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.

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.

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.

Imaging changes following surgery for ischiofemoral impingement.

Partial resection of the lesser trochanter (LT plasty) has been increasingly recommended to treat ischiofemoral impingement. However, there is a lack of studies on the imaging findings following LT plasty. The purpose of this study was to assess magnetic resonance imaging (MRI) changes on the lesser trochanter and surrounding musculotendinous structures following LT plasty to treat ischiofemoral impingement. Twenty-one patients (21 hips) were studied. The LT length and cross-sectional area of the iliopsoas muscle were measured on MRI before and after surgery. The MRIs were performed on average 11 months (range, 3 to 25 months) after surgery. The mean ± standard deviation amount of LT resected (difference between pre- and postoperative LT length) was 7.3 mm ± 2.5 mm. The iliopsoas cross-sectional area decreased after the LT plasty in 95% of the hips (20/21) by an average of 35% ± 16%. The reduction in iliopsoas size had no significant correlation with improvement on the modified Harris Hip Score at a mean follow-up of 17 months after surgery (r = -0.13, P = 0.58). The iliopsoas muscle size decreased on average 35% following endoscopic LT plasty. The decrease was not correlated with midterm functional outcomes.

Anterior Electronic Hip Pain Drawings Are Helpful for Diagnosis of Intra-articular Sources of Pain: Lateral or Posterior Drawings Are Unreliable.

Purpose: The purpose of this study was to determine the accuracy of electronic hip pain drawing to diagnose intra-articular source of pain in nonarthritic hips, defined by response to an intra-articular injection. Methods: A retrospective assessment was performed in consecutive patients who had an intra-articular injection completed within a 1-year period. Patients were classified as responders or nonresponders to intra-articular hip injection. A positive injection was defined as greater than 50% hip pain relief within 2 hours after injection. Electronic pain drawings collected before injection were then evaluated according to the hip region marked by the patients. Results: Eighty-three patients were studied after applying inclusion and exclusion criteria. Anterior hip pain on drawing had a sensitivity of 0.69, specificity of 0.68, positive predictive value (PPV) of 0.86, and negative predictive value (NPV) of 0.44 for intraarticular source of pain. Posterior hip pain on drawing had a sensitivity of 0.59, specificity of 0.23, PPV of 0.68, and NPV of 0.17 for intra-articular source of pain. Lateral hip pain on drawing had a sensitivity of 0.62, specificity of 0.50, PPV of 0.78, and NPV of 0.32 for intraarticular source of pain. Conclusion: Anterior hip pain on electronic drawing has a sensitivity of 0.69 and specificity of 0.68 for intra-articular source of pain in nonarthritic hips. Lateral and posterior hip pain on electronic pain drawings are not reliable to rule out intra-articular hip disease. Level of Evidence: Level III, case-control study.

Efficacy and safety of switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed Asian adults living with HIV: A pooled analysis from three international phase III randomized trials.

OBJECTIVES: Data on switching to bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) in virologically suppressed Asian people living with HIV are limited. We performed a pooled analysis of virologically suppressed Asian participants from three international phase III trials to evaluate the efficacy and safety of switching to B/F/TAF. METHODS: Virologically suppressed people living with HIV were randomized to switch to B/F/TAF or to stay on baseline regimens. The primary endpoint was the proportion of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48. We analysed the incidence of adverse events (AEs), laboratory abnormalities, and changes in relevant tolerability parameters through 48 weeks. RESULTS: Overall, 136 Asian participants were included. The proportions of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48 were low in both arms (0% for B/F/TAF vs 1.4% for those who stayed on baseline regimens). Those who switched to B/F/TAF had virological suppression rates similar to those who stayed on baseline regimens (100% vs 95.9%, p = 0.2485), with no treatment-emergent resistance. Drug-related AEs occurred in three participants in each arm; none were serious. No participants discontinued the study drug because of AEs, and no deaths were observed. No significant differences were observed between the arms in the median changes in estimated glomerular filtration rate, body weight, and most lipid parameters. Switching from tenofovir disoproxil fumarate-containing regimens to B/F/TAF resulted in a significant decrease in tubular proteinuria compared with those who stayed on baseline regimens (p < 0.01). CONCLUSIONS: Virologically suppressed Asian people living with HIV who switched to B/F/TAF maintained 100% virological suppression at week 48, with no treatment-emergent drug resistance and safety profiles comparable to those seen in people who stayed on baseline regimens. CLINICAL TRIAL NUMBER: ClinicalTrials.gov (NCT02603120, NCT02652624, and NCT02603107).

Bictegravir/emtricitabine/tenofovir alafenamide in older individuals with HIV: Results of a 96-week, phase 3b, open-label, switch trial in virologically suppressed people ≥65 years of age.

OBJECTIVES: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is an effective treatment for HIV-1 infection; however, clinical trial data in older people living with HIV (PLWH) are lacking. The primary 24-week and secondary 48-week analyses of study GS-US-380-4449 (NCT03405935), which assessed the efficacy and safety of switching to B/F/TAF in older PLWH, have been published. Here we report the results of the final 96-week analyses from the study. METHODS: In this 96-week, phase 3b, open-label, single-arm trial, virologically suppressed PLWH aged ≥65 years switched from elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen to B/F/TAF. Viral suppression, resistance, immune response, safety, tolerability and adherence were evaluated through week 96. RESULTS: Of 90 participants screened, 86 were enrolled and switched to B/F/TAF. No participants had HIV-1 RNA ≥50 copies/ml (by FDA Snapshot algorithm) at weeks 72 or 96; virologic suppression rates were 94.2% (81/86; 95% CI 87.0-98.1) and 74.4% (64/86; 95% CI 63.9-83.2), respectively. No treatment-emergent resistance was observed, and CD4 counts remained stable. There were no study drug-related serious adverse events. Three participants experienced drug-related treatment-emergent adverse events that led to premature drug discontinuation. There were no clinically relevant changes from baseline to week 96 in fasting lipid parameters, and the median change in body weight at week 96 was 0.0 kg (IQR -2.3, 2.0). Median self-reported adherence was 100% (IQR 100-100%). CONCLUSIONS: Switching to B/F/TAF is an effective long-term option for virologically suppressed adults ≥65 years of age, with favourable safety and tolerability profiles in this population.

Hip physical examination extension loss and radiographic osseous findings in patients with low back pain and nonarthritic hips.

The association between hip and spine abnormalities is frequent, and limitation in hip extension has been linked with low back pain. The purpose of this study was to assess the radiographic osseous findings in nonarthritic hips of patients with hip pain, low back pain, and limited hip extension. Ninety patients (92 hips) were included in this study. Hip extension was tested in the contralateral decubitus position with the hip in neutral abduction/adduction and neutral rotation. In sequence, hip extension was tested by adding passive abduction, followed by internal/external rotation of the hip. A hip extension limitation was defined as less than zero degrees of extension. Imaging studies were assessed for the following osseous morphologies: decreased ischiofemoral space (≤17 mm), increased femoral torsion (≥30°), decreased femoral torsion (≤5°), and posterior acetabular overcoverage. Fifty-seven out of 92 hips (62%) had at least one osseous imaging finding for limitation in hip extension: decreased ischiofemoral space (38/92, 41%), increased femoral torsion (5/92, 5%), decreased femoral torsion (24/92, 26%), and posterior acetabular overcoverage (21/92, 23%). Decreased ischiofemoral space, femoral torsional abnormalities, and/or posterior acetabular wall overcoverage are observed in imaging studies of most individuals with limitation of hip extension and low back pain.

High efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide in people with suppressed HIV and preexisting M184V/I.

OBJECTIVE: We investigated the prevalence of preexisting M184V/I and associated risk factors among clinical trial participants with suppressed HIV and evaluated the impact of M184V/I on virologic response after switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). DESIGN: Participant data were pooled from six clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed people with HIV. METHODS: Preexisting drug resistance was assessed by historical genotypes and/or baseline proviral DNA genotyping. Virologic outcomes were determined by last available on-treatment HIV-1 RNA. Stepwise selection identified potential risk factors for M184V/I in a multivariate logistic regression model. RESULTS: Altogether, 2034 participants switched treatment regimens to B/F/TAF and had follow-up HIV-1 RNA data, and 1825 of these participants had baseline genotypic data available. Preexisting M184V/I was identified in 182 (10%), mostly by baseline proviral DNA genotype ( n  = 167). Most substitutions were M184V ( n  = 161) or M184V/I mixtures ( n  = 10). Other resistance substitutions were often detected in addition to M184V/I ( n  = 147). At last on-treatment visit, 98% (179/182) with preexisting M184V/I and 99% (2012/2034) of all B/F/TAF-treated participants had HIV-1 RNA less than 50 copies/ml, with no treatment-emergent resistance to B/F/TAF. Among adult participants, factors associated with preexisting M184V/I included other resistance, black race, Hispanic/Latinx ethnicity, lower baseline CD4 + cell count, advanced HIV disease, longer duration of antiretroviral therapy, and greater number of prior third agents. CONCLUSION: M184V/I was detected in 10% of virologically suppressed clinical trial participants at study baseline. Switching to B/F/TAF demonstrated durable efficacy in maintaining viral suppression, including in those with preexisting M184V/I.

Preemptive analgesia in hip arthroscopy: intra-articular bupivacaine does not improve pain control after preoperative peri-acetabular blockade.

INTRODUCTION: Literature addressing postoperative pain management after hip arthroscopy is relatively scarce. This study aimed to assess if there was added analgesic benefit associated with postoperative intra-articular bupivacaine blockade for patients who received preoperative peri-acetabular blockade for hip arthroscopy procedures. METHODS: 52 patients were included in this comparative cohort study. Group 1 consisted of 20 patients who received preoperative peri-acetabular blockade and postoperative intra-articular blockade. The control group (Group 2), consisted of 32 patients who received only preoperative peri-acetabular blockade. Postoperative pain was recorded via visual analogue scale (VAS) pain scores, analgesic consumption, and pain diaries for 2 weeks postoperatively. RESULTS: Postoperative VAS pain scores were significantly lower in the experimental group at the 30-minute recovery room assessment (VAS scores Group 1: 1.1; Group 2: 3.00, p = 0.034). Other than the 30-minute recovery room assessment, VAS pain scores, narcotic medication consumption, and non-narcotic analgesic consumption did not differ between the 2 groups at any time point in the study period. CONCLUSIONS: This study did not demonstrate significant clinical benefit for patients who receive postoperative intra-articular blockade in addition to preoperative peri-acetabular blockade with bupivacaine 0.5%. We recommend the use of preoperative peri-acetabular bupivacaine blockade without intra-articular blockade postoperatively for pain control in the setting of hip arthroscopy surgery.

Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials.

BACKGROUND: Preexisting drug resistance limits the utility of HIV antiretroviral therapy. Studies have demonstrated safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), including in patients with M184V/I substitutions. SETTING: We investigated virologic outcomes through 48 weeks of B/F/TAF treatment in individuals with preexisting primary integrase strand transfer inhibitor resistance (INSTI-R). METHODS: Preexisting INSTI-R was retrospectively evaluated from 7 B/F/TAF studies. INSTI-R was assessed by historical genotypes and/or baseline RNA or DNA sequencing. Viral loads were measured at all visits. RESULTS: Preexisting primary INSTI-R substitutions were detected in 20 of the 1907 participants (1.0%). The 20 participants were predominantly male (75%), were Black (65%), had HIV-1 subtype B (85%), and had baseline median CD4 counts of 594 cells/mm3 and median age of 52 years. Most of the participants (n = 19) were virologically suppressed at baseline and had one primary INSTI-R substitution, E92G, Y143C/H, S147G, Q148H/K/R, N155S, or R263K, +/-secondary substitutions. All suppressed participants maintained virologic suppression throughout 48 weeks without any viral blips. One treatment-naive participant had virus with Q148H+G140S that was fully sensitive to bictegravir but only partially to dolutegravir (phenotype <2.5-fold change and >4-fold change, respectively). With a baseline viral load of 30,000 copies/mL, this participant was virologically suppressed by week 4 and maintained <50 copies/mL through week 48. CONCLUSIONS: This small cohort with primary INSTI-R achieved and/or maintained virologic suppression through 48 weeks of B/F/TAF treatment. Consistent with the potent in vitro activity of bictegravir against most INSTI-R patterns, B/F/TAF may be a potential treatment option for patients with select preexisting INSTI-R, if confirmed by further studies.

Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study.

BACKGROUND: With the highest rates of HIV/AIDS in the United States, Black Americans are still underrepresented in HIV medical research. SETTING: BRAAVE (NCT03631732) is a randomized, phase 3b, multicenter, open-label US study. METHODS: Adults identifying as Black or African American and virologically suppressed on 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus third agent were randomized (2:1) to switch to open-label bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) once daily or stay on baseline regimen (SBR) for 24 weeks, after which SBR had delayed switch to B/F/TAF. Resistance to non-NRTIs, protease inhibitors, and/or NRTIs was permitted; integrase strand transfer inhibitor resistance was exclusionary. Primary endpoint was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 24 (snapshot algorithm; noninferiority margin of 6%). RESULTS: Of 558 screened, 495 were randomized/treated (B/F/TAF n = 330; SBR n = 165). Overall, 32% were ciswomen, 2% transwomen, and 10% had an M184V/I mutation. At week 24, 0.6% on B/F/TAF vs 1.8% on SBR had HIV-1 RNA ≥50 copies/mL (difference -1.2%; 95% confidence interval -4.8% to 0.9%), demonstrating noninferiority of B/F/TAF vs SBR. Proportions with HIV-1 RNA <50 copies/mL at week 24 were 96% B/F/TAF and 95% SBR and remained high at week 48. No participant had treatment-emergent resistance to study drug. Treatments were well tolerated. Study drug-related adverse events, mostly grade 1, occurred in 10% of participants on B/F/TAF through week 48 and led to discontinuation in 9 participants through week 48. CONCLUSIONS: For Black Americans with HIV, switching to B/F/TAF was noninferior to continuing a variety of regimens, including those with pre-existing NRTI mutations.

Usefulness of magnetic resonance imaging to diagnose greater trochanteric-ischial impingement.

Extra-articular impingement between the femur and ischium is increasingly recognized as a cause of hip pain. The purpose of this study was to assess the diagnostic parameters for greater trochanteric-ischial impingement (GTI) in magnetic resonance imaging (MRI) studies. Seven patients (seven hips) diagnosed with GTI were retrospectively identified. For each of these seven patients, three controls were matched by gender, height, and weight to create a control group of 21 asymptomatic hips. The same technique and positioning were utilized to acquire the MRIs in the GTI and control groups. The MRI was performed with the lower limbs in a functional position reproducing the midstance phase of the gait cycle. The greater trochanteric-ischial distance was measured in the axial cut showing the shortest distance between the greater trochanter and the ischial tuberosity. The mean greater trochanteric-ischial distance was 26.2 mm in the GTI group and 33.8 mm in the control group (P < 0.01). Greater trochanteric-ischial distance ≤28 mm had a sensitivity of 86% and specificity of 86% in identifying GTI. In conclusion, utilizing MRI with functional positioning of the lower limbs, greater trochanter-ischial distance ≤28 mm is helpful to diagnose GTI in women.

Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, phase 2/3 trial.

BACKGROUND: Bictegravir is a potent integrase strand-transfer inhibitor (INSTI) with a high genetic barrier to resistance. Bictegravir, coformulated with emtricitabine and tenofovir alafenamide, is recommended by key European and US HIV treatment guidelines as the preferred single-tablet regimen for adults and adolescents. The aim of this study was to assess the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents with HIV. METHODS: In this single-arm, open-label trial, we enrolled virologically suppressed children and adolescents (aged 6 to <18 years) with HIV at 22 hospital clinics in South Africa, Thailand, Uganda, and the USA. Eligible participants had a bodyweight of at least 25 kg, were virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ART regimen for at least 6 months before screening, had a CD4 count of at least 200 cells per µL, and an estimated glomerular filtration rate of at least 90 mL/min per 1·73 m2 by the Schwartz formula at screening. All participants received the fixed-dose regimen of coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily. Pharmacokinetic analysis was used for dosing confirmation, and results compared with adult values. The primary outcomes were area under the curve at the end of the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) of bictegravir, and incidence of treatment-emergent adverse events and laboratory abnormalities at week 24. Efficacy and safety analyses included all participants who received at least one dose of study drug. We report the 48-week results. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Between Sept 29, 2016 and Feb 16, 2018, we enrolled 102 participants. 100 participants received bictegravir, emtricitabine, and tenofovir alafenamide (cohort 1 [adolescents aged 12 to <18 years], n=50; cohort 2 [children aged 6 to <12 years], n=50). The mean bictegravir AUCtau was 89 100 ng × h/mL (coefficient of variation 31·0%) in adolescents (cohort 1) and 128 000 ng × h/mL (27·8%) in children (cohort 2). Compared with adults, bictegravir Ctau was 35% lower in adolescents and 11% lower in children. The 90% CIs of both parameters were within the predefined pharmacokinetic equivalence boundary and within overall range of exposures observed in adults and deemed to be safe and efficacious (geometric least-squares mean ratio [GLSM] 86·3% [90% CI 80·0-93·0] for AUCtau and 65·4% [58·3-73·3] for Ctau in adolescents; GLSM 125% [90% CI 117-134] for AUCtau and 88·9% [80·6-98·0] for Ctau for children). Bictegravir, emtricitabine, and tenofovir alafenamide was well tolerated; most adverse events were grade 2 or less in severity and no study drug-related serious adverse events were reported. One participant discontinued study drug due to adverse events (grade 2 insomnia and anxiety). Virological suppression (HIV-1 RNA <50 copies per mL) was maintained by all 100 participants at week 24 and by 98 (98%) of 100 at week 48; no participants had treatment-emergent resistance. INTERPRETATION: In adolescents and children with HIV, the bictegravir, emtricitabine, and tenofovir alafenamide single-tablet regimen was well tolerated and maintained virological suppression. Our data support the treatment of HIV in adolescents and children with this single-tablet regimen. At present, the single-tablet regimen is recommended as first-line treatment in the USA for adolescents and as an alternative regimen in children and has the potential to represent an important regimen in the paediatric population. FUNDING: Gilead Sciences.

Iliopsoas Muscle/Tendon Proportions at Three Levels of Described Arthroscopic Tenotomy: An Anatomic Study in Fresh Cadaveric Specimens.

PURPOSE: To calculate the iliopsoas muscle/tendon ratio at 3 levels of arthroscopic iliopsoas tenotomy sites in fresh cadaveric specimens. METHODS: An anatomic study design was performed using 16 iliopsoas musculotendinous units from the level of the hip joint to their insertion on the lesser trochanter. All specimens came from 16 fresh cadaveric specimens (10 male, 6 female), with a median age of 41 years (range 31-55.25 years). Circumferential measurements of the composite musculotendinous unit and the iliopsoas tendon were then made at the lesser trochanter insertion, the site of transcapsular tenotomy, and the site of tenotomy at the level of the labrum. Anatomical variance of the iliopsoas tendon at the insertion on the lesser trochanter and muscular extension below the lesser trochanter level also were described. The difference between the median circumference of the iliopsoas musculotendinous units or the isolated tendons at the 3 levels was calculated. RESULTS: The median circumference of the iliopsoas musculotendinous unit at the level of the labrum, orbicularis zone (transcapsular tenotomy site), and the lesser trochanter was 140.9 mm (range 137.9-148.9), 136.7 mm (range 132.9-140), and 99.5 mm (range 96.5-104.8), respectively. The median circumference of the iliopsoas tendon at these same levels was 25.6 mm (range 22.7-33.7), 28.9 mm (range 25.1-32.2), and 30.9 mm (range 27.9-36.1), respectively. Accordingly, the proportions of the iliopsoas muscle/tendon at the level of the labrum, the transcapsular tenotomy site, and the lesser trochanter insertion were 18% tendon/82% muscle, 21% tendon/79% muscle, and 31% tendon/69% muscle, respectively. CONCLUSIONS: The proportions of the iliopsoas muscle/tendon at the level of the labrum, the transcapsular tenotomy site and the lesser trochanter insertion were 18% tendon/82% muscle, 21% tendon/79% muscle, and 31% tendon/69% muscle, respectively. The distal muscular projection below the tendinous insertion on the lesser trochanter may maintain the functional connection of the iliopsoas between origin and insertion even after releasing the tendon. CLINICAL RELEVANCE: This finding may have implications for a new understanding of arthroscopic tenotomy of the iliopsoas around the hip, as previously described muscle/tendon proportions were not calculated in fresh cadavers.

Weight Change Following Antiretroviral Therapy Switch in People With Viral Suppression: Pooled Data from Randomized Clinical Trials.

BACKGROUND: We sought to identify factors associated with weight gain in randomized clinical trials of antiretroviral therapy (ART) switch. METHODS: We explored the effects of demographic factors, clinical characteristics, and ART on weight gain in a pooled analysis of 12 prospective clinical trials, wherein virologically suppressed people living with human immunodeficiency virus (PWH) were randomized to switch or remain on a stable baseline regimen (SBR). RESULTS: Both PWH randomized to switch ART (n = 4166) and those remaining on SBR (n = 3150) gained weight. Median weight gain was greater in those who switched (1.6 kg, interquartile range [IQR], -.05 to 4.0 vs 0.4 kg, [IQR], -1.8 to 2.4 at 48 weeks, P < .0001), with most weight gain occurring in the first 24 weeks after switch. Among baseline demographic and clinical characteristics, only younger age and lower baseline body mass index were associated with any or ≥10% weight gain. By week 48, 4.6% gained ≥10% weight (6.4% of switch and 2.2% of SBR), the greatest risk was with switch from efavirenz (EFV) to rilpivirine (RPV) or elvitegravir/cobicistat and switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). Switch from abacavir to TAF was associated with less weight gain than switch from TDF to TAF and was not associated with increased risk for ≥10% weight gain. CONCLUSIONS: Moderate weight gain after ART switch was common and usually plateaued by 48 weeks. Baseline ART was a predictor of post-switch weight gain; participants who switched off of EFV and TDF had the greatest weight gain. The biological mechanisms that underlie the differential effects of switching ART agents on weight and associated clinical implications require further study.

Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naive participants.

OBJECTIVES: Two Phase 3, randomized, double-blind, active-controlled studies of initial HIV-1 treatment demonstrated that bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) was non-inferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC; Study 1489) or to DTG+F/TAF (Study 1490) through 144 weeks. In both studies, there was no emergent resistance to study drugs. Here, the 3 year resistance analysis and impact of baseline resistance substitutions on treatment response are described. METHODS: Population sequencing of HIV-1 protease and reverse transcriptase (RT) was performed at screening. Retrospective baseline next generation sequencing of protease, RT and integrase (IN) was analysed at a ≥ 15% cutoff. Resistance analyses were performed on participants with confirmed viral rebound of HIV-1 RNA ≥200 copies/mL through Week 144 or last visit who did not resuppress to <50 copies/mL while on study drug. RESULTS: Transmitted primary drug resistance substitutions were present in the following proportions of participants: integrase strand transfer inhibitor (INSTI) resistance (-R) in 1.3% (17/1270) of participants; NRTI-R in 2.7% (35/1274); NNRTI-R in 14.1% (179/1274); and PI-R in 3.5% (44/1274). These pre-existing resistance substitutions not associated with study drug did not affect treatment outcomes. One participant in the B/F/TAF group had pre-existing bictegravir and dolutegravir resistance substitutions (Q148H+G140S in integrase) at baseline and suppressed and maintained HIV-1 RNA <50 copies/mL through Week 144. In total, 21 participants qualified for resistance testing [1.3% (8/634) B/F/TAF; 1.9% (6/315) DTG/ABC/3TC; 2.2% (7/325) DTG+F/TAF]; none had emergent resistance to study drugs. CONCLUSIONS: Treatment with B/F/TAF, DTG/ABC/3TC, or DTG+F/TAF achieved high, durable rates of virological suppression in HIV-1 treatment-naive participants. The presence of pre-existing resistance substitutions did not affect treatment outcomes, and there was no treatment-emergent resistance.

Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People with HIV Aged ≥ 65 Years: Week 48 Results of a Phase 3b, Open-Label Trial.

INTRODUCTION: We report the 48-week results of an ongoing study to assess the efficacy and safety of switching older people with HIV to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). METHODS: This was a 96-week, phase 3b, open-label, single-arm study (GS-US-380-4449; NCT03405935). Virologically suppressed individuals aged ≥ 65 years receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen were switched to B/F/TAF. Primary endpoint was the percentage of participants with HIV-1 RNA < 50 copies/ml at week 24. RESULTS: Eighty-six participants (median age 69 [range 65-80] years; 87% male; 95% white) were enrolled and treated in five European countries. Rates of virologic suppression were 97.7% at week 24 and 90.7% at week 48; none had HIV-1 RNA ≥ 50 copies/ml, and 100% had virologic suppression by missing = excluded analysis at both time points. No treatment-emergent resistance was observed. There were no grade 3-4 study drug-related adverse events (AEs) or study drug-related serious AEs or deaths. Three AEs led to premature discontinuation; one (moderate abdominal discomfort) was attributed to the study drug by the investigator. At week 48, median changes from baseline in weight and estimated glomerular filtration rate were + 0.1 kg (interquartile range [IQR] - 1.0, 2.3) and - 6.0 ml/min (IQR - 10.2, 0.0), respectively. There were no clinically relevant changes from baseline to week 48 in fasting lipid parameters. Treatment satisfaction improved, and health-related quality of life was maintained from baseline through week 48. Median adherence to the study drug was 98.6% (IQR 96.0, 100). CONCLUSIONS: Switching to B/F/TAF was effective and well tolerated through 48 weeks in virologically suppressed adults aged ≥ 65 years. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03405935.

Low Back Pain Improves After Surgery for Lesser Trochanteric-Ischial Impingement.

PURPOSE: To assess the effects of surgery for lesser trochanteric-ischial impingement (LTI) on low back pain. METHODS: The records of patients with LTI who underwent endoscopic partial resection of the lesser trochanter (LT) between May of 2017 and February of 2019 were reviewed. Inclusion criteria were the presence of low back pain in association with hip pain, diagnosis of LTI, and partial resection of the LT to treat LTI. Exclusion criteria were less than 12 months of postoperative follow-up and hip or spine surgery after the LTI surgery. Patients were assessed before surgery and at the most recent follow-up with the modified Harris Hip Score and Oswestry Disability Index for lumbar spine. RESULTS: Thirty patients (31 hips) met the inclusion criteria. Four patients were lost to follow-up. Two patients with borderline dysplasia and grade 1 and 2 osteoarthritis underwent total hip arthroplasty after the partial resection of the LT. The results are presented considering the remaining 24 patients (25 hips). The average age at surgery was 51 years (range 32-65 years). The mean follow-up after the surgery for LTI was 19 months (range 12-35 months). The mean ± SD ODI improved from 48% ± 15 before the LTI surgery to 21% ± 22 (P < .001) at the most recent follow-up. Improvement in the Oswestry Disability Index above the minimal clinical important difference was observed in 16 patients (67%) following the LTI surgery. The mean ± SD modified Harris Hip Score improved from 55.8 ± 14 before LTI surgery to 81.3 ± 14.3 (P < .001). CONCLUSIONS: Decrease in low back pain above the minimal clinically important difference is observed in 2 of 3 patients after partial resection of the LT. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Femoral Derotation Osteotomy Improves Hip and Spine Function in Patients With Increased or Decreased Femoral Torsion.

PURPOSE: To evaluate the outcomes of proximal femoral derotation osteotomy (PFDO) on the hip and spine function of patients with abnormal femoral torsion. METHODS: This retrospective study included patients who underwent PFDO to treat increased or decreased femoral torsion between July 2014 and February 2019. The exclusion criteria were: previous fracture, fixation of slipped capital femoral epiphysis or osteotomy in the ipsilateral femur; PFDO associated to varus or valgus osteotomy; Tönnis grade 2 or 3 osteoarthritis; and PFDO performed to treat knee abnormalities. Hip function was assessed through the modified Harris Hip Score (mHHS). A subgroup of consecutive patients with low back pain before the PFDO and operated after 2017 had the spine function assessed through the Oswestry disability index (ODI). RESULTS: A total of 37 hips (34 patients) were studied: 15 hips with increased femoral torsion and 22 with decreased femoral torsion. Eight patients were male and 26 were female. The average age at PFDO was 33 years (range, 15-54 years). At a mean follow-up of 24 months (range, 12-65 months), the mean mHHS improved from 58.1 ± 14.3 before PFDO to 82 ± 15.6 at the most recent follow-up (P < .001). Improvement in the mHHS above the minimum clinically important difference (MCID) was observed in 33 hips (89%). In the subgroup of 14 consecutive patients with ODI available, the ODI improved from a mean of 45% ± 16% before the PFDO to 22% ± 17% at the most recent follow-up (P = .001). Nine (64.3%) of the 14 patients presented improvement in the ODI above the MCID. Revision procedure with a larger intramedullary nail was necessary in 2 hips to treat nonunion. CONCLUSION: Proximal femoral derotation osteotomy improves the hip and spine function in patients with increased or decreased femoral torsion and nonarthritic hips. LEVEL OF EVIDENCE: Level IV, therapeutic case series.