Bictegravir/emtricitabine/tenofovir alafenamide plus doravirine in highly treatment-experienced men with multidrug-resistant HIV.

OBJECTIVE: To evaluate the safety and efficacy of switching highly treatment-experienced people with HIV (HTE PWH) from rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF) plus dolutegravir (DTG) to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus doravirine (DOR). A pharmacokinetic (PK) analysis was conducted to assess the potential interaction between BIC and DOR. DESIGN AND METHODS: This open-label switch trial enrolled HTE PWH from a primary care private practice in the United States. Eligible participants were male, aged ≥45 years, with documented viral resistance to protease inhibitors, nucleoside reverse transcriptase inhibitors, and/or nonnucleoside reverse transcriptase inhibitors but no resistance to RPV or DOR, and no K65R or T69 insertion mutations. Virologic suppression (≤50 copies/ml) while on RPV/FTC/TAF plus DTG for ≥6 months was required prior to enrollment. The primary endpoint of the study was virologic suppression (<50 and <200 copies/ml) at 48 weeks. Secondary endpoints included safety, tolerability, changes in body mass index (BMI), and identification of PK parameters of BIC and DOR. RESULTS: Twenty males [median age: 65 years (range, 46-74), median time since HIV diagnosis: 37 years (range, 12-42)] completed the study. BIC/FTC/TAF plus DOR was well tolerated with no serious or treatment-related adverse events reported and no appreciable changes in BMI from baseline to Week 48. At Week 48, 100% of participants had <50 viral copies/ml. PK parameters for BIC and DOR ( n  = 10) were consistent with published data. CONCLUSIONS: Switching from RPV/FTC/TAF plus DTG to BIC/FTC/TAF plus DOR was well tolerated and efficacious in HTE men aged ≥45 years with HIV.

Mosquito Exposure and Chikungunya and Dengue Infection Among Travelers During the Chikungunya Outbreak in the Americas.

AbstractTravelers are at risk for arbovirus infection. We prospectively enrolled 267 Department of Defense beneficiaries traveling to chikungunya-outbreak regions in the Americas between December 2013 and May 2015 and assessed travel characteristics and serologic exposure to chikungunya virus (CHIKV) and dengue virus (DENV). Ten ill-returning travelers were also assessed retrospectively. Self-reported mosquito exposure was common (64% of 198 evaluable travelers saw mosquitoes; 53% of 201 reported ≥ 1 bite). Increased exposure was associated with active-duty travelers (odds ratio [OR] = 2.6 [1.3-5.4] for seeing mosquitoes) or travelers visiting friends and relatives (VFR) (OR = 3.5 [1.0-10.0] for high-intensity bite exposure). Arbovirus infection was defined as seroconversion on plaque reduction neutralization testing (PRNT) of pre- and posttravel sera. For ill subjects enrolled posttravel, infection was defined by a positive convalescent PRNT and/or a positive reverse transcription polymerase chain reaction for CHIKV or DENV. We identified seven cases of arbovirus infection: four with CHIKV, five with DENV, and two with both. The composite attack rate for CHIKV and DENV infection was 3.7% of 108 evaluable, immunologically naïve, prospectively assessed travelers; there was serologic and/or polymerase chain reaction evidence of arbovirus infection in three of four evaluable (three of 10 total) ill-returning travelers. We identified both symptomatic and asymptomatic cases. Military purpose of travel and VFR travel accounted for five of seven cases. Pretravel counseling is important and should target higher risk groups. Given a shared vector between CHIKV, DENV, and Zika virus (ZIKV), this study can also help guide counseling for travelers to ZIKV-outbreak regions.

Predictors for physical activity in adolescent girls using statistical shrinkage techniques for hierarchical longitudinal mixed effects models.

We examined associations among longitudinal, multilevel variables and girls' physical activity to determine the important predictors for physical activity change at different adolescent ages. The Trial of Activity for Adolescent Girls 2 study (Maryland) contributed participants from 8th (2009) to 11th grade (2011) (n=561). Questionnaires were used to obtain demographic, and psychosocial information (individual- and social-level variables); height, weight, and triceps skinfold to assess body composition; interviews and surveys for school-level data; and self-report for neighborhood-level variables. Moderate to vigorous physical activity minutes were assessed from accelerometers. A doubly regularized linear mixed effects model was used for the longitudinal multilevel data to identify the most important covariates for physical activity. Three fixed effects at the individual level and one random effect at the school level were chosen from an initial total of 66 variables, consisting of 47 fixed effects and 19 random effects variables, in additional to the time effect. Self-management strategies, perceived barriers, and social support from friends were the three selected fixed effects, and whether intramural or interscholastic programs were offered in middle school was the selected random effect. Psychosocial factors and friend support, plus a school's physical activity environment, affect adolescent girl's moderate to vigorous physical activity longitudinally.

Epidemiology and self-treatment of travelers' diarrhea in a large, prospective cohort of department of defense beneficiaries.

BACKGROUND: Infectious diarrhea is a common problem among travelers. Expert guidelines recommend the prompt use of antibiotics for self-treatment of moderate or severe travelers' diarrhea (TD). There is limited data on whether travelers follow these self-treatment guidelines. We evaluated the risk factors associated with TD, the use of TD self-treatment, and the risk of irritable bowel syndrome (IBS) during travel. METHODS: Department of Defense beneficiaries traveling outside the United States for ≤6.5 months were enrolled in a prospective cohort study. Participants received pre- and post-travel surveys, and could opt into a travel illness diary and follow-up surveys for symptoms of IBS. Standard definitions were used to assess for TD and IBS. Suboptimal self-treatment was defined as the use of antibiotics (with or without antidiarrheal agents) for mild TD, or the use of antidiarrheals alone or no self-treatment in cases of moderate or severe TD. RESULTS: Twenty-four percent of participants (270/1,120) met the criteria for TD. The highest incidence was recorded in Africa [8.6 cases/100 person-weeks, 95% confidence interval (CI): 6.7-10.5]. Two hundred and twelve participants with TD provided information regarding severity and self-treatment: 89 (42%) had mild TD and 123 (58%) had moderate or severe TD. Moderate or severe TD was independently associated with suboptimal self-treatment [OR 10.4 (95% CI: 4.92-22.0)]. Time to last unformed stool did not differ between optimal and suboptimal self-treatment. IBS occurred in 4.5% (7/154) of TD cases and in 3.1% (16/516) of cases without TD (p = 0.39). Among TD cases, a lower incidence of IBS was noted in participants who took antibiotics [4.8% (5/105) vs 2.2% (1/46)] in those who did not, but the difference did not reach statistical significance (p = 0.60). CONCLUSIONS: Our results suggest the underutilization of antibiotics in travelers with moderate or severe TD. Further studies are needed to systematically evaluate pre-travel instruction and traveler adherence to self-treatment guidelines, and the impact of suboptimal self-treatment on outcomes.

Minimal interaction between gatifloxacin and oxycodone.

Previous studies have demonstrated a significant reduction in the oral bioavailability of trovafloxacin and ciprofloxacin when administered concomitantly with an intravenous opiate, such as morphine. This decrease in absorption results in a 36% and 50% lower AUC for trovafloxacin and ciprofloxacin, respectively, which could cause clinical failures. The authors investigated the possibility of a similar interaction between oxycodone and gatifloxacin. Twelve healthy volunteers were randomized in an open-label, two-way crossover study to receive oxycodone (5 mgpo Q4H) andgatifloxacin (400 mg po 1 h) after starting the oxycodone or gatifloxacin 400 mg po alone. Blood samples were drawn at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours postdosing. No significant difference was noted (p > 0.05) in AUC (31.6 +/- 7.3 vs. 31.7 +/- 7.1) and Cmax (3.2 +/- 0.6 vs. 3.0 +/- 0.6) for gatifloxacin versus gatifloxacin/oxycodone regimens; however, the tmax (1.8 +/- 0.8 vs. 4.3 +/- 1.5) was significantly delayed (p < 0.001). It was concluded that oral oxycodone and gatifloxacin can be administered concomitantly without a significant decrease in bioavailability.

Clinical efficacy and pharmacoeconomics of a continuous-infusion piperacillin-tazobactam program in a large community teaching hospital.

STUDY OBJECTIVE: To compare continuous versus intermittent administration of piperacillin-tazobactam with regard to clinical, microbiologic, and economic outcomes. DESIGN: Prospective, open-label controlled study SETTING: Community teaching hospital. PATIENTS: Ninety-eight hospitalized patients prescribed piperacillin-tazobactam. INTERVENTION: Substitutions were implemented so that 47 patients initially prescribed intermittent infusion of piperacillin-tazobactam were switched to continuous infusion of this drug combination. Dosages varied in accordance with the type of infection and each patient's renal function. Fifty-one other patients with similar demographics and types of infection received intermittent infusion with piperacillin-tazobactam. MEASUREMENTS AND MAIN RESULTS: Clinical success rates were 94% for the continuous-infusion group and 82% for the intermittent-infusion group (p=0.081). Microbiologic success rates were 89% for the continuous-infusion group and 73% for the intermittent-infusion group (p=0.092). Days to normalization of fever were significantly lower (p=0.012) in the continuous-infusion group (1.2 +/- 0.8 days) than in the intermittent-infusion group (2.4 +/- 1.5 days). Level 1 and level 2 costs/patient were both reduced by continuous infusion, although the difference was statistically significant only for level 2 costs ($399.38 +/- 407.22 for continuous infusion vs $523.49 +/- 526.85 for intermittent infusion, p=0.028). CONCLUSION: Continuous infusion of piperacillin-tazobactam provided clinical and microbiologic outcomes equivalent to those for intermittent infusion. Compared with intermittent infusion, continuous infusion significantly shortened the time to temperature normalization, while also offering a significant reduction in level 2 expenditures.