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Background. Dolutegravir-based 2-drug regimens (DTG 2DRs) are now accepted as alternatives to 3-drug regimens for HIV antiretroviral treatment (ART); however, literature on physician drivers for prescribing DTG 2DR is sparse. This study evaluated treatment patterns of DTG 2DR components in clinical practice in the US. Methods. This was a retrospective chart review in adult patients in care in the US with HIV-1 who received DTG 2DR prior to July 31, 2017, with follow-up until January 30, 2018. Primary objectives of the study were to determine reasons for patients initiating DTG 2DR and to describe the demographics and clinical characteristics. All analyses were descriptive. Results. Overall, 278 patients received DTG 2DR (male: 70%; mean age: 56 years). Most patients were treatment experienced (98%), with a mean 13.5 years of prior ART. DTG was most commonly paired with darunavir (55%) or rilpivirine (27%). The most common physician-reported reasons for initiating DTG 2DR were treatment simplification/streamlining (30%) and avoidance of potential long-term toxicities (20%). Before starting DTG 2DR, 42% of patients were virologically suppressed; of those, 95% maintained suppression while on DTG 2DR. Of the 50% of patients with detectable viral load before DTG 2DR, 79% achieved and maintained virologic suppression on DTG 2DR during follow-up. There were no virologic data for 8% of patients prior to starting DTG 2DR. Only 15 patients discontinued DTG 2DR, of whom 4 (27%) discontinued due to virologic failure. Conclusions. Prior to commercial availability of the single-tablet 2DRs, DTG 2DR components were primarily used in treatment-experienced patients for treatment simplification and avoidance of long-term toxicities. Many of these patients achieved and maintained virologic suppression, with low discontinuation rates.

Background Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence. Methods In this phase ...

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 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

Background: Long-acting (LA) injectable antiretroviral therapy (ART) is a novel modality currently under development as an alternative to daily oral ART.Objective: The LATTE-2 study (ClinicalTrials...

HIV remains a major global health concern, with the Joint United Nations Programme on HIV/AIDS and the World Health Organization (WHO) estimating the number of people living with HIV (PLWH) to be ∼37.9 million in 2018.1,2 Improvements in HIV treatment efficacy are reflected in the increases in longevity of PLWH.3 Despite this progress, the effectiveness of current antiretroviral therapy (ART) is challenged by the need to maintain high levels of adherence to sustain virologic suppression.4 Factors related to regimen complexity, such as dosing frequency and pill burden, food considerations, stigma, and drug–drug interactions between oral antiretrovirals and commonly prescribed non-ART medications, are reported to contribute to this challenge.4–6 Furthermore, the emotional burden of living with HIV may be compounded by daily oral pill taking and additional complexities.7 Therefore, there is considerable interest in developing long-acting (LA) treatments that can address many of these issues while simplifying ART for PLWH.8 The recommended ART regimen for PLWH generally consists of daily doses of either an oral 2-drug or 3-drug combination.9,10 This combination typically involves an integrase strand transfer inhibitor (INSTI) (dolutegravir as the sole INSTI preferred for use in adults in the WHO guidelines9 and either dolutegravir, bictegravir, or raltegravir preferred in the US Department of Health and Human Services guidelines10), in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs); although, a single NRTI (lamivudine) in combination with dolutegravir has recently been recommended as a 2-drug regimen in HIV treatment guidelines.10 Cabotegravir (CAB) (GSK1265744) is an investigational INSTI and structural analog of dolutegravir.11 Rilpivirine (RPV) is a next-generation non-NRTI (NNRTI) currently approved as a once-daily oral tablet to be used in combination with other antiretrovirals for the treatment of HIV infection.12,13 Both compounds are formulated as LA agents to be administered intramuscularly (IM), with oral formulations of RPV and a new formulation of CAB in development.13 These oral formulations have been used during an oral lead-in phase in the ATLAS14 and FLAIR15 studies to assess safety and tolerability before study participants transitioning to LA therapy with CAB and RPV. This 2-drug oral combination therapy of CAB and RPV was assessed in the LATTE ({"type":"clinical-trial","attrs":{"text":"NCT01641809","term_id":"NCT01641809"}}NCT01641809) study and shown to provide similar antiviral activity compared with efavirenz plus dual NRTIs.16 A single IM injection of CAB LA 800 mg or RPV LA 1200 mg demonstrated sustained mean or geometric mean plasma concentrations above their respective in vitro protein-adjusted 90% inhibitory concentrations (PA-IC90) at 32 weeks postdose for CAB LA17 (PA-IC90 0.166 μg/mL), and 24 weeks postdose for RPV LA18 (PA-IC90 12 ng/mL), providing rationale to investigate the 2 drugs as an LA combination regimen. In the LATTE-2 ({"type":"clinical-trial","attrs":{"text":"NCT02120352","term_id":"NCT02120352"}}NCT02120352) randomized, open-label phase 2b clinical trial, the injectable LA combination of CAB and RPV (CAB + RPV LA) as a 2-drug HIV-1 maintenance therapy, administered every 4 or 8 weeks, was similar to daily 3-drug oral therapy of CAB plus abacavir/lamivudine in maintaining viral suppression (plasma HIV-1 RNA

Background This study evaluated differences in viral suppression by race and region among PLWH in care at 10 community practices. Methods PLWH (≥18 yrs) starting a new ART between Jan’15-Sept’19 with viral load at regimen prescription (Rx) and ≥6 months (mo) of prior history were selected from Trio Health HIV EMR database. Logistic regression [LR] estimated the association of covariates with outcome “viremic” (viral load >50 cells/ml) among those with viral load recorded 12-15 mo after baseline (BSL). Sensitivity analyses were conducted using viral loads at 9-15 mo, in patients (pts) on their BSL regimens for ≥12 mo, and pts with dispensing data. Covariates: BSL suppression, gender, race, age, payer, region (South vs non-South), BSL single vs multi-tablet regimen (STR vs MTR), and switch status from BSL regimen. Multicollinearity was not present. Results Of 20271 PLWH, 10373 (51%) were treated in South (41% not suppressed at BSL including 30% treatment-naïve [TN]) and 9898 (49%) in non-South (32% not suppressed including 26% TN). The following groups had higher suppression rates at 12-15 mo: males (83%) vs females (80%) p=0.003; white (85%) vs black (78%) and other known race (78%) p< 0.001; insured by commercial or Medicare insurance (both 85%) vs Medicaid (76%) or uninsured (71%) p< 0.001; treated in non-South (88%) vs South (77%) p< 0.001; age ≥50 (87%) vs < 50 (80%) p< 0.001, those who did not switch from BSL regimen (84%) vs switchers (82%) p< 0.001; on STR (84%) vs MTR (81%) p< 0.001. In LR, pts less likely to be suppressed at 12-15 mo were: < 50 adjusted odds ratio (aOR)=0.76 (0.67-0.88), unspecified gender vs female aOR=0.51 (0.28-0.92), black vs white aOR=0.65 (0.56-0.74), other race (Asian, etc.) vs white aOR=0.73 (0.59-0.91), insured by Medicaid vs commercially aOR=0.64 (0.50-0.82), uninsured vs commercially insured aOR=0.63 (0.53-0.75), treated in South aOR=0.43 (0.38-0.50), switched from BSL regimen aOR=0.75 (0.66-.086), on MTR vs STR aOR=0.81 (0.72-0.92), viremic at BSL aOR=0.41 (0.36-0.47). Sensitivity analyses results were similar. Conclusion Our findings highlighted higher rates of viremia among younger, black or other non-white race, pts treated in the South, on Medicaid or uninsured, on MTR, even after accounting for other characteristics. Disclosures Keith M. Rawlings, MD, ViiV Healthcare (Employee) Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV Healthcare (Consultant, Research Grant or Support) Julie Priest, MSPH, GlaxoSmithKline (Employee, Shareholder) Janna Radtchenko, MBA, Trio Health (Employee) Joseph Mrus, MD, MSc, ViiV Healthcare (Employee) Moti Rampogal, MD, Gilead Sciences (Consultant, Research Grant or Support, Speaker’s Bureau)Janssen (Consultant, Research Grant or Support, Speaker’s Bureau)Merck (Consultant, Research Grant or Support)ViiV Healthcare (Consultant, Research Grant or Support, Speaker’s Bureau) Alan Oglesby, MPH, ViiV Healthcare (Employee) Richard A. Elion, MD, Gilead Sciences (Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau)Jannssen (Speaker’s Bureau)Proteus (Research Grant or Support)Trio Health (Employee)ViiV Healthcare (Advisor or Review Panel member, Research Grant or Support)

Background Cabotegravir (CAB) and rilpivirine (RPV) are under development as a novel long-acting (LA) regimen for maintenance of HIV virologic suppression. Pooled Week 48 data from pivotal Phase 3 trials demonstrated noninferiority of CAB LA + RPV LA vs. current antiretroviral regimen (CAR) on the primary endpoint, proportion of subjects with HIV-1 RNA ≥50 c/mL (1.9% and 1.7%, respectively). Adherence to dosing visits, use of oral dosing (bridging) to cover planned missed injections and injection tolerability were examined for subjects in the ATLAS and FLAIR studies. Methods Virologically suppressed subjects (HIV-1 RNA < 50 c/mL) were randomized to switch to CAB LA + RPV LA or to continue CAR. On-time injections occurred Q4 weeks within a +7-day dosing window of the projected dosing date. Adherence to LA therapy was calculated as the number of on-time injection visits divided by the number of expected dosing visits through Week 48. Injection visits outside the pre-specified window and missed injection visits with/without the use of oral dosing were quantified. Injection tolerability was assessed via adverse event reporting. Results A total of 14,682 injections of CAB and RPV were administered to 581 subjects during 6,920 injection visits. 98% of injection visits took place within the allowed ±7-day dosing window with 3,194 (46%) on the projected dosing date. Forty-six ( Conclusion Subjects receiving CAB LA + RPV LA demonstrated high rates of adherence to injection visits through week 48, with 98% of injections occurring within the ±7-day dosing window. Oral bridging with CAB and RPV was an effective strategy for maintaining viral load suppression to cover missed injection visits. Injections were well-tolerated with few associated discontinuations. Disclosures All Authors: No reported Disclosures.

The Gender, Race And Clinical Experience (GRACE) study was conducted between October 2006 and December 2008 to evaluate sex- and race-based differences in outcomes after treatment with a darunavir/ritonavir-based antiretroviral regimen. Between June 2010 and June 2011, former participants of the GRACE trial at participating sites were asked to complete a 40-item questionnaire as part of the GRACE Participant Survey study, with a primary objective of assessing patients' characteristics, experiences, and opinions about participation in GRACE. Of 243 potential survey respondents, 151 (62%) completed the survey. Respondents were representative of the overall GRACE population and were predominantly female (64%); fewer were black, and more reported recreational drug use compared with nonrespondents (55% vs. 62% and 17% vs. 10%, respectively). Access to treatment (41%) and too many blood draws (26%) were reported as the best and worst part of GRACE, respectively. Support from study site staff was reported as the most important factor in completing the study (47%). Factors associated with nonadherence, study discontinuation, and poor virologic response in univariate analyses were being the primary caregiver for children, unemployment, and transportation difficulties, respectively. Patients with these characteristics may be at risk of poor study outcomes and may benefit from additional adherence and retention strategies in future studies and routine clinical care.

The Gender, Race, and Clinical Experience (GRACE) study was designed to assess sex-based differences in darunavir/ ritonavir-based therapy and to enroll a female population representative of the racial demographics of women with human immunodeficiency virus (HIV)/AIDS in the United States. Here, we report week 48 results, stratified by race. GRACE was a multicenter, open-label, phase 3b study. Patients received 600 mg of darunavir and 100 mg of ritonavir twice daily plus an investigator-selected optimized background regimen. Virologic response (HIV-1 RNA50 copies/ mL) and safety were assessed over 48 weeks. Post hoc multivariate analyses were performed to investigate factors associated with response. Of 429 patients enrolled, 61.5% were black, 22.4% were Hispanic, and 15.2% were white. Black patients had more advanced disease at baseline, and more black patients discontinued (32.6%) than Hispanic (24%) or white (26.2%) patients. In the intent-to-treat population, similar response rates were seen in Hispanic (61.5%) and white patients (60.0%); lower response rates were observed in black patients (48.5%). Similar trends were observed in the nonvirologic failure censored population. The multivariate analysis revealed that being of a nonblack race was significantly associated with improved response (P = .009). Overall, darunavir/ritonavir-based therapy was well tolerated, regardless of race. Diarrhea, nausea, and rash were the most commonly reported grade 2 to 4 adverse events (at least possibly related to darunavir/ritonavir). Darunavir/ritonavir treatment is safe and effective in treatment-experienced patients, irrespective of sex or race. Despite the controlled trial environment, more black patients discontinued and experienced virologic failure than Hispanic or white patients.

Gender-based differences in lipids have been noted in antiretroviral clinical trials. We present the metabolic and anthropometric data from the GRACE (Gender, Race And Clinical Experience) study by gender. Treatment-experienced adults received darunavir/ritonavir (DRV/r) 600/100 mg twice daily, plus a background regimen, over 48 weeks. Fasting blood samples were obtained for lipid, glucose, and insulin measurements at baseline and at weeks 24 and 48/early discontinuation. Anthropometric measurements were taken at baseline and at weeks 12, 24, and 48/discontinuation. The Assessment of Body Change and Distress questionnaire was administered at baseline and regular intervals. Descriptive statistics as well as comparisons using a Wilcoxon rank-sum test are reported. Four hundred twenty-nine patients (women, n=287; men, n=142) enrolled in GRACE; 94 women (32.8%) and 33 men (23.2%) discontinued the trial. Median changes in triglycerides from baseline to week 48 were higher in men (25 mg/dL versus 8 mg/dL; p=0.006); the mean change in triglycerides was higher in men than in women in all racial subgroups. Other lipid and glucose level changes were similar between genders. Anthropometric parameters increased for both genders, with larger increases in women. Patients' perceptions of body changes concurred with physical measurements. The proportion of women who were “satisfied” or “very satisfied” with their bodies increased from 45.2% to 57.8% from baseline to week 48 (p=0.005), while the proportion of men who were “satisfied” or “very satisfied” with their bodies increased from 56.3% to 61.5% from baseline to week 48 (p=0.317). DRV/r-based therapy was associated with small to moderate changes in metabolic parameters, and few between-gender differences were observed. Levels of self-reported, body-related distress improved for women and men over 48 weeks.

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.

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 versuas 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.

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.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.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.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 scoreor = 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).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.

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.To estimate the direct and indirect effects of spirituality/religion on patients' perceptions of living with HIV/AIDS.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.Four hundred and fifty outpatients with HIV/AIDS from 4 sites in 3 cities.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.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.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.

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

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.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.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.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.

We sought to assess health values of patients coinfected with HIV/hepatitis C (HCV) and compare them with those of patients singly infected with HIV or HCV and to characterize and assess the relationship of clinical and nonhealth-related factors with health values.We studied a total of 203 subjects infected with HIV, HCV, or both.We assessed rating scale (RS), time tradeoff (TTO), and standard gamble (SG) values, and we explored associations of health values with the Mental Component Summary (MCS) and Physical Component Summary (PCS) of the SF-12; number of bothersome symptoms from the HIV Symptoms Index; spirituality, as assessed by the Functional Assessment of Chronic Illness Therapy, Spiritual Well-being scale; as well as with a number of demographic, clinical, and psychosocial characteristics.Of the 203 subjects, 59 (29%) had HIV monoinfection, 69 (34%) had HCV monoinfection, and 75 (37%) were coinfected. The mean (SD) health values for the cohort were: RS = 0.69 (0.23), TTO= 0.88 (0.24), and SG = 0.78 (0.30). Infection type was related, albeit differently, to TTO values (mean values for patients with coinfection = 0.82; HIV = 0.91; and HCV = 0.91 [P0.05]) and SG values (coinfection = 0.77; HIV = 0.70; and HCV = 0.87; P0.05). In multivariable models, RS scores were significantly associated with sexual orientation, PCS scores, MCS scores, symptoms, and spirituality (adjusted R = 0.61); TTO with symptoms and spirituality (adjusted R = 0.23); and SG with infection type, PCS scores, and symptoms (adjusted R = 0.24).Health values and their correlates varied by method of assessment. Health values appear to be driven more by symptoms, health status, and spirituality than by number of viral infections.

To evaluate the cost-effectiveness of rapid HIV testing followed by treatmentwith 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 costeffective 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 $2.1million 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.

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 some-what 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 alter-native for use in HIV/AIDS decision analyses and costeffectiveness 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.

Objective: To assess the cost-effectiveness of various strategies to evaluate heart murmurs in children. Methods: We modeled 6 strategies to follow the initial examination by the pediatrician: (1) refer suspected pathologic murmurs to a cardiologist, (2) obtain a chest radiograph (CXR) and electrocardiogram (ECG) and refer suspected pathologic murmurs to a cardiologist, (3) refer suspected pathologic murmurs for an echocardiogram (ECHO), (4) obtain a CXR and ECG and refer suspected pathologic murmurs for an ECHO, (5) refer all patients with murmurs to a cardiologist, or (6) refer all patients with murmurs for an ECHO. Results: The least effective was strategy 1, which detects 82% of pathologic murmurs at $72 per patient evaluated. Strategy 5 detects 95% of pathologic murmurs at $38,000 per additional case detected over strategy 1. The most effective, strategy 6, detects 100% of pathologic murmurs at $158,000 per additional case detected over strategy 5. Strategies 2, 3, and 4 were not cost-effective. The results were sensitive to the costs of cardiology referral and ECHO. Conclusions: Adding a CXR and ECG to the pediatrician's evaluation, or selectively referring directly to ECHO increases costs with little gain in accuracy. Given the current cost constraints present in health care, whether the optimal strategy involves referring to a cardiologist or obtaining an ECHO for all patients with murmurs depends on how much society should allocate to diagnose pathologic murmurs. (J Pediatr 2002;141:504-11)

We report darunavir, ritonavir, and etravirine pharmacokinetics in cervicovaginal fluid and blood plasma for women from the G ender, R ace a nd C linical E xperience (GRACE) study. Eight women received darunavir-ritonavir (600/100 mg) twice daily (b.i.d.); two also received etravirine (200 mg) b.i.d. Week 4 paired blood plasma and cervicovaginal fluid samples were collected over 12 h. Darunavir and etravirine cervicovaginal fluid exposures were higher than blood plasma exposures; ritonavir cervicovaginal fluid exposure was lower than blood plasma exposure. The high exposures of darunavir and etravirine in cervicovaginal fluid warrant further evaluation of these drugs for use in HIV-1 prevention.

Objectives To determine the net health consequences, costs, and cost-effectiveness of alternative delivery strategies for HIV-infected pregnant women with detectable HIV RNA in the USA. Design Cost-effectiveness analysis using a probabilistic decision model. Methods The model compared two strategies: elective Cesarean section and vaginal delivery. Data for HIV transmission rate, maternal death rate, health-related quality of life and costs were obtained from the literature, national databases, and a tertiary hospital's cost accounting system. Model outcomes included total lifetime costs, quality-adjusted life expectancy, maternal death rate, HIV transmission rate, and incremental cost-effectiveness ratios. Results Elective Cesarean section resulted in a vertical HIV transmission rate of 34.9 per 1000 births compared with 62.3 per 1000 births for vaginal delivery. Elective Cesarean section was more effective (38.7 quality adjusted life years per mother and child pair) and less costly ($10600 per delivery) than trial of labor (38.2 combined quality adjusted life years at a cost of $14500 per delivery). However, elective Cesarean section increased maternal mortality by 2.4 deaths per 100000 deliveries. The results were consistent over a wide range of the variables, but were sensitive to the risk of HIV transmission with vaginal delivery and the relative risk of HIV transmission with elective Cesarean section. Conclusions In pregnant HIV-infected women with detectable HIV RNA, elective Cesarean section would reduce total costs and increase overall quality-adjusted life expectancy for the mother-child pair, albeit at a slight loss of quality adjusted life expectancy to the mother.

Due to stable incidence and improved survival rates, there are an increasing number of patients living with HIV/AIDS in the USA. Although highly effective, current antiretroviral therapies are associated with a variety of side effects. The role side effects play on health outcomes has not been fully examined. The current study assessed the association of medication side effects with (1) self-assessed health status; (2) work productivity and activity impairment; and (3) healthcare resource utilization. Data were from a cross-sectional patient-reported survey fielded in the USA using a dual methodology of Internet and paper questionnaires. A total of 953 patients living with HIV/AIDS who were currently taking a medication for their condition were included in the analyses. The most frequent side effects reported by patients were fatigue (70.72%), diarrhea (62.96%), insomnia (58.97%), dizziness (52.78%), neuropathy (52.68%), joint pain (52.36%), nausea (51.63%), and abdominal pain (50.37%). The presence of each side effect was associated with reduced self-assessed health status, increased productivity loss, increased activity impairment, and increased healthcare resource use. Controlling for CD4 cell counts in regression modeling did little to diminish the impact of side effects. Although not all side effects were associated with all outcomes, every side effect was associated with worse health status, some measure of increased work productivity loss, and/or some measure of increased healthcare resource use. Patients are living longer with HIV and, therefore, spending a greater length of time on treatment. The results of the current study suggest that many of these patients are experiencing a wide array of side effects from these therapies. These side effects have demonstrated a profound association with self-assessed health, work productivity, and healthcare resource use. Improved management of these side effects or development of treatments with a better side effect profile may have a substantial humanistic and economic benefit.

The aim of antiretroviral treatment is long-term suppression of plasma HIV RNA50 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 suppression50 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 RNA50 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 RNA50 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.

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

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.

A comprehensive study comparing the costs and efficacies of darunavir/ritonavir 800/100 mg qd and the other ritonavir-boosted (/r) protease inhibitors (PIs) recommended for treatment-naïve individuals with HIV-1 infection would help health care decision makers identify the value of each boosted PI.A cost-efficacy model was developed to compare the five recommended boosted PIs, each used with a tenofovir-based nucleotide/nucleoside reverse transcriptase inhibitor backbone. Efficacy was measured by virologic response (ie, HIV-1 ribonucleic acid50 copies/mL) at 48 weeks, based on a systematic review and meta-analysis of recent clinical trials. One-year antiretroviral therapy costs and 48-week efficacy values were used to generate the efficiency frontier and cost-efficacy ratios.Darunavir/r was the most efficacious boosted PI, with an incremental cost-efficacy ratio of $27,390 per additional individual with virologic response, compared with fosamprenavir/r. All other regimens were dominated. Darunavir/r combination therapy also had one of the lowest average costs ($26,287) per individual with virologic response, resulting in a maximal number of individuals successfully treated within a fixed budget. The model results were robust in variability and sensitivity analyses.Darunavir/r 800/100 mg qd combination therapy represents a cost-efficacious option for treatment-naïve individuals with HIV-1 infection in the United States.

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.

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.

Adherence to antiretroviral therapy (ART) in pregnancy is crucial to optimize its efficacy and minimize mother-to-child transmission. Our objective was to examine adherence patterns to ART and health behaviors during and after pregnancy among HIV-positive women enrolled in A5084, a prospective, observational, multisite study. Between 2002-2005, HIV-infected women between 20 and 34 weeks'gestation completed at least 1 self-reported adherence questionnaire antepartum (AP), and were followed through 12 weeks' postpartum (PP). Questionnaires also addressed tobacco, alcohol, and illicit drugs use. Adherence was defined as reporting not having missed any doses for more than 3 months. Exact McNemar's tests were used for paired binary data and exact logistic regression was used for predictors of nonadherence. We report on 149 women (55% black, 26% Hispanic, 32% less than 25 years, 9% with AIDS, 100% on ART). PP, 31 (21%) women stopped ART and 18 (12%) withdrew from the study. AP, 57% reported adherence to ART and PP, 45% (p = 0.03, n = 87). AP, 11% reported ongoing alcohol use and 23% tobacco use compared to 37% and 30% PP (p < 0.0001, n = 103; p = 0.07, n = 99, respectively). Although 39% ever used marijuana (n = 116) and 25% used illicit drugs (n = 107), few participants reported use during the study. In multivariate analyses, those who had ever used illicit drugs had 5.95 times higher odds (p = 0.002) and those who missed prenatal vitamins had 4.84 times higher odds (p = 0.001) of ART nonadherence. Women reporting a history of illicit drug use and/or having missed prenatal vitamins should be targeted for programs to enhance adherence to ART during pregnancy.

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 P = 0.02), have detectable HCV RNA (84% vs 70.5%, P = 0.018), have HCV RNA levels >6 log 10 IU/mL (60% vs 38%, P = 0.001), and have lower mean serum ALT levels (50.4IU/mL vs 73.7IU/mL, P = 0.006). In multivariable analyses, the following factors predicted an ALT level >50IU/mL: log 10 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 log 10 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.

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.

Health-related quality of life (HRQoL) has become an important facet of HIV/AIDS research. There are 2 approaches to measuring HRQoL: the health status approach, which describes functioning in one or more domains, and the utility/value/preference approach, which assesses the desirability of health states against an external metric. In general, health status measures emanate from the social science paradigm via classical test theory, which assumes that a psychological construct is composed of a set of domains1; the domains are generally composed of a set of related questions selected through empirical analyses and scale aggregation.2 Patients’ overall HRQoL, in turn, is determined by summing (weighted or unweighted) subscale scores. The advantage of the health status approach is that it usually yields instruments that are valid, reliable, and responsive to change. Utility measures originate from an economic or health policy perspective in which the goal is to evaluate the effectiveness or cost-effectiveness of different tests or treatments. Scores range from 0.0 to 1.0 and are determined by having the respondent value health states against an external metric such as risk (usually of death), time, or money. Health status and utility measures have been used extensively in empirical research but correlations between the 2 types of measures tend to be modest at best,3 an indication that they tap distinct constructs. Typically, the unit of analysis for health status measures is either the total instrument score or separate subscale (e.g., physical functioning) scores. Such analyses reduce the ability to understand how respondents experience the disease across domains of function. Furthermore, patients with a chronic disease such as HIV/AIDS often provide disparate accounts of their HRQoL, even when experiencing similar symptomatology, because responses are informed by their perception of functioning as well as by their internal beliefs and values regarding their health status.4–6 Identifying latent classes of patients-subpopulations where membership is not known but inferred from the data, may help one understand how patients experience life with HIV/AIDS across multiple domains, while at the same time identifying systematic differences in self-reported health among respondents. Because physical and psychosocial functioning are not predictable solely from a clinical diagnosis, researchers have used cluster analysis to identify latent subclasses in a number of patient populations, including cardiac transplant candidates,7 patients with symptomatic peripheral arterial disease,8 and patients with malignant melanoma,9 to better identify the specific level of physical and psychosocial functioning common within a class. Information derived from such studies can be used in a number of ways. For example, Turk et al.10,11 identified a 3-class typology based on patients’ responses on the Multidimensional Pain Inventory that appears to be consistent across pain-associated conditions, including fibromyalgia,10 temporomandibular joint disorder,12 low back pain, headache,6 and cancer.13 Based on their conceptualization, the authors tailored patient interventions.14,15 Researchers in the field of HIV/AIDS have used similar techniques to identify typologies of patients at risk of contracting HIV by studying a community-based sample16 and a sample of American Indians.17 Only one study, however, derived classifications using patients’ perceptions of their HRQoL. In that study, Bult et al.18 used latent class analysis to classify a sample of HIV-positive and HIV-negative patients into 4 classes by analyzing responses to utility measures and to the SF-36 Heath Survey.19 The purpose of this paper was to develop an alternative method of conceptualizing HRQoL by combining latent profile analysis (LPA) and regression modeling. LPA is similar to other methods of identifying latent classes, such as cluster analysis, but LPA (1) can accommodate a mixture of underlying probability distributions20; (2) utilizes posterior membership probability estimates and maximum likelihood methods to classify cases and derive misclassification rates21; (3) does not require scaling observed variables when working with normal distributions having unknown variances20; (4) does not require variables to have the same type of scaling, thus allowing for both dichotomous and polytomous items within the same analysis20; (5) is model-based, allowing the clinical researcher to determine the optimal solution using fit indices to judge fit across models22; and (6) LPA has been shown, using simulated data, to outperform K-means cluster analysis when group membership is known by the researchers.16 Despite its advantages, LPA is rarely used to derive subclasses of patients with chronic health conditions. Combining LPA and regression analyses may provide a more complete representation of patients’ self-reported function.

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. 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. 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. 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

To assess primary care residents' beliefs regarding the role of spirituality and religion in the clinical encounter with patients.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.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).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.

Background: In studies evaluating the general US population, patients in primary care, and patients with chronic conditions, women consistently report poorer health-related quality of life (HRQoL) than men; however, studies evaluating HRQoL in patients with HIV/AIDS have not completely corroborated those findings. The objective of this study was to evaluate gender differences in HRQoL for participants in a large randomized trial comparing antiretroviral regimens. Methods: AIDS Clinical Trials Group (ACTG) 320 was a randomized, blinded, placebo-controlled trial comparing the 3-drug regimen of indinavir + zidovudine (or stavudine) + lamivudine with the 2-drug combination of zidovudine (or stavudine) + lamivudine in subjects with CD4 cell counts less than 200 cells/μl and no prior treatment with protease inhibitors. Nine quality of life domains scored on 0–100 scales were assessed using the ACTG QOL 601-602 Health Survey at 3 points in the trial: baseline, 24 weeks and 40 weeks. Differences between men and women in HRQoL scores were assessed using the Wilcoxon rank-sum test and generalized estimating equation (GEE) models. Results: Overall, 202 females and 976 males were randomized to one of two treatment arms. Female participants were more likely to be black or Hispanic and tended to be younger. At baseline, females reported lower HRQoL scores than males in all of the domains except social functioning, and at week 40, women scored lower in all of the domains except overall health. In repeated measures models, women were found to score lower in all HRQoL domains except overall health, with significant differences of 3.5–6.7 points in 3 of the 9 quality of life domains: physical functioning, pain, and energy/fatigue. HRQoL scores improved for participants in the study over time and in response to potent treatment, and the improvements were similar for men and women. Conclusions: Women with HIV/AIDS report substantially poorer HRQoL than men with HIV/AIDS in several HRQoL domains. However, changes in domain scores over time and in response to treatment do not differ significantly by gender, implying that changes in domain scores may be better HRQoL outcomes to compare between HIV-infected men and women in clinical trials than mean domain scores.

Objectives To use measures of organ dysfunction derived from administrative data to assess clinical and economic outcomes in hospitalized children. Study design We used the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic and procedure codes to evaluate organ dysfunction in all patients, excluding neonates, in the Healthcare Cost and Utilization Project Kids' Inpatient Database (KID). We adapted consensus clinical definitions to characterize organ dysfunction in terms of degree of impairment, type of organ system involvement, and number of dysfunctional organ systems. Univariate and multivariable models were constructed to determine the impact of organ dysfunction on in-hospital mortality and resource use. Results Patients with organ dysfunction (n = 51,386) were younger and more often male than those without organ dysfunction, and they had significantly higher in-hospital mortality and resource use. Organ dysfunction, assessed in terms of degree, type, and number of dysfunctional organ systems, was consistently associated with all hospital outcomes. In multivariable models, types of organ system failures were most predictive of in-hospital mortality, whereas degree of organ system involvement allowed for a better assessment of resource use. Conclusions Administrative data can be used to characterize multiple dimensions of organ dysfunction in children. Hospitalizations involving organ dysfunction are associated with significant clinical and economic consequences.

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.

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 an other 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.

BACKGROUND Women account for an increasing proportion of patients with HIV-1 but remain underrepresented in antiretroviral clinical trials. OBJECTIVE To evaluate sex-based differences in efficacy and adverse events in treatment-experienced, HIV-positive women and men receiving darunavir-ritonavir therapy over 48 weeks. DESIGN Multicenter, open-label, phase 3b study designed to enroll a high proportion of women, with sample size determined on the basis of a noninferiority design with a maximum allowable difference of 15% in virologic response favoring men. (ClinicalTrials.gov registration number: NCT00381303) SETTING 65 sites in the United States, Puerto Rico, and Canada. PATIENTS 287 women and 142 men. INTERVENTION Patients received darunavir-ritonavir, 600/100 mg twice daily, plus an investigator-selected optimized background regimen. MEASUREMENTS Virologic response (HIV RNA

Radiolabeled analogues of 2-deoxyglucose are widely used to trace glucose metabolism in cell cultures, whole organs, and intact animals, although kinetic differences in transport and phosphorylation between these compounds and glucose exist. The present studies were undertaken to determine the effects of insulin stimulation on the phosphorylation of 2-deoxyglucose compared to glucose in the intact, saline-perfused working rat heart. Rates of glucose utilization determined from tritiated glucose differed from rates estimated from the accumulation of [14C]2-deoxyglucose in a nonconstant manner when comparing rates in the absence or presence of physiologic levels of insulin (13 microU/ml). The fraction of monophosphorylated hexoses that was accounted for by [14C]2-deoxyglucose 6-phosphate was dramatically decreased in hearts perfused in the presence of insulin. Additionally, hexokinase activity associated with the mitochondrial fraction of tissue extracts was increased in hearts stimulated by insulin. While this redistribution of hexokinase to the mitochondria did not affect the apparent affinity constant for glucose, hexokinase bound to mitochondria exhibited an 8.5-fold decrease in the affinity for 2-deoxyglucose when compared with hexokinase present in the cytosolic fraction. The findings are consistent with an insulin-mediated preferential uptake and phosphorylation of glucose compared to deoxyglucose. The results also imply that the redistribution of hexokinase and the differential effect of insulin on its affinity for tracer and tracee are responsible for changes in the "lumped constant" (i.e., the correction factor used to equate 2-deoxyglucose to glucose uptake). These changes must be taken into account when regional myocardial glucose metabolism is assessed by the 2-deoxyglucose method.

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.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.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.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.

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. 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. 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 versus $30,537; 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). 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.

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.

PURPOSE: To compare the costs of different strategies of testing and treating chlamydia cervicitis in adolescent females in the juvenile justice system. METHODS: Using a decision analytic model, we compared 5 strategies: 1) do nothing; 2) treat everyone with a single 1 gm dose of azithromycin; 3) screen for current symptoms or history of a sexually transmitted disease (SH) and treat those who have a positive screen; 4) screen with urine ligase chain reaction (LCR) and treat those who have a positive test; 5) screen with cervical LCR and treat those who have a positive test. Chlamydia prevalence and SH screen test characteristics were determined from a cohort study conducted at a juvenile detention center. Treatment and testing costs were taken from the cost accounting system at an urban teaching facility. LCR test characteristics, treatment efficacy, and complication (pelvic inflammatory disease, infertility, chronic pelvic pain, and ectopic pregnancy) rates and costs were derived from the literature. Future costs were discounted at a 3% annual rate in the base case. RESULTS: In this cohort (241 females, 59.8% African American, 40% Caucasian, mean age 14.8 years) with a prevalence of chlamydia of 16.8%, empiric treatment (Strategy 2) was the least expensive strategy, but screening with urine LCR (Strategy 4) was only minimally more expensive (see table). Although changes in a number of variables affected the total costs, only changes in chlamydia prevalence and the pelvic inflammatory disease rate would render strategies other than 2 or 4 to be preferred. For example, if the prevalence of chlamydia were between 0 and 3.5%, then doing nothing (Strategy 1) would be the least expensive strategy; between 3.5% and 5.6%, SH (Strategy 3) would be least expensive; between 5.6% and 16.4%, urine LCR (Strategy 4) would be least expensive; and if the prevalence of chlamydia were greater than 16.4%, then empiric therapy (Strategy 2) would be least expensive. CONCLUSION: In a detained adolescent female population, empiric treatment for chlamydia cervicitis or treatment based on urine LCR results are nearly equivalent in cost and are less costly than other strategies.