Potentially Traumatic Events of Women of Color in an Urban Adult Basic Education Program.

Adult Basic Education (ABE) in the United States is an important tool for underrepresented and underserved communities to achieve the goal of high school graduation following noncompletion of K-12 education. Largely in urban settings, ABE centers serve millions of students annually, especially historically and contemporarily marginalized groups. ABE provides critical resources and skills to meet the educational needs of diverse peoples seeking to advance their station in life. ABE centers may serve students with potentially traumatic events (PTE), diagnosable trauma, and related poorer outcomes. Alarmingly, a paucity of research exists that examines the presence of PTEs for ABE students, particularly people and women of color. In the present research, the Patient Health Questionnaire 9-item and Generalized Anxiety Disorder 7-item measures were used to weigh depression and anxiety scores across the Life Events Checklist for the DSM-5 (LEC-5) trauma types in a sample (N=170) of predominantly women of color. We examined three respondent groups based on proximity and frequency of PTEs: (1) denied; (2) witnessed/learned about; and (3) experienced. Results indicate that those experiencing higher levels of PTEs (namely, sexual assault, unwanted/uncomfortable sexual experience, and sudden accidental death) also experienced higher ratings of depression and anxiety. More research is indicated, as women of color within ABE settings could benefit from tailored resources for prevention, intervention, and treatment.

Week 240 Efficacy and Safety of Fostemsavir Plus Optimized Background Therapy in Heavily Treatment-Experienced Adults with HIV-1.

INTRODUCTION: Efficacy and safety of the attachment inhibitor fostemsavir + optimized background therapy (OBT) were evaluated through 48 and 96 weeks in the phase 3 BRIGHTE trial in heavily treatment-experienced (HTE) adults failing their current antiretroviral regimen. Here, we report 240-week efficacy and safety of fostemsavir + OBT in adults with multidrug-resistant human immunodeficiency virus (HIV)-1 in BRIGHTE. METHODS: Heavily treatment-experienced adults failing their current regimen entered the randomized cohort (RC; 1-2 fully active antiretrovirals available) or non-randomized cohort (NRC; no fully active antiretrovirals available) and received open-label fostemsavir + OBT (starting Day 8 in RC and Day 1 in NRC). Endpoints included proportion with virologic response (HIV-1 RNA < 40 copies/mL, Snapshot), immunologic efficacy, and safety. RESULTS: At Week 240, 45% and 22% of the RC and NRC, respectively, had virologic response (Snapshot); 7% of the RC and 5% of the NRC had missing data due to coronavirus disease 2019 (COVID-19)-impacted visits. In the observed analysis, 82% of the RC and 66% of the NRC had virologic response. At Week 240, mean change from baseline in CD4+ T-cell count was 296 cells/mm3 (RC) and 240 cells/mm3 (NRC); mean CD4+/CD8+ ratio increased between Weeks 96 and 240 (RC 0.44 to 0.60; NRC 0.23 to 0.32). Between Weeks 96 and 240, four participants discontinued for adverse events, one additional participant experienced a drug-related serious adverse event, and six deaths occurred (median last available CD4+ T-cell count, 3 cells/mm3). COVID-19-related events occurred in 25 out of 371 participants; all resolved without incident. CONCLUSION: Through ~5 years, fostemsavir + OBT demonstrated durable virologic and immunologic responses with no new safety concerns between Weeks 96 and 240, supporting this regimen as a key therapeutic option for HTE people with multidrug-resistant HIV-1. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02362503.

Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1.

BACKGROUND: Ibalizumab, a humanized IgG4 monoclonal antibody, blocks the entry of human immunodeficiency virus type 1 (HIV-1) by noncompetitive binding to CD4. METHODS: In this single-group, open-label, phase 3 study, we enrolled 40 adults with multidrug-resistant (MDR) HIV-1 infection in whom multiple antiretroviral therapies had failed. All the patients had a viral load of more than 1000 copies of HIV-1 RNA per milliliter. After a 7-day control period in which patients continued to receive their current therapy, a loading dose of 2000 mg of ibalizumab was infused; the viral load was quantified 7 days later. Through week 25 of the study, patients received 800 mg of ibalizumab every 14 days, combined with an individually optimized background regimen including at least one fully active agent. The primary end point was the proportion of patients with a decrease in viral load of at least 0.5 log10 copies per milliliter from baseline (day 7) to day 14. RESULTS: A total of 31 patients completed the study. The mean baseline viral load was 4.5 log10 copies per milliliter, and the mean CD4 count was 150 per microliter. Of the 40 patients in the intention-to-treat population, 33 (83%) had a decrease in viral load of at least 0.5 log10 copies per milliliter from baseline (P<0.001 for the comparison with the control period). The mean viral-load decrease was 1.1 log10 copies per milliliter. During the control period, 1 patient, who received the optimized background regimen prematurely, had a decrease in viral load of 0.5 log10 copies per milliliter. At week 25, patients who had received ibalizumab plus an optimized background regimen had a mean decrease of 1.6 log10 copies per milliliter from baseline; 43% of the patients had a viral load of less than 50 copies per milliliter, and 50% had a viral load of less than 200 copies per milliliter. Among 10 patients who had virologic failure or rebound, in vitro testing identified 9 who had a lower degree of susceptibility to ibalizumab than at baseline. The most common adverse event was diarrhea (in 20% of patients). Four patients died from causes related to underlying illnesses; 1 had a serious adverse event (the immune reconstitution inflammatory syndrome) that was deemed to be related to ibalizumab therapy. CONCLUSIONS: In patients with MDR HIV-1 infection who had advanced disease and limited treatment options, ibalizumab had significant antiviral activity during a 25-week study. Evidence of the emergence of diminished ibalizumab susceptibility was observed in vitro in patients who had virologic failure. (Funded by the Orphan Products Clinical Trials Grants Program of the Food and Drug Administration and TaiMed Biologics; TMB-301 ClinicalTrials.gov number, NCT02475629 .).

Pilot study of a brief dialectical behavior therapy skills group for jail inmates.

Regulating emotions, refraining from impulsive, maladaptive behavior, and communicating effectively are considered primary treatment needs among jail inmates. Dialectical behavior therapy (DBT; Linehan, 1993a) skills address these deficits and have been implemented in long-term correctional settings, but have yet to be adapted for general population inmates in short-term jail settings. This study assessed the feasibility and acceptability of a DBT skills group in a jail setting, as well as its utility in improving coping skills and emotional/behavioral dysregulation. Male jail inmates participated in an 8-week DBT skills group and completed pre- and posttest assessments of coping skills, emotional/behavioral dysregulation, and measures of treatment acceptability. Out of 27 who started therapy, 16 completed it, primarily due to involuntary attrition such as transfer to another correctional facility. Although several logistical issues arose during this pilot study, preliminary results suggest that a brief DBT skills group is feasible and acceptable in a jail setting, and may improve coping skills and reduce externalization of blame among general population jail inmates. This study lays the groundwork for larger, controlled trials of abbreviated DBT skills groups for general population inmates in short-term jail settings. (PsycINFO Database Record

Is There a Dark Side to Mindfulness? Relation of Mindfulness to Criminogenic Cognitions.

In recent years, mindfulness-based interventions have been modified for use with inmate populations, but how this might relate to specific criminogenic cognitions has not been examined empirically. Theoretically, characteristics of mindfulness should be incompatible with distorted patterns of criminal thinking, but is this in fact the case? Among both 259 male jail inmates and 516 undergraduates, mindfulness was inversely related to the Criminogenic Cognitions Scale (CCS) through a latent variable of emotion regulation. However, in the jail sample, this mediational model also showed a direct, positive path from mindfulness to CCS, with an analogous, but nonsignificant trend in the college sample. Post hoc analyses indicate that the Nonjudgment of Self scale derived from the Mindfulness Inventory: Nine Dimensions (MI:ND) largely accounts for this apparently iatrogenic effect in both samples. Some degree of self-judgment is perhaps necessary and useful, especially among individuals involved in the criminal justice system.

Does psychopathy differentially predict treatment-seeking during incarceration versus postrelease?

The notion that high psychopathy inmates seek treatment for non-therapeutic reasons is frequently assumed but lacking empirical evidence. In a sample of 217 suburban jail inmates, we examined whether psychopathy differentially predicted treatment-seeking during incarceration (when extrinsic benefits exist), but not post-release. Overall, analyses revealed no evidence to support this notion. High psychopathy offenders did not artificially seek treatment at a higher rate than their less psychopathic peers during or following incarceration. Further, there was no evidence psychopathy was associated with treatment-seeking for present-oriented reasons (e.g., to reduce their sentence) during incarceration. Inmates high in psychopathy, particularly Factor 1, were more likely to request access to the jail law library than their lower-psychopathy peers. Taken together, these findings challenge common assumptions regarding psychopathic offenders' treatment-seeking behaviors and motivations. Clinicians can anticipate that inmates seeking treatment will represent the full range of psychopathy, both during incarceration and upon rejoining the community.

Significant improvements in self-reported gastrointestinal tolerability, quality of life, patient satisfaction, and adherence with lopinavir/ritonavir tablet formulation compared with soft gel capsules.

BACKGROUND: The tablet formulation of ritonavir-boosted lopinavir (LPV/r; Kaletra) has many advantages over the soft gel capsule (SGC) formulation, including lower pill count, no refrigeration requirement, and no dietary restrictions. These advantages may help improve patient compliance and therefore increase adherence to treatment. However, there are limited data regarding patient preferences and only recently was the comparative efficacy and tolerability data of LPV/r SGC versus tablet formulation presented at an international conference. To address this deficit, we conducted a market research survey to assess potential tolerability benefits, patient satisfaction, changes in adherence, and formulation preference in patients switching from SGCs to the tablet formulation. Data from 332 patients who switched from LPV/r SGCs twice-daily (BID) to tablets BID and 41 patients who switched from LPV/r SGCs BID or once daily (QD) to tablets QD were analyzed. RESULTS: Switching from SGCs to a tablet formulation of LPV/r was associated with increased patient satisfaction, tolerability and self-reported adherence to treatment; gastrointestinal side effects were reduced. In addition, respondents indicated that they preferred the tablet formulation to the SGC. CONCLUSION: The LPV/r tablet formulation provides HIV-infected patients with multiple benefits over the SGC in terms of tolerability and convenience. Additional assessments to further define the tolerability profile of the LPV/r tablet, including studies using once-daily dosing, are warranted.

Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis.

OBJECTIVE: TMC125-C223 is an open-label, partially blinded, randomized clinical trial to evaluate the efficacy and safety of two dosages of etravirine (TMC125), a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild-type and NNRTI-resistant HIV-1. DESIGN: A total of 199 patients were randomly assigned 2: 2: 1 to twice-daily etravirine 400 mg, 800 mg and control groups, respectively. The primary endpoint was a change in viral load from baseline at week 24 in the intention-to-treat population. METHODS: Patients had HIV-1 with genotypic resistance to approved NNRTIs and at least three primary protease inhibitor (PI) mutations. Etravirine groups received an optimized background of at least two approved antiretroviral agents [nucleoside reverse transcriptase inhibitors (NRTI) and/or lopinavir/ritonavir and/or enfuvirtide]. Control patients received optimized regimens of at least three antiretroviral agents (NRTIs or PIs and/or enfuvirtide). RESULTS: The mean change from baseline in HIV-1 RNA at week 24 was -1.04, -1.18 and -0.19 log10 copies/ml for etravirine 400 mg twice a day, 800 mg twice a day and the control group, respectively (P < 0.05 for both etravirine groups versus control). Etravirine showed no dose-related effects on safety and tolerability. No consistent pattern of neuropsychiatric symptoms was observed. There were few hepatic adverse events, and rashes were predominantly early onset and mild to moderate in severity. CONCLUSION: Etravirine plus an optimized background significantly reduced HIV-1-RNA levels from baseline after 24 weeks in patients with substantial NNRTI and PI resistance, and demonstrated a favorable safety profile compared with control.

Improvement in sexual functioning and satisfaction in nonresponders to testosterone gel: clinical effectiveness in hypogonadal, HIV-positive males.

Impairment in gonadal function with reduced testosterone (T) levels is commonly associated with HIV infection and patients often complain of diminished libido and sexual dysfunction. The effectiveness of Testim 1% (Auxilium Pharmaceuticals, Inc., Norristown, Pennsylvania) topical T gel was evaluated in HIV-positive males who failed to experience satisfactory symptom relief following prior treatment with AndroGel 1% (Solvay Pharmaceuticals, Inc., Marietta, Georgia). In this open-label study, consecutive subjects were randomly assigned to experimental treatment with Testim 1% (5 g) or to maintenance therapy (control group) with AndroGel 1% (5 g). Twenty-four experimental subjects and 24 control subjects were followed for 4 weeks to evaluate improvements in sexual functioning and satisfaction. Changes from baseline in the 5 domains of the Brief Male Sexual Function Inventory (BMSFI) were compared between groups. The average percentage improvement favored the experimental treatment in all 5 comparisons of the BMSFI, including sexual drive (53% vs 18%, P < 0.001), erectile function (49% vs 7%, P < 0.004), ejaculatory function (15% vs 8%, P < 0.14), problem assessment (59% vs 12%, P < 0.003), and sexual satisfaction (58% vs 9%, P < 0.006). A greater percentage of subjects also reported satisfaction with the experimental treatment (85% vs 48%, P < 0.03), and these subjects were less likely to require upward dose titration at the final follow-up visit (30% vs 74%, P = 0.01). It is hypothesized that the results of the current study may be explained, in part, by an improved pharmacokinetic profile of the experimental intervention. Consideration of Testim 1% gel in HIV patients who have an inadequate response to prior T therapy is encouraged, although it is difficult to estimate the contribution of nonspecific study effects (eg, placebo) in this trial.

Once-daily versus twice-daily lamivudine, in combination with zidovudine and efavirenz, for the treatment of antiretroviral-naive adults with HIV infection: a randomized equivalence trial.

A randomized, double-blind, double-dummy controlled, multicenter trial was conducted that involved 554 antiretroviral-naive human immunodeficiency virus-infected adults (plasma HIV type 1 [HIV-1] RNA level, >or=400 copies/mL; CD4(+) cell count, >100 cells/mm(3)) and compared a 300-mg once-daily (q.d.) regimen of lamivudine (3TC) versus a 150-mg twice-daily (b.i.d.) regimen of 3TC, combined with zidovudine (300 mg b.i.d.) and efavirenz (600 mg q.d.), during a 48-week period. Treatments were considered equivalent if the 95% confidence interval (CI) for the difference in proportions of patients achieving an HIV-1 RNA level of <400 copies/mL was within the bound of -12% to 12%. At week 48 of the study, an intent-to-treat analysis in which patients with missing data were considered to have experienced treatment failure showed that the 3TC q.d. and 3TC b.i.d. regimens were equivalent (HIV-1 RNA level <400 copies/mL, 178 [64%] of 278 vs. 174 [63%] of 276; treatment difference, 1% [95% CI, -7.1% to 8.9%]; HIV-1 RNA level <50 copies/mL, 165 [59%] of 278 vs. 168 [61%] of 276; treatment difference, 1.7% [95% CI, -9.7% to 6.6%]). Median increase above baseline in CD4(+) cell count was similar (q.d. group, +144 cells/mm(3); b.i.d. group, +146 cells/mm(3)), and the incidences of adverse events, disease progression, and HIV-associated conditions were comparable.

Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV.

BACKGROUND: Atazanavir, an azapeptide protease inhibitor (PI), has pharmacokinetics that allow once-daily dosing, and it is not associated with significant PI-associated dyslipidemia. METHODS: A randomized, double-blind, double-dummy, active-controlled, 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily. The 810 treatment-naive patients were stratified by HIV RNA level. The primary efficacy end point was the proportion of treated patients with HIV RNA levels <400 copies/mL through week 48. RESULTS: At week 48, HIV RNA levels were <400 copies/mL in 70% of patients receiving atazanavir and 64% of patients receiving efavirenz (intent-to-treat, difference; 95% confidence interval: 5.2%; -1.2%, 11.7%). Median CD4 cell counts increased at comparable magnitudes and rates in the 2 treatment arms (mean change at week 48: 176 cells/mm with atazanavir, 160 cells/mm with efavirenz). Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol, fasting low-density lipoprotein cholesterol, or fasting triglycerides over 48 weeks of therapy. Atazanavir-linked bilirubin elevations infrequently resulted in treatment discontinuation (<1%). Atazanavir treatment did not increase fasting glucose or insulin levels. CONCLUSIONS: For initial HIV treatment, a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine.

CD4 cell response to 3 doses of subcutaneous interleukin 2: meta-analysis of 3 Vanguard studies.

BACKGROUND: In advance of a large clinical end point trial evaluating the effectiveness of subcutaneous interleukin 2 (scIL-2) for treatment of patients with human immunodeficiency virus (HIV) infection, 3 identically designed Vanguard trials were conducted in Buenos Aires, Argentina; Bangkok, Thailand; and Houston, Texas. To more precisely quantitate the effect on CD4 cell response of 3 different doses of scIL-2 that were administered twice daily for 5 days every 8 weeks, the results of these 3 trials were pooled in a meta-analysis. METHODS: Two hundred eighteen HIV-1-infected subjects who were receiving antiretroviral therapy and who had a baseline CD4 cell count of > or =350 cells/mm3 were consecutively randomized to receive scIL-2 at a dose of 1.5 mIU (n=36) or a control regimen (n=36); or scIL-2 at a dose of 4.5 mIU (n=36) or a control regimen (n=36); or scIL-2 at a dose of 7.5 mIU (n=37) or a control regimen (n=37). After completion of 3 cycles of therapy, the subjects were enrolled in an extension phase (months 6-12). Subjects were encouraged to receive additional cycles of scIL-2 to maintain a CD4 cell count of more than twice the baseline count or >1000 cells/mm3. RESULTS: After completion of 3 cycles of scIL-2, the mean CD4 cell count changes from baseline (calculated as changes from baseline in a scIL-2 group minus changes from baseline in its contemporaneous control group) were 67 (P=.14), 339 (P<.0001), and 605 cells/mm3 (P<.0001) for the 1.5, 4.5, and 7.5 mIU dose groups, respectively (P<.0001 for differences among dose groups). Between months 6 and 12, a total of 78%, 39%, and 32% of subjects assigned to the 1.5, 4.5, and 7.5 mIU dose groups, respectively, needed at least 1 additional cycle to achieve the CD4 cell count goal. At 12 months, the differences in the mean change in CD4 cell count from baseline between each scIL-2 dose group and its contemporaneous control group were 184, 369, and 432 cells/mm3, respectively (P=.01 for differences among dose groups). CONCLUSIONS: Although CD4 cell count increases were seen in all 3 dose groups, higher scIL-2 doses resulted in greater CD4 cell count changes after 6 months, compared with control groups.

Therapy with atazanavir plus saquinavir in patients failing highly active antiretroviral therapy: a randomized comparative pilot trial.

OBJECTIVES: To assess the safety, efficacy of atazanavir (400 and 600 mg)/saquinavir (1200 mg) once daily versus ritonavir/saquinavir (400 mg/400 mg) twice daily with two nucleoside reverse transcriptase inhibitors (NRTIs) in highly active antiretroviral therapy failure. DESIGN AND METHODS: Randomized, multinational, 48-week, pilot trial with antiretroviral-experienced patients having at least 1000 HIV-1 RNA copies/ml, 100 x 106 CD4 cells/l (75 x 106 cells/l without AIDS diagnosis) and virological response to a prior regimen. Efficacy was evaluated by HIV-1 RNA and CD4 cell changes from baseline to 48 weeks. RESULTS: Comparable efficacy across groups at 48 weeks: mean HIV-1 RNA decreases, 1.44, 1.19 and 1.66 log(10) copies/ml (P = NS) and comparable virological response (> 1.0 log(10) decrease HIV-1 RNA or HIV-1 RNA < 400 copies/ml) was achieved in 41, 29 and 35% (P = NS); and mean CD4 cell increases, 109, 55 and 149 x 106 cells/l in atazanavir 400-mg, atazanavir 600-mg and ritonavir groups, respectively. There were fewer adverse event discontinuations in the atazanavir groups (9%, 11%) versus the ritonavir group (30%) and atazanavir lacked adverse effects on lipids. In the atazanavir 400-mg, atazanavir 600-mg and ritonavir groups the mean changes from baseline at 48 weeks in fasting low-density lipoprotein (LDL) cholesterol concentrations were -0.6, -6.7 and 23.2%, respectively and in fasting triglyceride concentrations they were -4.8, -27.1 and 93.0%, respectively (P < 0.05, LDL cholesterol; P < 0.001, fasting triglyceride; atazanavir/saquinavir versus ritonavir/saquinavir). CONCLUSIONS: In antiretroviral-experienced patients, once-daily atazanavir/saquinavir was safe and well tolerated, showing comparable efficacy to twice-daily ritonavir/saquinavir, both with two NRTIs. Small lipid changes from baseline with atazanavir/saquinavir were not clinically significant in comparison with the prompt, marked and sustained changes of a magnitude suggesting clinical relevance achieved in the ritonavir/saquinavir group.