Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment.

Lenacapavir is a novel, first-in-class, multistage inhibitor of HIV-1 capsid function approved for the treatment of multidrug-resistant HIV-1 infection in combination with other antiretrovirals for heavily treatment-experienced people with HIV. Two Phase 1, open-label, parallel-group, single-dose studies assessed the pharmacokinetics (PK) of lenacapavir in participants with moderate hepatic impairment [Child-Pugh-Turcotte (CPT) Class B: score 7-9] or severe renal impairment [15 ≤ creatinine clearance (CLcr) ≤29 mL/min] to inform lenacapavir dosing in HIV-1-infected individuals with organ impairment. In both studies, a single oral dose of 300 mg lenacapavir was administered to participants with normal (n = 10) or impaired (n = 10) hepatic/renal function who were matched for age (±10 years), sex, and body mass index (±20%). Lenacapavir exposures [area under the plasma concentration-time curve from time 0 to infinity (AUCinf) and maximum concentration (Cmax)] were approximately 1.47- and 2.61-fold higher, respectively, in participants with moderate hepatic impairment compared to those with normal hepatic function, whereas lenacapavir AUCinf and Cmax were approximately 1.84- and 2.62-fold higher, respectively, in participants with severe renal impairment compared to those with normal renal function. Increased lenacapavir exposures with moderate hepatic or severe renal impairment were not considered clinically meaningful. Lenacapavir was considered generally safe and well tolerated in both studies. These results support the use of approved lenacapavir dosing regimen in patients with mild (CPT Class A: score 5-6) or moderate hepatic impairment as well as in patients with mild (60 ≤ CLcr ≤ 89 mL/min), moderate (30 ≤ CLcr ≤ 59 mL/min), and severe renal impairment.

Compassionate Use of Remdesivir in Pregnant Women With Severe Coronavirus Disease 2019.

BACKGROUND: Remdesivir is efficacious for severe coronavirus disease 2019 (COVID-19) in adults, but data in pregnant women are limited. We describe outcomes in the first 86 pregnant women with severe COVID-19 who were treated with remdesivir. METHODS: The reported data span 21 March to 16 June 2020 for hospitalized pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection and room air oxygen saturation ≤94% whose clinicians requested remdesivir through the compassionate use program. The intended remdesivir treatment course was 10 days (200 mg on day 1, followed by 100 mg for days 2-10, given intravenously). RESULTS: Nineteen of 86 women delivered before their first dose and were reclassified as immediate "postpartum" (median postpartum day 1 [range, 0-3]). At baseline, 40% of pregnant women (median gestational age, 28 weeks) required invasive ventilation, in contrast to 95% of postpartum women (median gestational age at delivery 30 weeks). By day 28 of follow-up, the level of oxygen requirement decreased in 96% and 89% of pregnant and postpartum women, respectively. Among pregnant women, 93% of those on mechanical ventilation were extubated, 93% recovered, and 90% were discharged. Among postpartum women, 89% were extubated, 89% recovered, and 84% were discharged. Remdesivir was well tolerated, with a low incidence of serious adverse events (AEs) (16%). Most AEs were related to pregnancy and underlying disease; most laboratory abnormalities were grade 1 or 2. There was 1 maternal death attributed to underlying disease and no neonatal deaths. CONCLUSIONS: Among 86 pregnant and postpartum women with severe COVID-19 who received compassionate-use remdesivir, recovery rates were high, with a low rate of serious AEs.

Discontinuation of tenofovir disoproxil fumarate for presumed renal adverse events in treatment-naïve HIV-1 patients: meta-analysis of randomized clinical studies.

BACKGROUND: Safety and efficacy of tenofovir disoproxil fumarate (TDF) as a component of antiretroviral therapy (ART) have been demonstrated in clinical trials. TDF nephrotoxicity has been reported in both HIV-infected and noninfected patients. This meta-analysis explored the frequency of discontinuation attributed to renal adverse events (AEs) in randomized, controlled clinical studies that used TDF-containing regimens for ART-naïve, HIV-infected patients. METHODS: A literature search of 4 electronic databases through October 31, 2013 was utilized. RCTs included were limited to randomized, prospective, comparative design in ART treatment-naïve adults with HIV-1 infections receiving ART. Studies included trials containing TDF treatment regimens, with or without a non-TDF control group. Study design, follow-up, size of study population, treatment group, patient demographics, number of patients exposed to TDF or non-TDF control, baseline characteristics, investigator-defined criteria for renal AEs, and number of discontinuations due to a presumed renal AEs were extracted. RESULTS: Twenty-one clinical studies met the selection criteria. Treatment duration ranged from 48 to 288 weeks. Renal AEs led to study drug discontinuation in 44 of 10,129 patients exposed to TDF (0.43%; 95% CI, 0.32%-0.58%) and 2 of 2,013 patients exposed to non-TDF-containing regimens (0.10%; 95% CI, 0.01%-0.36%). In 5 randomized, controlled studies that included a non-TDF comparator, the estimated risk difference between the treatment groups (TDF vs non-TDF) was 0.50% (95% CI, 0.13%-0.86%; P = .007). CONCLUSIONS: In clinical studies using TDF-containing regimens, the rate of discontinuations due to renal AEs was low, but was slightly higher than in studies using non-TDF comparators.

A study of the pharmacokinetics, safety, and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed pregnant women with HIV.

OBJECTIVE: The objective of this study was to assess the pharmacokinetics, safety, and efficacy and confirm the dose of once-daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; B/F/TAF) during pregnancy. DESIGN: An open-label, multicenter, single-arm, phase 1b study (NCT03960645) was conducted in 33 virologically suppressed pregnant women with HIV-1. METHODS: Participants received B/F/TAF (50/200/25 mg) from the second or third trimester through ∼16 weeks postpartum. Steady-state maternal plasma pharmacokinetic samples were collected at the second and third trimesters and 6 and 12 weeks postpartum for BIC, FTC, and TAF. Neonates ( n  = 29) were followed from birth to 4-8 weeks with sparse washout pharmacokinetic sampling for BIC and TAF. The proportion of participants with HIV-1 RNA less than 50 copies/ml at delivery (missing = excluded) was evaluated. RESULTS: Mean areas under the concentration-time curve over the dosing interval (AUC tau ) for BIC, FTC, and TAF were lower during pregnancy versus postpartum but were closer to AUC tau values for nonpregnant adults with HIV reported in other studies. Geometric least-squares mean ratios for BIC, FTC, and TAF AUC tau during pregnancy versus postpartum ranged from 41 to 45%, 64 to 69% and 57 to 78%, respectively. Mean BIC trough concentrations during pregnancy were more than 6.5-fold greater than the protein-adjusted 95% effective concentration. In neonates, the median BIC half-life was 43 h. Virologic suppression was maintained in all adult participants throughout the study, with no virologic failure or treatment-emergent resistance to HIV-1, no discontinuations because of adverse events, and no perinatal transmission. CONCLUSION: Exposures to BIC, FTC, and TAF were lower during pregnancy than postpartum. However, mean BIC trough concentrations were maintained at levels indicative of efficacious exposure, and FTC/TAF data were concordant with published literature in this population. Pharmacokinetic and safety data, combined with maintenance of robust virologic suppression, suggest that once-daily B/F/TAF without dose adjustment is appropriate during pregnancy.

Switch to bictegravir/emtricitabine/tenofovir alafenamide from dolutegravir-based therapy.

OBJECTIVE: To evaluate the efficacy and safety of 96 weeks of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) treatment in participants switching from dolutegravir (DTG)-based therapy. DESIGN: Studies 1489 (NCT02607930) and 1490 (NCT02607956) were phase 3 randomized, double-blind, active-controlled, first-line therapy trials in people with HIV-1. After 144 weeks of DTG-based or B/F/TAF treatment, participants could enter a 96-week open-label extension (OLE) of B/F/TAF. METHODS: A pooled analysis evaluated viral suppression (HIV-1 RNA <50 copies/ml) and changes in CD4 + cell count at OLE Weeks 48 and 96, treatment-emergent resistance, safety, and tolerability after switch from a DTG-based regimen to B/F/TAF. Outcomes by prior treatment were summarized using descriptive statistics and compared by two-sided Wilcoxon rank sum test. RESULTS: At OLE Week 96, participants who switched to B/F/TAF ( N  = 519) maintained high levels of virologic suppression (99.5 and 99.1% in those switching from DTG/abacavir/lamivudine and DTG+F/TAF, respectively) and CD4 + cell count, with no treatment-emergent resistance to B/F/TAF. Twenty-one participants experienced drug-related adverse events after switching, with diarrhea, weight gain, and headache occurring most commonly. There were no cases of proximal renal tubulopathy, drug-related Grade 4 adverse events, or serious adverse events. Two participants discontinued B/F/TAF due to treatment-related adverse events. Participants who switched from DTG/abacavir/lamivudine experienced statistically significant greater weight gain than those who switched from DTG+F/TAF; however, median weight change from the blinded phase baseline to OLE Week 96 was numerically similar across treatment groups. CONCLUSION: This medium-term analysis demonstrates the safety and efficacy of switching to B/F/TAF from a DTG-containing regimen in people with HIV-1.

Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study.

BACKGROUND: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg. METHODS: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUCtau for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7-119·7); Ctau was 34·6% lower than adults (65·4%, 49·1-87·2). Both parameters were within the target exposure range previously found in adults, children, or both". Grade 3-4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3-4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48. INTERPRETATION: Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg. FUNDING: Gilead Sciences.

Bictegravir/emtricitabine/tenofovir alafenamide as initial treatment for HIV-1: five-year follow-up from two randomized trials.

Background: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a single-tablet regimen recommended for HIV-1 treatment. The safety and efficacy of B/F/TAF as initial therapy was established in two Phase 3 studies: 1489 (vs dolutegravir [DTG]/abacavir/lamivudine) and 1490 (vs DTG + F/TAF). After 144 weeks of randomized follow-up, an open-label extension evaluated B/F/TAF to 240 weeks. Methods: Of 634 participants randomized to B/F/TAF, 519 completed the double-blinded treatment, and 506/634 (80%) chose the 96-week open-label B/F/TAF extension, which was completed by 444/506 (88%) participants. Efficacy was based on the secondary outcome of the proportion of participants with HIV-1 RNA <50 copies/mL at Week 240 by missing = excluded and missing = failure methods. All 634 participants who were randomized to B/F/TAF and received at least one dose of B/F/TAF were included in efficacy and safety analyses. (Study 1489: ClinicalTrials.govNCT02607930; EudraCT 2015-004024-54. Study 1490: ClinicalTrials.govNCT02607956; EudraCT 2015-003988-10). Findings: Of those with available virologic data, 98.6% (95% CI [97.0%-99.5%], 426/432) maintained HIV-1 RNA <50 copies/mL at Week 240 (missing = excluded); when missing virologic data were considered as failure, 67.2% (95% CI [63.4%-70.8%], 426/634) maintained HIV-1 RNA <50 copies/mL. Mean (SD) change in CD4+ count from baseline was +338 (236.2) cells/µL. No treatment-emergent resistance to B/F/TAF was detected. Adverse events led to drug discontinuation in 1.6% (n = 10/634) of participants (n = 5 with events considered drug-related). No discontinuations were due to renal adverse events. Median (IQR) total cholesterol increased 21 (1,42) mg/dL from baseline; the change in total cholesterol:HDL was 0.1 (-0.5,0.6). Median (IQR) weight change from baseline was +6.1 kg (2.0, 11.7) at Week 240. In Study 1489, hip and spine bone mineral density mean percent changes from baseline were ≤0.6%. Interpretation: Through 5 years of follow-up, B/F/TAF maintained high rates of virologic suppression with no treatment-emergent resistance and rare drug discontinuations due to adverse events. These results demonstrate the durability and safety of B/F/TAF in people with HIV. Funding: Gilead Sciences.

Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 and hepatitis B coinfection (ALLIANCE): a double-blind, multicentre, randomised controlled, phase 3 non-inferiority trial.

BACKGROUND: For most adults with HIV-1 and hepatitis B virus (HBV) coinfection, initial recommended treatment is a tenofovir-containing antiretroviral regimen, but no randomised studies have compared tenofovir disoproxil fumarate with tenofovir alafenamide. We aimed to investigate whether bictegravir, emtricitabine, and tenofovir alafenamide is non-inferior to dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for viral suppression in individuals with HIV-1 and HBV coinfection at 48 and 96 weeks. METHODS: We did this randomised, double-blind, active-controlled, phase 3, non-inferiority trial at 46 outpatient centres in China, Dominican Republic, Hong Kong, Japan, Malaysia, South Korea, Spain, Taiwan, Thailand, Turkey, and the USA. Eligible participants were treatment-naive adults (aged ≥18 years) with plasma HIV-1 RNA of at least 500 copies per mL and plasma HBV DNA of at least 2000 IU/mL. Participants were randomly assigned (1:1) to receive daily oral bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or dolutegravir 50 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg, each with corresponding matching placebo. Randomisation was stratified by hepatitis B e antigen (HBeAg) status (positive vs negative), HBV DNA (<8 vs ≥8 log10 IU/mL), and CD4 count (<50 vs ≥50 cells per µL) at screening. All investigators, participants, and staff providing treatment, assessing outcomes, and collecting data were masked to study treatment for 96 weeks. Coprimary endpoints were the proportion of participants with plasma HIV-1 RNA less than 50 copies per mL (defined by the US Food and Drug Administration snapshot algorithm) and plasma HBV DNA less than 29 IU/mL (using the missing-equals-failure approach) at week 48, with a prespecified non-inferiority margin of -12%. Coprimary endpoints were assessed in the full analysis set, which included all randomly assigned participants who received at least one dose of study drug and had at least one post-baseline HIV-1 RNA or HBV DNA result while on study drug. Safety endpoints were assessed in all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03547908. FINDINGS: Between May 30, 2018 and March 16, 2021, 381 participants were screened, of whom 243 initiated treatment (121 in the receive bictegravir, emtricitabine, and tenofovir alafenamide group; 122 in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group). At week 48, both endpoints met the criteria for non-inferiority: 113 (95%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 111 (91%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HIV-1 RNA less than 50 copies per mL (difference 4·1, 95% CI -2·5 to 10·8; p=0·21), and 75 (63%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group versus 53 (43%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HBV DNA suppression (difference 16·6, 5·9 to 27·3; nominal p=0·0023). Drug-related adverse events up to week 96 occurred in 35 (29%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 34 (28%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group. One (1%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group reported a serious adverse event (cryptococcal meningitis attributed to immune reconstitution inflammatory syndrome) that was deemed to be treatment-related. INTERPRETATION: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is an effective therapy for adults with HIV-1 and HBV coinfection starting antiviral therapy. FUNDING: Gilead Sciences.

Air-gun injuries: initial evaluation and resultant morbidity.

Severity of injuries from air-powered weapons can be underappreciated. Transformation of these weapons into toys makes them available to children. Our experience reveals the underestimated injury severity and emphasizes need for prompt trauma evaluation. Retrospective chart review of children sustaining air-gun injuries and evaluated at a single, pediatric hospital from 1991 to 2002 was performed. Medical record numbers were retrieved from a trauma data base. Data included age, weapon type, firing distance, injury site, radiographic studies, operative intervention, length of stay, and long-term disability. Ocular injuries were excluded secondary to known severity. All other injuries and treatments are described. Thirty-four children, average age 10 years +/- 3.3 years, sustained 35 injuries from 1991 through 2002. Twenty-one children required admission, 19 children required surgery, and 5 children experienced long-term disability. Average time to definitive care was 3 hours 12 minutes. Sites of injury included head, neck, chest, abdomen, and extremities. Average hospital stay was 4.3 days. In the pediatric population, air-gun injuries can be underestimated. Lack of collateral tissue damage makes wounds appear innocuous to unsuspecting medical personnel resulting in delayed care. During initial evaluation, injuries from air guns deserve the same respect as those caused by conventional firearms.

Simplification to rilpivirine/emtricitabine/tenofovir disoproxil fumarate from ritonavir-boosted protease inhibitor antiretroviral therapy in a randomized trial of HIV-1 RNA-suppressed participants.

OBJECTIVE: To evaluate the efficacy and safety of antiretroviral simplification from a ritonavir-boosted protease inhibitor-based regimen [protease inhibitor+RTV+two nucleos(t)ide reverse transcriptase inhibitors (NRTIs); ≥6 months of exposure prior to study entry with no prior treatment failure] to the single-tablet regimen (STR) rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) in virologically suppressed, HIV-1-infected participants. DESIGN: Phase 3b, randomized, open-label, international, 48-week switch study. METHODS: Participants were randomized 2 : 1 to switch to RPV/FTC/TDF immediately or stay on their baseline protease inhibitor+RTV+2NRTIs regimen with a delayed switch to RPV/FTC/TDF at week 24. The primary endpoint was noninferiority (12% margin) of RPV/FTC/TDF compared with protease inhibitor+RTV+ two NRTIs in maintaining plasma HIV-1 RNA less than 50 copies/ml at week 24 by Snapshot analysis. RESULTS: A total of 476 participants were randomized and received at least one dose of study drug. Demographics and baseline characteristics were similar between arms. The primary objective of noninferiority at week 24 was met: HIV-1 RNA less than 50 copies/ml by Snapshot analysis, 93.7% of RPV/FTC/TDF versus 89.9% of protease inhibitor+RTV+ two NRTIs (difference 3.8%, 95% confidence interval -1.6 to 9.1%). Through week 48, 89.3% of participants in the immediate switch group maintained virologic suppression. High rates of suppression were maintained with RPV/FTC/TDF regardless of participant's pre-antiretroviral HIV-1 RNA level. Overall development of resistance mutations after switching to RPV/FTC/TDF was low. Decreases in total cholesterol, low-density lipoprotein (LDL), and triglycerides were significantly greater among RPV/FTC/TDF recipients than those in the protease inhibitor+RTV+ two NRTIs group. CONCLUSION: Switching to the STR RPV/FTC/TDF from an RTV-boosted protease inhibitor regimen in virologically suppressed, HIV-1-infected participants maintained virologic suppression with a low risk of virologic failure, while improving total cholesterol, LDL, and triglycerides.

The frequency of adjusted renal dosing of tenofovir DF and its effects on patient outcomes.

Tenofovir disoproxil fumarate (TDF), a nucleotide reverse transcriptase inhibitor used in the treatment of human immunodeficiency virus (HIV) and hepatitis B, is renally eliminated and has been associated with renal toxicities. Dose adjustments are recommended for patients with creatinine clearance (CrCL) <50 mL/min. We retrospectively determined the frequency in which HIV clinic providers adjusted TDF doses in patients with CrCL <50 mL/min over a 2-year period and compared clinical outcomes in patients who had TDF dose adjustments based on CrCL <50 mL/min versus those who did not. Thirty-nine patients with CrCL <50 mL/min were identified. Dose-adjusted patients (N = 9) continued their TDF-based antiretroviral regimens for 21 months longer following the first CrCL < 50 mL/min (P = .0193) and had gains in CD4 cell counts over 12 months (P = .0009). There were no statistically significant differences in CrCL or percentage of patients with detectable HIV-1 RNA at 6 and 12 months following first CrCL <50 mL/min in those who did versus did not have a TDF dose adjustment. In summary, HIV providers often failed to dose-adjust TDF in patients with CrCL <50 mL/min, but dose-adjusted patients appeared to stay on their TDF-based regimens longer and have greater gains in CD4 cells. Larger, prospective studies are needed to validate these results.

Assessing the effectiveness of pharmacy-based adherence interventions on antiretroviral adherence in persons with HIV.

A key factor to the successful treatment of HIV is good adherence to antiretroviral therapy (ART). We developed a pharmacist-managed adherence clinic and designed a study to assess the impact of the adherence interventions by measuring the proportion of patients with 95% or greater adherence to ART before and after referral to the program. HIV providers referred patients with adherence problems to a pharmacist-managed adherence clinic. Interventions included scheduled clinic visits with the HIV Clinical Pharmacist and monthly refill reminders from pharmacy staff members over a 6-month period. Those aged 18-75, prescribed an ART regimen for a minimum of 3 months, and who filled their medications exclusively at the clinic pharmacy were eligible for study participation. The Proportion of Days Covered (PDC) served as a surrogate marker of overall adherence. A total of 34 patients were referred to the pharmacy clinic for adherence counseling, of whom 28 enrolled in the study. The proportion of participants with 95% or greater adherence to their ART regimen increased from 7% at baseline to 32% postintervention (p = 0.01). A subanalysis of the PDC revealed an overall increase from a baseline adherence mean of 60% to 81% postintervention (p < 0.0001). There was a notable trend toward an increase in the proportion of participants with an undetectable HIV-1 viral load (58-73%, baseline and postintervention, respectively, p = 0.10), but no statistically significant improvement in CD4 cell count. Clinical pharmacy interventions improved overall adherence to ART regimens in these patients with HIV.

Enoxaparin inhibits fibrin sheath formation and decreases central venous catheter colonization following bacteremic challenge.

OBJECTIVE: Inhibition of fibrin sheath formation by enoxaparin decreases catheter colonization. Fibrin-binding radioactive tracer and catheter weights quantify fibrin reduction. DESIGN: Controlled experimental study of central venous line colonization. SETTING: Animal laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Central venous lines were introduced into right external jugular veins of 254 animals in three groups: enoxaparin, Fibrimage, and catheter weight. The enoxaparin group (n = 196) received daily enoxaparin injections (n = 97) or catheter implantation only (n = 99); 176 received tail vein injections of Staphylococcus epidermidis on postoperative day (POD) 10. Twenty rats received saline injections as a control. On POD 13, catheters were removed and incubated in broth at 37 degrees C for 48 hrs. Turbid samples were plated. In the Fibrimage group (n = 39), 20 rats receiving enoxaparin were compared with 19 controls without enoxaparin; all received S. epidermidis injections on POD 10. Fibrimage, fibrin-binding radiolabeled tracer, was given 1 hr before catheter removal. In the weight group (n = 19), six rats received enoxaparin; 13 did not. All received injections of S. epidermidis on POD 10. MEASUREMENTS AND MAIN RESULTS: Positive plates underwent analytic profile index testing, ensuring correlation with inoculum. Results were compared using Fisher's exact or chi-square tests. Gamma counts were determined in the Fibrimage group. Catheter tip weights were recorded. Results from the Fibrimage and weight groups were compared using Student's t-test. The enoxaparin group had fewer catheters colonized (17 of 77) vs. no enoxaparin (42 of 99; p < .01). Pericatheter sheaths contained less fibrin compared with controls. Fibrimage group gamma counts were significantly decreased for the enoxaparin subgroup (x = 2244 counts per minute) vs. controls (x = 3767 counts per minute; p < .0002). The weight of catheter tips treated with enoxaparin (x = 39 mg) vs. controls (x = 90 mg) was also significantly decreased (p < .0001). CONCLUSIONS: Enoxaparin decreases the amount of fibrin surrounding central venous catheters. The incidence of catheter colonization decreases when the amount of fibrin within the pericatheter sheath decreases.

The negative impact of the repeal of the Arkansas motorcycle helmet law.

BACKGROUND: On July 1, 1997, Arkansas became the first state in 14 years to repeal their adult helmet law. We examined the clinical and financial impact of this repeal. METHODS: A 6-year retrospective review was conducted of the University of Arkansas for Medical Sciences trauma registry including the 3 years before and the 3 years after the repeal of the helmet law. A head and neck Abbreviated Injury Scale (AIS) score >or= 3 was considered severe. All patients admitted to the hospital or who died in the emergency department were included in the study. The database of the Arkansas Highway and Transportation Department was also used to determine the number of crashes and fatalities occurring statewide (1995-1999). RESULTS: Although total and fatal crashes in Arkansas were not significantly different (1995-1996 vs. 1998-1999), nonhelmeted deaths at the scene of a crash significantly increased from 19 of 48 (39.6%) (1995-1996) to 40 of 53 (75.5%) (1998-1999) (p < 0.0001). Before repeal, 25% of nonfatal crash admissions were nonhelmeted (18 of 73). This significantly increased to 54% (52 of 96, p< 0.001) after repeal. Overall, patients who were nonhelmeted had significantly higher AIS scores for head and neck, significantly more severe head injuries (AIS score >or= 3), 47% (33 of 70) versus 20% (20 of 99), and significantly longer length of intensive care unit stay. Financially, patients without helmets had significantly higher unreimbursed charges compared with their helmeted counterparts, resulting in a total of 982,560 dollars of additional potentially lost revenue over the length of the study. CONCLUSION: Repeal of the mandatory helmet law was associated with an increase in the nonhelmeted crash scene fatality rate. After the repeal, there was a disproportionately higher admission rate for nonhelmeted motorcycle crash survivors. These patients had an increased use of hospital resources and poorer reimbursement of charges compared with their helmeted counterparts. This resulted in significantly higher unreimbursed charges. States considering repeal of their mandatory adult helmet laws should consider the potential negative financial impact on their health care system and the increased morbidity associated with nonhelmeted motorcycle riders involved in a crash.