Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression.

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 3, open-label, multicenter, noninferiority trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy, we randomly assigned participants (1:1) to either continue their oral therapy or switch to monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and long-acting rilpivirine, a nonnucleoside reverse-transcriptase inhibitor. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter or higher at week 48, determined with the use of the Food and Drug Administration snapshot algorithm. RESULTS: Treatment was initiated in 308 participants per group. At week 48, HIV-1 RNA levels of 50 copies per milliliter or higher were found in 5 participants (1.6%) receiving long-acting therapy and in 3 (1.0%) receiving oral therapy (adjusted difference, 0.6 percentage points; 95% confidence interval [CI], -1.2 to 2.5), a result that met the criterion for noninferiority for the primary end point (noninferiority margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 92.5% of participants receiving long-acting therapy and in 95.5% of those receiving oral therapy (adjusted difference, -3.0 percentage points; 95% CI, -6.7 to 0.7), a result that met the criterion for noninferiority for this end point (noninferiority margin, -10 percentage points). Virologic failure was confirmed in 3 participants who received long-acting therapy and 4 participants who received oral therapy. Adverse events were more common in the long-acting-therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy and was mild or moderate in most cases; 1% withdrew because of this event. Serious adverse events were reported in no more than 5% of participants in each group. CONCLUSIONS: Monthly injections of long-acting cabotegravir and rilpivirine were noninferior to standard oral therapy for maintaining HIV-1 suppression. Injection-related adverse events were common but only infrequently led to medication withdrawal. (Funded by ViiV Healthcare and Janssen; ATLAS ClinicalTrials.gov number, NCT02951052.).

Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial.

BACKGROUND: Cabotegravir and rilpivirine are antiretroviral drugs in development as long-acting injectable formulations. The LATTE-2 study evaluated long-acting cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through 96 weeks. METHODS: In this randomised, phase 2b, open-label study, treatment-naive adults infected with HIV-1 initially received oral cabotegravir 30 mg plus abacavir-lamivudine 600-300 mg once daily. The objective of this study was to select an intramuscular dosing regimen based on a comparison of the antiviral activity, tolerability, and safety of the two intramuscular dosing regimens relative to oral cabotegravir plus abacavir-lamivudine. After a 20-week induction period on oral cabotegravir plus abacavir-lamivudine, patients with viral suppression (plasma HIV-1 RNA <50 copies per mL) were randomly assigned (2:2:1) to intramuscular long-acting cabotegravir plus rilpivirine at 4-week intervals (long-acting cabotegravir 400 mg plus rilpivirine 600 mg; two 2 mL injections) or 8-week intervals (long-acting cabotegravir 600 mg plus rilpivirine 900 mg; two 3 mL injections) or continued oral cabotegravir plus abacavir-lamivudine. Randomisation was computer-generated with stratification by HIV-1 RNA (<50 copies per mL, yes or no) during the first 12 weeks of the induction period. The primary endpoints were the proportion of patients with viral suppression at week 32 (as defined by the US Food and Drug Administration snapshot algorithm), protocol-defined virological failures, and safety events through 96 weeks. All randomly assigned patients who received at least one dose of study drug during the maintenance period were included in the primary efficacy and safety analyses. The primary analysis used a Bayesian approach to evaluate the hypothesis that the proportion with viral suppression for each long-acting regimen is not worse than the oral regimen proportion by more than 10% (denoted comparable) according to a prespecified decision rule (ie, posterior probability for comparability >90%). Difference in proportions and associated 95% CIs were supportive to the primary analysis. The trial is registered at ClinicalTrials.gov, number NCT02120352. FINDINGS: Among 309 enrolled patients, 286 were randomly assigned to the maintenance period (115 to each of the 4-week and 8-week groups and 56 to the oral treatment group). This study is currently ongoing. At 32 weeks following randomisation, both long-acting regimens met primary criteria for comparability in viral suppression relative to the oral comparator group. Viral suppression was maintained at 32 weeks in 51 (91%) of 56 patients in the oral treatment group, 108 (94%) of 115 patients in the 4-week group (difference 2·8% [95% CI -5·8 to 11·5] vs oral treatment), and 109 (95%) of 115 patients in the 8-week group (difference 3·7% [-4·8 to 12·2] vs oral treatment). At week 96, viral suppression was maintained in 47 (84%) of 56 patients receiving oral treatment, 100 (87%) of 115 patients in the 4-week group, and 108 (94%) of 115 patients in the 8-week group. Three patients (1%) experienced protocol-defined virological failure (two in the 8-week group; one in the oral treatment group). Injection-site reactions were mild (3648 [84%] of 4360 injections) or moderate (673 [15%] of 4360 injections) in intensity and rarely resulted in discontinuation (two [<1%] of 230 patients); injection-site pain was reported most frequently. Serious adverse events during maintenance were reported in 22 (10%) of 230 patients in the intramuscular groups (4-week and 8-week groups) and seven (13%) of 56 patients in the oral treatment group; none were drug related. INTERPRETATION: The two-drug combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4 weeks or every 8 weeks was as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression through 96 weeks and was well accepted and tolerated. FUNDING: ViiV Healthcare and Janssen R&D.

Risk factors predictive of anemia development during telaprevir plus peginterferon/ribavirin therapy in treatment-experienced patients.

BACKGROUND & AIMS: Anemia is a common adverse event associated with telaprevir-based triple therapy of chronic, genotype 1 hepatitis C. Identification of patients at risk of developing anemia could allow evaluation of suitability for therapy, and aid in determining frequency of anemia monitoring and treatment management. METHODS: This post-hoc analysis utilized data from the no lead-in telaprevir, peginterferon and ribavirin arm of the REALIZE study. Anemia was defined as a single occurrence of hemoglobin <10 g/dl at any point during treatment. Pre-treatment factors with potential to act as prognostic indicators of anemia including age, sex, BMI, and baseline hemoglobin were analysed by univariate and multivariate logistic regression analyses. Nomograms (graphical representations of risk factors) were developed to predict the likelihood of developing anemia. RESULTS: Among the 265 patients, 102 (38%) had anemia, with 78/102 (77%) developing anemia on or before week 12. Most patients developed anemia after week 2 and an inverse correlation was found between week 2 hemoglobin and the likelihood of developing anemia. Overall, 60% of patients (60/100) with week 2 hemoglobin <13 g/dl subsequently developed anemia. The multivariate analysis revealed older age (>45 years), lower BMI (≤25 mg/m(2)) and baseline hemoglobin (continuous variable) were significantly associated with the probability of developing anemia during telaprevir treatment. CONCLUSIONS: These analyses indicate the potential of using predictive risk factors such as low baseline and on-treatment hemoglobin to identify patients at risk of developing anemia on telaprevir-based triple therapy, which may increase the potential for treatment success by careful patient monitoring.

The association of HIV/AIDS treatment side effects with health status, work productivity, and resource use.

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.

Assessing darunavir/ritonavir-based therapy in a racially diverse population: 48-week outcomes from GRACE.

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 RNA < 50 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.

Darunavir, ritonavir, and etravirine pharmacokinetics in the cervicovaginal fluid and blood plasma of HIV-infected women.

We report darunavir, ritonavir, and etravirine pharmacokinetics in cervicovaginal fluid and blood plasma for women from the Gender, Race and Clinical Experience (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.

Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial.

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 <50 copies/mL using a time-to-loss of virologic response [TLOVR] algorithm) and adverse events were assessed over 48 weeks. RESULTS: 67% of patients were women; 84% of patients were black or Hispanic. A higher proportion of women discontinued treatment than men (32.8% vs. 23.2%; P = 0.042); more women than men discontinued treatment for reasons other than virologic failure. Response rates in women and men at week 48 were 50.9% and 58.5%, respectively (intention-to-treat TLOVR), and 73.0% and 73.5%, respectively (TLOVR censored for patients who withdrew for reasons other than virologic failure). The absolute difference in response, based on logistic regression and adjusted for baseline log(10) viral load and CD4(+) cell count, was -9.6 percentage points (95% CI, -19.9 to 0.7 percentage points; P = 0.067) for intention-to-treat TLOVR and -3.9 percentage points (CI, -13.9 to 6.0 percentage points; P = 0.438) for TLOVR population that censored patients who withdrew for reasons other than virologic failure. Adverse events were similar between the sexes. The most common grade 2 to 4 adverse events that were considered at least possibly treatment related in women and men were nausea (5.2% and 2.8%, respectively), diarrhea (4.5% and 4.9%, respectively), and rash (2.1% and 2.8%, respectively). LIMITATION: Baseline characteristics differed between sexes. CONCLUSION: Nonsignificant, sex-based differences in response were found during the 48-week study; however, these differences were probably due to higher discontinuation rates in women, suggesting that additional efforts are needed to retain women in clinical trials.

Comparative cost-efficacy analysis of darunavir/ritonavir and other ritonavir-boosted protease inhibitors for first-line treatment of HIV-1 infection in the United States.

PURPOSE: 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. METHODS: 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 acid < 50 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. RESULTS: 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. CONCLUSION: 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.

Real-World Experience with Dolutegravir-Based Two-Drug Regimens.

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.

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.

Patient-reported tolerability and acceptability of cabotegravir + rilpivirine long-acting injections for the treatment of HIV-1 infection: 96-week results from the randomized LATTE-2 study.

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.gov identifier NCT02120352) showed that cabotegravir LA + rilpivirine LA maintained virologic suppression through 96 weeks and included further exploration of patient-reported treatment outcomes with an LA injectable form of treatment.Methods: Two-hundred and eighty-six virologically suppressed participants on oral cabotegravir + abacavir/lamivudine once-daily tablets (induction period) were randomized to cabotegravir LA + rilpivirine LA once every 4 weeks (n = 115), once every 8 weeks (n = 115), or the continuation of the oral tablet regimen (n = 56) during the maintenance period. Patient-reported outcome measures included the HIV Medications Questionnaire (HIVMQ) and the HIV Treatment Satisfaction Questionnaire status (HIVTSQ[s]) and change (HIVTSQ[c]) versions at prespecified study visits through Week 96 of the randomized maintenance period.Results: Most participants in the LA injectable groups reported injection-site-related adverse events; however, participants in the 4-week (median HIVTSQ[s] total score, 63.5; post hoc P = 0.02) and 8-week (65.0; post hoc P < 0.001) LA injectable groups were significantly more satisfied with treatment than participants in the oral maintenance group (60.0) at Week 96. This was consistent with results from the HIVTSQ[c] at Week 32, which revealed that participants in both LA groups were significantly more satisfied with therapy compared with patients receiving oral ART (both post hoc P < 0.001).Conclusion: Participants who received LA injectable therapy had high levels of treatment satisfaction and favorably viewed convenience and lifestyle-related aspects of the therapy.

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.

Efficacy and Safety of a Single-Dose Mebendazole 500 mg Chewable, Rapidly-Disintegrating Tablet for Ascaris lumbricoides and Trichuris trichiura Infection Treatment in Pediatric Patients: A Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study.

This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of a new chewable, rapidly-disintegrating mebendazole (MBZ) 500 mg tablet for Ascaris lumbricoides and Trichuris trichiura infection treatment. Pediatric patients (1-15 years; N = 295; from Ethiopia and Rwanda) excreting A. lumbricoides and/or T. trichiura eggs were enrolled. The study had a screening phase (3 days), a double-blind treatment phase (DBP, 19 days), and an open-label phase (OLP, 7 days). Patients received MBZ or placebo on day 1 of DBP and open-label MBZ on day 19 ± 2 after stool sample collection. Cure rates (primary endpoint), defined as species-specific egg count of 0 at the end of DBP, were significantly higher in the MBZ group than placebo for A. lumbricoides (83.7% [72/86; 95% CI: 74.2%; 90.8%] versus 11.1% [9/81; 95% CI: 5.2%; 20.1%], P < 0.001) and for T. trichiura (33.9% [42/124; 95% CI: 25.6%; 42.9%] versus 7.6% [9/119; 95% CI: 3.5%; 13.9%], P < 0.001). Egg reduction rates (secondary endpoint) were significantly higher in the MBZ group than placebo for A. lumbricoides (97.9% [95% CI: 94.4; 99.9] versus 19.2% [95% CI: -5.9; 41.5]; P < 0.001) and T. trichiura (59.7% [95% CI: 33.9; 78.8] versus 10.5% [95% CI: -16.8; 32.9]; P = 0.003). Treatment-emergent adverse events (TEAEs) in MBZ group occurred in 6.3% (9/144) of patients during DBP and 2.5% (7/278) during OLP. No deaths, serious TEAEs, or TEAEs leading to discontinuations were reported. A 500 mg chewable MBZ tablet was more efficacious than placebo for the treatment of A. lumbricoides and T. trichiura infections in pediatric patients, and no safety concerns were identified.

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.