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.

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.

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.

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.

Molecular Evaluation of Traditional Chicken Farm-Associated Bioaerosols for Methicillin-Resistant Staphylococcus aureus Shedding.

The outbreak of airborne pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) through bioaerosol, and their molecular characterization around domestic poultry farming areas, was not completely understood. This imposes risk of a MRSA-associated health threat for the relevant livestock food production units. To address this issue, the present study investigated the role of bioaerosol in transmitting MRSA strains in poultry house settings by combining molecular typing, phylogenetic classification, antibiotic susceptibility, and virulence gene distribution patterns. The present study highlights that all 18 bioaerosol and stool samples collected were MRSA positive, with a unique set of virulence factors. Out of 57 isolated MRSA isolates, 68.4% and 19.3% consisted of SCCmec I and IV elements, respectively, which are commonly linked with hospital-acquired and livestock-associated MRSA strains. It is worth noting that the exfoliative toxin eta and etb genes were carried by 100% and 70.2% of all isolates, respectively. Only 17.5% of strains showed the presence of enterotoxin entC. These MRSA isolates were resistant to chloramphenicol (C), ciprofloxacin (CIP), clindamycin (DA), erythromycin (E), and tetracycline (T), signifying their multi-drug resistance traits. A cluster of phylogenetic analysis described that 80.7% and 15.8% of total isolates belonged to Staphylococcus aureus protein A (spa) type t002 and t548. Whereas 3.5% were reflected as a new spa type. Additionally, as per the chi-squared test score value, these two spa types (t002 and t548) have a distribution correlation with HA-MRSA and LA-MRSA in all the samples (p < 0.005, chi-squared test; degree of freedom = 1). Ultimately, this study highlights the prevalence of MRSA colonization in the conventional poultry farm environment, showing the risk of bioaerosol transmission, which needs epidemiological attention and prevention strategies.

Characteristics of HIV-positive pregnant women and HIV- and antiretroviral therapy-exposed fetuses: A case-control study.

INTRODUCTION: This study determined risk factors, obstetric comorbidities, and fetal conditions among HIV-positive mothers to improve their maternal care. METHODOLOGY: This retrospective case-control study included HIV-positive pregnant women 18 years of age or older and age-, parity-, and delivery method-matched HIV-negative controls between 2011 and 2018. Those who had stillbirth were excluded. Baseline demographics, labor process, CD4 count, plasma HIV viral load, and antiretroviral therapy (ART) regimen were recorded. Fetal conditions were recorded as well. RESULTS: Forty HIV-positive women (45 parities; 22 via NSD, 23 via C/S) were included, with 45 HIV-negative parities as controls. Twenty-nine (72.5%) HIV-positive women had illicit drug use. In the HIV-positive group, 17% received ART prior to first perinatal visit, and 75.6% reached viral suppression pre-delivery. Zidovudine and ritonavir-boosted lopinavir were the majorly prescribed ART. Mild perineal lacerations via NSD were observed in HIV-positive women. Fetal body weight was lower in HIV- and ART-exposed fetuses (2665 vs 3010 g, p < 0.001). Preterm delivery PTB (28.9% vs 8.9%, p= 0.015) and small-for gestational age SGA (28.9% vs 8.8%, p = 0.003) rates were higher in the HIV-positive group. There was no vertical transmission of HIV. CONCLUSIONS: HIV-positive women tend to deliver fetuses with low body weight and have higher SGA and PTB rates. Given that most women received zidovudine and protease inhibitors, benefits of newer agents for HIV-positive pregnancies should be studied.

Dual therapy with ritonavir-boosted protease inhibitor (PI) plus lamivudine versus triple therapy with ritonavir-boosted PI plus two nucleos(t)ide reverse-transcriptase inhibitor in HIV-infected patients with viral suppression.

BACKGROUND: Dual antiretroviral regimens are attractive options to optimize the combination antiretroviral therapy in light of potential toxicities with long-term cumulative exposure to nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). METHODS: In this retrospective observational study, we included HIV-infected patients on suppressive antiretroviral therapy with plasma viral load (PVL) < 200 copies/mL for at least 6 months who were switched to dual regimens containing lamivudine (3TC) (150 mg twice daily or 300 mg once daily) plus lopinavir/ritonavir (LPV/r) 250/50 mg twice daily or darunavir/ritonavir (DRV/r) 800/100 mg once daily. Patients maintaining on suppressive triple therapy with DRV/r or LPV/r plus two NRTIs were included for comparisons. The primary endpoint was the proportion of patients with PVL <50 copies/mL after 48 weeks of follow-up. RESULTS: In total, 364 patients were included with 93 (25.5%) switched to dual therapy After 48 weeks of observation, PVL <50 copies/mL was observed in 96.8% and 94.1% of dual-therapy and triple-therapy group, respectively, in per-protocol analysis (difference 2.7%; 95% CI -2.5%-7.9%). Nineteen patients (3 [3.2%] in dual-therapy and 16 [7.6%] in triple-therapy group) developed virologic failure, with none having emergent M184V resistance-associated mutation. A statistically significant increase of cholesterol level (13 mg/dL versus 2 mg/dL, p = 0.003) and high-density lipoprotein (3 mg/dL versus -2 mg/dL, p = 0.019) were observed in dual-therapy than in triple-therapy group. Changes of triglyceride, low-density lipoprotein and glycated hemoglobin levels were similar between the two groups. CONCLUSION: Dual therapy with DRV/r or LPV/r plus lamivudine demonstrated similar effectiveness in maintaining viral suppression to triple therapy.

Clinical features of acute human immunodeficiency virus infection in Taiwan: A multicenter study.

BACKGROUND/PURPOSE: Acute HIV infection is characterized by a high concentration of HIV RNA in the plasma and rapid depletion of the CD4 cell count. This multicenter, retrospective observational study aimed to characterize the manifestations of acuteHIV infection in Taiwan. METHODS: Between 1 January 2012 and 31 December 2016, all patients aged 20 years or greater who presented with acute HIV infection were included. Demographic and clinical characteristics of the patients at diagnosis were collected. Baseline laboratory assessment included hemogram, CD4 count, plasma HIV RNA load (PVL), serologic markers of syphilis and hepatitis A, B, and C viruses, and serum biochemistry. RESULTS: The proportion of acute HIV infection was 6.9% among the patients with newly diagnosed HIV infection during the study period. The most common presenting symptoms of acute HIV infection were fever, fatigue, and myalgia. The median PVL at diagnosis was 5.9 log10 copies/ml, and median CD4 count was 307 cells/mm3. A total of 68 patients (27%) had baseline CD4 count less than 200 cells/mm3. Multiple logistic regression analysis, showed that the baseline CD4 count (OR, 4.02; p = 0.013) and aspartate aminotransaminase levels (OR, 3.49; p = 0.002) were associated with high PVL (>5 log10 copies/ml); and high baseline PVL (OR, 2.64; p = 0.002) was associated with symptomatic acute HIV infection. CONCLUSIONS: Manifestations of acute HIV infection are nonspecific and of wide spectrum ranging from fever to severe illness. A higher proportion of patients with initial CD4 counts of 200 cells/mm3 or less during acute HIV infection warrants early, timely diagnosis and treatment to prevent rapid disease progression.