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.

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.

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.

Non-opioid recreational drug use and a prolonged HIV outbreak among men who have sex with men in Taiwan: An incident case-control study, 2006-2015.

BACKGROUND/PURPOSE: Limited data are available on the role of illicit non-injecting drug use in a prolonged HIV outbreak that predominantly affected men who have sex with men (MSM) in Taiwan since 2006. We aimed to assess associations between specific types of drug use and incident HIV infections in this outbreak. METHODS: We conducted a retrospective case-control study among MSM clients at voluntary counselling and testing (VCT) service at National Taiwan University Hospital (Taipei, Taiwan). We used BED IgG-capture enzyme immunoassay to identify incident HIV infection (cases), individually matched to HIV-negative MSM clients (controls) by HIV testing date. We used a structured questionnaire to obtain the information on illicit drug use and sexual risk behaviors. RESULTS: From a total of 15,305 MSM client visits during 2006-2015, 387 cases were matched to 1012 controls. Use of inhaled nitrites (adjusted odds ratio [aOR] 2.1), MDMA (aOR 2.9), amphetamines (aOR 1.6), and ketamine (aOR 1.5) were independently associated with incident HIV infection. Polydrug (≥2 drugs) use was associated with the highest risk (aOR 4.3; 95% CI 2.6-7.2). While the proportion of MSM VCT clients who reported use of any recreational drug remained stable during 2006-2015 (average: 9.7%, P: 0.38), there was a shift in specific types of drug use, from MDMA/ketamine to inhaled nitrites/amphetamine, after 2011 (all Ps < 0.05). CONCLUSION: Non-opioid recreational drugs use is associated with incident HIV infection in this prolonged HIV outbreak. There is an urgent need to formulate an effective public health response to mitigate the risk.

Participation in cancer screening among people living with HIV at a university hospital.

Between March and October, 2018, 1248 people living with HIV completed questionnaire interviews for cancer screening, of whom 46.9% (n = 585) completed free-of-charge cancer screening. Time constraint (50.1%) was the most common reason provided for refusal to participate in cancer screening. None of the participants were diagnosed with any of the four cancers.

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.

Estimated risk of cardiovascular disease among the HIV-positive patients aged 40 years or older in Taiwan.

BACKGROUND: Cardiovascular disease (CVD) is an emerging cause of morbidity and mortality among HIV-positive patients receiving successful combination antiretroviral therapy, but their CVD risk has been rarely investigated in Asia-Pacific region. We aimed to assess the CVD risk of HIV-positive Taiwanese outpatients. METHODS: We did cross-sectional questionnaire interviews to collect information of HIV-positive Taiwanese patients aged 40-79 at the HIV clinics of a medical center from 1 March to 31 August, 2017. The Framingham Risk Score (FRS), Atherosclerotic Cardiovascular Disease (ASCVD) risk score and Data-Collection on Adverse effects of Anti-HIV Drugs (D:A:D) risk score were used to estimate their CVD risk. RESULTS: Of the screened 1251 patients, 1006 (80.4%) with complete data to assess their CVD risk were included for analyses. The prevalence of patients aged 40-75 and with a high CVD risk was 30.6% by FRS, 3.7% by D:A:D (R) risk score, and 22.2% by ASCVD risk score. In multiple logistic regression, older age, current smoking, higher systolic blood pressure, and higher triglyceride and fasting glucose levels were independently associated with the ASCVD risk score ≥7.5%. If current smokers aged 55-59 had stopped smoking, the proportions of them with a 10-year CVD risk of ≥10% by FRS and ≥7.5% by ASCVD risk score would have decreased by 35.3% and 20.0%, respectively. CONCLUSIONS: Higher CVD risk estimates among HIV-positive Taiwanese aged 40-75 were associated with an older age, current smoking, higher systolic blood pressure, hypertriglyceridemia, and hyperglycemia. Smoking cessation could potentially lead to significant decreases of CVD risk.

Pretreatment triglycerides-to-high density lipoprotein cholesterol ratio in postmenopausal women with endometrial cancer.

Raised triglycerides (TG) and reduced high density lipoprotein cholesterol (HDL-c) are components of metabolic syndrome. Both high TG and metabolic syndrome have been reported to be risk factors of endometrial cancer. Therefore, triglycerides-to-high density lipoprotein cholesterol ratio (TG/HDL-c ratio) may be a useful biological indicator in managing endometrial cancer. We aimed to explore the association between pretreatment TG/HDL-c ratio and endometrial cancer in postmenopausal women, and to evaluate its potential role in the disease. Pretreatment serum lipid profile and TG/HDL-c ratio were retrospectively analyzed for 167 postmenopausal women with endometrial cancer and 464 matched noncancer controls. Compared with controls, pretreatment TG/HDL-c ratio in endometrial cancer patients significantly elevated regardless of whether patients had diabetes or overweight/obesity (P < 0.05). Further analyses showed that pretreatment TG/HDL-c ratio increased significantly with advanced tumor stage. Interestingly, TG/HDL-c ratio of type I endometrial cancer patients was higher than those with type II endometrial cancer. A positive association was found between pretreatment TG/HDL-c ratio and tumor stage (adjusted r = 0.176, P = 0.027) in endometrial cancer group. Receiver operating characteristic curve analysis yielded the cut-off value of 1.52 for TG/HDL-c ratio to discriminate patients with cancer from controls (area under the curve, 0.689; sensitivity, 51.5%; specificity, 84.1%). Multivariate logistic regression model identified TG/HDL-c ratio ≥ 1.52 (odds ratio = 4.123; P < 0.001) as an independent predictor of endometrial cancer. TG/HDL-c ratio was positively associated with endometrial cancer clinical features, such as tumor stage and pathogenetic type. Accordingly, pretreatment TG/HDL-c ratio might be a potential marker for endometrial cancer.

Incidence and risk factors of herpes zoster in human immunodeficiency virus-positive patients initiating combination antiretroviral therapy in Taiwan.

BACKGROUND/PURPOSE: To obtain current epidemiological data for better vaccination policies, this study aimed to assess the incidence and risk factors of herpes zoster in human immunodeficiency virus (HIV)-positive patients initiating combination antiretroviral therapy (cART) in Taiwan. METHODS: Between June, 2012 and May, 2015, we prospectively identified zoster cases in HIV-positive patients initiating cART. Clinical information was collected on demographics, prior zoster, plasma HIV-1 RNA load (PVL), and CD4 count at baseline and during follow up. A case-control study by 1:2 matched pairs was used to identify the risk factors for zoster development. RESULTS: During the 3-year study period, 826 patients with a mean age of 32.9 years were included, and 7.7% had prior zoster. The mean baseline CD4 count and PVL were 286 cells/µL and 4.90 log10 copies/mL, respectively. Fifty-four (6.5%) patients developed zoster after initiation of cART, with 43 episodes (79.6%) occurring within 1 year of cART initiation, which corresponded to an overall incidence rate of 3.61/100 person-years. The multivariate analysis revealed that prior zoster (adjusted odds ratio = 3.143; 95% confidence interval, 1.385-7.133) and baseline CD4 count < 200 cells/µL (adjusted odds ratio = 2.034; 95% confidence interval, 1.020-4.057) were independent risk factors for zoster in HIV-positive patients initiating cART. In case-control study, prior zoster and baseline PVL > 5 log10 copies/mL were risk factors for zoster development after cART initiation in multivariate analysis. CONCLUSIONS: Herpes zoster occurred in 6.5% of HIV-positive Taiwanese patients after initiation of cART, which was associated with prior zoster and baseline CD4 count < 200 cells/µL or baseline PVL > 5 log10 copies/mL.

Altered mean platelet volume in children with Henoch-Schonlein purpura and its association with disease activity.

Background Henoch-Schonlein purpura is a systemic small-vessel vasculitis that occurs mainly in children. A review of the literature has suggested a correlation between mean platelet volume and several inflammatory disorders. However, to the best of our knowledge, any potential correlation between mean platelet volume and Henoch-Schonlein purpura has not been reported in the literature. Therefore, our study aimed to evaluate the role of mean platelet volume concentrations in patients with Henoch-Schonlein purpura. Methods This study included 97 children with Henoch-Schonlein purpura and 120 healthy individuals as controls. Results Mean platelet volume concentrations were found to be significantly lower in Henoch-Schonlein purpura patients compared with healthy controls (8.1 ± 0.86 vs. 9.4 ± 0.81, P < 0.001). Similarly, significant negative correlations were observed between mean platelet volume and neutrophil count, platelet count and erythrocyte sedimentation rate in patients with Henoch-Schonlein purpura (r=-0.327, P = 0.001; r=-0.419, P < 0.001; r=-0.255, P = 0.012). Interestingly, mean platelet volume was significantly lower in the acute phase compared with the convalescent phase of Henoch-Schonlein purpura patients (7.8 ± 0.86 vs. 8.3 ± 0.77, P = 0.002). A cut-off value for mean platelet volume was 7.85 with area under the curve of 0.726 to identify acute phase vs. convalescent phase in patients with Henoch-Schonlein purpura. Mean platelet volume was independently associated with Henoch-Schonlein purpura in logistic regression analysis (odds ratio = 0.114, 95% confidence interval = 0.053-0.243, P < 0.001). Conclusions Our results suggest that mean platelet volume is inversely associated with disease in patients with Henoch-Schonlein purpura, and mean platelet volume may be a useful marker to identify active disease in Henoch-Schonlein purpura patients.

Vitamin D deficiency may predict a poorer outcome of IgA nephropathy.

BACKGROUND: Experimental studies showed that 25-hydroxy-vitamin D [25(OH)D] deficiency (defined as 25-hydroxy-vitamin D < 15 ng/ml) has been associated with CKD progression. Patients with IgA nephropathy have an exceptionally high rate of severe 25(OH)D deficiency; however, it is not known whether this deficiency is a risk factor for progression of IgA nephropathy. We conducted this study to investigate the relationship between the plasma level of 25(OH)D and certain clinical parameters and renal histologic lesions in the patients with IgA nephropathy, and to evaluate whether the 25(OH)D level could be a good prognostic marker for IgA nephropathy progression. METHODS: A total of 105 patients with biopsy-proven IgA nephropathy were enrolled between 2012 and 2015. The circulating concentration of 25(OH)D was determined using serum samples collected at the time of biopsy. The primary clinical endpoint was the decline of estimated glomerular filtration rate (eGFR; a 30 % or more decline compared to the baseline). RESULTS: Mean eGFR decreased and proteinuria worsened proportionally as circulating 25(OH)D decreased (P < 0.05). The 25(OH)D deficiency was correlated with a higher tubulointerstitial score by the Oxford classification (P = 0.008). The risk for reaching the primary endpoint was significantly higher in the patients with a 25(OH)D deficiency compared to those with a higher level of 25(OH)D (P = 0.001). As evaluated using the Cox proportional hazards model, 25(OH)D deficiency was found to be an independent risk factor for renal progression [HR 5.99, 95 % confidence intervals (CIs) 1.59-22.54, P = 0.008]. CONCLUSION: A 25(OH)D deficiency at baseline is significantly correlated with poorer clinical outcomes and more sever renal pathological features, and low levels of 25(OH)D at baseline were strongly associated with increased risk of renal progression in IgAN.

Willingness of human immunodeficiency virus-positive patients to donate their organs for transplantation in Taiwan: a cross-sectional questionnaire survey.

BACKGROUND: With the introduction of combination antiretroviral therapy (cART) that has significantly improved survival, human immunodeficiency virus (HIV)-positive patients may be potential organ donors to HIV-positive recipients in a few countries. Organ shortage remains a challenge for organ transplantation in Taiwan, where organ donation by HIV-positive patients remains prohibited by law. METHODS: We assessed the willingness of organ donation (should they be pronounced brain dead, and the ban on HIV-positive organ donation be lifted) among HIV-positive patients who received regular HIV care at a university hospital in a cross-sectional survey between May and August 2015 with the use of an anonymous, self-administered questionnaire interview. RESULTS: Of the 1010 participants, 93.7% were receiving cART with the latest mean CD4 count and plasma HIV RNA load of 587 cells/mm3 and 2.73 log10 copies/mL, respectively. Overall, 71.9% were willing to donate organs. In multivariate analysis, factors associated with willingness to donate organs included college or graduate school diploma (odds ratio [OR] 1.571, 95% confidence interval [CI] 1.166-2.191), registered willingness to donate in the National Health Insurance system (OR 9.430, 95% CI 1.269-70.051), and knowledge of the information on HIV-positive deceased donors (HIVDD) (OR 1.673, 95% CI 1.073-2.608). CONCLUSIONS: We concluded that a significant proportion (71.9%) of HIV-positive Taiwanese patients were willing to donate their organs. The willingness was associated with a higher education level, prior registered willingness to donate organs, and awareness of HIVDD.

Transmitted drug resistance of HIV-1 strains among individuals attending voluntary counselling and testing in Taiwan.

BACKGROUND: Genotypic drug resistance testing for HIV-1 has been integrated into voluntary counselling and testing (VCT) programmes to investigate the trends of transmitted drug resistance (TDR), including integrase mutations, among individuals with recent or chronic HIV infections in Taiwan. METHODS: Between 2006 and 2014, 745 of 21 886 subjects (3.4%) tested HIV positive in the VCT service. The BED assay was used to identify recent HIV infections. Genotypic resistance mutations were interpreted using the WHO 2009 list. Integrase resistance mutations were analysed using the Stanford HIV Drug Resistance Database. RESULTS: Three-hundred-and-sixty (48.3%) patients were recently infected with HIV-1. Of 440 patients linked to HIV care with analysable reverse transcriptase and protease genes, 49 (11.1%) were infected with HIV-1 harbouring at least one resistance-associated mutation (RAM). The prevalence of TDR to NRTIs, NNRTIs and PIs was 4.1%, 6.4% and 2.3%, respectively. TDR prevalence did not change significantly during the study period. CD4 counts ≤500 cells/mm(3) and hepatitis B surface antigen positivity were independent factors associated with acquiring drug-resistant HIV. The prevalence of integrase mutations was 3.2%. Among the seven major integrase mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R and N155H), only one strain harbouring the Q148R mutation was detected. We found no statistically significant difference between patients with chronic infection and those with recent infection in the prevalence of drug-resistant mutations to any of the four classes of antiretroviral agents. CONCLUSIONS: The prevalence of TDR of HIV-1 strains to available antiretroviral agents is moderately high, but transmission of HIV-1 with drug-resistant mutations remains stable in Taiwan.

Increasing incidence of recent hepatitis C virus infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan.

OBJECTIVES: The incidence of hepatitis C virus (HCV) infection among HIV-negative men who have sex with men (MSM) is rarely investigated in the Asia-Pacific region. We aimed to estimate the incidence rate of and factors associated with recent HCV infection among the clients seeking voluntary counselling and testing (VCT) services for HIV in Taiwan. METHODS: During 2006-2013, 12 143 clients sought VCT services for HIV. Clients with subsequent follow-up tests at an interval of 6 months or longer were included to estimate the incidence rate of HCV seroconversion. Phylogenetic analysis of HCV sequences from VCT clients and HIV-positive patients was performed. RESULTS: The overall HCV seroprevalence at baseline was 0.3%. Of 2150 clients testing negative for anti-HCV antibody at baseline with a total of 5074.99 person-years of follow-up (PYFU), 17 (0.8%) developed HCV seroconversion, leading to an overall incidence rate of 3.35 per 1000 PYFU (95% CI 1.76 to 4.94), which increased from 2.28 (95% CI 0.05 to 4.51) in 2006-2009, to 3.33 (95% CI 0.86 to 5.80) in 2010 to 2011 and 4.94 per 1000 PYFU (95% CI 0.99 to 8.99) in 2012-2013; the incidence of early syphilis increased from 11.91 to 13.28 and 31.78 per 1000 PYFU in the three corresponding periods. In multivariate analysis, having HIV-positive partners (adjusted HR (AHR) =3.756; 95%CI 1.180 to 11.955) and developing a rapid plasma reagin titre of 4 or greater (AHR=9.978; 95% CI 1.550 to 64.233) were significantly associated with HCV seroconversion. CONCLUSIONS: An increasing trend of recent HCV infection occurs among individuals seeking VCT services in Taiwan. Having HIV-positive partners and having syphilis are independently associated with recent HCV seroconversion.

Seroincidence of HIV and prevalence of transmitted drug resistance of HIV-1 strains among persons seeking voluntary counselling and testing in Taiwan.

INTRODUCTION: The total case number of persons who are newly diagnosed with HIV continues to increase in Taiwan and men who have sex with men (MSM) have re-emerged as the leading risk group for HIV transmission. In this study, we aimed to estimate the incidence rate of HIV infection among those individuals who sought voluntary counselling and testing (VCT) service at a university hospital. METHODS: Between 1 April, 2006 and 31 December, 2013, 18,246 tests for HIV antibody were performed among 12143 individuals at the VCT service. A total of 2157 individuals who tested negative for anti-HIV antibody had subsequent follow-up tests at the same VCT service, which composed the study population for estimation of incidence rate of recent HIV infection. The BED assays were used to identify recent HIV infections that occurred within the previous six months before seeking VCT service. RESULTS: During the 6.5-year study period, 647 individuals were diagnosed as being HIV-positive, with an overall HIV seroprevalence of 3.55% (95% CI 3.27-3.82). The overall incidence rate of HIV infection was estimated 4.13 per 100 person-years of follow-up (95% CI 3.67-4.69 per 100 person-years of follow-up). MSM had an estimated 10-fold higher seroprevalence and seroincidence of HIV than heterosexuals. Of 647 clients testing positive for HIV, 603 clients were MSM (93.2%) and 477 patients (70.8%) subsequently sought HIV care at the hospital; 226 (47.4%) were diagnosed as having recent HIV infections by the BED assay, while 244 (51.2%) long-term infection and 7 without data by the BED assay. Of those patients, 173 (75.6%) and 178 patients (73.0%) with recent HIV infection and long-term infection had data of transmitted drug resistance mutations, respectively. The prevalence of transmitted drug resistance mutations to any class of antiretroviral therapy was 9.0% and 10.6% (p=0.68), respectively, of the HIV-1 strains from the patients with recent HIV infection and long-term infection, respectively. CONCLUSIONS: The seroincidence rate of HIV among persons seeking VCT was estimated 4.13 per 100 person-years of follow-up. The prevalence of transmitted drug resistance to any class of antiretroviral agents was similar between those who were recently infected with HIV and those who had long-term infection in Taiwan.

Antiretroviral therapy (ART) management of Low-Level Viremia in Taiwan (ALLEVIATE).

INTRODUCTION: This retrospective study aimed to investigate that if switch of combination antiretroviral therapy (cART) would result in viral suppression (<40 copies/mL) at 48 weeks for patients with persistent low-level viremia after having received cART for six months or more at two hospitals designated for HIV care in Taiwan. MATERIALS AND METHODS: Between January 2001 and January 2013, patients were enrolled if plasma HIV RNA load (PVL) were >20 to <1000 copies/mL detected for six months or more (1, 2). Using a standardized data collection form, we recorded data of PVL and CD4 count before cART and at the detection of low-level viremia, serologies for hepatitis B and C virus, risk factors, duration of cART exposure, years of HIV diagnosed and ever experiencing treatment failure. The strategy of switch is based on the clinical guidelines of BHIVA, which suggest change of cART from non-nucleoside reverse-transcriptase inhibitors (nNRTIs) or unboosted protease inhibitor (PI) to boosted PI, newer boosted PI or ARV of different mechanism (3). RESULTS: In this study, 165 patients were enrolled, 119 patients (72.1%) did not switch (Group 1), and 46 patients (27.9%) switched previous regimens to ARV of different mechanism (Group 2). The two groups differed significantly in the proportion of injecting drug users (IDU) (Group 1 vs Group 2, 10.9 vs 26.1%) and median PVL (67 vs 159 copies/mL), and the proportion of PVL<200 copies/mL (84.0% vs 58.7%) when low-level viremia was first detected. In Group 1, 39 (32.8%) continued two nucleoside reverse-transcriptase inhibitors (NRTIs) plus nNRTI; 29 (24.4%) 2 NRTIs plus PI, 47 (39.5%) 2 NRTIs plus boosted PI, and 4 (3.3%) 2 NRTIs plus integrase inhibitor (II). In Group 2, two (4.3%) switched to 2 NRTIs plus PI, 38 (82.6%) 2 NRTIs plus boosted PI, three (6.5%) 2 NRTIs plus II and three (6.5%) boosted PI plus II. In multivariate analysis, IDUs (adjusted odds ratio [AOR], 6.757; 95% CI 2.427-18.868) and PVL of 200-999 copies/mL at enrollment (AOR, 4.902; 95% CI 1.992-12.048) were more likely to be switched. At 48 weeks, patients in Group 2 were more likely to achieve PVL<40 copies/mL than Group 1 (82.6% vs 63.0%, p=0.016), while no difference was observed in achieving PVL <200 copies/mL between the two groups (95.7% vs 92.4%, p=0.729). CONCLUSIONS: According to the clinical guidelines of BHIVA, patients with low-level viremia who switched to cART consisting of 2 NRTIs plus boosted PI or newer mechanisms were more likely to re-establish viral suppression to <40 copies/mL at week 48.

Effectiveness of a reduced dose of efavirenz plus 2 NRTIs as maintenance antiretroviral therapy with the guidance of therapeutic drug monitoring.

INTRODUCTION: Wide inter-patient variation of plasma efavirenz (EFV) concentrations has been observed, and a substantial proportion of HIV-positive patients may have unnecessarily higher plasma EFV concentrations than recommended while receiving EFV-containing combination antiretroviral therapy (cART) at the currently recommended daily dose of 600 mg. A lower daily dose (400 mg) of EFV has recently been demonstrated to be as efficacious as the recommended 600 mg when combined with tenofovir/mtricitabine in a multinational clinical trial, with a lower incidence of adverse effects. We aimed to use a therapeutic drug monitoring (TDM)-guided strategy to optimize the EFV dose in HIV-positive Taiwanese patients. MATERIALS AND METHODS: The plasma EFV concentrations at 12 hours (C12) after taking the previous dose were determined among HIV-positive adults who had received EFV-containing cART with viral suppression (plasma HIV RNA load (PVL) <200 copies/mL). For those with EFV C12 >2.0 mg/L, EFV (Stocrit, MSD) was reduced to half a tablet daily. Determinations of EFV C12 were repeated 4-12 weeks after switch using high-performance liquid chromatography. CYP2B6 G516T polymorphisms were determined using polymerase-chain-reaction restriction fragment-length polymorphism. RESULTS: Between April 2013 and June 2014, 111 patients (95.5% male; mean age, 39 years; 96.4% with PVL <40 copies/ml; 26.4% HBsAg-positive and 7.5% anti-HCV-positive) with plasma C12 efavirenz >2.0 mg/L were switched to a reduced dose (1/2# hs) of EFV; 45.5% of them had CYP2B6 G516T or TT genotypes; and 32.4% weighed 60 kg or less. The mean baseline EFV C12 before switch was 3.65 mg/L (interquartile range (IQR), 2.62-4.17) for 111 patients, which decreased to 1.96 mg/L (IQR, 1.53-2.33) for 64 patients who had completed follow-up of C12 EFV 4 weeks after switch, with a reduction of 49.4% (IQR, 38.9-57.0%). As of 10 July, 2014, all of the 38 patients (100%) who had completed at least one follow-up of PVL achieved undetectable PVL (<40 copies/ml) following switch to a reduced dose of EFV after a mean observation of 13 weeks (IQR, 7-15 weeks). CONCLUSIONS: Switch to cART containing a half tablet of EFV (1/2#) in HIV-positive Taiwanese patients with higher plasma EFV concentrations who had achieved viral suppression could maintain successful viral suppression with the guidance of TDM.