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In the age of progressive antimicrobial resistance and increased difficulty combating infections in immunocompromised hosts, there has been renewed interest in the use of nontraditional therapeutics for infections. Herein, we review the use of investigational non‐pharmaceutical anti‐infective agents targeting fungal, bacterial, and viral infections in patients with hematologic malignancies, focusing on those receiving hematopoietic cell transplantation or cellular therapies. We discuss immune checkpoint inhibitors, granulocyte transfusions, bone marrow colony‐stimulating factors, bacteriophages, fecal microbiota transplantation, and virus specific T‐cell therapy. Although there is promising early experience with many of these treatments, further studies will be required to define their optimal role in the therapeutic armamentarium against infections in immunocompromised hosts. [ABSTRACT FROM AUTHOR]

Studies describing invasive fungal infections (IFIs) after chimeric antigen receptor-modified T-cell (CAR-T-cell) therapy are limited. Although post-CAR-T-cell IFIs appear to be uncommon, they are associated with significant morbidity and mortality. Specific risk factors for IFIs in CAR-T-cell recipients have not been fully characterized and are often extrapolated from variables contributing to IFIs in patients with other hematologic malignancies or those undergoing hematopoietic cell transplant. Optimal prophylaxis strategies, including the use of yeast versus mold-active azoles, also remain ill-defined. Further research should investigate key risk factors for IFIs and establish an evidence-based approach to antifungal prophylaxis in these patients in order to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives. To report demographics, regional variations, and indications for preexposure prophylaxis (PrEP) use for HIV prevention in the Veterans Health Administration (VHA). Methods. We identified persons initiating tenofovir/emtricitabine for the PrEP indication in the United States between July 2012 and April 2016 in a VHA national database. We stratified PrEP use by provider type and VHA region. We calculated PrEP initiation rate for each region with VHA population data. Results. Of the 825 persons who initiated PrEP during the observation period, 67% were White and 76% were men who have sex with men. People who inject drugs and transgender persons represented less than 1% each of the cohort. The majority of PrEP initiations were clustered in 3 states, leading with California (28%) followed by Florida (9%) and Texas (8%).The Southeast had one of the lowest PrEP rates at 10 PrEP initiations per 100 000 persons in care. Infectious disease specialists issued more than two thirds of index PrEP prescriptions. Conclusions. Uptake of PrEP in the VHA is uneven along geographic and risk categories. Understanding the reasons behind these gaps will be key in expanding the use of this important prevention tool. [ABSTRACT FROM AUTHOR]

Background. The COBAS AMPLICOR HIV-1 MONITOR Test, version 1.5 (Amplicor) has been replaced with the COBAS AmpliPrep/ COBAS TaqMan HIV-1 Test, version 2.0 (TaqMan 2.0), a real-time polymerase chain reaction human immunodeficiency virus type 1 (HIV-1) assay with higher sensitivity and broader dynamic range. HIV-1 RNA values at the 50 copies/mL cutoff drive major patient management decisions and clinical study outcomes. Methods. A total of 2217 samples were collected from 1922 HIV-1-infected subjects taking antiretroviral therapy for at least 48 weeks and had at least 2 consecutive samples with HIV-1 RNA <50 copies/mL by Amplicor from 7 recent clinical trials. HIV-1 RNA results were obtained from the Amplicor and TaqMan 2.0 assays in parallel by a reference laboratory. Results. The overall concordance between assay results was 96% at the cutoff of 50 copies/mL. However, statistically significant discordance at the 50 copies/mL cutoff was found between the assays for 3.9% of samples (n = 87). By TaqMan 2.0, virologic failure defined as HIV-1 RNA ≥50 copies/mL was reported for 2.8% more samples than Amplicor. Of these 87 samples, 68 samples fell within the predicted range of assay variability. Retesting of HIV-1 RNA by TaqMan 2.0 confirmed the discordance in only 28 of the 87 samples. Conclusions. The TaqMan 2.0 assay reports fewer subjects below the clinical endpoint of HIV-1 RNA <50 copies/mL in HIV clinical trials than the Amplicor assay. This difference must be considered when assessing disease progression, designing clinical trials, and comparisons with historical trials that used the Amplicor assay. [ABSTRACT FROM AUTHOR]

Background: Cases of HIV, while infrequent, have been reported during tenofovir disoproxil fumarate/emtricitabine use as preexposure prophylaxis (PrEP). We describe the incidence of HIV and patterns of PrEP use within the Veterans Health Administration (VHA). Methods: We conducted a retrospective cohort study among persons initiating PrEP in the VHA between July 2012 and April 2016 using national VHA data. We defined time on PrEP and time at risk of HIV exposure as the total time from the first PrEP fill to exhaustion of supply of the final PrEP prescription. We identified incident cases of HIV infection after PrEP initiation based on laboratory data. Medication adherence measures and days without pills were calculated using pharmacy fill data. We used a chart review to determine patient-reported PrEP use around the time of diagnosis. Results: We identified 825 unique patients initiating PrEP; they were 97% men and 67% white, with a mean age of 41 years. Six HIV infections were observed during the study period, yielding an HIV incidence of 0.8 (Poisson exact 95% confidence interval: 0.3 to 1.8) cases per 100 person-years. Two cases occurred during active PrEP use by self-report and perfect adherence based on fill data. Both were infected with viruses containing the M184V mutation. Four additional cases were diagnosed after self-reported discontinuation. Conclusions: HIV infection was rare in a nationwide cohort of PrEP users. Although most of the infections occurred during inconsistent PrEP use, infections during periods of high measured adherence were also observed. These findings highlight the importance of PrEP persistence during periods of risk. [ABSTRACT FROM AUTHOR]

Bacteria of Bacillus species sporulate upon starvation, and the resultant dormant spores germinate when the environment appears likely to allow the resumption of vegetative growth. Normally, the rates of germination of individual spores in populations are very heterogeneous, and the current work has investigated whether spore-to-spore communication enhances the synchronicity of germination. In order to do this work, time-lapse optical images of thousands of individual spores were captured during germination, and an image analysis algorithm was developed to do the following: (i) measure the positions and germination rates of many thousands of individual spores and (ii) compute pairwise correlations of their germination. This analysis showed that an individual spore's germination rate was dependent on its distance from other spores, especially at short distances. Thus, spores that were within a few micrometers exhibited an increased synchronicity in germination, suggesting that there is a mechanism for short-range communication between such spores during germination. However, two molecules known to be germinants that are released during germination, L-alanine and the 1:1 chelate of Ca2+ and dipicolinic acid, did not mediate spore-to-spore communication during germination. [ABSTRACT FROM AUTHOR]

The simultaneous nutrient germination of hundreds of individual wild-type spores of three Bacillus species and a number of Bacillus subtilis strains has been measured by two new methods, and rates of release of the great majority of the large pool of dipicolinic acid (DPA) from individual spores of B. subtilis strains has been measured by Raman spectroscopy with laser tweezers. The results from these analyses and published data have allowed a number of significant conclusions about the germination of spores of Bacillus species as follows. (i) The time needed for release of the great majority of a Bacillus spore's DPA once rapid DPA release had begun (Δ Trelease) during nutrient germination was independent of the concentration of nutrient germinant used, the level of the germinant receptors (GRs) that recognize nutrient germinants used and heat activation prior to germination. Values for Δ Trelease were generally 0.5 to 3 min at 25 to 37°C for individual wild-type spores. (ii) Despite the conclusion above, germination of individual spores in populations was very heterogeneous, with some spores in wild-type populations completing germination ≥ 15-fold slower than others. (iii) The major factor in the heterogeneity in germination of individual spores in populations was the highly variable lag time, Tlag, between mixing spores with nutrient germinants and the beginning of Δ Trelease. (iv) A number of factors decrease spores' Tlag values including heat activation, increased levels of GRs/spore, and higher levels of nutrient germinants. These latter factors appear to affect the level of activated GRs/spore during nutrient germination. (v) The conclusions above lead to the simple prediction that a major factor causing heterogeneity in Bacillus spore germination is the number of functional GRs in individual spores, a number that presumably varies significantly between spores in populations. [ABSTRACT FROM AUTHOR]

Background: Alagille syndrome is a rare genetic disease that often presents with severe cholestasis and pruritus. There are no approved drugs for management. Maralixibat, an apical, sodium-dependent, bile acid transport inhibitor, prevents enterohepatic bile acid recirculation. We evaluated the safety and efficacy of maralixibat for children with cholestasis in Alagille syndrome.Methods: ICONIC was a placebo-controlled, randomised withdrawal period (RWD), phase 2b study with open-label extension in children (aged 1-18 years) with Alagille syndrome (NCT02160782). Eligible participants had more than three times the normal serum bile acid (sBA) levels and intractable pruritus. After 18 weeks of maralixibat 380 μg/kg once per day, participants were randomly assigned (1:1) to continue maralixibat or receive placebo for 4 weeks. Subsequently, all participants received open-label maralixibat until week 48. During the long-term extension (204 weeks reported), doses were increased up to 380 μg/kg twice per day. The primary endpoint was the mean sBA change during the RWD in participants with at least 50% sBA reduction by week 18. Cholestastic pruritus was assessed using observer-rated, patient-rated, and clinician-rated 0-4 scales. The safety population was defined as all participants who had received at least one dose of maralixibat. This trial was registered with ClinicalTrials.gov, NCT02160782, and is closed to recruitment.Findings: Between Oct 28, 2014, and Aug 14, 2015, 31 participants (mean age 5·4 years [SD 4·25]) were enrolled and 28 analysed at week 48. Of the 29 participants who entered the randomised drug withdrawal period, ten (34%) were female and 19 (66%) were male. In the RWD, participants switched to placebo had significant increases in sBA (94 μmol/L, 95% CI 23 to 164) and pruritus (1·7 points, 95% CI 1·2 to 2·2), whereas participants who continued maralixibat maintained treatment effect. This study met the primary endpoint (least square mean difference -117 μmol/L, 95% CI -232 to -2). From baseline to week 48, sBA (-96 μmol/L, -162 to -31) and pruritus (-1·6 pts, -2·1 to -1·1) improved. In participants who continued to week 204 (n=15) all improvements were maintained. Maralixibat was generally safe and well tolerated throughout. The most frequent adverse events were gastrointestinal related. Most adverse events were self-limiting in nature and mild-to-moderate in severity.Interpretation: In children with Alagille syndrome, maralixibat is, to our knowledge, the first agent to show durable and clinically meaningful improvements in cholestasis. Maralixibat might represent a new treatment paradigm for chronic cholestasis in Alagille syndrome.Funding: Mirum Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: Integrase strand transfer inhibitors (INSTIs) coadministered with two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) are recommended as first-line treatment for HIV, and coformulated fixed-dose combinations are preferred to facilitate adherence. We report 48-week results from a study comparing initial HIV-1 treatment with bictegravir-a novel INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug interactions-coformulated with the NRTI combination emtricitabine and tenofovir alafenamide as a fixed-dose combination to dolutegravir administered with coformulated emtricitabine and tenofovir alafenamide.Methods: In this randomised, double-blind, multicentre, placebo-controlled, non-inferiority trial, HIV-infected adults were screened and enrolled at 126 outpatient centres in 10 countries in Australia, Europe, Latin America, and North America. Participants were previously untreated adults (HIV-1 RNA ≥500 copies per mL) with estimated glomerular filtration rate of at least 30 mL/min. Chronic hepatitis B virus or hepatitis C co-infection was allowed. We randomly assigned participants (1:1) to receive oral fixed-dose combination bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg or dolutegravir 50 mg with coformulated emtricitabine 200 mg and tenofovir alafenamide 25 mg, with matching placebo, once a day for 144 weeks. Investigators, participants, study staff, and those assessing outcomes were masked to treatment group. All participants who received at least one dose of study drug were included in primary efficacy and safety analyses. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of less than 50 copies per mL at week 48 (US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of -12%. This study is registered with ClinicalTrials.gov, number NCT02607956.Findings: Between Nov 11, 2015, and July 15, 2016, 742 participants were screened for eligibility, of whom 657 were randomly assigned to treatment (327 with bictegravir, emtricitabine, and tenofovir alafenamide fixed-dose combination [bictegravir group] and 330 with dolutegravir plus emtricitabine and tenofovir alafenamide [dolutegravir group]). 320 participants who received the bictegravir regimen and 325 participants who received the dolutegravir regimen were included in the primary efficacy analyses. At week 48, HIV-1 RNA <50 copies per mL was achieved in 286 (89%) of 320 participants in the bictegravir group and 302 (93%) of 325 in the dolutegravir group (difference -3·5%, 95·002% CI -7·9 to 1·0, p=0·12), showing non-inferiority of the bictegravir regimen to the dolutegravir regimen. No treatment-emergent resistance to any study drug was observed. Incidence and severity of adverse events were similar between groups, and few participants discontinued treatment due to adverse events (5 [2%] of 320 in the bictegravir group and 1 [<1%] 325 in the dolutegravir group). Study drug-related adverse events were less common in the bictegravir group than in the dolutegravir group (57 [18%] of 320 vs 83 [26%] of 325, p=0·022).Interpretation: At 48 weeks, virological suppression with the bictegravir regimen was achieved and was non-inferior to the dolutegravir regimen in previously untreated adults. There was no emergent resistance to either regimen. The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated compared with the dolutegravir regimen.Funding: Gilead Sciences Inc. [ABSTRACT FROM AUTHOR]

Objectives: To prevent invasive fungal disease (IFD) in adult patients undergoing remission-induction chemotherapy for newly diagnosed acute lymphoblastic leukaemia (ALL).Patients and methods: In a double-blind multicentre Phase 3 study, patients received prophylactic liposomal amphotericin B (L-AMB) at 5 mg/kg intravenously or placebo twice weekly in a 2:1 random allocation during remission-induction treatment. The primary endpoint was the development of proven or probable IFD. Secondary endpoints included those focused on the safety and tolerability of prophylactic L-AMB.Results: Three hundred and fifty-five patients from 86 centres in Europe and South America received at least one dose of L-AMB ( n =  237) or placebo ( n =  118). Rates of proven and probable IFD assessed independently were 7.9% (18/228) in the L-AMB group and 11.7% (13/111) in the placebo group ( P  =   0.24). Rates of possible IFD were 4.8% (11/228) in the L-AMB and 5.4% (6/111) in the placebo group ( P  =   0.82). The remission-induction phase was a median of 22 days for both groups. Overall mortality was similar between the groups: 7.2% (17/237) for L-AMB and 6.8% (8/118) for placebo ( P  =   1.00). Hypokalaemia and creatinine increase were significantly more frequent with L-AMB.Conclusions: The IFD rate among adult patients undergoing remission-induction chemotherapy for newly diagnosed ALL was 11.7% in the placebo group, and was not significantly different in patients receiving L-AMB, suggesting that the L-AMB regimen studied is not effective as prophylaxis against IFD. The IFD rate appears higher than previously reported, warranting further investigation. Tolerability of L-AMB was what might be expected. Further studies are needed to determine the optimal antifungal strategy during remission-induction chemotherapy of ALL. [ABSTRACT FROM AUTHOR]

Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide(E/C/F/TAF) has high efficacy and improved renal and bone safety in multiple phase 3 trials; TAF single agent is being studied in 2 phase 3 trials in patients with chronic hepatitis B. We report the results of an open-label, noncomparative switch study evaluating the efficacy and safety of E/C/F/TAF in HIV/hepatitis B virus (HBV)-coinfected adults. At 48 weeks, 91.7% of the 72 participants maintained or achieved virologic suppression (HIV-1 RNA <50 copies/mL; HBV DNA <29 IU/mL). Seroconversion occurred in 2.9% of hepatitis B surface antigen-positive participants and in 3.3% of HBV e antigen-positive participants; 40% of those with abnormal alanine aminotransferase normalized. E/C/F/TAF was associated with improved renal function and reduced bone turnover. These data support the use of E/C/F/TAF in treating HIV/HBV coinfection. [ABSTRACT FROM AUTHOR]

This 96-week, randomized, open-label study was designed to assess the efficacy and safety of two single-tablet regimens in treatment naïve HIV-1-infected adults: rilpivirine (RPV) + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and efavirenz (EFV) + FTC/TDF. Assessments included patient-reported Medication Adherence Self-Report Inventory, SF-12v2 Quality of Life assessment, HIV Treatment Satisfaction Questionnaire, and HIV Symptom Index Questionnaire through Week 48. Additional evaluations included study drug discontinuations due to treatment-emergent adverse events (TEAEs). A total of 786 participants (n=394 RPV/FTC/TDF, n=392 EFV/FTC/TDF) were included. Fewer RPV/FTC/TDF-treated than EFV/FTC/TDF-treated participants discontinued study drug due to TEAEs (2.5% vs. 8.7%), with 41% (14/34) TEAE-related discontinuations in the EFV/FTC/TDF group occurring within the first four weeks of treatment. Treatment adherence and satisfaction remained high through Week 48 and quality of life improved from baseline in both groups. There were no significant between-group differences in virologic success (HIV-1 RNA <50 copies/mL) regardless of adherence (<95% or ≥95%). Significant between-group differences favouring RPV/FTC/TDF were observed for the HIV SIQ symptoms of difficulty falling or staying asleep (p = .022) and diarrhea or loose bowel movements (p = .002). In conclusion, 48-week treatment with RPV/FTC/TDF or EFV/FTC/TDF was associated with high adherence, high treatment satisfaction, and improved quality of life. TEAE-related discontinuations and patient-reported symptoms indicate that RPV/FTC/TDF may be somewhat better tolerated than EFV/FTC/TDF. [ABSTRACT FROM PUBLISHER]

Summary: Background: Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (tenofovir) might be a safe and efficacious switch option for virologically suppressed patients with HIV who have neuropsychiatric side-effects on a non-nucleoside reverse transcriptase inhibitor (NNRTI) or who are on a multitablet NNRTI-containing regimen and want a regimen simplification. We assessed the non-inferiority of such a switch compared with continuation of an NNRTI-containing regimen. Methods: STRATEGY-NNRTI is a 96 week, international, multicentre, randomised, open-label, phase 3b, non-inferiority trial enrolling adults (≥18 years) with HIV-1 and plasma HIV RNA viral load below 50 copies per mL for at least 6 months on an NNRTI plus emtricitabine and tenofovir regimen. With a computer-generated randomisation sequence, we randomly allocated participants (2:1; blocks of six, stratified by efavirenz use at screening) to switch to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir (switch group) or continue the NNRTI plus emtricitabine and tenofovir regimen (no-switch group). Key eligibility criteria included no history of virological failure and an estimated glomerular filtration rate of 70 mL per min or greater. The primary endpoint was the proportion of participants with plasma viral loads below 50 copies per mL at week 48 based on a snapshot algorithm with a non-inferiority margin of 12% (assessed by modified intention to treat). This trial is ongoing and is registered at ClinicalTrials.gov, number NCT01495702. Findings: Between Dec 29, 2011, and Dec 13, 2012, we randomly allocated 439 participants to treatment: 290 participants in the switch group and 143 participants in the no-switch group received treatment and were included in the modified intention-to-treat population. At week 48, 271 (93%) of 290 participants in the switch group and 126 (88%) of 143 participants in the no-switch group maintained plasma viral loads below 50 copies per mL (difference 5·3%, 95% CI −0·5 to 12·0; p=0·066). We detected no treatment-emergent resistance in either group. Safety events leading to discontinuation were uncommon in both groups: six (2%) of 291 participants in the switch group and one (1%) of 143 in the no-switch group. Interpretation: Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir seems to be efficacious and well tolerated in virologically suppressed adults with HIV and might be a suitable alternative for patients on an NNRTI with emtricitabine and tenofovir regimen considering a regimen modification or simplification. Funding: Gilead Sciences. [ABSTRACT FROM AUTHOR]

Introduction Cobicistat, a component of stribild (STB), is known to inhibit renal creatinine secretion. A detailed analysis of the renal safety profile of STB in two Phase 3b switch studies of virologically-suppressed individuals on stable therapy: STRATEGY(S)-PI (STB vs a RTV-boosted protease inhibitor [PI] with emtricitabine and tenofovir DF [FTC/TDF]); and STRATEGY(S)-NNRTI (STB versus a non-nucleoside reverse transcriptase inhibitor [NNRTI] with FTC/TDF) is herein described. Materials and Methods Baseline eGFR ≥70 mL/min was an inclusion criterion. The renal safety profile of STB was examined by baseline eGFR through week 48 (i.e., changes in eGFR, renal tubular laboratory abnormalities, investigator-reported renal adverse events leading to discontinuation and unreported subclinical proximal renal tubulopathy [PRT]). Subclinical PRT was defined as a confirmed serum-creatinine increase ≥0.4 mg/dL and two or three markers of renal tubular dysfunction (hypophosphatemia, normoglycemic glycosuria, proteinuria) occurring at the same visit at least once and with no alternative etiologies. Results In S-PI, 433 subjects (STB 293; PI 140) and in S-NNRTI, 434 subjects (STB 291; NNRTI 143) were randomized and treated. Most (>85%) STB subjects had a baseline eGFR ≥90 mL/min. STB subjects with baseline eGFR <90 mL/min had smaller declines in eGFR compared to those with baseline eGFR ≥90 mL/min and similar occurrences of renal tubular laboratory abnormalities (Table 1). Rate of renal adverse events leading to study drug discontinuation were similar for the STB group (one PRT in a subject with baseline tubular laboratory abnormalities consistent with underlying PRT and one isolated increase in serum creatinine) and PI group (one isolated decrease in eGFR); none in the NNRTI group. The case of PRT improved after study drug discontinuation. There were no cases of unreported subclinical PRT in any group. Conclusions In this virologically suppressed patient population, the renal safety of STB did not differ by baseline eGFR. The renal discontinuation rate was low in the STB group, similar to the RTV-boosted PI group, and consistent with published historical rates. [ABSTRACT FROM AUTHOR]

Introduction Simplification to Stribild (STB) was statistically superior to continuation of a ritonavir-boosted protease inhibitor (PI+RTV) with emtricitabine and tenofovir DF (FTC/TDF) at week (W) 48 in virologically suppressed HIV adults (1). We report the W48 efficacy and safety of STB versus RTV-boosted darunavir (DRV) with FTC/TDF in suppressed subjects. Material and Methods Virologically suppressed subjects on PI+RTV with FTC/TDF regimens for ≥6 months were randomized (2:1) to switch to STB vs continue their PI regimen. Eligibility criteria included no documented resistance to FTC and TDF, no history of virologic failure and eGFR ≥70 mL/min. The primary endpoint was the proportion of subjects in the modified ITT population who maintained HIV-1 RNA <50 copies(c)/mL at W48 by FDA snapshot algorithm (12% non-inferiority margin). Subgroup analysis by PI use (DRV [173], atazanavir [174], lopinavir [72], Other PI [13]) at screening was pre-specified. Results Four hundred twenty-nine subjects were randomized and treated (mITT set). In the DRV subgroup, 113 switched to STB; 60 continued a RTV-boosted DRV with FTC/TDF. At W48, 95% STB versus 92% DRV maintained HIV-1 RNA <50 c/mL. No emergent resistance was detected in either group. Median increases from baseline in CD4 count at week 48 (cells/µL): 28 STB versus 29 DRV (p=0.81). Discontinuations due to adverse events were 3% STB versus 2% DRV; one case of isolated decrease in eGFR in the DRV group and no cases of proximal renal tubulopathy in either group. There were statistically significant decreases in the frequency of diarrhoea reported on the HIV Symptom Index at week 4 to week 48 compared to baseline after switching to STB. There was a greater but non-progressive decrease from baseline in eGFR in the STB vs DRV group; median changes (mL/min) at week 48: −8.5 vs −0.6, consistent with the known cobicistat inhibition of renal creatinine secretion. Switch to STB was associated with a higher treatment ease (convenience, flexibility, demand, lifestyle, understanding) score (range: −15 to 15) at week 4 (median: 12 vs 9; p=0.006) and week 24 (median: 13 vs 8; p=0.001). Conclusions In this small group of virologically suppressed subjects, simplification to STB versus continuation of a RTV-boosted DRV with FTC/TDF was safe, well-tolerated, and associated with a high rate of virologic suppression at week 48. There was more treatment ease with STB use. [ABSTRACT FROM AUTHOR]

Introduction Switch to Stribild (STB) was non-inferior to continuation of a non-nucleoside reverse transcriptase inhibitor (NNRTI) with emtricitabine and tenofovir DF (FTC/TDF) at week 48 in virologically suppressed HIV adults []. We report the Week 48 efficacy and safety of STB versus nevirapine (NVP) or rilpivirine (RPV) with FTC/TDF in suppressed subjects. Materials and Methods Virologically suppressed subjects on an NNRTI with FTC/TDF regimens for ≥6 months were randomized (2:1) to switch to STB versus continue their NNRTI regimen. Eligibility criteria included no documented resistance to FTC and TDF, no history of virologic failure and eGFR ≥70 mL/min. The primary endpoint was the proportion of subjects in the modified ITT population who maintained HIV-1 RNA <50 copies(c)/mL at Week 48 by FDA snapshot algorithm (12% non-inferiority margin). Subgroup analysis by non-EFV NNRTI use (NVP [74]; RPV [19]; etravirine [3]) at screening was pre-specified. Results The mITT population included 433 subjects who were randomized and treated. In the non-EFV NNRTI subgroup, 59 switched to STB; 37 continued a non-EFV NNRTI (27 NVP, 10 RPV) with FTC/TDF. At week 48, 97% STB versus 95% non-EFV NNRTI maintained HIV-1 RNA <50 c/mL. No emergent resistance was detected in either group. No difference in median increases from baseline in CD4 count at week 48 (cells/µL): 25 STB versus 55 non-EFV NNRTI (p=0.78). No discontinuation due to adverse events; no cases of proximal renal tubulopathy. As expected, there were no significant changes in the frequency of neuropsychiatric symptoms (i.e. anxiety, insomnia, dizziness, vivid dreams, weird/intense dreams, and nightmares) reported on the HIV Symptom Index at week 48 compared to baseline after switching to STB. There was a greater but non-progressive decrease from baseline in eGFR in the STB versus non-EFV NNRTI group; median changes (mL/min) at week 48: −9.1 versus −1.4. Switch to STB was associated with a higher treatment ease (convenience, flexibility, demand, lifestyle, understanding) score (range: −15 to 15) at week 4 (median: 14 vs 11; p=0.047) and week 24 (median: 14 vs 12.5; p=0.038). Conclusions In this small group of virologically suppressed subjects, switch to STB vs continuation of NVP or RPV with FTC/TDF was safe, well-tolerated, and associated with a high rate of virologic suppression at week 48. There was more treatment ease with STB use. [ABSTRACT FROM AUTHOR]