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Objectives: This study evaluated the efavirenz (EFV) mid-dose plasma concentration (C12), clinical efficacy, and safety after the switch to a single-tablet regimen containing tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and 400-mg EFV in virally suppressed HIV-positive Taiwanese who were receiving co-formulated TDF, emtricitabine (FTC), and 600-mg EFV., Methods: In this single-arm, open-label study, HIV-positive adults who had undetectable plasma HIV RNA load (<50 copies/ml) for 6 months or longer while receiving co-formulated TDF, FTC, and 600-mg EFV with EFV C12 of ≥1 mg/L were enrolled. The participants were switched to co-formulated TDF, 3TC, and 400-mg EFV and followed for 24 weeks. The primary endpoint was the proportion of participants with EFV C12 ≥ 1 mg/L at Week 4. The secondary endpoints included virologic response and change of CD4 lymphocyte count up to Week 24. Specific adverse effects associated with EFV were recorded before and after the switch., Results: From December 2018 to January 2019, 50 participants were enrolled. EFV C12 remained ≥1 mg/L in 48 (96.0%) participants with a median reduction of 38.9% (interquartile range 29.0-44.4) at Week 4 after switch. All participants had undetectable plasma HIV RNA by Week 12, whereas 96.0% of them remained so at Week 24. Significant increases of CD4 lymphocyte count were observed at Weeks 12 and 24. Thirty-three participants (66.0%) reported improvement of pre-existing adverse effects., Conclusion: Switch to coformulated TDF, 3TC, and 400-mg EFV in virally suppressed HIV-positive Taiwanese maintained effective EFV concentration and viral suppression while the adverse effects were reduced., (Copyright © 2020. Published by Elsevier B.V.)

Background: Pharmacogenetic studies have shown that slow and intermediate metabolizers of efavirenz (EFV) gained less weight compared with extensive metabolizers. It is hypothesized that increased EFV exposure suppresses weight gain. We investigated the effect of EFV mid-dose plasma concentration (C12) on long-term weight change among virologically suppressed people living with HIV (PLWH)., Methods: Participants in a prospective EFV pharmacokinetic study were included if they had been taking EFV-containing combination antiretroviral therapy for more than 240 weeks and had 3 or more weight measurements. The weight changes and time to ≥5% of weight gain over 192 weeks were compared between PLWH with higher and those with lower EFV C12 (using mean population C12 as the cutoff). EFV C12 and CYP2B6 516G>T polymorphism were examined in generalized estimating equations and in a Cox proportional hazards model for associations with weight gain, after adjustments for age, sex, companion antiretroviral agent, CD4 lymphocyte count, and plasma HIV RNA., Results: One hundred eighteen PLWH were included. PLWH with higher EFV C12 had less mean weight gain compared with those with lower C12 after 192 weeks (-0.09 vs +1.58 kg, P = 0.033). PLWH with higher C12 were less likely to gain ≥5% weight in Kaplan-Meier analysis (P = 0.0003). In both generalized estimating equations and Cox proportional hazards models, a higher EFV C12 was associated with less weight gain, while CYP2B6 516G>T was not, after adjustments made for confounding factors., Conclusions: Our findings support that increased EFV exposure was associated with less weight gain., Competing Interests: C.-C.H. received research support from Gilead Sciences, Merck, and ViiV, speaker honoraria from Gilead Sciences and ViiV, and served on advisory boards for Gilead Sciences and ViiV. The remaining authors have no funding or conflicts of interest to disclose. This does not potentially influence what is written in the submitted work., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The efficacy and safety of switching from tenofovir disoproxil fumarate-based antiretroviral therapy to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (E/C/F/TAF) has not been widely investigated in HIV/hepatitis B virus (HBV)-coinfected Asian population., Methods: Between February and October 2018, HIV/HBV-coinfected patients who had achieved HIV viral suppression with tenofovir disoproxil fumarate-containing regimens were switched to E/C/F/TAF. Assessments of plasma HBV and HIV viral load, HBV serology, renal function, lipid profiles, and bone mineral density (BMD) were performed at weeks 24 and 48 after switch., Results: A total of 274 HIV/HBV-coinfected participants were enrolled, with 12.8% testing HBeAg-positive and 94.2% having plasma HBV DNA <20 IU/mL at baseline. At weeks 24 and 48, 92.7% and 89.8% achieved plasma HBV DNA <20 IU/mL; 4.7% and 5.1% had HBV DNA ≥20 IU/mL; and 2.6% and 5.1% had no data, respectively. At weeks 24 and 48, 95.6% and 94.2% of participants maintained HIV RNA <50 copies/mL, respectively. Compared with baseline, the median urine β2-microglobulin-to-creatinine ratio at week 48 decreased significantly from 165 to 90 μg/g (P < 0.001). The mean BMD of the spine and hip improved at week 48 (+1.77% and +1.33%, respectively). Significantly higher lipid profiles were observed after switch to E/C/F/TAF. Thirteen (4.7%) patients withdrew from the study before week 48, with 7 (2.6%) patients because of adverse effects., Conclusions: Switch to E/C/F/TAF maintained HBV and HIV viral suppression and resulted in the improvement of proteinuria and BMD of the spine and hip but increased lipid levels in HIV/HBV-coinfected patients at week 48., Competing Interests: C.-C.H. has received research support from Gilead Sciences, Merck, and ViiV and speaker honoraria from Gilead Sciences and ViiV, and served on advisory boards for Gilead Sciences and ViiV. The remaining authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background/purpose: Early initiation of antiretroviral therapy (ART) reduces the risks for serious infections and mortality. We aimed to assess the outcomes of initiating ART among HIV-positive Taiwanese according to the CD4 cut-off values by the WHO recommendations., Methods: We reviewed medical records of patients with newly diagnosed HIV infection between 2004 and 2015 and 3 groups of patients were defined according to the timing of ART initiation based on CD4 count recommended by WHO: Group 1 between 2004 and 2009; Group 2 between 2010 and 2012; and Group 3 between 2013 and 2015. The primary outcome was all-cause mortality. All patients were followed until 2 years after the last patient was included in each group., Results: Of 2022 patients included, the mortality rate was 18.28, 14.01, and 9.10 deaths per 1000 person-years of follow-up (PYFU) in Groups 1, 2, and 3, respectively. In multivariable Cox regression analysis, factors associated with mortality were age (per 1-year increase, adjusted hazard ratio [AHR], 1.06; 95% CI, 1.05-1.08), presence of AIDS-defining disease at HIV diagnosis (AHR, 4.81; 95% CI, 2.99-7.74), solid-organ malignancy (AHR, 3.10; 95% CI, 1.86-5.18), and initiation of ART (AHR, 0.09; 95% CI, 0.05-0.16). By competing risk regression model for non-AIDS-related death, the AHR for Group 3 versus Group 1 was 0.27 (95% CI, 0.09-0.80)., Conclusions: While continued efforts are needed to improve early diagnosis and linkage to care, initiation of cART improved survival among HIV-positive patients in Taiwan according to the increasing CD4 cut-off values that were recommended by the WHO., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: Real-world experience regarding the effectiveness of co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/C/FTC/TAF) as a switch regimen is sparse among people living with HIV (PLWH) harbouring the M184V/I mutation with or without thymidine analogue-associated mutations (TAMs)., Methods: In this retrospective multicentre study, PLWH who were switched to EVG/C/FTC/TAF after having achieved viral suppression (plasma HIV RNA <200 copies/mL) for 6 months or longer were included. Patients with archived M184V/I mutation (case patients) were matched to controls without M184V/I mutation at a 1:4 ratio. Patients with a history of virological failure or resistance to elvitegravir were excluded. The primary endpoint was virological non-success (plasma HIV RNA ≥50 copies/mL) at Week 48 of switch using a modified FDA snapshot analysis., Results: Overall, 100 case patients with the M184V/I mutation were identified, including 6 (6.0%) with K65R and 13 (13.0%) with at least one TAM, and were matched to 400 controls in terms of gender, age (mean = 40.3 versus 39.7 years) and cumulative exposure duration to tenofovir disoproxil fumarate (median = 146 versus 143 weeks). At Week 48, the rate of virological non-success for the case patients and controls was 5.0% (5/100) and 3.3% (13/400), respectively (difference = 1.7%; 95% CI = -2.9%-6.3%), while the rate of virological success was 88.0% and 89.5% for the case patients and controls, respectively. The presence of the K65R mutation or TAMs was not associated with virological non-response., Conclusions: Among virally suppressed PLWH, EVG/C/FTC/TAF is effective in maintaining viral suppression at Week 48 despite archived M184V/I mutation with or without TAMs., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Optimal efavirenz (EFV) dose that minimizes adverse effects while maintaining efficacy has yet to be elucidated. With a therapeutic drug monitoring (TDM)-guided strategy, we assessed the effectiveness of half-a-tablet EFV plus 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) in HIV-infected Taiwanese who had achieved viral suppression with full-dose (600 mg) EFV., Methods: HIV-infected adults receiving EFV-containing regimens who had plasma mid-dose EFV concentration (C12) ≥2.0 mg/L and had plasma HIV RNA load (PVL) <200 copies/mL were enrolled in this single-arm, open-label study by reducing EFV to half-a-tablet daily. The primary endpoint was PVL <50 copies/ml in an intention-to-treat (ITT) population at week 48. The secondary endpoints were the plasma EFV C12, the proportion of patients with plasma EFV C12 <1.0 mg/L, PVL <50 copies/ml at week 96 and week 144., Results: Between April 2013 and September 2016, 203 patients (93.6% male; median age, 39.0 years) were enrolled. The median EFV C12 before switch was 2.80 mg/L (interquartile range (IQR), 2.41-3.73), which decreased to 1.59 mg/L (IQR, 1.23-2.03) after switch with a reduction of 47.4% (IQR, 38.3-55.5%). In ITT analysis, 93.6%, 92.3% and 87.3% of the patients achieved PVL <50 copies/ml at weeks 48, 96 and 144, respectively. More than 70% of the patients reported alleviation of EFV-associated adverse effects following the switch., Conclusion: Under the guidance of TDM, switch to half-a-tablet EFV plus 2 NRTIs is effective in maintaining viral suppression in HIV-infected Taiwanese with EFV C12 ≥ 2.0 mg/L., (Copyright © 2018. Published by Elsevier B.V.)

Background Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. Materials and methods In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. Results From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P  = 0.001). Conclusions After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022. [ABSTRACT FROM AUTHOR]