WHAT IS THIS SUMMARY ABOUT?:This is a plain-language summary of an article that reported on two studies of the medication bictegravir/emtricitabine/tenofovir alafenamide (shortened to B/F/TAF). B/F/TAF is a single pill containing three different drugs used to treat human immunodeficiency virus (known as HIV). The drugs work together to lower the levels of HIV (called viral load) in the body and make the virus undetectable in the blood. Researchers measured whether B/F/TAF was safe and effective when taken over 5 years in over 400 people in 10 countries who had never taken HIV medication before. WHAT WERE THE RESULTS?:After 5 years, almost all (99%) of the people who took B/F/TAF had an undetectable viral load. This does not mean that they were cured, but that the levels of HIV were so low that the tests used by researchers could not detect the virus in the blood. CD4 is a type of immune system cell. HIV causes CD4 cell numbers to decrease. On average, the number of CD4 cells increased by more than 300 cells per microliter (cells/μL) of blood over 5 years. This means that the immune system was improving. HIV is able to change its genes to escape the effects of the drugs. This is known as HIV resistance to treatment. Nine people had a viral load high enough to suggest that the drugs might not be working, but no resistance to B/F/TAF was seen. Some people (less than one in three) experienced medical problems thought to be linked to B/F/TAF treatment, known as side effects. The most common side effects were headache, diarrhea, nausea, tiredness (fatigue), dizziness, and difficulty falling or staying asleep (insomnia). On average, people's body weight increased by 3 kg in the first year of taking B/F/TAF. This might be because their general health improved after starting HIV treatment. Weight gained after that time was similar to the level of weight gain expected in the general population. Very few people (less than 1 in 100) stopped taking B/F/TAF because of side effects thought to have been caused by B/F/TAF. WHAT DO THE RESULTS MEAN?:B/F/TAF was effective at treating HIV in people who had never taken HIV medication before. Most (70%) people were still taking B/F/TAF after 5 years.Clinical Trial Registration: NCT02607930 (Study 1489); NCT02607956 (Study 1490) (ClinicalTrials.gov).

Housing Mobility Programs (HMPs) support residential mobility to reduce economic segregation. One design feature of HMPs requires identifying areas to which moving will most improve outcomes. We show that ranking neighborhoods’ effects using current residents’ outcomes has strengths over using previous residents’ outcomes due to statistical uncertainty, bias from sorting over time, and lack of support. We simulate how the choice of neighborhood ranking and others affect an originally-intended outcome of HMPs: reducing racial segregation. HMP success on this dimension depends on the ability to port vouchers across jurisdictions, access to cars, and the range of neighborhoods targeted.

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.

This article summarizes the 2023 International Continence Society (ICS) Workshop 5 focused on neurologically mediated chronic pelvic pain (CPP) (Workshop 5). A team of experts share practical advice and tools for assessment, diagnosis and management relevant to pudendal neuropathy or other nerve entrapment, central nervous system diagnoses such as herniated disc, radiculopathy, Tarlov cyst, tethered cord, hip confounders, and systemic neuropathy such as small fiber neuropathy, neuroinflammatory disease (e.g. Lyme, Multiple Sclerosis) and central sensitization.

Introduction Alors que les traitements en un comprimé unique (STR) constituent aujourd'hui la norme pour le traitement du VIH dans le monde, certaines personnes vivant avec le VIH (PVVIH) prennent un traitement en comprimés multiples (MTR) en raison de résistances archivées, d'une intolérance ou d'interactions médicamenteuses. L'association du bictégravir (BIC), un inhibiteur de l'intégrase, et du lénacapavir (LEN), un inhibiteur de capside et premier de sa classe, pourrait simplifier le traitement des PVVIH en succès virologique (SV) pour lesquelles les STR ne sont pas indiqués. Nous présentons les résultats du critère principal à 24 semaines de l'étude de phase 2 évaluant le changement vers l'association BIC + LEN comparé au maintien du traitement oral en cours (MTO) chez les PVVIH en SV ayant un MTR complexe. Matériels et méthodes ARTISTRY-1 (NCT05502341) est une étude de phase 2/3 multicentrique, randomisée, en ouvert et en cours. Lors de la phase 2, 128 participants (≥ 6 mois avant le dépistage) ont été randomisés selon un rapport 2:2:1 pour recevoir par voie orale en une fois par jour BIC 75 mg + LEN 25 mg ou BIC 75 mg + LEN 50 mg, ou le maintien du MTO. Tous les participants recevant BIC + LEN ont reçu une dose de charge orale de 600 mg de LEN les jours 1 et 2 du traitement. Le critère d'évaluation principal était la proportion de participants avec un ARN du VIH ≥ 50 c/ml (FDA Snapshot) à la semaine 24. Les critères d'évaluation secondaires comprenaient la proportion de participants avec un ARN du VIH < 50 c/ml, la variation par rapport à l'inclusion du nombre de cellules CD4 et la proportion de participants présentant des événements indésirables survenus durant le traitement (EIDT) jusqu'à la semaine 24. Résultats 51 et 52 participants ont reçu respectivement BIC 75 mg + LEN 25 mg ou BIC 75 mg + LEN 50 mg et 25 ont continué leur MTO. A l'inclusion, 19 % des participants étaient des femmes, 31 % étaient noirs et 16 % étaient hispaniques ou latinos ; L'âge médian (Q1, Q3) était de 60 (56, 65) ans et les participants prenaient une médiane (intervalle) de 3 (2 à 9) comprimés par jour. A la semaine 24, l'ARN du VIH-1 était ≥ 50 c/ml chez 0/51 participant du groupe BIC 75 mg + LEN 25 mg, 1/52 (2 %) dans le groupe BIC 75 mg + LEN 50 mg (puis en succès <50 c/ml sans changement du traitement) et 0/25 dans le groupe MTO. Les taux de CD4 étaient comparables dans tous les groupes. Les EIDT les plus courants dans les deux groupes BIC + LEN jusqu'à la semaine 24 étaient la diarrhée (7 %), le COVID-19 (6 %) et la constipation (5 %). Des EIDT liés aux traitements sont survenus respectivement chez 18 %, 6 % et 0 % des participants. Conclusion Le changement de traitement pour BIC + LEN s'est avéré hautement efficace pour maintenir la suppression virologique chez les ayant un MTR complexe, avec des profils de tolérance similaires observés dans les deux groupes BIC + LEN. Ces données soutiennent l'utilisation de l'association de BIC et LEN pour les traitements complexes des PVVIH en SV. Un STR BIC/LEN sera évalué lors de la Phase 3 de l'étudeAucun lien d'intérêt

Background: In the phase 3 ALLIANCE study, both bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (DTG + F/TDF) achieved high rates of HIV-1 RNA suppression through week 96 in adults with HIV-1 and hepatitis B virus initiating treatment (NCT03547908). In this study, we quantify preexisting HIV-1 resistance, evaluate its effect on HIV-1 virologic suppression, and describe postbaseline HIV-1 resistance through week 96. Methods: Preexisting HIV-1 resistance was assessed by historical and/or screening genotyping. HIV-1 RNA suppression to <50 copies (c)/mL at week 96 was assessed by the preexisting resistance category. Postbaseline resistance was assessed in participants with HIV-1 RNA ≥200 c/mL through week 96. Results: Primary nucleoside/nucleotide reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, and protease inhibitor resistance substitutions were present at baseline in 4 (1.7%), 19 (7.9%), and 5 (2.1%) of 241 participants, respectively. Virologic suppression rates were high, irrespective of preexisting primary resistance substitutions, including M184I. Six participants (3 per group) had confirmed HIV-1 RNA ≥200 c/mL and did not resuppress to <50 c/mL while on study drugs; none of the 5 with postbaseline resistance data had treatment-emergent primary resistance substitutions. One participant on DTG + F/TDF with multiple virologic failures and documented nonadherence by pill count had treatment-emergent K70E and M184V/I, and subsequently resuppressed. Conclusion: In people with HIV-1 and hepatitis B virus treated with first-line B/F/TAF or DTG + F/TDF, preexisting HIV-1 resistance was uncommon and did not affect virologic suppression. No treatment-emergent HIV-1 resistance occurred with B/F/TAF, further supporting the high barrier to resistance of this regimen.

Background The capsular ligaments at the hip joint work in synchrony with the acetabulum and femoral head for articular stability. There is a lack of understanding about ischiofemoral ligament (ISFL) anatomy and function.Purpose To assess the insertion of the ISFL in non-arthritic adult hips.Material and Methods A retrospective analysis was performed in 72 patients who underwent magnetic resonance arthrogram (MRA) for the assessment of hip pain. The distribution of the ISFL components, the thickness, and the insertion site were assessed by concomitantly using the axial oblique, coronal, and sagittal MRA images.Results Two insertions of the ISFL anterior to the center of the femoral head were identified in 71 (99%) hips: (i) predominant anterior merging with the iliofemoral ligament as continuation of zona orbicularis, observed in all hips; and (ii) anterolateral junction of femoral neck and greater trochanter. Two ISFL parts (proximal and distal) were identified in 70 (97%) of the 72 studied hips. The proximal part was always thinner (mean 2.6 +/- 0.7 mm) and originated from the ischium at the acetabular rim. The distal part was a continuation of the zona orbicularis, and the mean thickness was 6.7 +/- 1.6 mm. Both parts merged as they coursed over the superior portion of the femoral head.Conclusion The predominant insertion of the ischiofemoral ligament is a merging to the iliofemoral ligament anteriorly. Surgical procedures such as hip arthroscopy involving the ISFL will affect the function of the iliofemoral ligament, and vice versa.

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.gov NCT02607930; EudraCT 2015-004024-54. Study 1490: ClinicalTrials.gov NCT02607956; 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/& mu;L. 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 & LE;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.

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.

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.

Background: Biktarvy use is currently approved for HIV-1 infection in treatment-naïve and treatmentexperienced individuals after a series of successful investigator-sponsored phase III trials.However, studies on real-world evidence of its efficacy, safety, and tolerability are limited.Method: This review used the PRISMA extension for scoping reviews checklist as a framework.The final search strategy used was: (Bictegravir* OR biktarvy) AND (efficac* OR safe* OR effect* OR tolerab* OR "side effect*" OR "adverse effect*").The last search was performed on the 12th of August 2021.We included results from PubMed, EMBASE, EMCARE, Medline, CINAHL and BNL.Studies were eligible if they reported on the Efficacy, effectiveness, safety, or tolerability of bictegravir-based ART.Relevant conference abstracts under 24 months old were included in addition to full-text articles.Studies were excluded if Gilead Sciences sponsored them, if the total population taking B/F/TAF was <20, or if B/F/TAF was used off-label for other conditions.Review articles, meta-analyses, case reports, preclinical studies, and non-English publications were excluded.Results: After de-duplication, 333 studies were selected from peer-reviewed articles, and 27 were selected for fulltext assessment after reviewing their title and abstract.Seventeen studies fulfilled the inclusion criteria after a full-text review.We found that the efficacy of Biktarvy in clinical practice was comparable to phase III trials.However, adverse effects and discontinuation rates were found to be higher in the included real-world studies.Overall treatment discontinuation rates due to adverse effects ranged between 1.9 to 12%.Notably, discontinuation due to rash and weight gain was found to be higher than in approval trials. Conclusion:We conclude that further investigation of adverse effects and discontinuation rates is required, through large-scale prospective cohort studies.Further studies are needed on biktarvy-associated rash and weight gain specifically.Although the cohorts in the included realworld studies showed more demographic diversity when compared to the drug approval trials, further studies are still required on underrepresented groups such as women, pregnant people, ethnic minorities, and older adults.

Background Adherence to daily oral antiretroviral therapy is important for sustaining HIV suppression. B/F/TAF Studies 1489, 1490, 4458, 1844 and 4030 demonstrated the noninferior efficacy of B/F/TAF versus DTG + 2 nucleoside reverse transcriptase inhibitors (NRTIs). We retrospectively assessed drug adherence and effect on virologic outcomes. Methods All studies were double-blind, placebo-controlled, and enrolled treatment-naïve (1489, 1490, 4458) or virologically suppressed (1844, 4030) adults. Participants were randomized 1:1 to receive B/F/TAF or DTG + 2 NRTIs (Table) plus placebo; as a result, all received multiple tablets. Participants with ≥ 1 returned pill bottle and ≥ 1 on-treatment HIV-1 RNA measurement were included in the analysis. Adherence was calculated by pill count; virologic outcome was assessed by last on-treatment HIV-1 RNA. Results Altogether, 2,622 participants were included (B/F/TAF: 1,306; DTG + 2 NRTIs: 1,316). The proportions of participants with high (≥ 95%), intermediate (≥ 85%‒< 95%) or low (< 85%) adherence were similar between the 2 groups; few had low adherence (B/F/TAF: 46 [3.5%]; DTG + 2 NRTIs: 69 [5.2%] through Week [W] 48). Overall, 98.5% (n=1,287) in the B/F/TAF group and 98.2% (n=1,292) in the DTG + 2 NRTI group had virologic suppression (HIV-1 RNA < 50 copies/mL) at last on-treatment visit through W48. In the B/F/TAF group, virologic suppression was similar in those with high and intermediate adherence versus those with low adherence; however, in the DTG + 2 NRTI group, virologic suppression was significantly higher in those with high and intermediate adherence compared with low adherence (P ≤ 0.002, Figure). Similar results were observed at W144 in 2 studies (1489, 1490) with additional follow-up data. Nine participants with low adherence had HIV-1 RNA ≥ 50 copies/mL at their last visit through W48: 3 subsequently resuppressed (B/F/TAF: 1; DTG + 2 NRTIs: 2), 5 discontinued (all DTG + 2 NRTIs) and 1 was lost to follow-up (B/F/TAF). Conclusion Overall, most participants receiving either placebo-controlled B/F/TAF or DTG + 2 NRTIs demonstrated ≥ 85% adherence. In those with suboptimal adherence, B/F/TAF treatment maintained high levels of virologic suppression, while those with suboptimal DTG + 2 NRTI adherence had reduced virologic suppression. Disclosures Kristen Andreatta, MS, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds Paul E. Sax, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Grant/Research Support David Alain Wohl, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Advisor/Consultant|Janssen: Honoraria|Theratech: Advisor/Consultant|Theratech: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Michelle L. D’Antoni, PhD, Gilead: Employment|Gilead: Stocks/Bonds Hailin Huang, PhD, Gilead: Employment Jason Hindman, PharmD, MBA, Gilead: Employment|Gilead: Stocks/Bonds Christian Callebaut, PhD, Gilead: Employment Hal Martin, MD, Gilead: Employment

Summary: 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.gov NCT02607930; EudraCT 2015-004024-54. Study 1490: ClinicalTrials.gov NCT02607956; 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.

Abstract Background People with HIV (PWH) who are initiated on guidelines-recommended first-line INSTI-based antiretroviral therapy routinely achieve rapid virologic suppression; however, those with a high baseline (BL) HIV-1 RNA and/or low CD4 count may be more challenging to manage in the short- and long-term. To further characterize long-term outcomes over 5 years in select subgroups, we analyzed results from two studies examining B/F/TAF as initial treatment stratified by BL HIV-1 RNA and/or CD4 count. Methods Adults with HIV were randomized to receive blinded initial treatment with B/F/TAF versus dolutegravir [DTG]/abacavir/lamivudine (Study 1489) or DTG+F/TAF (1490) for 144 weeks (W) of blinded treatment followed by an optional switch to open-label B/F/TAF for 96W. We present virologic response (HIV-1 RNA < 50 c/mL, missing=excluded and missing=failure) and study drug-related adverse events (DRAE) from a pooled analysis of participants originally randomized to B/F/TAF who had BL HIV-1 RNA 100,00-400,000 copies(c)/mL, HIV-1 RNA >400,000 c/mL and/or CD4 count < 200 cells/µL through W240. Results 634 adults (median age 32 years, 89% men, 33% Black/African descent, 24% Hispanic/LatinX) originally randomized to B/F/TAF were included for analysis. At BL, 80 participants had a BL CD4 count < 200 cells/µL and 119 participants had HIV-1 RNA >100,000 c/mL, of whom, 20 had HIV-1 RNA >400,000 c/mL. At W240, virologic suppression was high for the low CD4 count and/or high HIV-1 RNA subgroups (Table). No participant in the final resistance analysis developed virologic resistance to any component of B/F/TAF. Across the subgroups, the most common DRAEs were nausea, headache and diarrhea and there were no serious DRAEs. There was only one discontinuation due to a DRAE in the low CD4 count subgroup, and none in the high HIV-1 RNA subgroup. Conclusion Initial treatment with B/F/TAF was safe and efficacious over 5 years of follow-up in people with a high BL HIV-1 RNA and/or low CD4 count. These outcomes provide additional evidence that B/F/TAF is an effective and durable regimen for a broad range of PWH, including those with advanced disease. Disclosures Moti Ramgopal, MD, FACP, FIDSA, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Speakers Bureau|Janssen: Advisor/Consultant|Janssen: Speakers Bureau|Merck: Advisor/Consultant|Merck: Speakers Bureau|ViiV: Advisor/Consultant|ViiV: Speakers Bureau Axel Baumgarten, MD, AbbVie: Honoraria|Gilead Sciences: Honoraria|Janssen: Honoraria|MSD: Honoraria|ViiV: Honoraria Anton Pozniak, MD, FRCP, Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Honoraria|theratec: Honoraria|ViiV: Grant/Research Support|ViiV: Honoraria Chloe Orkin, MBChB, FRCP, MD, Gilead Sciences: Honoraria|GSK: Honoraria|Janssen: Honoraria|MSD: Honoraria Juan Manuel Tiraboschi, PhD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Debbie P. Hagins, MD, FAPCR, AAHIVS, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Speakers Bureau|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV: Advisor/Consultant|ViiV: Grant/Research Support Hailin Huang, PhD, Gilead Sciences, Inc.: Employer|Gilead Sciences, Inc.: Stocks/Bonds Kristin Andreatta, MSc, Gilead Sciences, Inc: Employee of Gilead Sciences|Gilead Sciences, Inc: Stocks/Bonds Nathan Unger, PharmD, AAHIVP, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Jason Hindman, PharmD, MBA, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Hal Martin, MD, Gilead Sciences: employee|Gilead Sciences: Stocks/Bonds Jared Baeten, MD, PhD, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Olayemi Osiyemi, MD, Gilead: Advisor/Consultant|gsk: Advisor/Consultant|viiv: Advisor/Consultant.