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PubMed | Institute of Infectious Diseases, Queen Elizabeth Hospital, Capital Medical University, Mahidol University and 19 more.
Type: Journal Article | Journal: PloS one | Year: 2016

In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use.We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression.Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. 30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of 60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018).Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.


Kumarasamy N.,Medical Center | Kumarasamy N.,Institute of Infectious Diseases | Patel A.,Vedant Institute of Medical science | Patel A.,Institute of Infectious Diseases | Pujari S.,Institute of Infectious Diseases
Indian Journal of Medical Research | Year: 2011

With the rapid scale up of antiretroviral therapy, there is a dramatic decline in HIV related morbidity and mortality in both developed and developing countries. Several new safe antiretroviral, and newer class of drugs and monitoring assays are developed recently. As a result the treatment guideline for the management of HIV disease continue to change. This review focuses on evolving science on Indian policy*antiretroviral therapy initiation, which drugs to start with, when to change the initial regimen and what to change.


Baldanti F.,Virology Unit | Baldanti F.,Experimental Research Laboratory | Paolucci S.,Virology Unit | Gulminetti R.,Experimental Research Laboratory | And 4 more authors.
Journal of Medical Virology | Year: 2010

The emergence of drug-resistance mutations in HIV-1 integrase of patients receiving HAART salvage regimens including raltegravir was investigated in 11 heavily pretreated patients (median number of treatment failures 12, range 5-22) within an expanded access program in Pavia, Italy. HIV-1 RNA levels in plasma, CD4 + T-cell counts and sequencing of HIV-1 reverse transcriptase (RT), protease (PR), gp41, and integrase geneswere performed at baseline and after 1, 2, 3, 6, and 12months. The treatment baseline median HIV-1 RNA levels in plasma decreased from 7,510 (range118-407,107) to<50 copies/ml (range< 50-7,562), while median CD4 + T-cell counts remained unchanged (from 212 cells/ml, range 10-764 to 262 cells/μl, range 13-760). Mutations at positions involved in raltegravir resistance (E92G, G140S, Q148H, and N155H) were detected in 4 of 11 (36.3%) patients as early as 1month after initiating salvage HAART. Of note, the E→G change at codon 92 was not reported previously. In two patients with raltegravir resistance, the simultaneous appearance of additionalmutations (Y143R and E170A) with an unclear impact on susceptibility to raltegravir or on integrase activity was observed. It is concluded that raltegravir resistant HIV-1 strains may emerge as early as 1month after initiating HAART salvage regimens. A newmutation associated with the emergence of raltegravir resistance is described, and the simultaneous appearance of primary and secondary mutations was observed. The effect of single and multiple mutations on integrase activity, raltegravir susceptibility, and on the capacity of viral replication remains to be elucidated. © 2009 Wiley-Liss, Inc.


Pavie J.,University Paris Diderot | Porcher R.,University Paris Diderot | Torti C.,Institute of Infectious Diseases | Medrano J.,Charles III University of Madrid | And 7 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2011

Background: Limited data are available on the use of unboosted atazanavir in combination with nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-experienced HIV-infected patients. Methods: We conducted a multicentre, retrospective study among patients with plasma HIV-1 RNA levels>50 copies/mL under antiretroviral therapy who switched to unboosted atazanavir+NRTIs between January 2002 and December 2008. Virological failure during follow-up was defined as a confirmed plasma HIV-1 RNA level >50 copies/mL. Baseline risk factors for virological failure were identified using Cox proportional hazards models. Results: A total of 886 patients were analysed. At baseline, median age was 44 years, 71.5% were males and median CD4 cell count was 490 cells/mm 3. NRTIs used in combination with atazanavir were tenofovir, abacavir and emtricitabine/lamivudine in 36.9%, 44.1% and 94.4% of patients, respectively. Median follow-up was 21 months. The 3 year probability of virological failure was 20.1%. Only a history of virological failure under NRTIs [hazard ratio (HR) 1.63, P=0.049] and under protease inhibitors (HR 2.04, P=0.006) were significantly associated with the risk of virological failure. Among the 431 patients without a prior history of virological failure, the 3 year probability of virological failure was 11.3%, and only hepatitis C virus co-infection (HR 2.25, P=0.026) and abacavir use (HR 0.43, P=0.04) were associated with the risk of virological failure. Safety of the switch was satisfactory, with improvement of the lipid profile. Conclusions: In patients with virological suppression and no prior history of virological failure, a switch to unboosted atazanavir in combination with NRTIs is associated with a low probability of virological failure and a good safety profile. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Rovida F.,Molecular Virology Unit | Percivalle E.,Molecular Virology Unit | Campanini G.,Molecular Virology Unit | Piralla A.,Molecular Virology Unit | And 3 more authors.
Journal of Clinical Virology | Year: 2011

Dengue virus infection is a growing global problem and reports of outbreaks in Asia and Latin America as well as sporadic infections in international travellers are increasing. Two imported cases of serotype-1 Dengue virus infection in a Northern Italy region with high density of Aedes albopictus vector are described: a 27-year-old man returning from Bali and a 25-years-old woman returning from Brazil. In both patients, viremia lasted for several days before disappearance. These cases stress the importance of investigating Dengue virus infections in febrile travellers, point to the potential for local outbreak of Dengue virus infection and emphasize the necessity of maintaining surveillance in non-endemic countries. © 2010 Elsevier B.V.


Paolucci S.,Molecular Virology Unit | Gulminetti R.,Institute of Infectious Diseases | Maserati R.,Institute of Infectious Diseases | Dossena L.,Molecular Virology Unit | Baldanti F.,Molecular Virology Unit
Current HIV Research | Year: 2011

Viral population in a long term non progressor carrying CRF02-AG HIV-1 virus variants with a truncated RT gene and attenuated virus replication was analyzed. The proportion of mutant and wild-type RT sequences was determined by clonal analysis of HIV-1 DNA and RNA from blood samples and peripheral blood mononuclear cell (PBMC) culture supernatants. Recombinant HIV-1 strains were generated by reverse genetics to evaluate the replicative capacity of RT variants in PBMC cultures. HIV-1 RNA and DNA sequences in PBMC cultures showed a mixture of stop codons (RT STOP), recombinant forms, (RT RF), and full length (RT FL) strains. In plasma, proportion of HIV-1 RNA sequences with a truncated RT gene fluctuated over time (0% in 2005, 100% in 2007 and 8.3% in 2010), while in proviral DNA was constant (96.5% to 100%). Reconstituted RT STOP strains were unable to replicate in PBMC. However, RT FL strains could trans-complement the loss of function of RT STOP variants. In vivo selection of stop codons in the RT gene resulted in the accumulation of replication-defective virus strains. Nevertheless, the observed release of defective viral particles in plasma was probably the result of viral protein complementation between replication-competent and replication-incompetent HIV-1 variants. The divergence in the proportion of RT STOP and RT FL variants as well as in the mutation's pattern to antiretroviral drug resistance between HIV- 1 plasma RNA and PBMC proviral DNA, suggested that circulating lymphocytes expressing full-length RT might be negatively selected for by a specific T-cell response, possibly contributing to the slow progression to AIDS observed in this patient. © 2011 Bentham Science Publishers Ltd.


Wang L.,Wuhan University | Chen H.,Institute of Infectious Diseases | Fan C.,Wuhan University | Gong Z.,Wuhan University
Journal of Medical Virology | Year: 2013

The objective of this study was to evaluate the short-term efficacy and safety of telbivudine therapy as compared to lamivudine therapy in liver failure patients with chronic hepatitis B virus (HBV) infection. These data were collected from 38 liver failure patients with chronic HBV infection who were randomly enrolled to one of the two treatments. All patients received comprehensive treatments; 20 patients were treated with telbivudine, and the other 18 patients were treated with lamivudine. The serum levels of HBV DNA, alanine aminotransferase, total bilirubin, prothrombin time activity, and creatine kinase were determined every 7 days for 8 weeks. The results showed that the serum HBV DNA levels in patients treated with either telbivudine or with lamivudine declined gradually after the 2nd week of treatment. However, HBV DNA levels in the telbivudine group fell to the lower limit of detection (<5+E2copies/ml) after the 5th week, which was more rapid than in the lamivudine group. In addition, the total bilirubin and prothrombin time activity of the patients with telbivudine treatment showed a more significant improvement as compared to the patients treated with lamivudine from the start of the 5th week. All patients tolerated telbivudine or lamivudine treatment well. The patients treated with telbivudine did not have elevated serum creatine kinase or myopathic symptoms during the 8-week treatment period. Thus, telbivudine treatment is superior to lamivudine treatment in improving the condition of patients with liver failure as a result of chronic HBV infection in the short term. © 2013 Wiley Periodicals, Inc.


Pujari S.N.,Institute of Infectious Diseases | Smith C.,University College London | Makane A.,Institute of Infectious Diseases | Youle M.,Royal Free Hospital | And 5 more authors.
BMC Infectious Diseases | Year: 2014

Background: Data on the renal safety of Tenofovir (TDF) in Low and Middle Income Countries (LMICs) is scarce. We compared development of various forms of renal impairment with use of TDF-containing antiretroviral therapy (ART) between a cohort from the Institute of Infectious Diseases (IID) Pune, Western India and the Royal Free Hospital (RFH) London, UK.Methods: This is a retrospective analysis of change in estimated glomerular filtration rates (eGFRs) at 6, 12 and 24 months post TDF initiation using the Modification of Diet in Renal Disease (MDRD) equation. In people living with Human Immunodeficiency virus (PLHIV) with pre-TDF eGFR > 90 ml/min/1.73 m2 time to development of and factors associated with progression to eGFR < 60 ml/min/1.73 m2 were calculated using standard survival methods.Results: A total of 574 (59% Caucasian) at the RFH, and 708 (100% Indian ethnicity) PLHIV from IID were included. Baseline median eGFR were similar; RFH 102 (IQR 89, 117), IID 100 (82, 119). At 24 months, mean (SD) decline in eGFR was -7(21) at RFH (p < 0.0001) and -7(40) at IID (p = 0.001). Amongst those with pre-TDF eGFR > 90 ml/min/1.73 m2 PLHIV at IID were more likely to develop an eGFR < 60 ml/min/1.73 m2 (aHR = 7.6 [95% CI 3.4, 17.4] p < 0.0001) and had a faster rate of progression estimated using Kaplan Meier methods. Risk factors included age (per 10 years older: aHR = 2.21 [1.6, 3.0] p < 0.0001) and receiving concomitant ritonavir boosted Protease Inhibitor (PI/r) (aHR = 2.4 [1.2, 4.8] p = 0.01).Conclusions: There is higher frequency of treatment limiting renal impairment events amongst PLHIV receiving TDF in Western India. As TDF scale up progresses, programs need to develop capacity for monitoring and treatment of renal impairment associated with TDF. © 2014 Pujari et al.; licensee BioMed Central Ltd.


Mocroft A.,University College London | Ryom L.,Copenhagen University | Begovac J.,University of Zagreb | D'Arminio Monforte A.,Institute of Infectious Diseases | And 6 more authors.
AIDS | Year: 2014

Objectives: To determine the relationship between measures of renal function [current estimated glomerular filtration rate (eGFR) and proportion of follow-up with a low eGFR (%FU ≤60 ml/min)] and fatal/nonfatal AIDS, non-AIDS events and all-cause mortality. Design: An observational, longitudinal cohort study of 12 155 persons from EuroSIDA. Methods: Persons with at least one eGFR measurement after 1 January 2004, using the CKD-EPI formula, were included. Poisson regression analyses were used to determine whether current eGFR or %FU of 60 ml/min or less were independent prognostic markers for clinical events. Results: During 61 425 person-years of follow-up (PYFU), the crude incidence of deaths was 11.1/1000 PYFU [95% confidence interval (CI) 10.0-12.1] at current eGFR more than 90 ml/min and 199.6 (95% CI 1144.3-254.3/1000 PYFU) when current eGFR was 30 ml/min or less. Corresponding figures for AIDS were 12.2 (11.1-13.3) and 63.9 (36.5-103.7) and for non-AIDS were 16.0 (14.8-17.3) and 203.6 (147.7-259.5). After adjustment, current eGFR of 30 ml/min or less was a strong predictor of death [adjusted incidence rate ratios (aIRR) 4.35; 95% CI 3.20-5.91] and non-AIDS events (3.63; 95% CI 2.57-5.13), although the relationship with AIDS was less strong (1.45; 95% CI 1.01-2.08). After adjustment, %FU of 60 ml/min or less was associated with a 22% increased incidence of death (aIRR 1.22 per 10% longer; 95% CI 1.18-1.27), a 13% increased incidence of non-AIDS events (95% CI 1.08-1.18) and a 15% increased incidence of AIDS events (95% CI 1.06-1.24). Conclusion: Both current eGFR and %FU of 60 ml/min or less were associated with death and non-AIDS events in HIV-positive persons. Our findings highlight the association between underlying renal dysfunction and morbidity and mortality in HIV infection, although reverse causality cannot be excluded. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Wang L.-W.,Renmin University of China | Wang L.-K.,Renmin University of China | Chen H.,Institute of Infectious Diseases | Fan C.,Renmin University of China | And 3 more authors.
World Journal of Gastroenterology | Year: 2012

AIM: To investigate the protective effects of ethyl pyruvate (EP) on acute-on-chronic liver failure (ACLF) in rats. METHODS: An ACLF model was established in rats, and animals were randomly divided into normal, model and EP treatment groups. The rats in EP treatment group received EP (40 mg/kg) at 3 h, 6 h, 12 h and 24 h after induction of ACLF. Serum endotoxin, high mobility group box-1 (HMGB1), alanine transaminase (ALT), tumor necrosis factor-α (TNF-α), interferon-α (IFN-γ), interleukin (IL)-10 and IL-18 levels, changes of liver histology and HMGB1 expressions in liver tissues were detected at 48 h after induction of ACLF. The effects of EP on the survival of ACLF rats were also observed. RESULTS: Serum levels of endotoxin (0.394 ± 0.066 EU/mL vs 0.086 ± 0.017 EU/mL, P < 0.001), HMGB1 (35.42 ± 10.86 μg/L vs 2.14 ± 0.27 μg/L, P < 0.001), ALT (8415.87 ± 3567.54 IU/L vs 38.64 ± 8.82 IU/L, P < 0.001), TNF-α (190.77 ± 12.34 ng/L vs 124.40 ± 4.12 ng/L, P < 0.001), IFN-γ (715.38 ± 86.03 ng/L vs 398.66 ± 32.91 ng/L, P < 0.001), IL-10 (6.85 ± 0.64 ng/L vs 3.49 ± 0.24 ng/L, P < 0.001) and IL-18 (85.19 ± 3.49 ng/L vs 55.38 ± 1.25 ng/L, P < 0.001) were significantly increased, and liver tissues presented severe pathological injury in the model group compared with the normal group. However, EP administration significantly improved hepatic histopathology and reduced the serum levels of endotoxin (0.155 ± 0.045 EU/mL vs 0.394 ± 0.066 EU/mL, P < 0.001) and inflammatory cytokines (11.13 ± 2.58 μg/L vs 35.42 ± 10.86 μg/L for HMGB1, 3512.86 ± 972.67 IU/L vs 8415.87 ± 3567.54 IU/L for ALT, 128.55 ± 5.76 ng/L vs 190.77 ± 12.34 ng/L for TNF-α, 438.16 ± 38.10 ng/L vs 715.38 ± 86.03 ng/L for IFN-γ, 3.55 ± 0.36 ng/L vs 6.85 ± 0.64 ng/L for IL-10, and 60.35 ± 1.63 ng/L vs 85.19 ± 3.49 ng/L for IL-18, respectively, P < 0.001), and the levels of HMGB1 in liver tissues regardless of treatment time after induction of ACLF. EP treatment at the four time points prolonged the median survival time of ACLF rats (60 h) to 162 h, 120 h, 102 h and 78 h, respectively (χ 2 = 41.17, P < 0.0001). CONCLUSION: EP administration can protect against ACLF in rats, and is a potential and novel therapeutic agent for severe liver injury. © 2012 Baishideng. All rights reserved.

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