Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan.

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.

Disclosure Concerns and the Correlation Among Gay, Bisexual, and Other Men Who Have Sex With Men Living With HIV Receiving Antiretroviral Therapy in Taiwan.

Gay, bisexual, and other men who have sex with men (GBMSM) are associated with the widespread human immunodeficiency virus (HIV) transmission in Taiwan. Additionally, little is known about disclosure patterns and rates, as well as factors influencing disclosure, among GBMSM living with HIV in the country. HIV prevention for GBMSM is effective when HIV status is disclosed. For instance, GBMSM disclosing their HIV status can result in early pre-exposure prophylaxis with a serodiscordant partner. In this cross-sectional study of 200 GBMSM living with HIV conducted from June to November 2020, we assessed internalized homophobia (IHP Scale) and social support (Multidimensional Scale of Perceived Social Support), as well as self-reported disclosure and non-disclosure. Among the participants, 75.5% revealed their HIV status within 3 months of diagnosis. Younger age, occupation type, and number of sexual partners were some factors associated with disclosure. Those receiving more social support and who experienced less IHP were more likely to reveal their HIV status. On the contrary, older GBMSM and GBMSM living with HIV who worked in educational enterprises still experienced severe IHP. Policymakers and healthcare practitioners should be aware of the problems faced by GBMSM living with HIV and offer practical assistance to improve their mental health.

Comparable clinical outcomes with same-day versus rapid initiation of antiretroviral therapy in Taiwan.

OBJECTIVES: WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. METHODS: We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. RESULTS: At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. CONCLUSIONS: SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.

Treatment responses to integrase strand-transfer inhibitor-containing antiretroviral regimens in combination with short-course rifapentine-based regimens for latent tuberculosis infection among people with HIV.

BACKGROUND: Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor (InSTI)-containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with HIV (PWH). METHODS: From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment, and the secondary outcomes included treatment completion rate and safety of LTBI regimens. RESULTS: During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200 copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate. CONCLUSION: Combinations of short-course rifapentine-based regimens and InSTI-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events.

Optimal Frequency of Hepatitis C Virus (HCV) RNA Testing for Detection of Acute HCV Infection Among At-risk People With Human Immunodeficiency Virus: A Multicenter Study.

Using 3-stage pooled-plasma hepatitis C virus (HCV) RNA testing performed quarterly among at-risk people with human immunodeficiency virus (PWH), we found that if testing had been performed every 6 or 12 months, 58.6%-91.7% of PWH who recently acquired HCV would be delayed for diagnosis and might contribute to onward HCV transmission with longer durations.

Evolution of estimated glomerular filtration rate in HIV/HCV-coinfected patients who received direct-acting antivirals: A multicenter retrospective study.

BACKGROUND: The short-term impact of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) combined with antiretroviral therapy (ART) on renal function in patients with HIV/HCV-coinfection remains controversial. METHODS: This multicenter, retrospective study aimed to sequentially record the estimated glomerular filtration rate (eGFR) at baseline, end of therapy (EOT), 12 weeks off-treatment (SVR12), and at time points after SVR12 (post-SVR12) and to identify the factors associated with an eGFR decline to <60 ml/min/1.73 m2 in HIV/HCV-coinfected patients receiving DAAs. The evolution of mean eGFRs between different ART and DAAs combinations among patients of different HIV transmission routes were compared using a generalized linear mixed effects model. The periods between baseline and EOT, between EOT and post-SVR12, and between baseline and post-SVR12 were defined as the on-treatment, post-treatment, and all-course periods, respectively. Acute kidney disease (AKD) was defined as a decline of eGFR to <60 ml/min/1.73 m2. RESULT: A total of 445 patients with baseline eGFRs >60 ml/min/1.73 m2 were included. We found that eGFRs declined during the on-treatment period in the tenofovir-containing ART and SOF-based DAA groups. There were no differences in the slope coefficient during the on-treatment and post-treatment periods among all risk groups except for people who inject drug. Increasing age and plasma HIV RNA >20 copies/ml before DAA treatment were factors independently associated with AKD during the on-treatment period while increasing age was independently associated with AKD during the all-course period. CONCLUSION: Only increasing age was an independent factor associated with AKD among HIV/HCV-coinfected patients during and after DAA treatments.

Week 96 Results of Switching from Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide among HIV/Hepatitis B Virus-Coinfected Patients.

Data regarding the durability of tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) in maintaining hepatitis B virus (HBV) viral suppression among HIV/HBV-coinfected patients are limited. Between February and October 2018, 274 HIV/HBV-coinfected participants who had achieved HIV RNA of <50 copies/mL with tenofovir disoproxil fumarate (TDF)-containing ART and switched to elvitegravir/cobicistat/emtricitabine/TAF were prospectively enrolled. Serial plasma HIV and HBV viral loads, HBV and hepatitis D virus (HDV) serology, renal parameters, metabolic profiles, and bone mineral density (BMD) were assessed through 96 weeks. At baseline and weeks 48, 72, and 96, 5.8%, 5.1%, 5.8%, and 5.1% of the participants had plasma HBV DNA of ≥20 IU/mL, and 0%, 0.7%, 1.5%, and 2.2% had HIV RNA of ≥50 copies/mL, respectively. Hepatitis B surface antigen (HBsAg) loss occurred in 1.5% of 274 participants, and hepatitis B e-antigen (HBeAg) loss or seroconversion occurred in 14.3% of 35 HBeAg-positive participants. Compared with baseline, the median urine protein-to-creatinine ratio (79 versus 63 mg/g, P < 0.001) and ß2-microglobulin-to-creatinine ratio (165 versus 83 µg/g, P < 0.001) continued to decrease at week 96. BMD of the spine and hip slightly increased (mean change, +0.9% and +0.5%, respectively). The median triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol increased from baseline to week 96 (116 versus 141, 166 versus 190, 99 versus 117, and 42 versus 47 mg/dL, respectively; all P < 0.001), and most of the increases occurred in the first 48 weeks of the switch. Our study showed that switching from TDF-containing ART to elvitegravir/cobicistat/emtricitabine/TAF maintained HBV and HIV viral suppression through 96 weeks among HIV/HBV-coinfected patients. Proteinuria continued to improve, while fasting lipids increased and BMD stabilized at 96 weeks after the switch. IMPORTANCE Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide as a maintenance therapy showed durable and high rates of viral suppression for HIV/HBV-coinfected patients, with only 5.1% and 2.2% of patients having HBV DNA of ≥20 IU/mL and HIV RNA of ≥50 copies/mL, respectively, at 96 weeks. Our study fills the data gap on the long-term clinical effectiveness of tenofovir alafenamide-containing antiretroviral therapy in people living with HIV who have HBV coinfection.

Switching to coformulated bictegravir, emtricitabine, and tenofovir alafenamide maintained viral suppression in adults with historical virological failures and K65N/R mutation.

OBJECTIVES: Real-world experience with coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is sparse as a switch regimen among people living with HIV (PLWH) having achieved viral suppression after previous virologic failures with the emergence of K65N/R. METHODS: In this retrospective study, PLWH aged ≥20 years who had previous virologic failures with emergent K65N/R were included for switching to BIC/FTC/TAF after having achieved plasma HIV RNA load (PVL) <200 copies/ml for ≥3 months. PLWH were excluded if integrase inhibitor resistance-associated mutations were detected. The primary end point was losing virologic control (PVL >50 copies/ml) at week 48 using a modified US Food and Drug Administration snapshot algorithm. RESULTS: A total of 72 PLWH with K65N/R who switched to BIC/FTC/TAF were identified. A total of 42 (59.7%) had concurrent M184V/I, and 9 (12.5%) had ≥1 thymidine analog mutations. The median duration of viral suppression was 4.7 years (interquartile range 2.3-5.8), and 97.2% (n = 70) had PVL <50 copies/ml before switching. After a median observation of 98.6 weeks (interquartile range 77.9-120.3), 94.4% (n = 68) continued BIC/FTC/TAF. At week 48, the rate of losing virologic control was 2.8% (2/72). M184V/I was not associated with viral rebound. CONCLUSION: Despite the emergence of K65N/R +/- M184V/I after virologic failures, BIC/FTC/TAF could be an option for simplification after viral suppression.

Care cascade of tuberculosis infection treatment for people living with HIV in the era of antiretroviral therapy scale-up.

Testing and treatment of tuberculosis infection (TBI) are recommended for people living with HIV (PLWH). We aimed to evaluate the care cascade of TBI treatment among PLWH in the era of antiretroviral therapy (ART) scale-up. This retrospective study included adult PLWH undergoing interferon-gamma release assay (IGRA)-based TBI screening during 2019-2021. PLWH testing IGRA-positive were advised to receive directly-observed therapy for TBI after active TB disease was excluded. The care cascade was evaluated to identify barriers to TBI management. Among 7951 PLWH with a median age of 38 years and CD4 count of 616 cells/mm3, 420 (5.3%) tested positive and 38 (0.5%) indeterminate for IGRA. The TBI treatment initiation rate was 73.6% (309/420) and the completion rate was 91.9% (284/309). More than 80% of PLWH concurrently received short-course rifapentine-based regimens and integrase strand transfer inhibitor (InSTI)-containing ART. The main barrier to treatment initiation was physicians' concerns and patients' refusal (85.6%). The factors associated with treatment non-completion were older age, female, anti-HCV positivity, and higher plasma HIV RNA. Our observation of a high TBI completion rate among PLWH is mainly related to the introduction of short-course rifapentine-based regimens in the InSTI era, which can be the strategy to improve TBI treatment uptake.

Real-world effectiveness of direct-acting antivirals in people living with human immunodeficiency virus and hepatitis C virus genotype 6 infections.

BACKGROUND: Hepatitis C virus (HCV) genotype 6 (HCV-6) infection is prevalent predominantly in Southeast Asia, and the data on the virologic response of HCV-6 to direct-acting antivirals (DAAs) are sparse in people living with human immunodeficiency virus (HIV) (PLWH). AIM: To assess the virologic response of HCV-6 to DAAs in PLWH. METHODS: From September 2016 to July 2019, PLWH coinfected with HCV-6 initiating DAAs were included. Laboratory investigations were performed at baseline, the end of treatment, and 12 wk off-therapy. RESULTS: Of the 349 PLWH included (mean age 48.9 years, 82.5% men), 80.5% comprised people who inject drugs, 18.1% men who have sex with men, and 1.4% heterosexuals. Coexistent hepatitis B virus infection was present in 12.3% of the included PLWH, liver cirrhosis 10.9%, hepatocellular carcinoma 0.9%, and previous HCV treatment experience 10.9%. The mean baseline plasma HCV RNA was 6.2 log10 IU/mL. Treatment with glecaprevir/pibrentasvir was initiated in 51.9%, sofosbuvir/ledipasvir 41.5%, sofosbuvir/velpatasvir 6.3%, and sofosbuvir/daclatasvir 0.3%. At DAA initiation, antiretroviral therapy containing tenofovir alafenamide was given in 26.4%, tenofovir disoproxil fumarate 34.4%, non-tenofovir alafenamide/tenofovir disoproxil fumarate 39.3%, non-nucleoside reverse-transcriptase inhibitors 30.4%, protease inhibitors 4.0%, and integrase strand transfer inhibitors 66.8%; 94.8% of the included patients had CD4 counts ≥ 200 cells/mm3 and 96.0% had plasma HIV RNA < 50 copies/mL. Overall, 96.8% achieved undetectable plasma HCV RNA (< 30 IU/mL) at end of treatment; and 92.3% achieved sustained virologic response 12 wk off-therapy in the intention-to-treat analysis (93.5% in patients receiving sofosbuvir-based DAAs and 91.2% in those receiving glecaprevir/pibrentasvir). CONCLUSION: Similar to the observation made in HIV-negative patients, sustained virologic response 12 wk off-therapy with DAAs is high in PLWH coinfected with HCV-6.

Changing epidemiology of shigellosis in Taiwan, 2010-2019: an emerging threat to HIV-infected patients and men who have sex with men.

Shigellosis appears to increase in certain at-risk populations in developed countries. Based on the nationwide surveillance, the annual incidence of shigellosis in Taiwan (1999-2019) was 0.38-5.77 cases per 100,000 people. Indigenous shigellosis has mostly affected men who have sex with men (MSM) and people living with HIV (PLWH) since 2015. In this retrospective study, compared with those diagnosed before 2015, indigenous cases diagnosed during 2015-2019 mostly occurred in male adults (96.0% vs 47.1%, P < 0.001), with a longer hospital stay (median 5.0 vs 3.5 days, P = 0.029) and different coinfections. The predominant strains in 2015 and 2016 were ciprofloxacin-resistant Shigella sonnei and azithromycin non-susceptible Shigella flexneri (S. flexneri) 3a, which had been replaced by ciprofloxacin-resistant S. flexneri 2a since 2018. Notably, six indigenous cases were caused by cefotaxime-resistant S. flexneri. Inappropriate use of empiric antibiotic treatment was common. In conclusion, there is an ongoing spread of ciprofloxacin-resistant shigellosis among PLWH and MSM and cefotaxime-resistant S. flexneri is an emerging threat in Taiwan.

Short-course daily isoniazid and rifapentine for latent tuberculosis infection in people living with HIV who received coformulated bictegravir/emtricitabine/tenofovir alafenamide.

INTRODUCTION: Short-course preventive therapy with 1-month course of daily administration of isoniazid (300-mg) plus rifapentine (600-mg) (1HP) and 3-month course of weekly administration of isoniazid (900-mg) plus rifapentine (900-mg) (3HP) has higher completion rates than 9-month course of daily isoniazid (9H) for individuals with latent tuberculosis infection (LTBI). We aimed to evaluate the effect, safety and tolerability of 1HP in people living with HIV (PLWH) and LTBI who received coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). METHODS: PLWH testing positive by interferon-gamma release assay and having received BIC/FTC/TAF for >2 weeks with plasma HIV RNA load (PVL) <200 copies/ml were enrolled. BIC trough plasma concentrations and cytokine profiles were determined before the first dose (day 1/baseline), 24 h after the 14th (day 15) and 28th (day 29) doses of 1HP. PVL were determined on days 15 and 29 of 1HP and every 3 months subsequently after discontinuation of 1HP. RESULTS: From November 2019 to December 2020, 48 PLWH with LTBI were enrolled. One participant (2.1%) discontinued 1HP on day 15 due to fever and generalized rashes with PVL of 72 copies/ml, which was <50 copies/ml in three subsequent determinations while on BIC/FTC/TAF over the 12 months of follow-up. The percentages of BIC trough plasma concentrations above the protein-adjusted 95% effective concentration (paEC95 = 162 ng/ml) were 56.3% and 37.0% on days 15 and 29, respectively. The percentage of PVL <200 copies/ml was 91.7% on day 15, 97.8% on day 29 and 100% at both months 3 and 6. After a median observation of 52 weeks (interquartile range, 51-55), all participants continued BIC/FTC/TAF with a median PVL of 20 copies/ml (range 20-331). Except for the participant who discontinued 1HP because of allergic reactions, none of the participants had relevant symptoms or increases of the cytokine levels assessed between baseline and days 15 and 29 of 1HP. CONCLUSIONS: BIC/FTC/TAF in combination with 1HP was well tolerated with a high completion rate. BIC trough plasma concentrations were significantly decreased with concurrent use of 1HP among PLWH with LTBI. While transient viral blips were observed during 1HP without causing subsequent treatment failure, such combination should be applied with caution.

Dual therapy with dolutegravir plus boosted protease inhibitor as maintenance or salvage therapy in highly experienced people living with HIV.

Real-world experience with dolutegravir (DTG) plus boosted protease inhibitor (bPI) as a two-drug regimen is limited for highly experienced HIV-positive patients with virological failure or intolerance to antiretroviral therapy. Patients receiving DTG plus bPI between September 2016 and June 2019 at 15 designated hospitals for HIV care in Taiwan were retrospectively included in this study. A standardised case record form was used to collect clinical data. The primary endpoint was virological response, defined as achieving or maintaining plasma HIV-RNA <50 copies/mL at Week 48. A total of 77 patients were included; 58 (75.3%) had documented genotypic resistance to 1-4 antiretroviral classes. The most commonly used PI was darunavir (87.0%; 67/77). Seven patients (9.1%) had no virological data at Week 48, including three with loss to follow-up, one severe hyperlipidaemia, one renal failure and cardiovascular disease, one superimposed HBV infection and one death from anal cancer. The virological response rate increased from 59.7% at baseline to 90.9% at Week 24 and 85.7% at Week 48. The only patient (1.3%) with virological failure at Week 48 had poor adherence and baseline low-level resistance to darunavir with resistance-associated mutations at M46L, I50V and V82A. Compared with baseline, mean total cholesterol increased by 20.1 mg/dL and weight by 2.8 kg at Week 48, while the estimated glomerular filtration rate decreased by 14.4 mL/min/1.73m2 (both P < 0.05). We conclude that a two-drug regimen containing DTG plus bPI was effective in highly-experienced HIV-positive patients, but metabolic impact and weight gain should be closely monitored.

Real-World Experience with Coformulated Ledipasvir and Sofosbuvir for HIV-Positive Patients with HCV Genotype 2 Infection: A Multicenter, Retrospective Study.

INTRODUCTION: While coformulated ledipasvir (90 mg)/sofosbuvir (400 mg) (LDV/SOF) is approved for the treatment of hepatitis C virus (HCV) genotype 2 (GT2) infection in Taiwan, Japan, and New Zealand, data regarding its use for HIV (Human Immunodeficiency Virus)-positive patients infected with HCV GT2 are sparse. We aimed to assess the effectiveness and tolerability of LDV/SOF for HIV-positive patients with HCV GT2 coinfection. METHODS: From January 2019 to July 2020, consecutive HIV-positive Taiwanese patients infected with HCV GT2 who received LDV/SOF were retrospectively included for analysis. The effectiveness was determined by sustained virologic response 12 weeks off-therapy (SVR12). RESULTS: Of the 114 patients (mean age, 38.6 years) initiating LDV/SOF during the study period, 0.9% had liver cirrhosis and 4.4% were HCV treatment-experienced. All patients had estimated glomerular filtration rate (eGFR) > 30 ml/min/1.73 m2 and were receiving antiretroviral therapy with 98.2% having CD4 counts ≥ 200 cells/mm3 and 93.9% plasma HIV RNA load < 50 copies/ml. Antiretrovirals prescribed included tenofovir alafenamide/emtricitabine in 42.1%, tenofovir disoproxil fumarate (TDF)/emtricitabine 18.4%, other nucleoside reverse transcriptase inhibitors (NRTIs) 39.5%, non-NRTIs 12.3%, protease inhibitors 13.2%, and integrase inhibitors 74.6%. All patients had undetectable plasma HCV RNA load at the end of treatment, and 96.5% achieved SVR12 in intention-to-treat analysis. The on-treatment eGFR decline was more pronounced in those receiving TDF-containing antiretroviral therapy (mean change, - 8.33 ml/min/1.73 m2), which was reversible after discontinuation of LDV/SOF. None of the patients interrupted LDV/SOF during the 12-week treatment course. CONCLUSION: Similar to the response observed among HIV-negative patients, LDV/SOF is effective for HIV-positive patients coinfected with HCV GT2.

Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide as Maintenance Treatment in HIV/HBV-Coinfected Patients.

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 ß2-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.

Sulbactam-enhanced cytotoxicity of doxorubicin in breast cancer cells.

BACKGROUND: Multidrug resistance (MDR) is a major obstacle in breast cancer treatment. The predominant mechanism underlying MDR is an increase in the activity of adenosine triphosphate (ATP)-dependent drug efflux transporters. Sulbactam, a ß-lactamase inhibitor, is generally combined with ß-lactam antibiotics for treating bacterial infections. However, sulbactam alone can be used to treat Acinetobacter baumannii infections because it inhibits the expression of ATP-binding cassette (ABC) transporter proteins. This is the first study to report the effects of sulbactam on mammalian cells. METHODS: We used the breast cancer cell lines as a model system to determine whether sulbactam affects cancer cells. The cell viabilities in the present of doxorubicin with or without sulbactam were measured by MTT assay. Protein identities and the changes in protein expression levels in the cells after sulbactam and doxorubicin treatment were determined using LC-MS/MS. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was used to analyze the change in mRNA expression levels of ABC transporters after treatment of doxorubicin with or without sulbactam. The efflux of doxorubicin was measures by the doxorubicin efflux assay. RESULTS: MTT assay revealed that sulbactam enhanced the cytotoxicity of doxorubicin in breast cancer cells. The results of proteomics showed that ABC transporter proteins and proteins associated with the process of transcription and initiation of translation were reduced. The mRNA expression levels of ABC transporters were also decreased when treated with doxorubicin and sulbactam. The doxorubicin efflux assay showed that sulbactam treatment inhibited doxorubicin efflux. CONCLUSIONS: The combination of sulbactam and doxorubicin enhances the cytotoxicity of doxorubicin in the breast cancer cells by inhibiting the expression of ABC transporter proteins and proteins associated with the process of transcription and initiation of translation, and blocking the efflux of doxorubicin. Co-treatment of doxorubicin and sulbactam can be used in breast cancer treatment to decrease the prescribed dose of doxorubicin to avoid the adverse effects of doxorubicin.

Less Severe but Prolonged Course of Acute Hepatitis A in Human Immunodeficiency Virus (HIV)-Infected Patients Compared With HIV-Uninfected Patients During an Outbreak: A Multicenter Observational Study.

Background: This multicenter retrospective cohort study aimed to compare the clinical presentations and evolution of acute hepatitis A (AHA) between human immunodeficiency virus (HIV)-infected patients and HIV-uninfected counterparts during the AHA outbreak. Methods: Clinical and laboratory data were collected from the medical records of the patients with AHA at the 14 hospitals around Taiwan between May 2015 and May 2017. Results: A total of 297 adult patients with AHA were included during the study period. Their mean age was 31.4 years (range, 19.0-76.1 years); 93.4% were men and 58.6% were men who have sex with men. Of 265 patients with known HIV serostatus, 166 (62.6%) were HIV infected. Compared with HIV-uninfected patients, HIV-infected patients had a lower peak alanine aminotransferase (ALT) level (median, 1312 vs 2014 IU/L, P = .003), less coagulopathy (6.0% vs 16.2%, P = .007), and less hepatomegaly or splenomegaly on imaging studies, but a higher rate of delayed resolution of hepatitis (38.8% vs 21.3%, P = .009). HIV-infected patients with plasma RNA load <1000 copies/mL while receiving combination antiretroviral therapy (cART) had a higher peak ALT level (median, 1420 vs 978 IU/L, P = .006) and less delay in resolution of hepatitis (30.6% vs 48.8%, P = .047) than patients without cART or with plasma RNA load ≥1000 copies/mL. Conclusions: During an AHA outbreak, HIV-infected patients had a lower severity, but delayed resolution, of AHA than HIV-uninfected patients. Better viral suppression by cART alleviated the impact of HIV infection on the disease course of AHA in HIV-infected patients.

Risk factors and clinical outcome of sulbactam nonsusceptibility in monomicrobial Acinetobacter nosocomialis bacteremia.

BACKGROUND: Sulbactam is an effective antimicrobial agent against multidrug-resistant Acinetobacter spp. This retrospective study evaluated the risk factors of sulbactam nonsusceptibility (SNS) in monomicrobial Acinetobacter nosocomialis bacteremia and its related outcome. METHODS: This 9-year retrospective study included 267 patients who were admitted to a large teaching hospital in Taiwan with monomicrobial A. nosocomialis bacteremia. A. nosocomialis was identified to the species level using molecular methods. Antimicrobial susceptibilities were determined by the agar dilution method. To identify the risk factors of acquiring resistant strains, significant clinical variables derived from univariate analysis were entered into multivariate analysis. Polymerase chain reaction was used to identify blaTEM. Clonality was determined by pulsed-field gel electrophoresis. RESULTS: A total of 41 of the 267 patients (15.4%) had SNS A. nosocomialis bacteremia. Compared to those with susceptible strains, these patients had higher 14-day mortality (17.1% vs. 7.5%, p = 0.049), were more likely to have higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, were more frequently admitted to the intensive care unit, and had previously received broad-spectrum antibiotics and underwent invasive procedures. In multivariate analysis, the independent risk factors were high APACHE II score and prior use of arterial line [odds ratio (OR), 1.048; 95% confidence interval (CI), 1.007-1.091; p = 0.022 and OR, 2.936; 95% CI, 1.339-6.441; p = 0.007, respectively]. No outbreak was identified and SNS isolates did not harbor blaTEM. CONCLUSION: For monomicrobial A. nosocomialis bacteremia, the mortality of patients with SNS strains was higher. The SNS strains are more commonly recovered from patients with higher APACHE score and receiving more invasive procedures, especially arterial line.

Efficacy of tigecycline for secondary Acinetobacter bacteremia and factors associated with treatment failure.

We describe the clinical outcome of 17 patients with secondary Acinetobacter bacteremia whose isolates had a tigecycline MIC of ≤2 mg/liter and who received tigecycline within 2 days of bacteremia onset. The 14-day mortality rate of the tigecycline cohort was 41.2% (7/17), which was significantly higher than that of those receiving other appropriate antimicrobial agents (13.8%, 9/65; P = 0.018). However, the percentages of end-stage renal disease and congestive heart failure were higher in the tigecycline cohort. The efficacy of tigecycline was contingent upon the illness severity and bacterial species. Tigecycline should be applied cautiously for treatment of Acinetobacter bacteremia.