PCR detection of human herpesviruses in colonic mucosa of individuals with inflammatory bowel disease: Comparison with individuals with immunocompetency and HIV infection.

BACKGROUND: Detection of human herpesviruses (HHVs) other than cytomegalovirus (CMV) in colonic mucosa of individuals with inflammatory bowel disease (IBD) remains unknown. This study identified eight HHVs in the colonic mucosa of individuals with IBD and compared the results with immunocompetent and human immunodeficiency virus (HIV)-infected individuals. METHODS: A total of 89 individuals who had colorectal ulcer on colonoscopy were enrolled: 26 with immunocompetency (n = 26), 41 with IBD, and 22 with HIV infection. We examined the colonic ulcers for the presence of eight HHVs-herpes simplex virus (HSV)-1/2, varicella zoster virus (VZV), CMV, Epstein-Barr virus (EBV), HHV-6, HHV-7, and HHV-8-using mucosal PCR. RESULTS: The IBD group had positivity rates of 0%, 0%, 0%, 53.7%, 24.4%, 39%, 39%, and 0% for HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8, respectively. The positivity rates of EBV and CMV in colonic mucosa increased significantly in the order of the immunocompetent, IBD, and HIV groups (EBV: 23.1%, 53.7%, 72.7%, P for trend = 0.0005; CMV, 7.7%, 24.4%, 54.5%, P for trend = 0.0003, respectively), but no increase was found in the other HHVs. Median mucosal EBV DNA values in the immunocompetent, IBD, and HIV groups were 0, 76, and 287 copies/µg DNA, respectively (P for trend = 0.002). Corresponding median mucosal CMV DNA values were 0, 0, and 17 copies/µg DNA (P for trend = 0.0001). There was no significant difference in the positivity rates of the eight HHVs between ulcerative colitis and Crohn's disease. CONCLUSION: The HHVs of EBV, CMV, HHV-6, and HHV-7, but not of HSV-1, HSV-2, VZV, or HHV-8, were identified in the colonic mucosa of IBD individuals. EBV and CMV in colonic mucosa was correlated with host immune status in increasing order of immunocompetent, IBD, and HIV-infected individuals.

Colonic cytomegalovirus detection by mucosal PCR and antiviral therapy in ulcerative colitis.

BACKGROUND: We aimed to identify the risk factors associated with colonic cytomegalovirus (CMV) infection in ulcerative colitis (UC) and to compare the clinical course between antiviral therapy-treated and -untreated groups in mucosal CMV-polymerase chain reaction (PCR) -positive cases. METHODS: We retrospectively selected 46 UC patients (>15 years old) in active phase who underwent colonoscopy with biopsy and were analyzed for CMV infection by mucosal PCR between October 2011 and December 2015 at our institution. Colonic CMV in inflamed mucosa was detected using quantitative real-time PCR. The clinical course was evaluated, including need for drug therapy/surgery or drug therapy intensification. In addition, we evaluated the clinical course between CMV-DNA- cases and CMV-DNA+ cases with low viral load. RESULTS: At baseline, CMV-DNA+ patients were significantly older, had higher endoscopic scores, and required higher corticosteroid doses during the past 4 weeks than CMV-DNA- patients (p< 0.05). No significant differences were observed in disease duration, disease distribution, laboratory data, or use of other medication between CMV-DNA+ and CMV-DNA- patients. In the anti-CMV-treated group with a median (range) DNA load of 16,000 (9,000-36,400), 3patients achieved remission without additional UC therapy, 2 required additional UC therapy, and 1 required colectomy despite azathioprine and infliximab therapy. In the CMV-untreated group with a median (range) DNA load of 919 (157-5,480), all patients achieved remission with UC therapy alone. No significant difference was observed in the clinical course between CMV-DNA- cases and CMV-DNA+ cases with low viral loads. CONCLUSIONS: Aging, endoscopic UC activity, and corticosteroid dose predispose to colonic CMV infection, as determined by mucosal PCR, in UC. UC treatment without anti-CMV therapy may be warranted, particularly in patients with low-load CMV-DNA. Anti-CMV therapy alone does not always achieve clinical response in UC even in cases with high-load PCR.

Single-nucleotide polymorphisms in the UDP-glucuronosyltransferase 1A-3' untranslated region are associated with atazanavir-induced nephrolithiasis in patients with HIV-1 infection: a pharmacogenetic study.

OBJECTIVES: Ritonavir-boosted atazanavir (atazanavir/ritonavir) is a widely used antiretroviral drug, though it can potentially cause nephrolithiasis. The aim of this study was to determine the relationship between polymorphisms in genes encoding proteins involved in metabolism and transportation of atazanavir, and atazanavir/ritonavir-induced nephrolithiasis in HIV-1-infected patients treated with atazanavir/ritonavir. METHODS: Nineteen SNPs in the ABCB1, NR1I2, UGT1A1, SLCO1B1 and CYP3A5 genes were examined in case patients with atazanavir/ritonavir-induced nephrolithiasis (n = 31) and controls (n = 47). Case patients were those with a clinical diagnosis of nephrolithiasis while on atazanavir/ritonavir, based on new-onset acute flank pain plus one of the following: (i) new-onset haematuria; (ii) documented presence of stones by either abdominal ultrasonography or CT; or (iii) confirmed stone passage. Control patients were consecutively enrolled among those with >2 years of atazanavir/ritonavir exposure free of nephrolithiasis. Genotyping was performed by allelic discrimination using TaqMan 5'-nuclease assays with standard protocols. Associations between alleles and atazanavir/ritonavir-induced nephrolithiasis were tested by univariate and multivariate logistic regression analyses. RESULTS: Multivariate analysis showed a significant association between atazanavir/ritonavir-induced nephrolithiasis and genotype T/C versus C/C at position c.211 (adjusted OR = 3.7; 95% CI, 1.13-11.9; P = 0.030), genotype G/C versus C/C at 339 (adjusted OR = 5.8; 95% CI, 1.56-21.3; P = 0.009) and genotype G/G or G/C versus C/C at 440 (adjusted OR = 5.8; 95% CI, 1.56-21.3; P = 0.009) of the UGT1A-3' untranslated region (UTR). CONCLUSIONS: This is the first known study to identify the association between SNPs in the UGT1A-3'-UTR and atazanavir-induced nephrolithiasis. Further studies are warranted to confirm this association and to elucidate how these SNPs might influence atazanavir exposure.

Low prevalence of transmitted drug resistance of HIV-1 during 2008-2012 antiretroviral therapy scaling up in Southern Vietnam.

BACKGROUND: The recent expansion of antiretroviral therapy (ART) program in resource-limited setting has raised concern about possible transmission of drug resistance (TDR). We assessed the prevalence of TDR over a 5-year period among treatment-naive individuals in Southern Vietnam during rapid ART scale-up. METHODS: Drug resistance mutations among antiretroviral-naive HIV-1-infected patients in Ho Chi Minh City were evaluated prospectively from 2008 to 2012 by HIV-1 pol gene sequencing. TDR was defined according to the World Health Organization list for surveillance of transmitted HIV-1 drug resistance in 2009. RESULTS: Pol sequence was obtained in 1389 individuals (median age: 30 years, males: 52.3%). Risks of HIV-1 infection included heterosexual contact in 60.7%, injection drug use in 22.4% and both 5.2%. The majority was infected with CRF01_AE (97%), whereas 19 were infected with subtype B. Over the 5-year study period, TDR was detected in 58 individuals (4.18%): 28 (2.02%) against nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), 19 (1.37%) against nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 15 (1.08%) against protease inhibitors (PIs), including 4 (0.29%) against both NRTIs and NNRTIs. The most common TDR was K103N (0.5%) for NNRTI. The annual prevalence of TDR remained low to moderate (2008: 2.4%; 2009: 5.2%; 2010: 5.48%; 2011: 2.72%; 2012: 5.36%), and there was no clear trend over time. CONCLUSIONS: There was no increase in TDR prevalence in Southern Vietnam during and after the 2008-2012 rapid scale up of ART.