Hypogonadism among HIV-positive men who have sex with men in Taiwan: Prevalence and associated factors.

BACKGROUND: Male hypogonadism is not uncommon in people with HIV (PWH), with estimated prevalence ranging from 9% to 16%. Existing data are limited on the serum testosterone levels in PWH in Asian populations. METHODS: We enrolled HIV-positive men who have sex with men (MSM) and had been on stable antiretroviral therapy and MSM without HIV between February 2021 and November 2022. Serum free testosterone levels, sex hormone-binding globulins and other associated hormones were measured. Multiple linear regression analysis was performed to assess the association between serum free testosterone levels and clinical variables collected. RESULTS: A total of 447 MSM with HIV and 124 MSM without HIV were enrolled. Compared with MSM without HIV, MSM with HIV had a higher age (median, 41 versus 29.5 years) and prevalence of symptomatic hypogonadism (8.3% versus 1.6%). Among MSM who were aged <35 years, there were no significant differences in the serum free testosterone levels and prevalences of hypogonadism between the two groups. In multiple linear regression analysis, serum free testosterone level significantly decreased with advanced age (a decrease of 1.14 pg/mL per 1-year increase) and a higher body-mass index (BMI) (a decrease of 1.07 pg/mL per 1-kg/m2 increase), but was not associated with HIV serostatus. CONCLUSION: We found that MSM with HIV had a higher prevalence of symptomatic hypogonadism than MSM without HIV in Taiwan, which could be attributed to age difference. Serum free testosterone levels were negatively correlated with age and BMI, but did not show a significant correlation with HIV serostatus.

Effectiveness and evolution of anti-SARS-CoV-2 spike protein titers after three doses of COVID-19 vaccination in people with HIV.

BACKGROUND: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). METHODS: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-µg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months. RESULTS: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-µg mRNA-1273, 467 (32.8%) 50-µg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-µg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). CONCLUSIONS: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-µg mRNA-1273 could generate a higher antibody response than with 50-µg mRNA-1273 and BNT162b2 vaccine.

Under-utilization of statins among people with HIV who were aged 40 years or older.

From June 2022 to April 2023, 1629 HIV-positive participants were assessed for the risk of atherosclerotic cardiovascular disease (ASCVD). The 10-year ASCVD risk of <5 %, 5 % to <7.5 %, ≥7.5 % to <20 % and ≥20 % were 59.9 %, 14.4 %, 20.7 % and 5.0 %, respectively; 440 (27.0 %) participants met the criteria for statin therapy, but only 171 (38.8 %) were prescribed statins.

Weight and metabolic changes among virally suppressed people with HIV who switched to co-formulated bictegravir/emtricitabine/tenofovir alafenamide.

OBJECTIVES: We aimed to investigate the evolution of weight, lipid profiles, and glucose homeostasis among virally suppressed people with HIV (PWH) who switched to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). METHODS: PWH with viral suppression who switched to BIC/FTC/TAF in Taiwan between October 2019 and May 2021 were followed for 96 weeks to examine changes in weight, lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG)), and glycated hemoglobin (HbA1c) levels. RESULTS: 889 PWH with an average weight of 72.1 kg at baseline were included. At week 96, more than 95% of PWH consistently maintained plasma HIV RNA load <50 copies/mL at each 24-week interval of follow-up, while the weight change was small (+0.7 kg, P < 0.0001), although statistically significant. Baseline levels of TC, LDL-C, HDL-C, TG, and HbA1c were 191.8 mg/dL, 114.2 mg/dL, 48.9 mg/dL, 174.3 mg/dL, and 5.31%, respectively. After 96 weeks, changes were observed in TC (-11.6 mg/dL, P < 0.0001), LDL-C (-3.4 mg/dL, P = 0.0084), HDL-C (+0.6 mg/dL, P = 0.1089), TG (-30.2, P < 0.0001), and HbA1c (+0.12%, P < 0.0001). A 5% or more weight gain was associated with age of 30-40 years, normal weight at baseline, and prior use of non-integrase inhibitors or tenofovir disoproxil fumarate. Obesity was associated with development of both dyslipidaemia and diabetes mellitus after switch. CONCLUSIONS: Stable switch to BIC/FTC/TAF maintained high rates of viral suppression and had a small effect on weight and metabolic changes in virally suppressed PWH. Follow-up of the weight and metabolic changes is warranted in PWH on long-term antiretroviral therapy.

Patient-reported outcomes among virally suppressed people living with HIV after switching to Co-formulated bictegravir, emtricitabine and tenofovir alafenamide.

BACKGROUND: While some evidence has suggested the benefits of co-formulated bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) in improving the quality of life of people living with HIV (PLWH), patient-reported outcome studies that focus on Asian population remain scarce. We aimed to determine the changes in HIV-related symptom burden in virally-suppressed PLWH switching to B/F/TAF in a real-world setting. METHODS: PLWH on stable antiretroviral therapy (ART) for ≥6 months with plasma HIV RNA <200 copies/mL who decided to switch to B/F/TAF were eligible for the study. Participants' experience with 20 symptoms were assessed using HIV Symptom Index at baseline and weeks 24 and 48. Responses were dichotomized in two ways: 1) present vs. not present; and 2) bothersome vs. not bothersome, and compared across time points. RESULTS: Six hundred and thirty participants (prior regimen, 94.4% integrase inhibitor-based) who completed week 48 visit were included in the analysis. Forty-eight weeks after switching to B/F/TAF, six symptoms were significantly less prevalent, and seven symptoms were significantly less bothersome. Improvement was more pronounced in participants whose prior regimen was elvitegravir-based versus dolutegravir-based. Logistic regression results showed that prior dolutegravir-based ART and pre-existing diabetes independently predicted improvement in diarrhea/loose bowels and muscle aches/joint pain, respectively. Despite the overall improvement, some symptoms persisted in a substantial proportion of participants. CONCLUSIONS: Virally-suppressed PLWH might benefit from a regimen switch to B/F/TAF to reduce the prevalence and level of bother of HIV-related symptoms. Nevertheless, additional multidisciplinary interventions are warranted to further alleviate the symptom burden of PLWH.

Cost-effectiveness of PARP inhibitors in malignancies: A systematic review.

OBJECTIVES: Poly (ADP-ribose) polymerase inhibitor (PARPi) have become a mainstay for the treatment of BRCA-mutant malignancies. PARPis are likely to be more effective but also bring an increase in costs. Thus, we aimed at evaluating the cost effectiveness of PARPis in the treatment of malignancies. METHODS: Studies of cost effectiveness of PARPis were searched from PubMed, Web of Science, and Cochrane Library. Key information was extracted from the identified studies and reviewed. Quality of the included studies was evaluated using Quality of Health Economic Studies (QHES) instrument. Modeling techniques, measurement of parameters and uncertainty analysis were analyzed across studies. Interventions and cost-effectiveness results were reported stratified by patient population. RESULTS: Among the 25 studies identified, we included 17 on ovarian cancer, 2 on breast cancer, 3 on pancreatic cancer, and 3 on prostate cancer that involved olaparib, niraparib, rucaparib, and talazoparib. All studies had a QHES score of above 75. In the maintenance therapy of ovarian cancer, additional administration of olaparib was cost-effective for newly diagnosed patients after first-line platinum-based chemotherapy but was not cost-effective for platinum-sensitive recurrent patients in majority studies. However, the economic value of other PARPis in ovarian cancer as well as all PARPis in other tumors remained controversial. Cost-effectiveness of PARPi was primarily impacted by the costs of PARPi, survival time, health utility and discount rate. Moreover, genetic testing improved the cost-effectiveness of PARPi treatment. CONCLUSIONS: PARPi is potentially cost-effective for patients with ovarian, pancreatic, or prostate cancer. Genetic testing can improve the cost-effectiveness of PARPi.

Evolution of anti-SARS-CoV-2 spike protein titers after two-dose of COVID-19 vaccination among people living with HIV.

Background: A community COVID-19 outbreak caused by the B.1.1.7 SARS-CoV-2 variant occurred in Taiwan in May 2021. High-risk populations such as people living with HIV (PLWH) were recommended to receive two doses of COVID-19 vaccines. While SARS-CoV-2 vaccines have demonstrated promising results in general population, real-world information on the serological responses remains limited among PLWH. Methods: PLWH receiving the first dose of SARS-CoV-2 vaccine from 2020 to 2021 were enrolled. Determinations of anti-SARS-CoV-2 spike IgG titers were performed every one to three months, the third dose of the SARS-CoV-2 vaccine or confirmed SARS-CoV-2 infection. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from analysis. Results: A total of 1189 PLWH were enrolled: 829 (69.7%) receiving two doses of the AZD1222 vaccine, 232 (19.5%) of the mRNA-1273 vaccine, and 128 (10.8%) of the BNT162b2 vaccine. At all time-points, PLWH receiving two doses of mRNA vaccines had consistently higher antibody levels than those receiving the AZD1222 vaccine (p <0.001 for all time-point comparisons). Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/mL within 12 weeks, included type 2 diabetes mellitus (DM) (adjusted odds ratio [aOR], 2.24; 95% CI, 1.25-4), a CD4 T cell count <200 cells/mm3 upon receipt of the first dose of vaccination (aOR, 3.43; 95% CI, 1.31-9) and two homologous AZD1222 vaccinations (aOR, 16.85; 95%CI, 10.13-28). For those receiving two doses of mRNA vaccines, factors associated with failure to achieve an anti-spike IgG titer >899 BAU/mL within 12 weeks were a CD4 T cell count <200 cells/mm3 on first-dose vaccination (aOR, 3.95; 95% CI, 1.08-14.42) and dual BNT162b2 vaccination (aOR, 4.21; 95% CI, 2.57-6.89). Conclusions: Two doses of homologous mRNA vaccination achieved significantly higher serological responses than vaccination with AZD1222 among PLWH. Those with CD4 T cell counts <200 cells/mm3 and DM had consistently lower serological responses.

Low-level viraemia and virologic failure among people living with HIV who received maintenance therapy with co-formulated bictegravir, emtricitabine and tenofovir alafenamide versus dolutegravir-based regimens.

Real-world experience with low-level viraemia (LLV) and its impact remain less reported among people living with HIV (PLWH) who receive antiretroviral therapy (ART) containing second-generation integrase strand transferase inhibitors, including dolutegravir and bictegravir. This retrospective cohort study included virally suppressed PLWH who achieved plasma HIV-RNA viral load (PVL) <50 copies/mL for ≥6 months and were switched to either dolutegravir- or bictegravir-based ART. Incidence rates of developing LLV events (PVL, 50-200 copies/mL) and virologic failure (VF) (PVL ≥1000 copies/mL) were compared between the dolutegravir and bictegravir cohorts. A total of 623 and 862 PLWH switched to dolutegravir-based and bictegravir-based ART, respectively, were included. The incidence rate of developing LLV was 6.2 per 100 person-years of follow-up (PYFU) in the bictegravir cohort and 3.8 per 100 PYFU in the dolutegravir cohort [incidence rate ratio (IRR) = 1.63, 95% confidence interval (CI), 0.90-2.95; P = 0.08], while rates of VF were 0.69 per 100 PYFU and 0.95 per 100 PYFU, respectively, in the bictegravir and dolutegravir cohorts (IRR = 0.72, 95% CI 0.12-3.39; P = 0.34). Presence of LLV events was not associated with subsequent VF in multivariate analysis. Secondary analysis also demonstrated that resistance-associated mutations (RAMs) to nucleoside reverse transcriptase inhibitors (NRTIs) before switch were not associated with adverse virologic outcomes in either cohort. In conclusion, among virally suppressed PLWH, the incidences of developing LLV or VF were similar after switch to dolutegravir- or bictegravir-based ART. Pre-existing RAMs to NRTIs or LLV events were not associated with subsequent VF.

Pharmacist-led standardization of total parenteral nutrition improves postoperative nutritional status in colorectal cancer patients.

Background: Total parenteral nutrition (TPN) is an essential treatment for patients who undergo abdominal surgery. Due to the gap of knowledge background between clinicians and pharmacists, the participation of the latter may improve TPN standardization. However, the impact on clinical outcome is unknown. In this study, we evaluated the impact of appropriacy and efficacy of TPN prescription, after a pharmacist-led TPN standardization program introduced. Methods: A pharmacist-led TPN standardization program was introduced in the Zhejiang Cancer Hospital and the clinical outcomes were assessed. The TPN standardization program includes a pre-established standard multidisciplinary evaluation standard, a computerized TPN management system and regular evaluations of TPN prescription performed by pharmacists. Any concerns were identified and improved via discussed with doctors. To evaluate the effect of pharmacists' intervention in nutritional status and postoperative complications, an observational before-and-after cohort study was performed. All patients admitted in hospital with colorectal cancer (CRC) and receiving abdominal surgery in June 2019 (pre-intervention cohort) and June 2020 (post-intervention cohort) were retrospectively analyzed. Nutritional status of patients was evaluated using the levels of postoperative serum albumin, prealbumin, total protein, and their decrease extent. Surgical or TPN-related complications and recovery time were collated as the clinical outcomes. Results: There were no significant differences in the basic clinical information of the two cohorts, suggesting that the two groups are comparable. The average postoperative prealbumin levels were elevated in 2020 compared to 2019 (192.3±5.5 mg/L for 2019 and 229.5±4.8 mg/L for 2020, P<0.001). In addition, the post-intervention cohort showed a lower postoperative infection rate (11.6% vs. 18.2%), shorter duration of infection (9.4±1.4 vs. 7.7±1.0 days), lower incidence of postoperative albumin decrease (25.2% vs. 76.7%), prealbumin decrease (71.5% vs. 78.9%), and total protein decrease (25.2% vs. 72.2%), and lower incidence of TPN-related hypoglycemia (5.4% vs. 15.3%). Conclusions: Pharmacist-led TPN standardization improved the postoperative clinical outcomes in patients with colorectal cancer (CRC).

Pharmacist-Led Management Improves Treatment Adherence and Quality of Life in Opioid-Tolerant Patients With Cancer Pain: A Randomized Controlled Trial.

INTRODUCTION: Opioid-tolerant patients are more likely to deviate from recommended treatments and to experience inadequate analgesia than opioid-naive ones. The aim of this study was to examine whether pharmacist-led management could help improve treatment adherence and quality of life. METHODS: Eligible patients were randomized in a 1:1 ratio to control group and intervention group. The control group received routine education and support, while the intervention group received additional individualized pharmacist-led care. The primary endpoint was treatment adherence in the per-protocol analysis, as evaluated by blinded assessors. An interim analysis was planned when 30% patients completed the study. Alpha was divided into the interim analysis (0.015) and the final analysis (0.035). RESULTS: In the interim analysis (97 and 87 patients in the control and intervention groups, respectively), the primary endpoint was met. Pharmacist-led intervention significantly increased treatment adherence (93.3 vs. 79.8%; OR: 2.25; 95% CI 1.02, 4.94; P = 0.013), quality of life (0.81 ± 0.17 vs. 0.72 ± 0.25; P = 0.008), and reporting of adverse events (82.7 vs. 61.9%; OR: 1.88; 95% CI 1.16, 3.07; P = 0.004). The two groups did not differ in pain control rate (66.7 vs. 57.1%; OR: 1.25; 95% CI 0.87, 1.78; P = 0.218), breakthrough pain-free rate (66.7 vs. 61.9%; OR: 1.12; 95% CI 0.78, 1.59; P = 0.532) and pain score (1.97 ± 1.04 vs. 2.15 ± 1.24; P = 0.522). CONCLUSIONS: Pharmacist-led management improved treatment adherence, quality of life, and the reporting of adverse events in opioid-tolerant patients with cancer pain. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03455023.

Use of dietary supplements containing polyvalent cations and antacids among people with HIV and its impact on viral suppression.

Dietary supplements and medications containing polyvalent cations can interact with integrase strand transfer inhibitors (INSTIs) and decrease exposure to INSTIs. In this cross-sectional study of 513 people with HIV (PWH) who were on stable antiretroviral therapy, 57.5% and 6.6% reported concurrent use of dietary supplements and antacids, respectively. In the multivariable analysis, the use of antacids, but not dietary supplements containing polyvalent cations, was associated with HIV viremia in PWH who received INSTI-based ART.

Comparison of Proteomics Profiles Between Xenografts Derived from Cell Lines and Primary Tumors of Thyroid Carcinoma.

Patient-consistent xenograft model is a challenge for all cancers but particularly for thyroid cancer, which shows some of the greatest genetic divergence between human tumors and cell lines. In this study, proteomic profiles of tumor tissues from patients, included anaplastic thyroid carcinoma (ATC) and papillary thyroid carcinoma, and xenografts (8305C, 8505C, FRO, BAPAP and IHH4) were obtained using HPLC-tandem mass spectrometry and compared based on all proteins detected (3,961), cancer-related proteins and druggable proteins using pairwise Pearson's correlation analysis. The human tissue showed low proteomic similarity to the ATC cell lines (8305C, r = 0.344-0.416; 8505C, 0.47-0.579; FRO, 0.267-0.307) and to PTC cell lines (BCPAP, 0.303-0.468; IHH4, 0.262-0.509). Human tissue showed the following similarity to cell lines at the level of 135 cancer-related pathways. The ATC cell lines contained 47.4% of the cancer-related pathways (19.26%-33.33%), while the PTC cell lines contained 40% (BCPAP, 25.93%; IHH4, 28.89%). In patient tumor tissues, 44-60 of 76 and 52-53 of 93 druggable proteins were identified in ATC and PTC tumors, respectively. Ten and 29 druggable proteins were not identified in any of the ATC and PTC xenografts, respectively. We provide a reference for CDX selecting in in vivo studies of thyroid cancer.

Ongoing transmission of Entamoeba histolytica among newly diagnosed people living with HIV in Taiwan, 2009-2018.

Recent outbreaks of enterically transmitted infections, including acute hepatitis A and shigellosis, have raised the concerns of increasing Entamoeba histolytica infection (EHI) among people living with HIV (PLWH) in Taiwan. This study investigated the prevalence of EHI, its temporal trends, and associated factors among newly diagnosed PLWH in Taiwan. Medical records of newly diagnosed PLWH at six medical centers in Taiwan between 2009 and 2018 were reviewed. The annual prevalence of invasive amoebiasis and seroprevalence of E. histolytica were determined and examined by the Cochran-Armitage test. The clinical characteristics associated with invasive amoebiasis and seropositivity for E. histolytica were analyzed in multivariable regression models. Among 5362 patients seeking HIV care at six medical centers in Taiwan during the 10-year study period, 119 (2.2%) had invasive amoebiasis at the time or within six months of their HIV diagnosis. Among 3499 who had indirect hemagglutination antibody (IHA) determined, 284 (8.1%) had positive IHA (≥1:32) and 205 (5.9%) had high-titre IHA (≥1:128). The prevalence of invasive amoebiasis increased from 1.3% in 2012 to 3.3% in 2018 (p = 0.024). Invasive amoebiasis was independently associated with a greater age, men who have sex with men, rapid plasma reagin titre ≥1:4, and concurrent shigellosis and giardiasis. Increasing prevalence of invasive amoebiasis among newly diagnosed PLWH in Taiwan calls for strategies to prevent ongoing transmission in this population. Routine screening of EHI for early diagnosis and treatment is recommended, especially among men who have sex with men and those who present with other sexually or enterically transmitted infections.

Predictors and impact of cytotoxic second-line chemotherapy for stage IIIa-IV nonsmall lung cancer patients in China: A retrospective institution analysis of 132 patients.

OBJECTIVE: To investigate the predictors and impact of cytotoxic second-line chemotherapy for stage IIIa-IV nonsmall cell lung cancer (NSCLC) patients in China. METHODS: Medical records of 132 patients who underwent chemotherapy from January 2008 to December 2010 in our hospital were retrospectively reviewed. The response of first-line gemcitabine (GEM) and platinum doublets chemotherapy was evaluated, and the overall survival (OS) of all patients was followed. Further, risk factors of receipt cytotoxic second-line chemotherapy or not were identified and evaluated by univariate analyses. RESULTS: Sixty-six cases have undergone cytotoxic second-line chemotherapy for lung cancer. The OS between patients received first-line GEM plus platinum doublets chemotherapy and patients without cytotoxic second chemotherapy had no statistical difference (P = 0.73). Smoking or not might be a meaningful predictor for cytotoxic second-line therapy among these patients in this investigation (P < 0.05). Other factors, such as age (≥ 65 or < 65), gender, alcohol use, hypertension, diabetes mellitus, histology type, number of cycles of first-line chemotherapy, and response of first-line chemotherapy had no statistical difference between patients received first-line GEM plus platinum doublets chemotherapy and patients received cytotoxic second chemotherapy (P > 0.05). In the sub-analysis, we found that the OS between patients received first-line GEM plus platinum doublets chemotherapy and patients without cytotoxic second chemotherapy had statistical difference in the population whose OS < 540 days (P = 0.019). Moreover, in these patients, the blood type was found to be a selected factor in receiving cytotoxic second-line chemotherapy or not (P < 0.05). Whereas other factors were not shown their selected effect (P > 0.05). CONCLUSION: This study demonstrated that though the essentiality of cytotoxic second-line chemotherapy for stage IIIa-IV EGFR mutation indefinite NSCLC is unclear, patients who are blood type AB with poor prognosis and short OS might be a dominant population for cytotoxic second-line chemotherapy.