavir/ritonavir and US$ 33,603 for raltegravir/etravirine/maraviroc. In summary, when treating highly treatment-experienced patients, cost-savings could be made by using combinations of newer antiretrovirals in preference to recycled nucleoside analogs and enfuvirtide.

Pharmacoeconomics of darunavir.

Darunavir boosted with ritonavir (DRV/r) in combination with other antiretrovirals (ARVs) was initially approved in 2006 for the treatment of HIV infection in ARV treatment-experienced adults and has subsequently been approved for use in treatment-naive adults in 2008. Clinical studies have shown that DRV/r in combination with other ARVs achieves superior levels of undetectable plasma HIV RNA and generates significant CD4 increases, which reduce the risk of HIV disease progression. Economic evaluations, based on data from controlled clinical trials, found DRV/r combination therapy to generate savings in hospital costs and other non-ARV costs of care in treatment-experienced patients, to maximize the number of patients reaching undetectable plasma HIV RNA, to improve health-related quality of life and quality-adjusted life expectancy, and to be cost effective across different patient populations.

Darunavir outcomes study: comparative effectiveness of virologic suppression, regimen durability, and discontinuation reasons for three-class experienced patients at 48 weeks.

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.

Pharmacoeconomics of etravirine.

HIV infection, particularly multidrug-resistant HIV, continues to be a major societal and economic challenge worldwide. Etravirine, a new (US FDA approved in 2008) non-nucleoside reverse transcriptase inhibitor, has been shown to be very effective in treating patients who have failed prior antiretroviral therapy. Clinical studies demonstrated that etravirine in combination with other antiretrovirals achieved superior levels of undetectable plasma HIV RNA and CD4 cell count increases that led to reductions in risk of death and development of AIDS-defining illnesses when compared with placebo. Etravirine was also shown to be generally well tolerated, with favorable CNS and psychiatric tolerability profiles. In addition, etravirine in combination with other antiretrovirals has been shown to improve quality of life and quality-adjusted life expectancy. Economic evaluations showed that the addition of etravirine to a regimen was associated with lower costs per person with an undetectable viral load and lower hospital-related costs compared with placebo.

Change in quality of life after being diagnosed with HIV: a multicenter longitudinal study.

The objective of this study was to assess in patients with HIV perceptions of life pre-HIV versus post-HIV diagnosis and examine whether such perceptions change over time. We conducted interviews and chart reviews of 347 outpatients with HIV from three cities in 2002-2004. In two interviews 12-18 months apart, patients compared their life now with their life before HIV was diagnosed. Independent variables included demographic and clinical characteristics; HIV-specific health status, symptoms, and concerns; spirituality/religion; social support; self-perception; and optimism. The patients' mean (standard deviation [SD]) age was 44.8 (8.3) years; half were minorities; and 269 (78%) were taking antiretroviral therapy. Comparing life at time 1 versus before diagnosis, 109 (31%) patients said their life was better at time 1, 98 (28%) said it was worse, and the rest said it was about the same or did not know. By time 2, approximately one fifth of the patients changed their answers to indicate life improvement and one sixth changed them to indicate life deterioration. In multivariable analysis, change in perception for the better between time 1 and time 2 (versus prediagnosis) was positively associated with time 1 positive religious coping scores, whereas change in perception for the worse was associated with study site, heterosexual orientation, a detectable viral load, shorter duration of HIV, lower spirituality scores, and lower positive religious coping scores. We conclude that many patients with HIV feel that their life is better than it was before their diagnosis, although results of such comparisons often change over time.

Early virologic suppression with three-class experienced patients: 24-week effectiveness in the darunavir outcomes study.

OBJECTIVE: To evaluate 24-week virologic effectiveness of novel antiretroviral regimens for treatment of three-class experienced adult patients in a clinical practice setting following the US Food and Drug Administration approval of darunavir (DRV) for this population. DESIGN: A prospective cohort study. SETTING: A single-center, academic HIV clinic. PARTICIPANTS: Three-class antiretroviral-experienced patients changing regimens between July 2006 and May 2008. Sociodemographic, psychosocial, and clinical characteristics were collected at baseline and during prospective follow-up. OUTCOME MEASURES: Plasma HIV viral load below 50 copies/ml and change in CD4 cell count at 24 weeks following regimen change. The Stanford Genotype Database was used to analyze HIV genotype resistance results and determine the number of active drugs in each regimen. Multivariate models and propensity score methods were employed to assess outcome measures. RESULTS: Among 109 three-class experienced patients, who previously received an average of 10.5 prior antiretrovirals, 55% achieved viral load below 50 copies/ml at 24 weeks. Treatment strategy was classified as nonprotease inhibitor (n = 25), DRV/ritonavir (DRV/r) (n = 51), or other protease inhibitor (n = 33). The number of active drugs was not significantly different across strategies (P = 0.24). In multivariate analysis, patients treated with DRV/r (65%, odds ratio = 4.24 vs. nonprotease inhibitor strategy, 95% confidence interval = 1.28-14.06), raltegravir (65%, odds ratio = 3.10, 95% confidence interval = 1.12-8.62), or both were more likely to achieve viral load below 50 copies/ml. CONCLUSION: Among antiretroviral-experienced patients changing regimens, those treated with DRV/r, raltegravir, or both were more likely to achieve a viral load below 50 copies/ml at 24 weeks. The effectiveness of these agents in routine clinical care mirrors their efficacy in clinical trials and has ushered in a new era in the therapy of three-class experienced patients.

Development of an electronic medical record-based clinical decision support tool to improve HIV symptom management.

Common symptoms associated with HIV disease and its management are often underrecognized and undertreated. A clinical decision support tool for symptom management was developed within the Veterans Health Administration electronic medical record (EMR), aiming at increasing provider awareness of and response to common HIV symptoms. Its feasibility was studied in March to May 2007 by implementing it within a weekly HIV clinic, comparing a 4-week intervention period with a 4-week control period. Fifty-six patients and their providers participated in the study. Patients' perceptions of providers' awareness of their symptoms, proportion of progress notes mentioning any symptom(s) and proportion of care plans mentioning any symptom(s) were measured. The clinical decision support tool used portable electronic "tablets" to elicit symptom information at the time of check-in, filtered, and organized that information into a concise and clinically relevant EMR note available at the point of care, and facilitated clinical responses to that information. It appeared to be well accepted by patients and providers and did not substantially impact workflow. Although this pilot study was not powered to detect effectiveness, 25 (93%) patients in the intervention group reported that their providers were very aware of their symptoms versus 27 (75%) control patients (p = 0.07). The proportion of providers' notes listing symptoms was similar in both periods; however, there was a trend toward including a greater number of symptoms in intervention period progress notes. The symptom support tool seemed to be useful in clinical HIV care. The Veterans Health Administration EMR may be an effective "laboratory" for developing and testing decision supports.

Biochemical and virologic parameters in patients co-infected with hepatitis C and HIV versus patients with hepatitis C mono-infection.

BACKGROUND: Previous studies of patients with hepatitis C virus (HCV) infection looking at the effect of human immunodeficiency virus (HIV) co-infection on biochemical parameters and HCV RNA level have shown conflicting results. Accurate characterization of the effect of HIV is important for evaluation and treatment of HCV in co-infected persons. METHODS: We studied 315 HCV mono-infected and 75 HCV-HIV co-infected subjects to determine the effect of HIV on biochemical parameters and HCV RNA and to determine the predictors of elevated serum alanine aminotransferase (ALT) levels and HCV RNA levels. RESULTS: The co-infected subjects were more likely to be African-American (55% vs 26%, P < 0.0005), have used injection drugs (68% vs 60%, P = 0.02), have detectable HCV RNA (84% vs 70.5%, P = 0.018), have HCV RNA levels >6 log10 IU/mL (60% vs 38%, P = 0.001), and have lower mean serum ALT levels (50.4 IU/mL vs 73.7 IU/mL, P = 0.006). In multivariable analyses, the following factors predicted an ALT level >50 IU/mL: log10 HCV RNA (OR, 1.15; 95% CI, 1.00 to 1.32); HIV co-infection (OR, 0.48; 95% CI, 0.25 to 0.89); and having ever been treated for HCV (OR, 1.92; 95% CI, 1.16 to 3.18). The only significant predictor of HCV RNA level >6 log10 IU/mL was HIV co-infection (OR, 2.75; 95% CI, 1.46 to 5.15). Significant predictors of having a detectable HCV RNA level were female sex (OR, 3.81; 95% CI, 1.18 to 12.25); HIV co-infection (2.45; 95% CI, 1.14 to 5.26); and ever being treated for HCV (OR, 1.96; 95% CI, 1.10 to 3.48). CONCLUSIONS: HCV-HIV co-infected persons have higher HCV RNA levels but lower serum ALT levels than HCV mono-infected patients. Criteria for performing liver biopsy and treating HCV infection in co-infected patients may need to be revisited.

Self-rated health of primary care house officers and its relationship to psychological and spiritual well-being.

BACKGROUND: The stress associated with residency training may place house officers at risk for poorer health. We sought to determine the level of self-reported health among resident physicians and to ascertain factors that are associated with their reported health. METHODS: A questionnaire was administered to house officers in 4 residency programs at a large Midwestern medical center. Self-rated health was determined by using a health rating scale (ranging from 0 = death to 100 = perfect health) and a Likert scale (ranging from "poor" health to "excellent" health). Independent variables included demographics, residency program type, post-graduate year level, current rotation, depressive symptoms, religious affiliation, religiosity, religious coping, and spirituality. RESULTS: We collected data from 227 subjects (92% response rate). The overall mean (SD) health rating score was 87 (10; range, 40-100), with only 4 (2%) subjects reporting a score of 100; on the Likert scale, only 88 (39%) reported excellent health. Lower health rating scores were significantly associated (P < 0.05) with internal medicine residency program, post-graduate year level, depressive symptoms, and poorer spiritual well-being. In multivariable analyses, lower health rating scores were associated with internal medicine residency program, depressive symptoms, and poorer spiritual well-being. CONCLUSION: Residents' self-rated health was poorer than might be expected in a cohort of relatively young physicians and was related to program type, depressive symptoms, and spiritual well-being. Future studies should examine whether treating depressive symptoms and attending to spiritual needs can improve the overall health and well-being of primary care house officers.

Religion, spirituality, and depressive symptoms in patients with HIV/AIDS.

BACKGROUND: Depression has been linked to immune function and mortality in patients with chronic illnesses. Factors such as poorer spiritual well-being has been linked to increased risk for depression and other mood disorders in patients with HIV. OBJECTIVE: We sought to determine how specific dimensions of religion, spirituality, and other factors relate to depressive symptoms in a contemporary, multi-center cohort of patients with HIV/AIDS. DESIGN: Patients were recruited from 4 medical centers in 3 cities in 2002 to 2003, and trained interviewers administered the questionnaires. The level of depressive symptoms was measured with the 10-item Center for Epidemiologic Studies Depression (CESD-10) Scale. Independent variables included socio-demographics, clinical information, 8 dimensions of health status and concerns, symptoms, social support, risk attitudes, self-esteem, spirituality, religious affiliation, religiosity, and religious coping. We examined the bivariate and multivariable associations of religiosity, spirituality, and depressive symptoms. MEASUREMENTS AND MAIN RESULTS: We collected data from 450 subjects. Their mean (SD) age was 43.8 (8.4) years; 387 (86.0%) were male; 204 (45.3%) were white; and their mean CD4 count was 420.5 (301.0). Two hundred forty-one (53.6%) fit the criteria for significant depressive symptoms (CESD-10 score > or = 10). In multivariable analyses, having greater health worries, less comfort with how one contracted HIV, more HIV-related symptoms, less social support, and lower spiritual well-being was associated with significant depressive symptoms (P<.05). CONCLUSION: A majority of patients with HIV reported having significant depressive symptoms. Poorer health status and perceptions, less social support, and lower spiritual well-being were related to significant depressive symptoms, while personal religiosity and having a religious affiliation was not associated when controlling for other factors. Helping to address the spiritual needs of patients in the medical or community setting may be one way to decrease depressive symptoms in patients with HIV/AIDS.

Modeling the effects of spirituality/religion on patients' perceptions of living with HIV/AIDS.

BACKGROUND: Spirituality/religion is an important factor in health and illness, but more work is needed to determine its link to quality of life in patients with HIV/AIDS. OBJECTIVE: To estimate the direct and indirect effects of spirituality/religion on patients' perceptions of living with HIV/AIDS. DESIGN: In 2002 and 2003, as part of a multicenter longitudinal study of patients with HIV/AIDS, we collected extensive demographic, clinical, and behavioral data from chart review and patient interviews. We used logistic regression and path analysis combining logistic and ordinary least squares regression. SUBJECTS: Four hundred and fifty outpatients with HIV/AIDS from 4 sites in 3 cities. MEASURES: The dependent variable was whether patients felt that life had improved since being diagnosed with HIV/AIDS. Spirituality/religion was assessed by using the Duke Religion Index, Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being-Expanded, and Brief RCOPE measures. Mediating factors included social support, self-esteem, healthy beliefs, and health status/health concerns. RESULTS: Approximately one-third of the patients felt that their life was better now than it was before being diagnosed with HIV/AIDS. A 1-SD increase in spirituality/religion was associated with a 68.50% increase in odds of feeling that life has improved--29.97% due to a direct effect, and 38.54% due to indirect effects through healthy beliefs (29.15%) and health status/health concerns (9.39%). Healthy beliefs had the largest effect on feeling that life had improved; a 1-SD increase in healthy beliefs resulted in a 109.75% improvement in feeling that life changed. CONCLUSIONS: In patients with HIV/AIDS, the level of spirituality/religion is associated, both directly and indirectly, with feeling that life is better now than previously. Future research should validate our new conceptual model using other samples and longitudinal studies. Clinical education interventions should focus on raising awareness among clinicians about the importance of spirituality/religion in HIV/AIDS.

Health-related quality of life in veterans and nonveterans with HIV/AIDS.

PURPOSE: To compare health-related quality of life (HRQoL) between patients receiving care in Veterans Administration (VA) settings (veterans) and non-VA settings (nonveterans), and to explore determinants of HRQoL and change in HRQoL over time in subjects living with HIV/AIDS. SUBJECTS: One hundred veterans and 350 nonveterans with HIV/AIDS from 2 VA and 2 university-based sites in 3 cities interviewed in 2002 to 2003 and again 12 to 18 months later. METHODS: We assessed health status (functional status and symptom bother), health ratings, and health values (time tradeoff [TTO] and standard gamble [SG] utilities). We also explored bivariate and multivariable associations of HRQoL measures with a number of demographic, clinical, spiritual/religious, and psychosocial characteristics. RESULTS: Compared with nonveterans, the veteran population was older (47.7 vs 42.0 years) and consisted of a higher proportion of males (97% vs 83%), of participants with a history of injection drug use (23% vs 15%), and of subjects with unstable housing situations (14% vs 6%; P<.05 for all comparisons). On scales ranging from 0 (worst) to 100 (best), veterans reported significantly poorer overall function (mean [SD]; 65.9 [17.2] vs 71.9 [16.8]); lower rating scale scores (67.6 [21.7] vs 73.5 [21.0]), lower TTO values (75.7 [37.4] vs 89.0 [23.2]), and lower SG values (75.0 [35.8] vs 83.2 [28.3]) than nonveterans (P<.05 for all comparisons); however, in multivariable models, veteran status was only a significant determinant of SG and TTO values at baseline. Among other determinants that were associated with multiple HRQoL outcomes in baseline and follow-up multivariable analyses were: symptom bother, overall function, religiosity/spirituality, depressive symptoms, and financial worries. CONCLUSIONS: Veterans reported significantly poorer HRQoL than nonveterans, but when controlling for other factors, veteran status was only a significant determinant of TTO and SG health values at baseline. Correlates of HRQoL such as symptom bother, spirituality/religiosity, and depressive symptoms could be fruitful potential targets for interventions to improve HRQoL in patients with HIV/AIDS.

Patterns of responses on health-related quality of life questionnaires among patients with HIV/AIDS.

BACKGROUND: Health-related quality of life (HRQoL) has become an important facet of HIV/AIDS research. Typically, the unit of analysis is either the total instrument score or subscale score. Developing a typology of responses across various HRQoL measures, however, may advance understating of patients' perspectives. METHODS: In a multicenter study, we categorized 443 patients' responses on utility measures (time-tradeoff, standard gamble, and rating scale) and the HIV/AIDS-Targeted Quality of Life (HAT-QoL) scale by using latent profile analysis to empirically derive classes of respondents. We then used linear regressions to identify whether class membership is associated with clinical measures (viral load, CD4, time since diagnosis, highly active antiretroviral therapy [HAART]) and psychosocial function (depressed mood, alcohol use, religious coping). RESULTS: Six classes were identified. Responses across the HAT-QoL subscales tended to fall into 3 groupings--high functioning (Class 1), moderate functioning (Classes 2 and 3), and low functioning (Classes 4 to 6); utility measures further distinguished individuals among classes. Regression analyses comparing those in Class 1 with those in the other 5 found significantly more symptoms of depression, negative religious coping strategies, and lower CD4 counts among subjects in Class 1. Those in Class 5 had been diagnosed with HIV longer, and members of Class 6 reported significantly less alcohol consumption, had higher viral loads, and were more likely to receive HAART. CONCLUSION: Patients with HIV respond differentially to various types of HRQoL measures. Health status and utility measures are thus complementary approaches to measuring HRQoL in patients with HIV.

Spirituality and religion in patients with HIV/AIDS.

BACKGROUND: Spirituality and religion are often central issues for patients dealing with chronic illness. The purpose of this study is to characterize spirituality/religion in a large and diverse sample of patients with HIV/AIDS by using several measures of spirituality/religion, to examine associations between spirituality/religion and a number of demographic, clinical, and psychosocial variables, and to assess changes in levels of spirituality over 12 to 18 months. METHODS: We interviewed 450 patients from 4 clinical sites. Spirituality/religion was assessed by using 8 measures: the Functional Assessment of Chronic Illness Therapy-Spirituality-Expanded scale (meaning/peace, faith, and overall spirituality); the Duke Religion Index (organized and nonorganized religious activities, and intrinsic religiosity); and the Brief RCOPE scale (positive and negative religious coping). Covariates included demographics and clinical characteristics, HIV symptoms, health status, social support, self-esteem, optimism, and depressive symptoms. RESULTS: The patients' mean (SD) age was 43.3 (8.4) years; 387 (86%) were male; 246 (55%) were minorities; and 358 (80%) indicated a specific religious preference. Ninety-five (23%) participants attended religious services weekly, and 143 (32%) engaged in prayer or meditation at least daily. Three hundred thirty-nine (75%) patients said that their illness had strengthened their faith at least a little, and patients used positive religious coping strategies (e.g., sought God's love and care) more often than negative ones (e.g., wondered whether God has abandoned me; P<.0001). In 8 multivariable models, factors associated with most facets of spirituality/religion included ethnic and racial minority status, greater optimism, less alcohol use, having a religion, greater self-esteem, greater life satisfaction, and lower overall functioning (R2=.16 to .74). Mean levels of spirituality did not change significantly over 12 to 18 months. CONCLUSIONS: Most patients with HIV/AIDS belonged to an organized religion and use their religion to cope with their illness. Patients with greater optimism, greater self-esteem, greater life satisfaction, minorities, and patients who drink less alcohol tend to be both more spiritual and religious. Spirituality levels remain stable over 12 to 18 months.

How do patients with HIV/AIDS understand and respond to health value questions?

BACKGROUND: Utility assessment involves assigning values to experienced or unfamiliar health states. Pivotal to utility assessment, then, is how one conceptualizes health states such as "current health" and "perfect health." The purpose of this study was to ascertain how patients with HIV think about and value health and health states. METHODS: We conducted open-ended in-depth interviews with 32 patients with HIV infection purposefully sampled from a multicenter study of quality of life in HIV. After undergoing computer-assisted utility assessment using the rating scale, time tradeoff, and standard gamble methods, patients were asked how they thought about the utility tasks and about the terms "current health" and "perfect health." RESULTS: Patients understood the health valuation tasks but conceptualized health states in different ways. Many patients believed that "perfect health" was a mythical health state, and some questioned whether it was even desirable. "Current health" was variably interpreted as the status quo; deteriorating over time; or potentially improving with the hope of a cure. CONCLUSION: Patients with HIV infection vary in the way they conceptualize health states central to utility assessment, such as perfect health and current health. Better understanding of these issues could make important methodologic and policy-level contributions.

Variations in self-rated health among patients with HIV infection.

PURPOSE: To assess how patients with HIV who are enrolled in a clinical trials cohort rate their health and to compare their ratings with those of patients with HIV from 2 other cohorts: the HIV Cost and Services Utilization Study (HCSUS), and Adult AIDS Clinical Trials Group protocol 320 (ACTG 320). METHODS: We analyzed baseline information for the 1649 subjects enrolled in the Adult AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) study prior to March 2002 who had self-rated health data available. We compared those results with results from 2 other groups: HCSUS, the only nationally representative sample of people in care for HIV in the U.S., which conducted baseline interviews in 1996 and 1997, and ACTG 320, a randomized, double-blinded, placebo-controlled trial comparing a 3-drug antiretroviral regimen with a 2-drug combination, which enrolled subjects in the same general time frame as HCSUS. We used t tests, Pearson correlations, and linear regression to determine factors associated with self-rated health and z scores to compare results between cohorts. RESULTS: The mean (SD) rating scale value on a 0-100 scale for ALLRT participants was 79.8 (16.8). Values were significantly lower for subjects who were older, had a history of injection drug use, had lower CD4 cell counts, or were beginning salvage antiretroviral therapy. Subjects in ALLRT reported significantly better self-rated health at baseline than those in HCSUS or ACTG 320 (11-12% higher rating scale values in ALLRT; p<0.05). When cohort differences were accounted for through regression and stratification, the differences in scores between subjects in ALLRT and HCSUS increased and the differences in scores between subjects in ALLRT and ACTG 320 diminished. CONCLUSIONS: Self-rated health varied significantly by age, CD4 count, injection drug use history, and salvage therapy status. Differences in self-rated health for clinical trials and non-clinical trials samples appear to be substantial and should be considered when applying trial results to clinical populations.

Religion, spirituality, and depressive symptoms in primary care house officers.

OBJECTIVE: The arduous nature of residency training places house officers at risk for depression. We sought to determine the prevalence of depressive symptoms in pediatric (PED), internal medicine (IM), family medicine (FM), and combined internal medicine-pediatric (IMPED) house staff, and spiritual/religious factors that are associated with prevalence of depressive symptoms. METHODS: PED, IM, FM, and IMPED residents at a major teaching program were asked to complete a questionnaire during their In-Training Examination. Depressive symptoms were measured with the 10-item Center for Epidemiologic Studies Depression Scale. Independent variables included demographics, residency program type, postgraduate level, current rotation, health status, religious affiliation, religiosity, religious coping, and spirituality. RESULTS: We collected data from 227 subjects. Their mean (SD) age was 28.7 (3.8) years; 131 (58%) were women; 167 (74%) were white; and 112 (49%) were PED, 62 (27%) were IM, 27 (12%) were FM, and 26 (12%) were IMPED residents. Fifty-seven house officers (25%) met the criteria for having significant depressive symptoms. Having depressive symptoms was significantly associated (P< .05) with residency program type, inpatient rotation status, poorer health status, poorer religious coping, and worse spiritual well-being. In multivariable analyses, having significant depressive symptoms was associated with program type, poorer religious coping, greater spiritual support seeking, and worse spiritual well-being. CONCLUSIONS: Depressive symptoms are prevalent among house officers and are associated with certain residency program types and with residents' spiritual and religious characteristics. Identifying residents with depressive symptoms and potentially attending to their spiritual needs may improve their well-being.

Gender differences in health-related quality of life of adolescents with cystic fibrosis.

BACKGROUND: Female patients with cystic fibrosis (CF) have consistently poorer survival rates than males across all ages. To determine if gender differences exist in health-related quality of life (HRQOL) of adolescent patients with CF, we performed a cross-section analysis of CF patients recruited from 2 medical centers in 2 cities during 1997-2001. METHODS: We used the 87-item child self-report form of the Child Health Questionnaire to measure 12 health domains. Data was also collected on age and forced expiratory volume in 1 second (FEV1). We analyzed data from 98 subjects and performed univariate analyses and linear regression or ordinal logistic regression for multivariable analyses. RESULTS: The mean (SD) age was 14.6 (2.5) years; 50 (51.0%) were female; and mean FEV1 was 71.6% (25.6%) of predicted. There were no statistically significant gender differences in age or FEV1. In univariate analyses, females reported significantly poorer HRQOL in 5 of the 12 domains. In multivariable analyses controlling for FEV1 and age, we found that female gender was associated with significantly lower global health (p < 0.05), mental health (p < 0.01), and general health perceptions (p < 0.05) scores. CONCLUSION: Further research will need to focus on the causes of these differences in HRQOL and on potential interventions to improve HRQOL of adolescent patients with CF.