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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 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.

Background: Mycoplasma genitalium is an emerging etiology of sexually transmitted infections (STIs) with increasing resistance to antimicrobials. Surveillance on the epidemiology of M. genitalium infection and antimicrobial resistance is warranted. Methods: Between September 2021 and August 2023, people with HIV (PWH) and people without HIV (PWoH) at risk of STIs were screened for M. genitalium infection using a multiplex polymerase-chain-reaction assay of specimens collected from the rectum, urethra, oral cavity, and vagina. The prevalences of resistance-associated mutations (RAMs) of M. genitalium to fluoroquinolones, macrolides, and tetracycline were investigated. Results: During the 2-year study period, 1021 participants were enrolled, including 531 PWH and 490 PWoH. Overall, 83 (8.1%) and 34 (7.6%) participants had M. genitalium infection at baseline and during follow-up, respectively, with the rectum being the most common site of detection (61.5%). With the first course of antimicrobial treatment, 27 of 63 (42.9%) participants with M. genitalium infection were cured during follow-up, including 24 of 58 (41.4%) who received doxycycline monotherapy. The prevalence of RAMs to macrolides, fluoroquinolones, and tetracyclines at baseline were 24.3%, 22.4%, and 7.9%, respectively. Though PWH had more M. genitalium infection (10.2% vs 5.9%, p = 0.01), a higher rate of RAMs to macrolides (41.0% vs 14.7%, p

ABSTRACT: 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

Background: Antiretroviral regimens containing a second-generation integrase strand-transfer inhibitor (INSTI) plus 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) are the recommended therapy for people with HIV (PWH) who are antiretroviral-naïve or on stable antiretroviral therapy (ART) with viral suppression. Real-world data on the virologic effectiveness of co-formulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among PWH with virologic failure while receiving other ART remain sparse. Methods: We retrospectively reviewed the medical records of PWH who had viral rebound with plasma HIV RNA >1000 copies/mL and were switched to either dolutegravir combined with 2 NRTIs or BIC/FTC/TAF. The primary end point was re-achieving viral suppression within the first 48 weeks of switch. The association between NRTI-related resistance-associated mutations (RAMs) and virologic effectiveness was examined. Results: Seventy-nine PWH with viral rebound while receiving other antiretroviral regimens were included. Within the first 48 weeks of switch, the overall probability of re-achieving viral suppression was 79.7% (82.5% [33/40] and 76.9% [30/39] for BIC/FTC/TAF and dolutegravir-based regimens, respectively, p = 0.78). PWH with a higher CD4 lymphocyte count (adjusted odds ratio, per 100-cell/mm3 increase, 1.41; 95% confidence interval, 1.02–1.95) were more likely to re-achieve viral suppression. Among PWH switching to BIC/FTC/TAF who had pre-existing RAMs to NRTIs before switch, 14 of 15 (93.3%) successfully achieved viral suppression. Conclusions: Switching to BIC/FTC/TAF and dolutegravir-based regimens could re-achieve viral suppression in four-fifth of the PWH who experienced viral rebound during treatment with other antiretroviral regimens. Pre-existing NRTI-related RAMs did not have adverse impact on the effectiveness of dolutegravir combined with 2 NRTIs or BIC/FTC/TAF.

Background: Understanding the risk behaviors associated with sexually-transmitted hepatitis C virus (HCV) infection among men who have sex with men (MSM) may inform the public health policies and interventions aiming to achieve HCV microelimination. Methods: HIV-positive MSM who had one of the following conditions were enrolled to undergo face-to-face questionnaire interviews to collect information on their sexual practices in the past 12 months: (1) elevation of aminotransferases in the past 6 months; (2) acquisition of sexually transmitted infections in the past 6 months; and (3) previous HCV infections. Plasma HCV RNA were tested at enrolment and every 3 months during follow-up. Baseline characteristics and risky behaviors were compared to identify factors associated with HCV viremia between HCV-viremic MSM and HCV-aviremic MSM in multivariate analysis. Results: Among 781 MSM with a median age of 36 years, 57 (7.3%) had HCV viremia and 724 (92.7%) no HCV viremia during follow-up. A high proportion (38.9%) of the participants reported having used recreational drugs in the past 12 months, with 34.4% of them having slamming, but only 4.8% reported having shared their injection equipment. In multivariate analysis, use of recreational drugs (adjusted odds ratio [aOR], 2.14; 95% CI, 1.16–3.96), having participated in group sex (aOR, 2.35; 95% CI 1.24–4.40) and having had condomless receptive anal intercourse (aOR, 1.97; 95% CI 1.07–3.62) were significantly associated with HCV viremia. Conclusion: Among high-risk HIV-positive MSM, use of recreational drugs and risky sexual contacts were associated with HCV viremia, suggesting the mucosal contacts as the major route of HCV transmission.

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

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the selective loss of spinal motor neurons (MNs) and concomitant muscle weakness. Mutation of SMN1 is known to cause SMA, and restoring SMN protein levels via antisense oligonucleotide treatment is effective for ameliorating symptoms. However, this approach is hindered by exorbitant costs, invasive procedures, and poor treatment responses of some patients. Here, we seek to circumvent these hurdles by identifying reliable biomarkers that could predict treatment efficacy. We uncovered that MiR34 exhibits consistent downregulation during SMA progression in both human and rodent contexts. Importantly, Mir34 family-knockout mice display axon swelling and reduced neuromuscular junction (NMJ) endplates, recapitulating SMA pathology. Introducing MiR34a via scAAV9 improved the motor ability of SMNΔ7 mice, possibly by restoring NMJ endplate size. Finally, we observed a consistent decreasing trend in MiR34 family expression in the cerebrospinal fluid (CSF) of type I SMA patients during the loading phase of nusinersen treatment. Baseline CSF MiR34 levels before nusinersen injection proved predictive of patient motor skills 1 year later. Thus, we propose that MiR34 may serve as a biomarker of SMA since it is associated with the pathology and can help evaluate the therapeutic effects of nusinersen.

Hepatitis C virus (HCV) reinfections after successful treatment with direct-acting antivirals (DAAs) pose a significant challenge to HCV elimination, especially among high-risk people living with HIV (PLWH). In this study, PLWH who had achieved HCV viral clearance with DAAs were included between January 2018 and June 2021. PLWH having acquired HCV infections after 2017 were classified as “recent-infection group,” and those before 2017 as “remote-infection group,” and the incidences of HCV reinfection were compared between two groups. Clinical and behavioural characteristics were evaluated to identify associated factors with HCV reinfection. A total of 284 PLWH were included: 179 in the recent-infection group and 105 in the remote-infection group. After a median follow-up of 2.32 years (interquartile range [IQR], 0.13–3.94), the overall incidence of HCV reinfection was 5.8 per 100 person-years of follow-up (PYFU). The incidence in the recent-infection group was significantly higher than that in the remote-infection group (9.8 vs. 0.4 per 100 PYFU, p

To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39–7.12%) in 2018 to 2.09% (95% CI, 1.60–2.77%) in 2021 (decline by 66.4% [95% CI, 55.4–74.7%]); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44–32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14–17.44) (decline by 53.2% [95% CI, 27.3–70.6%]). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.

ABSTRACT: Objectives: We aimed to investigate the incidence of low-level viremia (LLV) and its impact on virologic failure (VF) in people living with HIV (PLWH) on stable antiretroviral therapy (ART) who switched to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/c/FTC/TAF). Methods: PLWH aged 18 years or older who had received ART with plasma HIV RNA load (PVL)

Background: Human herpesvirus type 8 (HHV-8) can be transmitted through unprotected sex as HIV. We aimed to investigate the seroincidence of HHV-8 and associated factors among people living with HIV (PLWH). Methods: From 2014 to 2018, blood samples of PLWH on the first date of HIV care were determined for antibodies against HHV-8. Individuals testing HHV-8-seronegative at baseline were followed for at least four months to estimate the annual seroconversion rate. To identify the factors associated with HHV-8 seroconversion, we compared the clinical characteristics between seroconverters and non-seroconverters who were matched for observation duration. Results: The HHV-8 seroprevalence increased from 8.1% in 2014 to 20.0% in 2018. HHV-8 seroconversion occurred in 154 (14.7%) PLWH after a total of 2652.16 person-years of follow-up (PYFU), resulting in an overall incidence rate of 5.62 per 100 PYFU, which increased from 3.20 to 6.84 per 100 PYFU during the study period. HHV-8 seroconverters were less likely to have chronic hepatitis B virus (HBV) infection (1.9% vs 10.6%) and more likely to be antiretroviral-naïve on entry into care (87.7% vs 75.4%) (both p

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 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 899 BAU/mL within 12 weeks were a CD4 T cell count

Objectives: The impact of very low-level viremia (VLLV) and low-level viremia (LLV) are rarely investigated among people living with HIV (PLWH) receiving dolutegravir- vs protease inhibitor (PI)-based antiretroviral therapy (ART). Methods: Virally suppressed PLWH receiving long-term PI-containing ART were included in this study. The incidences of developing VLLV (plasma HIV RNA load (PVL) 20–49 copies/ml), LLV (PVL 50–999 copies/ml), and virological failure (any PVL ≥ 1000 copies/ml) were compared between those switched to dolutegravir-based ART and those remaining on PI-containing ART. Results: A total of 183 PLWH were switched to dolutegravir-based regimens and 309 remained on PI-containing regimens. The incidences of VLLV and LLV were 26.5 and 13.2 per 100 person-years of follow-up in the dolutegravir group, respectively, and 17.1 and 7.0 per 100 person-years of follow-up in the PI group; there were no statistically significant differences after adjusting for confounders. The rate of virological failure was 1.3 per 100 person-years of follow-up in the dolutegravir group and 1.9 per 100 person-years of follow-up in the PI group (p = 0.32). Neither VLLV nor LLV was related to subsequent virological failure. Conclusions: Among virally suppressed PLWH, the risk of developing VLLV or LLV were similar between those switched to dolutegravir-based therapy and those who continued PI-based therapy. VLLV and LLV were not associated with subsequent virological failure.

ABSTRACT Timely diagnosis and treatment of hepatitis C virus (HCV) infection may prevent its transmission. We evaluated the performance and cost reductions of the pooled plasma HCV RNA testing strategy to identify acute HCV infections among people living with HIV (PLWH). PLWH with sexually transmitted infections, elevated aminotransferases within the past 6 months or past HCV infections (high-risk) and those without (low-risk) were enrolled prospectively. Participants underwent three-stage pooled plasma HCV RNA testing every 12 to 24 weeks until detection of HCV RNA or completion of a 48-week follow-up. The three-stage strategy combined 20 individual specimens into a stage 1 pool, 5 individual specimens from the stage 1 pool that tested positive for HCV RNA in the stage 2 mini-pool, followed by testing of individual specimens of the stage 2 mini-pool tested positive for HCV RNA. A simulation was constructed to investigate the cost reductions and pooled sensitivity and specificity under different combinations of HCV prevalence and pool/mini-pool sizes. Between June 25, 2019 and March 31, 2021, 32 cases of incident HCV viremia were identified in 760 high-risk PLWH that were enrolled 834 times, giving an incidence rate of 56.6 per 1000 person-years of follow-up (PYFU). No cases of HCV viremia were identified in 557 low-risk PLWH during a total of 269.2 PYFU. Simulation analysis suggested that this strategy could reduce HCV RNA testing cost by 50% to 86% with HCV viremia prevalence of 1% to 5% and various pooled sizes despite compromised pooled sensitivity. This pooled plasma HCV RNA testing strategy is cost-saving to identify acute HCV infections in high-risk populations with HCV viremia prevalence of 1% to 5%. IMPORTANCE Our three-stage pooled plasma HCV RNA testing successfully identified HCV viremia in high-risk PLWH with a testing cost reduction of 84.5%. Simulation analysis offered detailed information regarding the selection of pool and mini-pool sizes in settings of different HCV epidemiology and the performance of HCV RNA testing to optimize the cost reduction.

Background: Optimal efavirenz (EFV) dose that minimizes adverse effects while maintaining efficacy has yet to be elucidated. With a therapeutic drug monitoring (TDM)-guided strategy, we assessed the effectiveness of half-a-tablet EFV plus 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) in HIV-infected Taiwanese who had achieved viral suppression with full-dose (600 mg) EFV. Methods: HIV-infected adults receiving EFV-containing regimens who had plasma mid-dose EFV concentration (C12) ≥2.0 mg/L and had plasma HIV RNA load (PVL)

Although the function of microRNAs (miRNAs) during embryonic development has been intensively studied in recent years, their postnatal physiological functions remain largely unexplored due to inherent difficulties with the presence of redundant paralogs of the same seed. Thus, it is particularly challenging to uncover miRNA functions at neural circuit level since animal behaviors would need to be assessed upon complete loss of miRNA family functions. Here, we focused on the neural functions of MiR34/449 that manifests a dynamic expression pattern in the spinal cord from embryonic to postnatal stages. Our behavioral assays reveal that the loss of MiR34/449 miRNAs perturb thermally induced pain response thresholds and compromised delicate motor output in mice. Mechanistically, MiR34/449 directly target Satb1 and Satb2 to fine-tune the precise number of a sub-population of motor synergy encoder (MSE) neurons. Thus, MiR34/449 fine-tunes optimal development of Satb1/2on interneurons in the spinal cord, thereby refining explicit sensory-to-motor circuit outputs.

Background: Increasing trends of HCV infection have been reported among HIV-positive men who have sex with men (MSM) in Europe, Australia and North America. The trends of recently acquired HCV infection among HIV-positive MSM are less clear in Asia–pacific region. Methods: All HIV-positive patients seeking care at a university hospital in Taiwan tested for anti-HCV IgG at least once annually to estimate the incidence of HCV seroconversion during 2011–2018. HCV genotyping and sequencing were performed and multivariate logistic regression analysis was conducted to identify the factors associated with HCV seroconversion among MSM. Findings: During the study period, 3495 HCV-seronegative patients (86·4% MSM) were included and 294 (8·4%) with recent HCV infection were identified, in whom 281 (95·6%) were MSM, during a total of 16,361·86 person-years of follow-up (PYFU), giving an overall incidence rate of 17·97 per 1000 PYFU, which increased from 14·28 per 1000 PYFU in 2011 to 25·38 per 1000 PYFU in 2018 (p

Background/Purpose: Treatment response to switch regimens containing unboosted atazanavir and tenofovir disoproxil fumarate (TDF)/lamivudine guided by therapeutic drug monitoring in human immunodeficiency virus-infected patients is rarely investigated. Methods: Consecutive patients with plasma human immunodeficiency virus RNA load  3 months were included for determinations of treatment response, plasma atazanavir concentrations, and single-nucleotide polymorphisms of MDR1, PXR, and UGT1A1 genes from 2010 to 2014. Treatment failure was defined as either discontinuation of atazanavir for any reason or plasma viral load â¥Â 200 copies/mL within 96 weeks. Results: During the study period, 128 patients switched to unboosted atazanavir with TDF/lamivudine (TDF group) and 186 patients switched to unboosted atazanavir with two other nucleoside reverse-transcriptase inhibitors (non-TDF group). There were no statistically significant differences in the distributions of single-nucleotide polymorphisms of MDR1 (2677 and 3435), PXR genotypes (63396), and UGT1A1*28 between the two groups. Recommended plasma atazanavir concentrations were achieved in 83.5% and 64.9% of the TDF group and non-TDF group, respectively (pÂ

It has been reported for decades that preschool children (age 4-7) tend to assign non-adult-like interpretations for sentences with pre-subject exclusive only. This study reports findings from two experiments investigating (1) the effects of (in)congruent implicit questions in discourse contexts and (2) word order transformation on children's interpretations of Mandarin pre-subject zhiyou 'only'. Experiment 1 showed that children performed non-adult-like in the incongruent discourse condition, similar to the patterns found in previous studies, but adult-like in the congruent discourse condition. Experiment 2 showed that using sentences similar to English 'Those who ate apples was only the boy' where the VP precedes the subject NP with zhiyou 'only' was not sufficient to overcome the processing difficulty caused by the incongruent discourse for preschool children. The results demonstrate that a congruent context taking the VP as the background (i.e., given and salient information) in Experiment 1, but not the syntactic manipulation in Experiment 2, is sufficient for children to interpret sentences with pre-subject zhiyou 'only' at an adult-like level of accuracy. The findings demonstrate that children have the syntactic knowledge for sentences with exclusive zhiyou 'only', but the discourse incongruence hinders them from correctly interpreting sentences with exclusive zhiyou 'only' when it is in pre-subject position. It has been reported for decades that preschool children (age 4-7) tend to assign non-adult-like interpretations for sentences with pre-subject exclusive only. This study reports findings from two experiments investigating (1) the effects of (in)congruent implicit questions in discourse contexts and (2) word order transformation on children's interpretations of Mandarin pre-subject zhiyou 'only'. Experiment 1 showed that children performed non-adult-like in the incongruent discourse condition, similar to the patterns found in previous studies, but adult-like in the congruent discourse condition. Experiment 2 showed that using sentences similar to English 'Those who ate apples was only the boy' where the VP precedes the subject NP with zhiyou 'only' was not sufficient to overcome the processing difficulty caused by the incongruent discourse for preschool children. The results demonstrate that a congruent context taking the VP as the background (i.e., given and salient information) in Experiment 1, but not the syntactic manipulation in Experiment 2, is sufficient for children to interpret sentences with pre-subject zhiyou 'only' at an adult-like level of accuracy. The findings demonstrate that children have the syntactic knowledge for sentences with exclusive zhiyou 'only', but the discourse incongruence hinders them from correctly interpreting sentences with exclusive zhiyou 'only' when it is in pre-subject position.

Objectives: To retrospectively investigate the incidence of and factors associated with skin rashes and hepatotoxicity in HIV-infected patients who initiated combination antiretroviral therapy (cART) containing nevirapine plus two nucleos(t)ide reverse-transcriptase inhibitors. Methods: The medical records of HIV-infected adult patients who started nevirapine-containing cART and continued follow-up for ≥4 weeks were reviewed at two hospitals in Taiwan between 2000 and 2012. Clinical data obtained at baseline and during follow-up were collected and analyzed. Results: Of the 338 patients included in the analysis, 13.0% tested positive for hepatitis B virus surface antigen and 7.9% tested positive for anti-hepatitis C virus antibody. The incidence of rashes was 21.6% and of hepatotoxicity was 25.5%. On multiple logistic regression analysis, a two-fold or greater increase from the upper limit of normal levels of aminotransferases at baseline was associated with rashes (adjusted odds ratio (aOR) 3.74, 95% confidence interval (CI) 1.56–8.96); higher CD4 counts (aOR for per 50 cells/μl increase 1.51, 95% CI 1.12–2.03) and the concurrent use of trimethoprim/sulfamethoxazole (aOR 14.01, 95% CI 1.98–98.95) were associated with hepatotoxicity. Conclusions: Abnormal liver function at baseline was significantly associated with skin rashes, while a higher CD4 count and the concurrent use of trimethoprim/sulfamethoxazole were associated with hepatotoxicity after the initiation of nevirapine-containing cART in HIV-infected Taiwanese patients.

Introduction HIV infection impairs maintenance of immunological memory, yet few studies of HIV‐positive adults receiving 7‐valent pneumococcal conjugate vaccine (PCV7) have followed them beyond the first year. We determined and compared the durability of serological responses and the clinical outcomes of HIV‐positive adults annually for five years following vaccination with one or two doses of PCV7. Methods In this non‐randomized clinical trial, 221 pneumococcal vaccine‐naïve HIV‐positive adults receiving one (n=109) or two doses four weeks apart (n=112) of PCV7 between 2008 and 2010 were longitudinally followed for evaluation of significant serological response and for episodes of pneumonia and invasive pneumococcal disease. Results At the time of vaccination, the two groups were well matched for age, risk factors, combination antiretroviral therapy (cART) coverage, CD4 count and plasma HIV RNA load (PVL). At the end of five years, the CD4 counts for the one‐ and two‐dose groups had increased from 407 and 406 to 550 and 592 cells/µL, respectively, and 82.4 and 81.6% of the participants had fully suppressed PVL. Significant immune responses to ≥2 serotypes persisted for 67.9 vs 78.6%, 64.2 vs 71.4%, 66.1 vs 71.4%, 57.8 vs 69.6% in the second, third, fourth and fifth years after one and two doses of PCV7 in the intention‐to‐treat analysis, respectively. In multivariate analysis, immunization with two doses of PCV7 (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.10 to 2.65, p=0.016), concurrent cART (OR 2.16, 95% CI 1.16 to 4.00, p=0.015) and CD4 proliferation (OR 1.12, 95% CI 1.01 to 1.27, p=0.031) were predictive of persistent serological responses in the fifth year. Only one patient in the one‐dose group had documented pneumococcal pneumonia (non‐bacteraemic) and none had invasive pneumococcal disease in the 6.5 years of follow‐up. Conclusions One or two doses of PCV7 achieve durable seroprotective responses in HIV‐treated participants; however, two doses may be more robust than one dose in a larger study population or in real‐world populations with less cART coverage.

Sequential addition of tenofovir disoproxil fumarate (TDF) is often needed for patients coinfected with HIV and hepatitis B virus (HBV) who develop HBV resistance to lamivudine after combination antiretroviral therapy (cART) containing only lamivudine for HBV. We aimed to assess the virological response of HBV to add-on TDF in patients coinfected with lamivudine-resistant HBV.Between November 2010 and December 2014, 33 HIV/HBV-coinfected patients with lamivudine-resistant HBV and 56 with lamivudine-susceptible HBV were prospectively included. TDF plus lamivudine was used to substitute zidovudine or abacavir plus lamivudine contained in cART in patients with lamivudine-resistant HBV infection, while patients with lamivudine-susceptible HBV infection received TDF plus lamivudine as backbone of cART. Serial determinations of plasma HBV DNA load, HBV serologic markers, and liver and renal functions were performed after initiation of TDF-containing cART.Of 89 patients included, 38.6% tested positive for HBV envelope antigen (HBeAg) at baseline. The plasma HBV DNA level at enrollment of lamivudine-resistant and lamivudine-susceptible group were 6.1 ± 2.2 log10 and 6.0 ± 2.2 log10 copies/mL, respectively (p = 0.895). The cumulative percentage of HBV viral suppression in lamivudine-resistant and lamivudine-susceptible group was 81.8% and 91.1% at 48 weeks, respectively (p = 0.317), which increased to 86.7% and 96.2% at 96 weeks, respectively (p = 0.185). At 48 weeks, 11 patients testing HBeAg-positive at baseline failed to achieve viral suppression. In multivariate analysis, the only factor associated with failure to achieve viral suppression at 48 weeks was higher HBV DNA load at baseline (odds ratio, per 1-log10 copies/mL increase, 1.861; 95% CI, 1.204-2.878). At 48 weeks, HBeAg seroconversion was observed in 5 patients (1 in the lamivudine-resistant group and 4 in the lamivudine-susceptible group; p = 0.166). During the study period, HBsAg levels decreased over time, regardless of lamivudine resistance. Loss of HBsAg was observed in 3 (3.4%) patients in the lamivudine-susceptible group.Add-on TDF-containing cART in patients coinfected with lamivudine-resistant HBV achieved a similar rate of HBV viral suppression compared to TDF-containing cART as initial regimen in patients coinfected with lamivudine-susceptible HBV. A higher baseline HBV DNA load and HBeAg positivity were associated with failure to achieve HBV viral suppression.

Nevirapine extended-release (NVP-XR) taken once daily remains an effective antiretroviral agent for patients infected with HIV-1 strains that do not harbor resistance mutations. Presence of tablet remnants of NVP XR in stools was reported in 1.19% and 3.05% of subjects in two clinical trials. However, the prevalence may have been underestimated because the information was retrospectively collected in the studies.Between April and December 2014, we prospectively inquired about the frequency of noticing tablet remnants of NVP XR in stools in HIV-1-infected patients who switched to antiretroviral regimens containing NVP XR plus 2 nucleos(t)ide reverse-transcriptase inhibitors. Patients were invited to participate in therapeutic drug monitoring of plasma concentrations of NVP 12 or 24 hours after taking the previous dose (C12 and C24, respectively) of NVP XR using high-performance liquid chromatography. The information on clinical characteristics, including plasma HIV RNA load and CD4 lymphocyte count, at baseline and during follow-up was recorded.During the 9-month study period, 272 patients switched to NVP XR-based regimens and 60 (22.1%) noticed tablet remnants of NVP XR in stools, in whom 54.2% reported noticing the tablet remnants at least once weekly. Compared with patients who did not notice tablet remnants, those who noticed tablet remnants had a higher mean CD4 lymphocyte count (629 vs 495 cells/mm3, P = 0.0002) and a similar mean plasma HIV RNA load (1.57 vs 1.61 log10 copies/mL, P = 0.76) on switch. At about 12 and 24 weeks after switch, patients who noticed tablet remnants continued to have a similar mean plasma HIV RNA load (1.39 vs 1.43 log10 copies/mL, P = 0.43; and 1.30 vs 1.37 log10 copies/mL, P = 0.26, respectively), but had a lower median NVP C12 (3640 vs 4730 ng/mL, P = 0.06), and a similar median NVP C24 (3220 vs 3330 ng/ml, P = 0.95) when compared with those who did not notice tablet remnants.The presence of tablet remnants of NVP XR in stools is not uncommon in HIV-1-infected Taiwanese patients receiving NVP XR-based antiretroviral regimens, which does not have an adverse impact on the virological and immunological outcomes.

Interferon-gamma release assays (IGRAs) have been used to identify individuals at risk for developing active tuberculosis (TB). However, data regarding the risk of TB development in HIV-infected patients testing positive for IGRAs remain sparse in the era of combination antiretroviral therapy.Between 2011 and 2013, 608 HIV-infected patients without active TB undergoing T-Spot.TB testing were enrolled in this prospective observational study at a university hospital designated for HIV care in Taiwan with a declining TB incidence from 72 per 100,000 population in 2005 to 53 per 100,000 population in 2012. All of the subjects were followed until September 30, 2014. The national TB registry was accessed to identify any TB cases among those lost to follow-up.T-Spot.TB tested negative in 534 patients (87.8%), positive in 64 patients (10.5%), and indeterminate in 10 patients (1.6%). In multivariate analysis, positive T-Spot.TB was significantly associated with older age (adjusted odds ratio [AOR], 1.172 per 10-year increase; 95% confidence interval [CI], 1.022-1.344, P=0.023), past history of TB (AOR, 13.412; 95% CI, 6.106-29.460, P