Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption.

BACKGROUND: Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption. METHODS: We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (<20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter). RESULTS: A total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (<20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy. CONCLUSIONS: UB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash. (Funded by United Biomedical and others; ClinicalTrials.gov number, NCT02369146.).

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial.

Background: Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile. Methods: DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment-naive adults with ≥1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 48 (Food and Drug Administration snapshot approach; non-inferiority margin 10%). Results: Of the 734 participants randomized, 728 were treated (364 per group) and included in the analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8% (294/364) of EFV/FTC/TDF recipients achieved <50 HIV-1 RNA copies/mL (difference 3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) were significantly different between DOR/3TC/TDF and EFV/FTC/TDF (-1.6 vs +8.7 mg/dL and -3.8 vs +13.3 mg/dL, respectively). Conclusions: In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non-HDL-C compared with EFV/FTC/TDF. Clinical Trials Registration: NCT02403674.

Early suboptimal ART adherence was associated with missed clinical visits in HIV-infected patients in Asia.

Missed clinic visits can lead to poorer treatment outcomes in HIV-infected patients. Suboptimal antiretroviral therapy (ART) adherence has been linked to subsequent missed visits. Knowing the determinants of missed visits in Asian patients will allow for appropriate counselling and intervention strategies to ensure continuous engagement in care. A missed visit was defined as having no assessments within six months. Repeated measures logistic regression was used to analyse factors associated with missed visits. A total of 7100 patients were included from 12 countries in Asia with 2676 (37.7%) having at least one missed visit. Patients with early suboptimal self-reported adherence <95% were more likely to have a missed visit compared to those with adherence ≥95% (OR = 2.55, 95% CI(1.81-3.61)). Other factors associated with having a missed visit were homosexual (OR = 1.45, 95%CI(1.27-1.66)) and other modes of HIV exposure (OR = 1.48, 95%CI(1.27-1.74)) compared to heterosexual exposure; using PI-based (OR = 1.33, 95%CI(1.15-1.53) and other ART combinations (OR = 1.79, 95%CI(1.39-2.32)) compared to NRTI+NNRTI combinations; and being hepatitis C co-infected (OR = 1.27, 95%CI(1.06-1.52)). Patients aged >30 years (31-40 years OR = 0.81, 95%CI(0.73-0.89); 41-50 years OR = 0.73, 95%CI(0.64-0.83); and >50 years OR = 0.77, 95%CI(0.64-0.93)); female sex (OR = 0.81, 95%CI(0.72-0.90)); and being from upper middle (OR = 0.78, 95%CI(0.70-0.80)) or high-income countries (OR = 0.42, 95%CI(0.35-0.51)), were less likely to have missed visits. Almost 40% of our patients had a missed clinic visit. Early ART adherence was an indicator of subsequent clinic visits. Intensive counselling and adherence support should be provided at ART initiation in order to optimise long-term clinic attendance and maximise treatment outcomes.

Changes in renal function with long-term exposure to antiretroviral therapy in HIV-infected adults in Asia.

PURPOSE: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD). RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

Factors associated with pre-treatment HIV RNA: application for the use of abacavir and rilpivirine as the first-line regimen for HIV-infected patients in resource-limited settings.

BACKGROUND: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome. METHODS: HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created. RESULTS: A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm3; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m2 (OR 2.4 vs. <18.5 kg/m2; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p < 0.01), CD4 count >350 cells/mm3 (OR 3.9 vs. <100 cells/mm3; 95% CI 2.0-4.1, p < 0.01), total lymphocyte count >2000 cells/mm3 (OR 1.7 vs. <1000 cells/mm3; 95% CI 1.3-2.3, p < 0.01), and no prior AIDS-defining illness (OR 1.8; 95% CI 1.5-2.3, p < 0.01). Receiver-operator characteristic (ROC) analysis yielded area under the curve of 0.70 (95% CI 0.67-0.72) among derivation patients and 0.69 (95% CI 0.65-0.74) among validation patients. A cut off score >25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients. CONCLUSION: A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.

Effects of unplanned treatment interruptions on HIV treatment failure - results from TAHOD.

OBJECTIVES: Treatment interruptions (TIs) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia. METHODS: Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for >1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Covariables with P < 0.10 in univariable analyses were included in multivariable analyses, where P < 0.05 was considered statistically significant. RESULTS: Of 4549 patients from 13 countries in Asia, 3176 (69.8%) were male and the median age was 34 years. A total of 111 (2.4%) had TIs due to AEs and 135 (3.0%) had TIs for other reasons. Median interruption times were 22 days for AE and 148 days for non-AE TIs. In multivariable analyses, interruptions >30 days were associated with failure (31-180 days HR = 2.66, 95%CI (1.70-4.16); 181-365 days HR = 6.22, 95%CI (3.26-11.86); and >365 days HR = 9.10, 95% CI (4.27-19.38), all P < 0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158). CONCLUSIONS: Duration of interruptions of more than 30 days was the key factor associated with large increases in subsequent risk of treatment failure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption.

Tracing subsequent dissemination of a cluster of gonococcal infections caused by an ST1407-related clone harbouring mosaic penA alleles in Taiwan.

OBJECTIVES: Successful clones of Neisseria gonorrhoeae multiantigen sequence typing sequence type (ST) 1407 and ST1407-related genotypes have been reported to cause cefixime and ceftriaxone treatment failure in many countries. We characterized the 47 isolates of a strain cluster of ST4378, a genotype that differs in the porB sequence by only one nucleotide from ST1407, in Taiwan during April 2006 to June 2012. METHODS: We identified 47 ST4378 isolates among our 2357 total isolates from the Gonococci-National Isolate Collection for Epidemiology. The corresponding patients' medical records were collected. The 47 isolates were further typed by multilocus sequence typing. Genes involved in ß-lactam (ponA), quinolone (gyrA and parC) and multidrug (mtrR, porB1b and pilQ) resistance were sequenced. Antimicrobial susceptibility was determined by the disc diffusion test and Etest. RESULTS: Cefixime MICs for the 47 isolates ranged from 0.016 to 0.19 mg/L and ceftriaxone MICs ranged from 0.012 to 0.094 mg/L. Forty-six of the 47 isolates had a mosaic penA allele type XXXIV and one had a new allele type XL, which appeared to be a recombinant of mosaic penA type XXXIV and non-mosaic penA type II. All of the isolates harboured nearly identical polymorphism in the ponA, gyrA, parC, mtrR, porB1b and pilQ genes. Among the 33 patients with known medical records, 25 (76%) were men who have sex with men (MSM), 3 (9%) were bisexual and 5 (15%) were heterosexual. Fourteen (42%) of the 33 patients had HIV, 8 (24%) had syphilis and 7 (21%) had both infections. CONCLUSIONS: This is the first report of a cluster of ST1407-related strains in Taiwan. ST4378 is a genotype that may develop to cause third-generation cephalosporin treatment failures. Our results showed that ST4378 strains primarily transmitted in a high-risk MSM/bisexual network. The potential of these strains to become untreatable and spread to other low-risk sexual networks should be closely monitored.

Draft genome sequence of a dominant, multidrug-resistant Neisseria gonorrhoeae strain, TCDC-NG08107, from a sexual group at high risk of acquiring human immunodeficiency virus infection and syphilis.

Neisseria gonorrhoeae infection is the second major cause of sexually transmitted diseases worldwide. Development of resistance to multiple classes of antimicrobials in N. gonorrhoeae has compromised treatment and disease control. Herein, we report the availability of the draft genome sequence of a multidrug-resistant N. gonorrhoeae isolate, TCDC-NG08107, which spread in groups of men who have sex with men (MSM) in Taiwan.

Risk factors for HIV-1 seroconversion among Taiwanese men visiting gay saunas who have sex with men.

BACKGROUND: Men having sex with men (MSM) accounts for 33.6% of all reported cases of HIV-1 infection in Taiwan. The aim of this study was to investigate the epidemiology of HIV-1 infection among MSM in gay saunas in Taiwan. METHODS: Patrons of 5 gay saunas were recruited for a weekly volunteer counseling and testing program from 2001 to 2005. Questionnaires were collected for a risk factor analysis. HIV-1 subtypes were determined using DNA sequencing and phylogenetic analyses. RESULTS: HIV-1 prevalence rates among MSM in gay saunas in 2001 through 2005 were 3.4%, 5.1%, 8.9%, 8.5%, and 8.3%, respectively. In total, 81 of 1, 093 (7.4%) MSM had HIV-1 infection. Fifty-two HIV-1 strains were genotyped, and all of them were subtype B. HIV-seropositive men were significantly younger than the seronegatives. Only 37.1% used condoms every time during sexual intercourse. A multivariate logistic regression analysis showed that the risk factors for HIV-1 were being uncircumcised (odds ratio (OR) = 2.19; 95% confidence interval (CI), 1.08~4.45); having sexual intercourse with at least 2 partners during each sauna visit (≥ 2 vs. ≤ 1, OR = 1.71; 95% CI, 1.02~2.89); and the role played during anal intercourse (versatile vs. an exclusively insertive role, OR = 2.76; 95% CI, 1.42~5.36). CONCLUSIONS: Overall, 7.4% Taiwanese MSM participating in this study had HIV-1 subtype B infection. Uncircumcised, being versatile role during anal intercourse, and having sex with more than one person during each sauna visit were main risk factors for HIV-1 infection.

Detection of hepatitis C virus subtypes 6a, 6n, 6w and mixed infections using a modified multiplex real-time polymerase chain reaction protocol.

BACKGROUND/PURPOSE: In the past few years, many new subtypes in hepatitis C virus (HCV) genotype 6 have been identified. The aim of this study was to modify the multiplex real-time polymerase chain reaction (RT-PCR) protocol and use it to determine the HCV subtypes of a group of Taiwanese injection drug users (IDUs). METHODS: We used 76 serum specimens collected in northern Taiwan in 2008. Multiplex RT-PCR was used for HCV subtyping among those serum samples having anti-HCV antibodies. Twenty cases were randomly selected for comparison with subtyping results from Inno-LiPa II tests and phylogenetic tree analysis using NS5B sequences. RESULTS: Multiplex RT-PCR assays showed that 60.5% (46/76) of IDUs had single HCV infection. Three out of 76 (3.9%) had double HCV infection (1b/6a, 2a/2b and 2b/6a). Besides this, 27.6% (21/76) had no HCV signal. One IDU had subtype 6n and two had subtype 6w infection. Inno-LiPa II tests misclassified all 6n and 6w cases as 1b subtype. CONCLUSION: Our modified multiplex RT-PCR protocol can be used to support molecular epidemiological studies and laboratory diagnoses of different HCV subtypes including genotype 6.

Characteristics and dissemination of mosaic penicillin-binding protein 2-harboring multidrug-resistant Neisseria gonorrhoeae isolates with reduced cephalosporin susceptibility in northern Taiwan.

Among 254 Neisseria gonorrhoeae isolates from a sexually transmitted infection (STI) clinic in northern Taiwan, 69 isolates were found to contain the mosaic penA (MA) gene and were associated with elevated cefixime and ceftriaxone MICs. Most of these MA gene-harboring isolates were also resistant to penicillin (71.4%) and ciprofloxacin (100%) and were from men who have sex with men (MSM) or from bisexual men (81.2%). Three major sequence types (ST835, ST2180, and ST2253) constituted 55.7% of these isolates. The major sequence types harboring the mosaic penA gene may represent major sexual networks responsible for the emergence/introduction and the spread of the multidrug-resistant clones in Taiwan.

Shall I trust the report? Variable performance of Sanger sequencing revealed by deep sequencing on HIV drug resistance mutation detection.

BACKGROUND: The clinical utilisation of deep sequencing in HIV treatment has been hindered due to its unknown correlation with standard Sanger genotyping and the undetermined value of minority drug resistance mutation (DRM) detection. OBJECTIVES: To compare deep sequencing performance to standard Sanger genotyping with clinical samples, in an effort to delineate the correlation between the results from the two methods and to find the optimal deep sequencing threshold for clinical utilisation. METHODS: We conducted a retrospective study using stored plasma collected from August 2014 to March 2018 for HIV genotyping with the commercial Sanger genotyping kit. Samples with available Sanger genotyping reports were further deep sequenced. Drug resistance was interpreted according to the Stanford HIV drug resistance database algorithm. RESULTS: At 15-25% minority detection thresholds, 9-15% cases had underestimated DRMs by Sanger sequencing. The concordance between the Sanger and deep sequencing reports was 68-82% in protease-reverse transcriptase region and 88-97% in integrase region at 5-25% thresholds. The undetected drug resistant minority variants by Sanger sequencing contributed to the lower negative predictive value of Sanger genotyping in cases harbouring DRMs. CONCLUSIONS: Use of deep sequencing improved detection of antiretroviral resistance mutations especially in cases with virological failure or previous treatment interruption. Deep sequencing with 10-15% detection thresholds may be considered a suitable substitute for Sanger sequencing on antiretroviral DRM detection.

Seroprevalence of chronic hepatitis B virus infection among taiwanese human immunodeficiency virus type 1-positive persons in the era of nationwide hepatitis B vaccination.

OBJECTIVES: We aimed to assess the impact of nationwide hepatitis B virus (HBV) vaccination program on the seroprevalence of HBV infection among human immunodeficiency virus (HIV)-positive persons in a country where most HBV exposure occurs during the perinatal period or in early childhood. METHODS: Data on HBV surface antigen (HBsAg), anti-HBV surface (anti-HBs), anti-HBV core (anti-HBc), and anti-hepatitis C virus (anti-HCV) antibody were retrospectively collected from 3,164 HIV-positive and 2,594 HIV-negative persons between 2004 and 2007. Comparisons of serological markers of HBV and HCV were made between HIV-positive and -negative adults born before and after the implementation of the HBV vaccination program in Taiwan in July 1984. RESULTS: Compared with HIV-negative persons, the adjusted odds ratio for HBsAg seropositivity was 1.100 (95% confidence interval, 0.921-1.315) among HIV-positive persons. Although the seroprevalence of anti-HCV antibody remained similar between HIV-positive persons born before and those born after 1984, the seroprevalence of HBsAg declined from 20.3 to 3.3% in HIV-positive persons (P<0.001) and from 15.5 to 8.5% in HIV-negative persons (P<0.001). Despite the high seroprevalence of anti-HCV antibody (97.1%) in HIV-positive injecting drug users (IDUs), there was no statistically significant difference in the seroprevalence of HBsAg (5.6% vs. 8.5%, P=0.75) or anti-HBc antibody (40.7% vs. 27.9%, P=0.14) between HIV-positive IDUs and HIV-negative persons who were born after 1984. CONCLUSIONS: Our study showed a significant decline of seroprevalence of HBV infection among both HIV-negative and -positive persons who were born in the era of the nationwide HBV vaccination in Taiwan.

Brief Report: Malignancies in Adults Living With HIV in Asia.

BACKGROUND: Hematological malignancies have continued to be highly prevalent among people living with HIV (PLHIV). This study assessed the occurrence of, risk factors for, and outcomes of hematological and nonhematological malignancies in PLHIV in Asia. METHODS: Incidence of malignancy after cohort enrollment was evaluated. Factors associated with development of hematological and nonhematological malignancy were analyzed using competing risk regression and survival time using Kaplan-Meier. RESULTS: Of 7455 patients, 107 patients (1%) developed a malignancy: 34 (0.5%) hematological [0.08 per 100 person-years (/100PY)] and 73 (1%) nonhematological (0.17/100PY). Of the hematological malignancies, non-Hodgkin lymphoma was predominant (n = 26, 76%): immunoblastic (n = 6, 18%), Burkitt (n = 5, 15%), diffuse large B-cell (n = 5, 15%), and unspecified (n = 10, 30%). Others include central nervous system lymphoma (n = 7, 21%) and myelodysplastic syndrome (n = 1, 3%). Nonhematological malignancies were mostly Kaposi sarcoma (n = 12, 16%) and cervical cancer (n = 10, 14%). Risk factors for hematological malignancy included age >50 vs. ≤30 years [subhazard ratio (SHR) = 6.48, 95% confidence interval (CI): 1.79 to 23.43] and being from a high-income vs. a lower-middle-income country (SHR = 3.97, 95% CI: 1.45 to 10.84). Risk was reduced with CD4 351-500 cells/µL (SHR = 0.20, 95% CI: 0.05 to 0.74) and CD4 >500 cells/µL (SHR = 0.14, 95% CI: 0.04 to 0.78), compared to CD4 ≤200 cells/µL. Similar risk factors were seen for nonhematological malignancy, with prior AIDS diagnosis showing a weak association. Patients diagnosed with a hematological malignancy had shorter survival time compared to patients diagnosed with a nonhematological malignancy. CONCLUSIONS: Nonhematological malignancies were common but non-Hodgkin lymphoma was more predominant in our cohort. PLHIV from high-income countries were more likely to be diagnosed, indicating a potential underdiagnosis of cancer in low-income settings.

Cotrimoxazole prophylaxis decreases tuberculosis risk among Asian patients with HIV.

INTRODUCTION: Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV-infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear. METHODS: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site. RESULTS: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person-years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow-up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co-infection, TB diagnosis, HIV VL, CD4 count and BMI. CONCLUSIONS: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.

Genotyping of Chlamydia trachomatis by microsphere suspension array.

The identification of Chlamydia trachomatis genotypes is important for both the study of molecular epidemiology and infection control. We have developed a microsphere suspension array assay that can identify C. trachomatis genotypes rapidly and accurately and also discriminate among multiple genotypes in one clinical specimen.

Molecular epidemiological identification of Neisseria gonorrhoeae clonal clusters with distinct susceptibility profiles associated with specific groups at high risk of contracting human immunodeficiency virus and syphilis.

From April 2006 to August 2007, a total of 146 Neisseria gonorrhoeae isolates collected from 139 male patients in Taipei, Taiwan, were analyzed by N. gonorrhoeae multiantigen sequence typing (NG-MAST) and antibiotic susceptibility testing. The resistance rates of all isolates to ciprofloxacin, cefpodoxime, and cefixime were 76.7 (112/146), 21.2 (31/146), and 16.4% (24/146), respectively. NG-MAST identified 71 sequence types (STs), of which 21 STs contained 2 to 21 isolates. The isolates that belonged to the three major ST clusters typically were from patients who had specific epidemiological characteristics (such as sexual orientation and human immunodeficiency virus status). The major ST clones exhibited distinct resistance profiles and are associated with specific groups at high risk of human immunodeficiency virus and syphilis infections.

Optimal timing for elective total hip replacement in HIV-positive patients.

INTRODUCTION: Evidence about the optimal timing for total hip replacement (THR) in HIV-positive patients is scant. HYPOTHESIS: Preoperative criteria: cluster of differentiation 4 (CD4) counts>200cells/mm3 and an undetectable HIV virus load before THR, improve infection rates, aseptic loosenings, and functional outcomes. MATERIALS AND METHODS: We recruited 16 HIV-positive patients who had undergone 25 THRs between 2003 and 2015. None had hemophilia, and none were intravenous drug users (IVDUs). RESULTS: Their mean age was 41.2 years (range: 24-60); minimum follow-up was 12 months (mean: 64.6); mean duration of prophylactic antibiotics was 2.9 days (range: 1-5); and mean hospital length of stay was 6.0 days (range: 4-11). No patients were treated with subsequent oral antibiotics. The mean preoperative CD4 count was 464.1±237.0 (range: 235-904)cells/mm3. There were no early superficial surgical site infections, late periprosthetic joint infections, or aseptic loosenings. Post-surgery Harris Hip score was significantly (p<0.001) better. DISCUSSION: A preoperative CD4 count>200cell/mm3 and an undetectable HIV virus load might indicate optimal timing for elective THRs in HIV-positive patients without hemophilia and not IVDUs. LEVEL OF EVIDENCE: IV, retrospective or historical series.