Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients.
Viral hepatitis; Seroepidemiology; Sexually transmitted diseases; Nucleoside reverse-transcriptase inhibitor; Vaccination
This case-control study aimed to characterize the factors associated with amebiasis, defined as presence of anti-Entamoeba histolytica antibody titers of ≧ 128 by indirect hemagglutination assay, among persons seeking voluntary counseling and testing (VCT) for human immunodeficiency virus (HIV) infection. Between April 2006 and September 2009, 57 of 4,802 persons (1.2%) seeking VCT services were seropositive for E. histolytica infection. Compared with 228 seronegative controls, case subjects were older (odds ratio [OR] for per 1-year increase, 1.098; 95% confidence interval [CI], 1.036, 1.165), less likely to hold bachelor degree or higher (OR, 0.359; 95% CI, 0.152, 0.846), and were more likely to be men who have sex with men (MSM) (OR, 8.382; 95% CI, 2.050, 34.266) and have oral-anal sex (OR, 4.016; 95% CI, 1.711, 9.427) in multiple logistic regression analysis. The MSM, fecal-oral contamination, lower educational achievement, and older age were associated with increased risk for amebiasis among persons seeking VCT for HIV infection.
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.
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.
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.
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.
serological response; anti-capsular antibody; immunogenicity; Streptococcus pneumoniae; invasive pneumococcal disease
HIV-infected patients remain at higher risk for pneumococcal disease than the general population despite immune reconstitution and suppression of HIV replication with combination antiretroviral therapy. Vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) composed of T-cell-independent antigens has been recommended to reduce the risk of pneumococcal disease in HIV-infected adults. However, given the heterogeneity of study design, execution and subjects enrolled, studies examining serological responses to PPV23 yielded conflicting results and observational studies of clinical effectiveness only provided moderate evidence to support the routine use of PPV23 in HIV-infected adults. Pneumococcal conjugate vaccine (PCV), with conjugation of the capsular polysaccharide to a protein carrier, is more immunogenic than PPV23 and has been demonstrated to protect against pneumococcal disease in HIV-infected children and recurrent invasive pneumococcal disease in HIV-infected adolescents and adults. Guidelines have recently been revised to recommend that HIV-infected patients aged 19 y or older receive one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by a booster vaccination with PPV23. In this paper, we review the studies using different vaccination strategies to improve immunogenicity among HIV-infected adult patients.
AIDS; immunodeficiency; immunogenicity; invasive pneumococcal disease; pneumococcal conjugate vaccine; pneumococcal disease; pneumococcal polysaccharide vaccine; Streptococcus pneumoniae
The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated.
In HIV-positive patients with early syphilis, the Jarisch-Herxheimer reaction was prospectively investigated using the same data collection form in 119 patients who received benzathine penicillin G between 2007 and 2009 and 198 who received azithromycin between 2012 and 2013, when shortage of benzathine penicillin G occurred in Taiwan. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance.
The overall incidence of the Jarisch-Herxheimer reaction was significantly lower in patients receiving azithromycin than those receiving benzathine penicillin G (14.1% vs. 56.3%, p<0.001). The risk increased with higher rapid plasma reagin (RPR) titres (adjusted odds ratio [AOR] per 1-log2 increase, 1.21; confidence interval [CI], 1.04–1.41), but decreased with prior penicillin therapy for syphilis (AOR, 0.37; 95% CI, 0.19–0.71) and azithromycin treatment (AOR, 0.15; 95% CI, 0.08–0.29). During the study period, 310 specimens were obtained from 198 patients with syphilis for PCR assays, from whom T. pallidum was identified in 76 patients, one of whom (1.3%) was found to be infected with T. pallidum harbouring the macrolide resistance mutation (A2058G). In subgroup analyses confined to the 75 patients infected with T. pallidum lacking resistance mutation, a statistically significantly lower risk for the Jarisch-Herxheimer reaction following azithromycin treatment was noted.
Treatment with azithromycin was associated with a lower risk for the Jarisch-Herxheimer reaction than that with benzathine penicillin G in HIV-positive patients with early syphilis. Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.
sexually transmitted diseases; spirochetal disease; macrolides; macrolide resistance; immunomodulation
Objectives: The objectives of this study were to compare the serologic responses at week 48 to primary vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) vs. 7-valent pneumococcal conjugate vaccine (PCV); and to identify factors associated with serologic response in HIV-infected adult patients with access to combination antiretroviral therapy (cART).
Methods: One hundred and four CD4-matched pairs of HIV-infected patients who underwent primary pneumococcal vaccination with 23-valent PPV or 7-valent PCV were enrolled for determinations of anti-capsular antibody responses against four serotypes (6B, 14, 19F and 23F) at baseline, 24 weeks and 48 weeks following vaccination. Significant antibody responses were defined as 2-fold or greater increase of antibody levels at week 48 compared with baseline. The logistic regression model was used to determine the factors associated with serologic response to at least one and two serotypes.
Results: At week 48, patients who received PCV demonstrated a statistically significantly higher response rate to at least 2 serotypes than those who received PPV (37.5% vs. 20.2%, p = 0.006). In multivariate analysis, factors associated with significant antibody responses to at least one or two serotypes included receipt of PCV (adjusted odds ratio [AOR], 2.42 [95% CI, 1.23–4.78] and 3.58 [95% CI. 1.76–7.28], respectively), and undetectable plasma HIV RNA load (< 400 copies/ml) at vaccination (AOR, 1.47 [95% CI, 0.60–3.64] and 3.62 [95% CI, 1.11–11.81], respectively).
Conclusions: Primary vaccination with 7-valent PCV achieved a significantly better serologic responses to one or two out of the four serotypes studied at week 48 than with 23-valent PPV in HIV-infected patients in the cART era. Suppression of HIV replication when primary vaccination was administered was associated with better serologic responses.
Streptococcus pneumoniae; pneumococcal conjugate vaccine; pneumococcal polysaccharide vaccine; HIV infection; immunogenicity; combination antiretroviral therapy
Studies of macrolide resistance mutations and molecular typing using the newly proposed enhanced typing system for Treponema pallidum isolates obtained from HIV-infected patients in the Asia-Pacific region are scarce. Between September 2009 and December 2011, we conducted a survey to detect T. pallidum using a PCR assay using clinical specimens from patients with syphilis at six major designated hospitals for HIV care in Taiwan. The T. pallidum strains were genotyped by following the enhanced molecular typing methodology, which analyzed the number of 60-bp repeats in the acidic repeat protein (arp) gene, T. pallidum repeat (tpr) polymorphism, and the sequence of base pairs 131 to 215 in the tp0548 open reading frame of T. pallidum. Detection of A2058G and A2059G point mutations in the T. pallidum 23S rRNA was performed with the use of restriction fragment length polymorphism (RFLP). During the 2-year study period, 211 clinical specimens were obtained from 136 patients with syphilis. T. pallidum DNA was isolated from 105 (49.8%) of the specimens, with swab specimens obtained from chancres having the highest yield rate (63.2%), followed by plasma (49.4%), serum (35.7%), and cerebrospinal fluid or vitreous fluid (18.2%) specimens. Among the 40 fully typed specimens, 11 subtypes of T. pallidum were identified. Subtype 14f/f (18 isolates) was the most common isolates, followed by 14f/c (3), 14b/c (3), and 14k/f (3). Among the isolates examined for macrolide resistance, none had the A2058G or A2059G mutation. In conclusion, we found that type 14 f/f was the most common T. pallidum strain in this multicenter study on syphilis in Taiwan and that none of the isolates exhibited 23S rRNA mutations causing resistance to macrolides.
Outbreaks of sexually transmitted hepatitis C virus (HCV) infections have been recently reported in HIV-infected men who have sex with men (MSM) in Europe, Australia, and North America. Little is known concerning whether this also occurs in other Asia-Pacific countries. Between 1994 and 2010, a prospective observational cohort study was performed to assess the incidence of recent HCV seroconversion in 892 HIV-infected patients (731 MSM and 161 heterosexuals) who were not injecting drug users. A nested case-control study was conducted to identify associated factors with recent HCV seroconversion, and phylogenetic analysis was performed using NS5B sequences amplified from seroconverters. During a total followup duration of 4,270 person-years (PY), 30 patients (3.36%) had HCV seroconversion, with an overall incidence rate of 7.03 per 1,000 PY. The rate increased from 0 in 1994 to 2000 and 2.29 in 2001 to 2005 to 10.13 per 1,000 PY in 2006 to 2010 (P < 0.05). After adjustment for age and HIV transmission route, recent syphilis remained an independent factor associated with HCV seroconversion (odds ratio, 7.731; 95% confidence interval, 3.131 to 19.086; P < 0.01). In a nested case-control study, seroconverters had higher aminotranferase levels and were more likely to have CD4 ≥ 200 cells/μl and recent syphilis than nonseroconverters (P < 0.05). Among the 21 patients with HCV viremia, phylogenetic analysis revealed 7 HCV transmission clusters or pairs (4 within genotype 1b, 2 within genotype 2a, and 1 within genotype 3a). The incidence of HCV seroconversion that is associated with recent syphilis is increasing among HIV-infected patients in Taiwan.
Antiretroviral therapy containing an integrase strand transfer inhibitor (INSTI) plus two NRTIs has become the recommended treatment for antiretroviral-naive HIV-1-infected patients in the updated guidelines. We aimed to determine the prevalence of INSTI-related mutations in Taiwan. Genotypic resistance assays were performed on plasma from ARV-naïve patients (N = 948), ARV-experienced but INSTI-naive patients (N = 359), and raltegravir-experienced patients (N = 63) from 2006 to 2015. Major INSTI mutations were defined according to the IAS-USA list and other substitutions with a Stanford HIVdb score ≧ 10 to at least one INSTI were defined as minor mutations. Of 1307 HIV-1 samples from patients never exposed to INSTIs, the overall prevalence of major resistance mutations to INSTIs was 0.9% (n = 12), with an increase to 1.2% in 2013. Of these 12 sequences, 11 harboured Q148H/K/R, one Y143R, and none N155H. Of 30 sequences (47.6%) with INSTI-resistant mutations from raltegravir-experienced patients, 17 harboured Q148H/K/R, 8 N155H, and 6 Y143C/R. Other than these major mutations, the prevalence of minor mutations were 5.3% and 38.1%, respectively, in ARV-naive and raltegravir-experienced patients. The overall prevalence of INSTI mutations remains low in Taiwan. Surveillance of INSTI resistance is warranted due to circulation of polymorphisms contributing to INSTI resistance and expected increasing use of INSTIs.
Existing data regarding the risk of hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins are limited by the small sample size. This population-based study aimed to examine the association between exposure to hypoprothrombinemia-inducing cephalosporins and hemorrhagic events using National Health Insurance Research Database in Taiwan.
A nationwide nested case-control study.
National Health Insurance Research database.
We conducted a nested case-control study within a cohort of 6191 patients who received hypoprothrombinemia-inducing cephalosporins and other antibiotics for more than 48 hours. Multivariable conditional logistic regressions were used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins (overall, cumulative dose measured as defined daily dose (DDD), and individual cephalosporins).
Within the cohort, we identified 704 patients with hemorrhagic events and 2816 matched controls. Use of hypoprothrombinemia-inducing cephalosporins was associated with increased risk of hemorrhagic events (aOR, 1.71; 95% CI, 1.42–2.06), which increased with higher cumulative doses (<3 DDDs, aOR 1.62; 3–5 DDDs, aOR 1.78; and >5 DDDs, aOR 1.89). The aOR for individual cephalosporin was 2.88 (95% CI, 2.08–4.00), 1.35 (1.09–1.67) and 4.57 (2.63–7.95) for cefmetazole, flomoxef, and cefoperazone, respectively. Other risk factors included use of anticoagulants (aOR 2.08 [95% CI, 1.64–2.63]), liver failure (aOR 1.69 [1.30–2.18]), poor nutritional status (aOR 1.41 [1.15–1.73]), and history of hemorrhagic events (aOR 2.57 [1.94–3.41]) 6 months prior to the index date.
Use of hypoprothrombinemia-inducing cephalosporins increases risk of hemorrhagic events. Close watch for hemorrhagic events is recommended when prescribing these cephalosporins, especially in patients who are at higher risk.
Human immunodeficiency virus (HIV)-infected patients are at an increased risk of tuberculosis (TB) and its recurrence following completion of anti-TB treatment. We investigated whether extending anti-TB treatment to 9 months or longer reduces TB recurrence.
HIV-infected patients who were diagnosed with pulmonary TB between 1997 and 2009 and who received anti-TB treatment for a duration between 5.5 and 12.5 months were identified from the National Health Insurance Research Database in Taiwan. Those who received any non-fluoroquinolone second-line anti-TB drug for >28 days were excluded. Factors associated with TB recurrence within 2 years after completion of anti-TB treatment were explored using Cox regression analysis. Sensitivity analysis was performed for a subpopulation fulfilling strict diagnostic criteria for HIV infection.
TB recurrence was observed in 18 (3.5%) of 508 HIV-infected patients. The recurrence rate declined from 5.4% to 1.0% after the implementation of directly observed therapy, short course (DOTS) in 2006 (p = 0.014). The recurrence rate was 5.9%, 5.2%, and 1.6% in patients who received anti-TB treatment for <195, 195–270, and >270 days, respectively (p = 0.066). Cox regression analysis revealed that TB diagnosed in the DOTS era (hazard ratio [HR]: 0.18 [0.04–0.77]) and anti-TB treatment for >270 days (HR: 0.24 [0.06–0.89]) were associated with a reduced risk of TB recurrence. Sensitivity analysis of 449 selected patients revealed that anti-TB treatment for >270 days was a significant factor.
In Taiwan, the 2-year TB recurrence rate in HIV-infected patients declined after implementation of DOTS. The risk of TB recurrence in HIV-infected patients can be further reduced by extending anti-TB treatment to 9–12.5 months.
Data are limited on the effectiveness and safety of peginterferon plus ribavirin in HIV-infected Asian patients with acute or chronic HCV infection. HIV-infected Taiwanese patients with acute HCV infection received peginterferon plus weight-based ribavirin for 24 weeks (n = 24), and those with chronic HCV genotype 1 or 6 (HCV-1/6) and HCV genotype 2 or 3 (HCV-2/3) infection received response-guided therapy for 12–72 and 24–48 weeks, respectively (n = 92). The primary endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA 24 weeks off-therapy. The SVR rates were 83% and 72% in patients with acute and chronic HCV infection (p = 0.30), and 68% and 72% in patients with chronic HCV-1/6 and HCV-2/3 infection (p = 0.48), respectively. While no factors predicted SVR in acute HCV and chronic HCV-2/3 infection, age (odds ratio [OR] per 1-year increase: 0.88, 95% confidence interval [CI]: 0.78–0.99, p = 0.04), HCV RNA (OR per 1-log10 increase: 0.18, 95% CI: 0.03–0.98, p = 0.03), IL28B genotype (OR: 5.52, 95% CI: 1.55–12.2, p = 0.02), and RVR (OR: 9.62, 95% CI: 3.89–15.3, p = 0.007) predicted SVR in chronic HCV-1/6 infection. In conclusion, the SVR rates of peginterferon plus ribavirin for 24 weeks and for response-guided 12–72 weeks are satisfactory in HIV-infected Taiwanese patients with acute and chronic HCV infection.
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.
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.
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.
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.
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.
Hepatitis C virus (HCV) infection has been increasingly recognized among HIV-infected men who have sex with men (MSM) worldwide. We investigated the trend of and factors associated with acute hepatitis C (AHC) among HIV-infected individuals in Taiwan.
The National Disease Surveillance System collects characteristics of AHC, HIV, syphilis, and gonorrhea cases through mandatory reports and patient interviews. Reported AHC patients in 2014 were interviewed additionally on sexual and parenteral exposures. Information on HCV genotypes were collected from the largest medical center serving HIV-infected Taiwanese. We defined an HIV/AHC case as a documented negative HCV antibody test result followed within 12 months by a positive test in a previously reported HIV-infected individual. Each case was matched to two HIV-infected, non-AHC controls for age, age of HIV diagnosis, sex, transmission route, HIV diagnosis date, and county/city. Conditional logistic regression was used to identify associated characteristics.
During 2001–2014, 93 of 6,624 AHC reports were HIV/AHC cases; the annual case count increased from one in 2009 to 34 in 2014. All were males (81 [87%] MSM) aged 21–49 years with AHC diagnosed 2–5,923 days after HIV diagnoses. Sixty-eight (73%) lived in the Taipei metropolitan area. Detected HCV genotypes were 2a (n = 6), 1b (n = 5), 1b + 2a (n = 1) and 2b (n = 1). Among 28 HIV/AHC patients interviewed in 2014, 13 (46%) reported engaging in unprotected sex ≤3 months before AHC diagnosis. Seventy-nine HIV/AHC cases were matched to 158 controls. HIV/AHC was associated with recent syphilis (adjusted odds ratio [aOR], 10.9; 95% confidence interval [CI], 4.2–28.6) and last syphilis >6 months (aOR, 2.9; 95% CI, 1.2–6.9).
HIV/AHC cases continued to increase particularly among sexually active HIV-infected MSM with a syphilis diagnosis in northern Taiwan. We recommend surveillance of associated behavioral and virologic characteristics and HCV counseling and testing for HIV-infected men in Taiwan.
This study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy.
We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT) 1A1*28 and multidrug resistance gene 1 (MDR1) G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed.
During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9%) with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%), unboosted atazanavir (34.4%), ritonavir-boosted lopinavir (20.4%), and ritonavir-boosted atazanavir (5.5%). The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12–35.16) and older age (AOR, 1.04; 95% CI, 1.00–1.09). The positive association between duration of exposure to ritonavir-boosted atazanavir and incident cholelithiasis was also found (AOR, per 1-year exposure, 1.49; 95% CI, 1.05–2.10). The associated factors with incident nephrolithiasis were hyperlipidemia (AOR, 3.97; 95% CI, 1.32–11.93), hepatitis B or C coinfection (AOR, 3.41; 95% CI, 1.09–10.62), and exposure to abacavir (AOR, 12.01; 95% CI, 1.54–93.54). Of 180 patients who underwent therapeutic drug monitoring of plasma atazanavir concentrations and pharmacogenetic investigations, we found that the atazanavir concentrations and UGT 1A1*28 and MDR1 G2677T/A polymorphisms were not statistically significantly associated with incident cholelithiasis and nephrolithiasis.
In HIV-positive patients in the era of combination antiretroviral therapy, a high prevalence of cholelithiasis and nephrolithiasis was observed, and exposure to ritonavir-boosted atazanavir for >2 years was associated with incident cholelithiasis.
New treatments, rapid and inexpensive identification methods, and measures to contain nosocomial transmission and outbreaks are urgently needed.
Mycobacterium abscessus complex comprises a group of rapidly growing, multidrug-resistant, nontuberculous mycobacteria that are responsible for a wide spectrum of skin and soft tissue diseases, central nervous system infections, bacteremia, and ocular and other infections. M. abscessus complex is differentiated into 3 subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. The 2 major subspecies, M. abscessus subsp. abscessus and M.
abscessus subsp. massiliense, have different erm(41) gene patterns. This gene provides intrinsic resistance to macrolides, so the different patterns lead to different treatment outcomes. M. abscessus complex outbreaks associated with cosmetic procedures and nosocomial transmissions are not uncommon. Clarithromycin, amikacin, and cefoxitin are the current antimicrobial drugs of choice for treatment. However, new treatment regimens are urgently needed, as are rapid and inexpensive identification methods and measures to contain nosocomial transmission and outbreaks.
Mycobacterium abscessus complex; Mycobacterium abscessus; Mycobacterium massiliense; Mycobacterium bolletii; multidrug resistant; nontuberculous; mycobacteria; outbreaks; cosmetic procedures; nosocomial; transmission; taxonomy; nomenclature; clinical disease; bacteria; identification methods
We evaluated the performance of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), the MALDI Bruker Biotyper system (microflex LT; Bruker Daltonik GmbH, Bremen, Germany), on the identification of 50 isolates of clinically encountered molds, including Penicillium marneffei (n = 28), Paecilomyces species (n = 12), Fusarium solani (n = 6), Rhizopus species (n = 3), and Pseudallescheria boydii (n = 1). The isolates were identified to species levels by sequence analysis of the internal transcribed spacer (ITS) regions using primers ITS1 and ITS4. None of the 28 genetically well characterized isolates of P. marneffei were identified as P. marneffei by MALDI-TOF MS, because P. marneffei was not present in either Bruker general library (DB 5627) or Bruker filamentous fungi library V1.0. However, the rate of accurate identification as P. marneffei (score value ≥ 2.000) was 85.7% based on newly created database from one P. marneffei strain (NTUH-3370) by MALDI Biotyper system. Sequencing analysis of these 22 non-P. marneffei isolates of molds revealed seven Paecilomyces variotii, six F. solani, four Paecilomyces lilacinus, and one each of Paecilomyces sinensis, Rhizopus arrhizus, R. oryzae, R. microspores, and P. boydii. Although all the seven P. variotii isolates, four of the six F. solani, two of the four P. lilacinus, and two of the three isolates of Rhizopus species, and the P. boydii isolate had concordant identification results between MALDI-TOF MS and sequencing analysis, the score values of these isolates were all of <1.700. This study indicated that the MALDI Bruker Biotyper is ineffective for identifying P. marneffei and other unusual molds because of the current database limitations. Therefore, it is necessary to continuously update the MALDI-TOF MS databases.
matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; Penicillium marneffei; Paecilomyces species; Fusarium solani; Rhizopus species; Pseudallescheria boydii
The transmission routes for human parvovirus 4 (PARV4) infections in areas with high seroprevalence are not known. In the work described here, persistent PARV4 viral replication was investigated by conducting a longitudinal study.
Ten healthcare workers each provided a blood sample at the beginning of the study (first sample) and 12 months later (second sample). The paired samples were tested for PARV4-positivity by immunoblotting analysis and nested polymerase chain reactions.
IgG antibodies against PARV4 were detected in six participants, three of whom also had IgM antibodies against PARV4. The immunoblotting results did not vary over time. PARV4 DNA was detected in the first blood sample from one participant who had IgG antibodies against PARV4 and in the second blood samples from 2 participants who had IgG and IgM antibodies against PARV4.
Detection of PARV4 DNA in the second blood samples from two seropositive participants suggests the existence of persistent PARV4 replication or reactivation of inactive virus in the tissues. The finding of persistent or intermittent PARV4 replication in individuals with past infections provides an important clue toward unraveling the non-parenteral transmission routes of PARV4 infection in areas where the virus is endemic.
Parvovirus 4; Persistent PARV4 infection; Latent PARV4 infection; Anti-PARV4 IgM
In a country hyperendemic for chronic hepatitis B virus infection, the authors found that the incidence of recent hepatitis D virus infection is increasing among HIV-infected patients over the 20-year study period, which is associated with syphilis and hepatitis flares.
Background. Superinfection with hepatitis D virus (HDV) may increase the risk for hepatitis flares and chronic hepatic complications in patients with chronic hepatitis B virus (HBV) infection. This retrospective observational study aimed to examine the incidence of and factors associated with recent HDV superinfection among individuals coinfected with human immunodeficiency virus (HIV) and HBV.
Method. Anti-HDV immunoglobulin G (IgG) was sequentially determined in 375 HIV/HBV-coinfected patients to estimate the HDV incidence between 1992 and 2012. Plasma HDV and HBV loads and HBV surface antigen (HBsAg) levels were determined for the HDV seroconverters. A nested case-control study was conducted to identify the associated factors with HDV seroconversion. Phylogenetic analysis was performed using HDV sequences amplified from HDV seroconverters and HDV-seropositive patients at baseline.
Results. During 1762.4 person-years of follow-up [PYFU], 16 patients seroconverted for HDV, with an overall incidence rate of 9.07 per 1000 PYFU, which increased from 0 in 1992–2001, to 3.91 in 2002–2006, to 13.26 per 1000 PYFU in 2007–2012 (P < .05). Recent HDV infection was associated with elevated aminotransferase and bilirubin levels and elevated rapid plasma reagin titers. Of the 12 patients with HDV viremia, 2 were infected with genotype 2 and 10 with genotype 4. HBsAg levels remained elevated despite a significant decline of plasma HBV DNA load with combination antiretroviral therapy that contained lamivudine and/or tenofovir.
Conclusions. Our findings show that the incidence of recent HDV infection in HIV/HBV-coinfected patients increased significantly from 1992–2001 to 2007–2011, and was associated with hepatitis flares and syphilis.
seroconversion; seroincidence; case-control study; syphilis; sexually transmitted diseases
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<0.001), and higher CD4 counts at enrollment (AOR, per 50-cell/μl increase, 1.062; 95% CI, 1.017-1.109, P=0.007). Of the 64 patients testing positive for T-Spot.TB, none received isoniazid preventive therapy and all but 5 received combination antiretroviral therapy at the end of follow-up with the latest CD4 count and plasma HIV RNA load being 592.8 cells/μL and 1.85 log10 copies/mL, respectively. One patient (1.6%) developed active TB after 167 person-years of follow-up (PYFU), resulting in an incidence rate of 0.599 per 100 PFYU. None of the 534 patients testing negative for T-Spot.TB developed TB after 1380 PYFU, nor did the 24 patients with old TB and positive T-Spot.TB tests develop TB after 62.33 PYFU.
The risk of developing active TB in HIV-infected patients with positive T-Spot.TB receiving combination antiretroviral therapy is low in Taiwan where the national TB program has led to a sustained decrease in TB incidence.
Combination antiretroviral therapy (cART) containing rilpivirine plus 2 NRTIs are effective antiretroviral (ARV) regimens for ARV-naive HIV-infected patients who had baseline plasma HIV RNA load (PVL) <5 log10 copies/mL and as switch therapy for those with viral suppression. In this study, we aimed to assess the short-term safety of rilpivirine-containing regimens among HIV-infected patients who initiated or switched to rilpivirine plus two NRTIs in Taiwan.
Materials and Methods
Between January and June 2014, medical records of all HIV-infected patients who initiated or switched to rilpivirine plus two NRTIs, during the follow-up were reviewed to assess the tolerance and adverse effects. Using a standardized data collection form, we recorded data of PVL and CD4 count, serologies for hepatitis B and C virus (HBV and HCV, respectively), haemogram, aminotransferases, bilirubin and serum creatinine before starting rilpivirine-containing regimens at four weeks and every 12 weeks thereafter.
During the study period, medical records of 246 patients initiated their first ARV therapy with rilpivirine-containing regimens (n=90) or switched to rilpivirine-containing regimen from other regimens (156). Of the 246 patients, 73.4% were men who have sex with men and 9.1% and 25.6% tested positive for HBsAg and anti-HCV antibody, respectively. Baseline CD4 was 395 cells/mm3 (range, 2-1581) and PVL, 2.76 log10 copies/mL (range, <1.3>7.0 log10 copies/mL). As of 10 July, 23 patients (9.3%) stopped rilpivirine-containing regimens due to gastrointestinal upset (n=4), skin rash (2), depression (2), poor sleep (3), anaemia (4, all being with zidovudine/lamivudine), nail hyperpigmentation (1), presence of transmitted drug resistance (4), and elevated aminotransferase levels (1). The proportion of the patients with aminotransferases of fivefold or higher than the upper limit of normal (ULN) was 1.7% and 1.5% for AST and ALT, respectively, before starting rilpivirine-containing regimens; the respective value was 1.4% and 2.4% after 12 weeks of cART.
Rilpivirine-containing regimens were generally well tolerated and less than 10% of the patients had to stop rilpivirine due to various reasons. Despite a higher prevalence of chronic HBV or HCV infection, rilpivirine-containing regimens did not cause significant changes of aminotransferases from baseline.
The incidence of recent hepatitis C virus infection (HCV) infection has been noted to be increasing among men who have sex with men (MSM), especially those with HIV infection, in several resource-rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994–2000, 2.29 in 2001–2005 to 10.13 per 1000 person-years of follow-up (PYFU) in 2006–2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who sought voluntary counselling and testing (VCT) service at a University Hospital.
Between May 2006 and December 2013, 18,246 tests for HIV antibody were performed among 12,143 individuals at the VCT services. A total of 2157 clients without HIV or HCV infection at baseline were included for estimation of incidence rate of recent HCV infection. Antibodies to HCV were determined with a third-generation enzyme immunoassay. A nested case-control study with four matched controls without HCV seroconversion for one HCV seroconverter was conducted to investigate the factors associated with recent HCV infection. Phylogenetic analysis was performed among the HCV strains obtained from VCT clients and patients coinfected with HIV and HCV between 2006 and 2013.
During the study period, 2157 clients received a total of 8260 tests. The HCV seroprevalence at baseline was 0.3%. Of the 2150 HCV-negative clients who contributed 5074.99 PYFU, 17 developed HCV seroconversion (incidence rate, 3.35 per 1000 PYFU; 95% CI, 1.76–4.94); the rate increased from 2.28 per 1000 PYFU (95% CI, 0.05–4.51) in 2006–2009, to 3.33 per 1000 PYFU (95% CI, 0.86–5.80) in 2010–2011, to 4.94 per 1000 PYFU (95% CI, 0.99–8.99) in 2012–2013. In case-control study, HCV seroconverters were more likely to have HIV-infected partners, recent syphilis and a Rapid Plasma Reagin (RPR) titre of 4 or greater. In multivariate analysis, having HIV-infected partners remained as the only independent associated factors with HCV seroconversion (AOR, 6.931; 95% CI, 1.064–45.163). Phylogenetic analysis revealed transmission pairs and clusters, with most clustered sequences derived from MSM.
Similar to the observation among HIV-infected patients who are not IDUs, increasing trends of recent HCV infection also occur among the individuals who sought VCT services in Taiwan. Having HIV-infected partners is independently associated with recent HCV seroconversion.
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.
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).
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.
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.
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.
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.
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.