Rapid CD4 decline after interruption of non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy in a resource-limited setting

<p>Abstract</p> <p>Background</p> <p>Non-nucleoside reverse transcriptase inhibitor (NNRTI) with stavudine and lamivudine is widely used as the first-line antiretroviral therapy (ART) in resource-limited settings. Lipodystrophy is common and options for switching ART regimen are limited; this situation can lead to patients' poor adherence and antiretroviral resistance. Treatment interruption (TI) in patients with high CD4 cell counts, lipodystrophy, and limited options may be an alternative in resource-limited settings. This study aimed to determine time to resume ART after TI and predictors for early resumption of ART in a resource-limited setting.</p> <p>Methods</p> <p>A prospective study was conducted in January 2005 to December 2006 and enrolled HIV-infected patients with HIV-1 RNA <50 copies/mL, CD4 > 350 cells/mm³, and willing to interrupt ART. CD4 cell count, HIV-1 RNA, lipid profile, and lipodystrophy were assessed at baseline and every 3 months. ART was resumed when CD4 declined to <250 cells/mm³or developed HIV-related symptoms. Patients were grouped based on ART regimens [NNRTI or protease inhibitor (PI)] prior to TI.</p> <p>Results</p> <p>There were 99 patients, 85 in NNRTI group and 14 in PI group. Mean age was 40.6 years; 46% were males. Median duration of ART was 47 months. Median nadir CD4 and baseline CD4 were 151 and 535 cells/mm³, respectively. Median CD4 change at 3 months after TI were -259 (NNRTI) and -105 (PI) cells/mm³(p = 0.038). At 13-month median follow-up, there was no AIDS-defining illness; 38% (NNRTI) and 29% (PI) of patients developed HIV-related symptoms. ART was resumed in 51% (NNRTI) and 36% (PI) of patients (p = 0.022). By Kaplan-Meier analysis, median time to resume ART was 5.5 (NNRTI) and 14.2 (PI) months (log rank test, p = 0.026). By Cox's regression analysis, NNRTI-based ART (HR 4.9; 95%CI, 1.5–16.3), nadir CD4 <100 cells/mm³(HR 2.7; 95%CI 1.4–5.3) and baseline CD4 <500 cells/mm³(HR 1.6; 95%CI, 1.2–3.1) were predictors for early ART resumption.</p> <p>Conclusion</p> <p>TI of NNRTI-based ART leads to rapid CD4 decline and high probability of early ART resumption and should be avoided. It is necessary to scale-up the options for HIV-infected patients with lipodystrophy in resource-limited settings.</p

Burden of cytomegalovirus reactivation post kidney transplant with antithymocyte globulin use in Thailand: A retrospective cohort study [version 1; referees: 2 approved]

Background: Cytomegalovirus (CMV) is an important cause of infectious complications after kidney transplantation (KT), especially among patients receiving antithymocyte globulin (ATG). CMV infection can result in organ dysfunction and indirect effects such as graft rejection, graft failure, and opportunistic infections. Prevention of CMV reactivation includes pre-emptive or prophylactic approaches. Access to valganciclovir prophylaxis is limited by high cost. Our objective is to determine the burden and cost of treatment for CMV reactivation/disease among KT recipients who received ATG in Thailand since its first use in our center. Methods: We conducted a single-center retrospective cohort study of KT patients who received ATG during 2010-2013. We reviewed patients’ characteristics, type of CMV prophylaxis, incidence of CMV reactivation, and outcome (co-infections, graft function and death). We compared the treatment cost between patients with and without CMV reactivation. Results: Thirty patients included in the study had CMV serostatus D+/R+. Twenty-nine patients received intravenous ganciclovir early after KT as inpatients. Only three received outpatient valganciclovir prophylaxis. Incidence of CMV reactivation was 43%, with a median onset of 91 (range 23-1007) days after KT. Three patients had CMV end-organ disease; enterocolitis or retinitis. Infectious complication rate among ATG-treated KT patients was up to 83%, with a trend toward a higher rate among those with CMV reactivation (P = 0.087). Patients with CMV reactivation/disease required longer duration of hospitalization (P = 0.018). The rate of graft loss was 17%. The survival rate was 97%. The cost of treatment among patients with CMV reactivation was significantly higher for both inpatient setting (P = 0.021) and total cost (P = 0.035) than in those without CMV reactivation. Conclusions: Burden of infectious complications among ATG-treated KT patients was high. CMV reactivation is common and associated with longer duration of hospitalization and higher cost

Clinical and radiologic manifestations of pulmonary cryptococcosis in immunocompetent patients and their outcomes after treatment

PURPOSEWe aimed to investigate clinical and radiologic manifestations of pulmonary cryptococcosis in immunocompetent patients and their outcomes after treatment.MATERIALS AND METHODSWe retrospectively reviewed the medical records, initial and follow-up chest computed tomography scans and/or radiographs for initial clinical and radiologic manifestations and outcomes following antifungal treatment of 12 immunocompetent patients diagnosed with pulmonary cryptococcosis between 1990 and 2012.RESULTSTwelve patients (age range, 21–62 years; males, eight patients [66.7%]) were included. Nine (75%) patients were symptomatic, eight of whom had disseminated infection with central nervous system involvement. Initial pulmonary abnormalities consisted of single nodules/masses (n=5), single segmental or lobar mass-like consolidation (n=3), multiple cavitary and noncavitary nodules (n=1), and multifocal consolidation plus nodules (n=3). These lesions ranged from less than 1 cm to 15 cm in greatest diameter. Distinct subpleural and lower lung predominance was observed. Seven patients (58.3%) had one or more atypical/aggressive findings, namely endobronchial obstruction (n=4), calcified (n=1) or enlarged (n=4) mediastinal/hilar lymph nodes, vascular compression (n=1), pericardial involvement (n=1), and pleural involvement (n=2). Following antifungal therapy, radiologic resolution was variable within the first six months of eight nonsurgical cases. Substantial (>75%) improvement with some residual abnormalities, bronchiectasis, cavitation, and/or fibrotic changes were frequently observed after 12–24 months of treatment (n=6).CONCLUSIONPulmonary cryptococcosis in immunocompetent patients frequently causes disseminated infection with atypical/aggressive radiologic findings that are gradually and/or incompletely resolved after treatment. The presence of nonenhanced low-attenuation areas within subpleural consolidation or mass and the absence of tree-in-bud appearance should raise concern for pulmonary cryptococcosis, particularly in patients presenting with meningitis

Performance of the QuickVue Influenza A+B Rapid Test for Pandemic H1N1 (2009) Virus Infection in Adults

To investigate the diagnostic accuracy of the QuickVue® Influenza A+B rapid test we conducted a prospective observational study in which this rapid test was compared with a real-time reverse transcription polymerase chain reaction (RT-PCR) for pandemic influenza A H1N1 (2009) infection in Austrian adults. The sensitivity, specificity, and positive and negative predictive values of the QuickVue test compared with the RT-PCR were 26% (95% CI 18–35), 98% (95% CI 92–100), 94% (95% CI 80–99) and 50% (95% CI 42–58), respectively. The prevalence of pandemic H1N1 (2009) virus infection among the 209 patients included in the study was 57%. Our data suggest that a positive QuickVue test provides considerable information for the diagnosis of pandemic influenza A H1N1 (2009) virus infection in young adults but that a negative QuickVue test result should, if relevant for patient management or public health measures, be verified using PCR

Transcriptional Activation of the Adenoviral Genome Is Mediated by Capsid Protein VI

Gene expression of DNA viruses requires nuclear import of the viral genome. Human Adenoviruses (Ads), like most DNA viruses, encode factors within early transcription units promoting their own gene expression and counteracting cellular antiviral defense mechanisms. The cellular transcriptional repressor Daxx prevents viral gene expression through the assembly of repressive chromatin remodeling complexes targeting incoming viral genomes. However, it has remained unclear how initial transcriptional activation of the adenoviral genome is achieved. Here we show that Daxx mediated repression of the immediate early Ad E1A promoter is efficiently counteracted by the capsid protein VI. This requires a conserved PPxY motif in protein VI. Capsid proteins from other DNA viruses were also shown to activate the Ad E1A promoter independent of Ad gene expression and support virus replication. Our results show how Ad entry is connected to transcriptional activation of their genome in the nucleus. Our data further suggest a common principle for genome activation of DNA viruses by counteracting Daxx related repressive mechanisms through virion proteins

1743. Impact of Cytomegalovirus Serostatus on Allograft Loss and Mortality within the First Year after Kidney Transplantation: An Analysis of the National Transplant Registry

Abstract Background Cytomegalovirus (CMV) infection is one of the leading causes of morbidity and mortality in kidney transplant (KT) recipients. We investigated the association of CMV serostatus and allograft outcome within the first year after KT. Methods All KT recipients from 2007 to 2017 were derived from the Thai Transplant Registry. The prevalence of allograft loss and mortality within the first year after KT was estimated by Kaplan–Meier analysis. CMV serostatus of the donor (D) and the recipient (R) was assessed as a prognostic factor of allograft loss and mortality by Cox proportional hazards models. Results During a 10-year study period, the population consisted of 4,556 KT recipients with a mean ± SD age of 43 ± 14 years and 63% were male. Fifty-two percent underwent deceased donor KT and 58% received induction therapy. Among 3,907 evaluable patients, the CMV seroprevalence were D+/R+ (88.9%), D+/R− (6.1%), D−/R+ (2.9%), and D−/R− (1.9%). The estimated prevalence of allograft loss and mortality within the first year were 3.8 and 2.8%, respectively. In univariate analysis, CMV D+/R- was significantly associated with mortality within the first year after KT [hazard ratio (HR), 2.10; 95% confidence interval [CI], 1.18–3.75 (P = 0.01)] however not with an allograft loss [HR, 1.51; 95% CI, 0.85–2.66 (P = 0.16)]. In multivariate analysis, CMV D+/R- serostatus was associated with mortality within the first year after KT [HR, 2.04; 95% CI, 1.05–3.95 (P = 0.04)]. Other independent prognostic factors for mortality were older recipient age, deceased donor KT, and hemodialysis after KT (Table 1). Conclusion In the setting where the donor and recipient CMV seropositivity is predominant, CMV seromismatch still negatively affects patient survival within the first year after KT. Disclosures All authors: No reported disclosures. </jats:sec