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.

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.

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.

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.

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.

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.

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.

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.

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.

Beliefs of primary care residents regarding spirituality and religion in clinical encounters with patients: a study at a midwestern U.S. teaching institution.

PURPOSE: To assess primary care residents' beliefs regarding the role of spirituality and religion in the clinical encounter with patients. METHOD: In 2003, at a major midwestern U.S. teaching institution, 247 primary care residents were administered a questionnaire adapted from that used in the Religion and Spirituality in the Medical Encounter Study to assess whether primary care house officers feel they should discuss religious and spiritual issues with patients, pray with patients, or both, and whether personal characteristics of residents, including their own spiritual well-being, religiosity, and tendency to use spiritual and religious coping mechanisms, are related to their sentiments regarding spirituality and religion in health care. Simple descriptive, univariate, and two types of multivariable analyses were performed. RESULTS: Data were collected from 227 residents (92%) in internal medicine, pediatrics, internal medicine/pediatrics, and family medicine. One hundred four (46%) respondents felt that they should play a role in patients' spiritual or religious lives. In multivariable analysis, this sentiment was associated with greater frequency of participating in organized religious activity (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.20-1.99), a higher level of personal spirituality (OR 1.05, 95% CI 1.02-1.08), and older resident age (OR 1.11, 95% CI 1.02-1.21; C-statistic 0.76). In general, advocating spiritual and religious involvement was most often associated with high personal levels of spiritual and religious coping and with the family medicine training program. Residents were more likely to agree with incorporating spirituality and religion into patient encounters as the gravity of the patient's condition increased (p < .0001). CONCLUSIONS: Approximately half of primary care residents felt that they should play a role in their patients' spiritual or religious lives. Residents' agreement with specific spiritual and religious activities depended on both the patient's condition and the resident's personal characteristics.

Impact of HIV/AIDS on care and outcomes of severe sepsis.

INTRODUCTION: There has been dramatic improvement in survival for patients with HIV/AIDS; however, some studies on patients with HIV/AIDS and serious illness have reported continued low rates of intensive care. The purpose of this study was to examine patterns of care and outcomes for patients with severe sepsis and HIV/AIDS and compare them with those of patients with severe sepsis without HIV/AIDS. METHODS: We assessed data from all 1999 discharge abstracts from all non-federal hospitals in six US states. Patient demographic characteristics, discharge diagnoses, resource use, and outcomes were extracted. Analyses were performed using chi-square, Wilcoxon rank sum, or regression techniques, as appropriate. RESULTS: We identified 74,020 patients with severe sepsis (7,638 (10.3%) had HIV/AIDS) using ICD-9-CM codes. Patients with severe sepsis and HIV/AIDS had a similar mean length of stay (16.9 days versus 17.7 days; p = 0.0669), had lower mean hospitalization cost (24,382 dollars versus 30,537 dollars; p < 0.0001), were less likely to be admitted to the intensive care unit (37% versus 56%; p < 0.0001), and had a greater mortality (29% versus 20%; p < 0.0001) than those without HIV/AIDS. After adjustment for cohort differences, patients with severe sepsis and HIV/AIDS had increased likelihood of death (OR (95% CI) = 2.41 (2.23-2.61)) and were substantially less likely to be admitted to the intensive care unit (OR (95% CI) = 0.54 (0.51-0.59)). When compared with those with severe sepsis and HIV/AIDS, patients with severe sepsis without HIV/AIDS were universally more likely to be admitted to the intensive care unit, even when they had comorbid illnesses with equal or worse expected in-hospital mortality (e.g., metastatic cancer). CONCLUSION: For patients with severe sepsis, there are differences in care and outcomes for those with HIV/AIDS. Further research is needed to examine the delivery of care for patients with severe sepsis and HIV/AIDS.

Evaluating adolescents in juvenile detention facilities for urogenital chlamydial infection: costs and effectiveness of alternative interventions.

CONTEXT: Adolescents in juvenile detention facilities present a unique opportunity to diagnose and treat sexually transmitted diseases. OBJECTIVE: To evaluate the effectiveness and costs of different strategies for the diagnosis and treatment of chlamydial infection in adolescents in juvenile detention.Design, Setting, and Subjects For a cohort of adolescents in a juvenile detention facility, sex-specific decision models were developed comparing strategies for diagnosing and treating chlamydial infection. These strategies included not screening, treating everyone, and testing (with leukocyte esterase [LE], ligase chain reaction [LCR], or history and symptoms) followed by treatment for those with positive test results. Two different time horizons were considered: immediate and extended. In the immediate time horizon, we performed a cost-effectiveness analysis looking only at the outcomes associated with treating current infections; in the extended time horizon, we performed a cost-minimization analysis comparing the estimated total costs of diagnosing and treating Chlamydia as well as those associated with complications occurring up to 20 years in the future. RESULTS: In males, the immediate-time-horizon evaluation revealed that treating on the basis of urine LE results produced the lowest incremental cost-effectiveness ratio ($80 per infection treated). In the extended-time-horizon cost-minimization analysis, treating males on the basis of urine LE results was again found to be the least expensive strategy ($10.11 per person). Two other strategies, confirming urine LE results with LCR ($10.96 per person) and screening with urine LCR ($14.04 per person), were found to be less expensive than not screening ($16.66 per person). In females, the immediate-time-horizon evaluation found that treating on the basis of symptoms and history resulted in treating about half the cases of chlamydial infection and produced the lowest incremental cost-effectiveness ratio ($74 per infection treated). More infections were treated when treatment was based on urine LCR results with only a small increase in the incremental cost per case treated ($95 per infection treated). In the extended-time-horizon cost-minimization analysis, treating all females empirically and treating based on results of urine LCR testing were the least expensive strategies ($18.81 and $18.98 per person, respectively). The results were sensitive to several variables, including prevalence of chlamydial infection, in both males and females. CONCLUSIONS: For adolescent males in juvenile detention facilities, screening with urine LE minimizes the costs associated with diagnosis, treatment, and sequelae of urogenital chlamydial infection. For adolescent females in juvenile detention, empiric treatment and that based on urine LCR test results are the optimal strategies for managing urogenital chlamydial infection.

Do medical house officers value the health of veterans differently from the health of non-veterans?

BACKGROUND: Little information is available regarding medical residents' perceptions of patients' health-related quality of life. Patients cared for by residents have been shown to receive differing patterns of care at Veterans Affairs facilities than at community or university settings. We therefore examined: 1) how resident physicians value the health of patients; 2) whether values differ if the patient is described as a veteran; and 3) whether residency-associated variables impact values. METHODS: All medicine residents in a teaching hospital were asked to watch a digital video of an actor depicting a 72-year-old patient with mild-moderate congestive heart failure. Residents were randomized to 2 groups: in one group, the patient was described as a veteran of the Korean War, and in the other, he was referred to only as a male. The respondents assessed the patient's health state using 4 measures: rating scale (RS), time tradeoff (TTO), standard gamble (SG), and willingness to pay (WTP). We also ascertained residents' demographics, risk attitudes, residency program type, post-graduate year level, current rotation, experience in a Veterans Affairs hospital, and how many days it had been since they were last on call. We performed univariate and multivariable analyses using the RS, TTO, SG and WTP as dependent variables. RESULTS: Eighty-one residents (89.0% of eligible) participated, with 36 (44.4%) viewing the video of the veteran and 45 (55.6%) viewing the video of the non-veteran. Their mean (SD) age was 28.7 (3.1) years; 51.3% were female; and 67.5% were white. There were no differences in residents' characteristics or in RS, TTO, SG and WTP scores between the veteran and non-veteran groups. The mean RS score was 0.60 (0.14); the mean TTO score was 0.80 (0.20); the mean SG score was 0.91 (0.10); and the median (25th, 75th percentile) WTP was 10,000 dollars (7600 dollars, 20,000 dollars) per year. In multivariable analyses, being a resident in the categorical program was associated with assigning higher RS scores, but no residency-associated variables were associated with the TTO, SG or WTP scores. CONCLUSION: Physicians in training appear not to be biased either in favor of or against military veterans when judging the value of a patient's health.

Cost-effectiveness of interventions to reduce vertical HIV transmission from pregnant women who have not received prenatal care.

To evaluate the cost-effectiveness of rapid HIV testing followed by treatment with zidovudine, nevirapine, or combination therapy for women presenting in the United States in active labor without prenatal care, the authors developed a decision analytic model from a societal perspective comparing 2 basic strategies: 1) not testing for HIV and 2) offering rapid HIV testing and treatment to women testing positive. HIV transmission rates, test characteristics, and costs were derived from the literature and local sources. Outcomes included number of infected infants, costs, and incremental cost-effectiveness in dollars per quality-adjusted life year saved. The authors found that offering rapid HIV testing and administering zidovudine treatment to women testing positive would prevent 27 cases of HIV each year and save $3,000,000/year compared with no intervention. If more expensive treatments were used (e.g., zidovudine rather than nevirapine, or combination therapy rather than monotherapy), the relative risk reduction in HIV transmission for the more expensive strategies would need to be only slightly better to make the more expensive strategies relatively cost effective in comparison with the less expensive strategies. In an analysis including empiric nevirapine prophylaxis, the authors found that empiric therapy would prevent 32 HIV cases and save $2.1 million per year compared with no intervention. In conclusion, rapid HIV testing and treatment for women presenting in labor without prior prenatal care would prevent HIV infections and save costs. At sites where rapid HIV testing is not possible, empiric treatment would also prevent HIV infection and saves costs and is thus preferred to a strategy of neither testing nor treating. Effectiveness in reducing transmission drives the cost-effectiveness ratio much more so than drug cost and should be the basis on which a particular prophylactic regimen is selected.

The impact of expected HIV transmission rates on the effectiveness and cost of ruling out HIV infection in infants.

OBJECTIVE: To quantify the costs and effectiveness of different strategies for ruling out HIV infection in infants born to HIV-infected mothers in the United States. METHODS: The authors assessed 4 different testing strategies that incorporated serial HIV DNA polymerase chain reaction (PCR) testing with or without enzyme-linked immunosorbent assay (ELISA) antibody testing. Testing costs, false reassurance rates, and incremental cost-effectiveness ratios were compared for the 4 strategies. RESULTS: In HIV-exposed infants, HIV DNA PCR testing at birth, 1 month, and 4 months of age results in a false reassurance rate of 21 per million (at a 2% transmission rate). Adding an ELISA test lowers the false reassurance rate to 0.052 per million at a cost of $570,000 per additional case detected; adding another PCR lowers the false reassurance rate to 1.49 per million at a cost of $720,000 per additional case detected compared with the 3-PCR strategy. At a high transmission rate (20%), there would be substantially more erroneously negative results (false reassurance rate is 256 per million with PCR testing at birth, 1 month, and 4 months) and consequently more favorable cost-effectiveness ratios with additional testing: $47,000 per additional case detected by adding 1 ELISA test and $59,000 per additional case detected by adding another PCR test. CONCLUSIONS: False-negative HIV results after serial testing in exposed infants are rare, and the incremental cost-effectiveness ratios of additional tests are substantial at low transmission rates. However, the false reassurance rate increases considerably with a 3-PCR strategy and additional testing becomes more cost-effective at greater transmission rates; therefore, additional testing may be warranted in infants at greater risk of infection.

Utilities derived from visual analog scale scores in patients with HIV/AIDS.

BACKGROUND: Visual analog scale (VAS) scores are used as global quality-of-life indicators and, unlike true utilities (which assess the desirability of health states v. an external metric), are often collected in HIV-related clinical trials. The purpose of this study was to derive and evaluate transformations relating aggregate VAS scores to utilities for current health in patients with HIV/AIDS. METHODS: HIV-specific transformations were developed using linear and nonlinear regression to attain models that best fit mean VAS and standard gamble (SG) utility values directly derived from 299 patients with HIV/AIDS participating in a multicenter study of health values. The authors evaluated the transformations using VAS and SG utility values derived directly from patients in other HIV/AIDS studies. Derived transformations were also compared with published transformations. RESULTS: A simple linear transformation was derived (u = 0.44v + 0.49), as was the exponent for a curvilinear model (u = 1 - [1 - v]1.6), where u = the sample mean utility and v the sample mean VAS score. The curvilinear transformation predicted values within 0.10 of the actual SG utility in 5 of 8 estimates and within 0.05 in 3 of 8 estimates (absolute error ranged from -0.01 to +0.21). The linear transformation performed somewhat better, predicting within 0.10 of the actual SG value in 6 of 8 cases and within 0.05 in 5 of 8 estimates (absolute error ranged from -0.05 to +0.13). An alternative linear model (u = v + 0.018) derived from the literature performed similarly to our linear model (7 of 8 predictions within 0.10, 1 of 8 estimates within 0.05, and absolute error ranging from -0.15 to +0.10), whereas an alternative published curvilinear model (u = 1 - [1 - v]2.3) performed the least well (2 of 8 estimates within 0.10 of the actual values and no estimates within 0.05). CONCLUSIONS: Predicted utilities are a reasonable alternative for use in HIV/AIDS decision analyses and cost-effectiveness analyses. Linear transformations performed better than curvilinear transformations in this context and can be used to convert aggregate VAS scores to aggregate SG values in large HIV/AIDS studies that collect VAS data but not utilities.

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.