[Show abstract][Hide abstract] ABSTRACT: Abstract
Background: HIV-1 subtype CRF01_AE originated in Africa and then passed to Thailand
where it established a major epidemic. Despite the global presence of CRF01_AE little is
known about its subsequent dispersal pattern.
Methods: We assembled a global dataset of 2,736 CRF01_AE sequences by pooling
sequences from public databases and patient-cohort studies. We estimated viral dispersal
patterns using statistical phylogeography run over bootstrap trees estimated by the maximum
likelihood (ML) method.
Results: We show that Thailand has been the source of viral dispersal to most areas
worldwide, including 17 out of 20 sampled countries in Europe. Japan, Singapore, Vietnam
and other Asian countries have played a secondary role in the viral dissemination. In contrast,
China and Taiwan have mainly imported infections from neighbouring Asian countries,
North America and Africa without any significant exporting transmissions.
Discussion: The central role of Thailand in the global spread of CRF01_AE can be probably
explained by the popularity of Thailand as a vacation destination characterized by sexual
tourism and by Thai emigration to the Western world. Our study highlights the unique case of
CRF01_AE, the only globally distributed non-B clade for which its global dispersal was not
originated in Africa.
[Show abstract][Hide abstract] ABSTRACT: We report the SVR12 final analysis of a phase 3 study of telaprevir in combination with peginterferon (P)/ribavirin (R) in HCV-genotype 1, treatment-naïve and -experienced patients with HCV/HIV co-infection (INSIGHT).
Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19626. · 4.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: With increased usage of antiretroviral drugs (ARVs) in HIV uninfected persons proper reporting on suspected unexpected serious adverse reactions (SUSARs) and continued insight into serious adverse events (SAEs) is needed for adequate information on ARVs safety in such populations. Methods: We have evaluated medical documentation of persons receiving ARVs after non-occupationally HIV exposure (nPEP) during five concomitant years (2009-2013). SAEs and SUSARs were evaluated by two HIV physicians and defined according to international standards. In statistical methods, Kaplan Meier survival analysis was used to estimate the probability of SAE and Cox proportional hazard models to identify independent predictors of developing SAE. Only the first SAE was included in these analyses. Results: In total, 375 persons received nPEP. The most common reason was needle stick (43%), followed by unprotected sexual intercourse (17%), rape (10%) and first aid (10%). In 84 (22%) cases, the source patient was either known to be HIV positive or within a high risk group (active injecting drug user). In total, 170 SAEs were reported, 139 persons had only one SAE and majority developed it within first two weeks. The most frequent first SAEs were gastrointestinal disorders (22%), followed by general symptoms (9%), hypersensitivity reactions (1.6%) and CNS symptoms (1.3%). The remaining events were laboratory abnormalities of liver and kidney function, haematological disorders, other and unknown, each contributing to less than 1% of all patients. 8 (2.1%) patients have developed a SUSAR (bradycardia, vivid dreams, lymphadenopathy of the neck, increased platelet count, swelling and pain of large joints, swelling of lower limbs, peripheral oedema and loss of concentration). 22 (5.9%) persons discontinued nPEP due to adverse event and 19 (5.1%) required a paid sick leave from work. In multivariate analyzes, only age was independent predictor of developing SAE (HR 1.17; [95% CI 1.03-1.34]; p=0.02). Conclusions: In our observation, SAEs in reaction to nPEP were frequent yet usually mild events, mostly occurring in first two weeks and rarely causing discontinuation. The only significant factor increasing the risk of SAE was age. SUSARs were rare and moderately significant. More insight into this important area is required in order to ascertain proper pharmacovigilance of ARVs usage in HIV uninfected persons.
Journal of the International AIDS Society 11/2014; 17(4(Suppl 3)):19733. · 4.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since the introduction of highly active antiretroviral treatment significant decrease of HIV related morbidity and mortality has been noted. Ritonavir boosted saquinavir is an alternatively recommended protease inhibitor. Therefore we evaluated log term efficacy and safety of saquinavir/r (SQV/r) containing initial antiretroviral regimen on the basis of Polish Observational Cohort of HIV/AIDS Patients (POLCA).Materials and Methods The analysed data were prospectively collected in routine clinical practice and included ART naive patients starting SQV/r regiment as their first ART.
[Show abstract][Hide abstract] ABSTRACT: Alisporivir (ALV) is an oral, investigational host-targeting agent, with pangenotypic activity against hepatitis C virus (HCV). This randomized, double-blind, placebo-controlled, Phase II study explored the efficacy and safety of ALV with peginterferon-α2a/ribavirin (PR) in patients with chronic HCV genotype 1 infection in whom prior PR had failed (43% relapsers, 34% null responders and 23% partial responders). Four-hundred-and-fifty-nine patients were randomized (1:1:1:1) to ALV 600 mg once daily (QD), ALV 800 mg QD, ALV 400 twice daily (BID) or placebo plus PR for 48 weeks. When the global ALV trial programme was put on clinical hold, all patients in this study had received ≥31 weeks of randomized treatment; patients completed 48 weeks on PR alone. All ALV groups demonstrated superior rates of complete early virologic response (cEVR; primary endpoint) vs PR alone (P ≤ 0.0131), with highest cEVR rate seen with ALV 400 mg BID (74% vs 36% with PR alone; P < 0.0001). Respective SVR12 rates (key secondary endpoint) were 65% vs 26% in prior relapsers, 63% vs 5% in partial responders and 68% vs 3% in null responders. In patients who received >40 weeks of randomized treatment, the SVR12 rate was 89% for ALV 400 mg BID vs 30% for PR alone (P = 0.0053). Rates of viral breakthrough and relapse were lowest with ALV 400 mg BID. One case of pancreatitis (fully recovered) occurred with ALV/PR. Common AEs were headache, fatigue, anaemia, neutropenia and nausea. Hypertension was infrequent, but more common with ALV. ALV merits further investigation in interferon-free regimens in combination with direct-acting antiviral agents.
Journal of Viral Hepatitis 11/2014; · 3.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: students planning to practice internal medicine are more likely to have condition-focused, rather than behaviour-focused approach to HIV testing -data from the English
[Show abstract][Hide abstract] ABSTRACT: Background & AimsPredictors of response to treatment with peginterferon plus ribavirin are well established. In these post-hoc analyses of the REALIZE study we sought to identify predictors of response for telaprevir-based triple therapyMethods
Patients from the REALIZE study with baseline data for all predictors evaluated (including baseline disease characteristics and demographics, prior treatment response, and baseline laboratory assessments) were included in the post-hoc analyses (n = 465). Univariate and multivariate analyses were used to evaluate factors predicting treatment outcomes.ResultsSustained viral response (SVR) rates were 86% in prior relapsers, 63% in prior partial responders, and 32% in prior null responders. In the final multivariate analysis, baseline factors predicting SVR were prior response to treatment (Odds ratio [OR] = 2.80; 95% confidence interval [CI], 2.13–3.69), low density lipoprotein (LDL) (≥2.6 mmol/L) (OR = 2.11; 95% CI, 1.52–2.93), HCV genotype (OR = 0.58; 95% CI, 0.36–0.93), and maximum alanine amino transferase and aspartate amino transferase (OR = 0.62; 95% CI, 0.40–0.97).Conclusions
Prior response to peginterferon plus ribavirin treatment and LDL levels are the main independent predictive markers of response with telaprevir-based triple therapy.This article is protected by copyright. All rights reserved.
Liver international: official journal of the International Association for the Study of the Liver 10/2014; · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background & AimsWe evaluated the antiviral response of Asian or Pacific Islander (API) patients with chronic hepatitis B (CHB) who had baseline high viral load (HVL), defined as pre-treatment hepatitis B virus (HBV) DNA ≥9 log10 copies/mL, following up to 288 weeks of tenofovir disoproxil fumarate (TDF) treatment.MethodsA total of 205 HBeAg-negative and HBeAg-positive self-described API patients were randomized to receive 48 weeks of TDF 300 mg (HVL n=18) or adefovir dipivoxil 10 mg (HVL n=15) in a blinded fashion, followed by open-label TDF for an additional 240 weeks. The proportions of HVL versus non-HVL patients with HBV DNA <400 copies/mL were compared. Mean declines in HBV DNA were evaluated in API versus non-API patients.ResultsThroughout the first 72 weeks of treatment, a smaller proportion of HVL API patients reached HBV DNA <400 copies/mL than non-HVL API patients. However, after this timepoint similar proportions of HVL and non-HVL API patients achieved HBV DNA <400 copies/mL (100% versus 97%, respectively), which was maintained through week 288, where 92% of HVL patients and 99% of non-HVL API patients on treatment had HBV DNA <400 copies/mL. During the 288 weeks of treatment, API patients had similar mean HBV DNA declines as non-API patients, regardless of whether patients were HVL or non-HVL. No API HVL patient had persistent viremia at week 288. No resistance was detected among HVL or non-HVL patients.ConclusionsAPI patients with HVL CHB achieve HBV DNA <400 copies/mL with long-term TDF treatment; however, achieving viral suppression may take longer for HVL patients relative to non-HVL API patients.This article is protected by copyright. All rights reserved.
Liver international: official journal of the International Association for the Study of the Liver 10/2014; · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
This prospective, randomized, single-centre study compared peginterferons alfa-2a and alfa-2b, combined with ribavirin, in treating patients infected with hepatitis C virus (HCV) genotype 1.
Hundred-and-one patients received 48 weeks of open-label treatment with peginterferon alfa-2a (180 μg/week) and 111 patients received peginterferon alfa-2b (1.5 μg/kg/week). All patients received the same dose of ribavirin 1000/1200 mg/day, depending on weight. The primary efficacy endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA (<50 IU/mL) 24 weeks after the end of treatment.
Early virologic response (EVR), defined as at least 2 log10 IU/mL reduction of viral load at 12 weeks, was more common in patients treated with peginterferon alfa-2a (88% vs. 74.8%; p = 0.04). However, the difference in SVR was not statistically significant (49.5% vs. 44.1%; p = 0.43).
Peginterferon alfa-2a treated patients were also more likely to be HCV RNA negative at the end of treatment (67.3% vs. 57.7%), but this difference did not reach statistical significance. Multivariate logistic regression analysis found that SVR was associated with low fibrosis stage (F1–2 by Scheuer; p = 0.001) and low serum HCV RNA level (<400,000 IU/L; p = 0.023). While both forms of peginterferon showed similar efficacy as measured by SVR, use of peginterferon alfa-2b could lower the number of patients receiving unnecessary treatment beyond 12 weeks.
Advances in Medical Sciences 09/2014; · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
Linkage to care after HIV diagnosis remains underinvestigated in Europe, yet delays in linkage to care are an important obstacle to controlling the HIV epidemic. The Test and Keep in Care (TAK) project aims to determine the prevalence of HIV-positive persons who are lost or late to care and factors associated with this.Methods
Data from community-based voluntary counselling and testing that occurred in 2010–2011 were linked with data from HIV clinics using unique test numbers. Persons not registered in HIV clinics were considered lost to care (LTC). For statistical analysis, nonparametric tests were used for comparison, and a multivariable logistic regression model was developed that included all variables with P < 0.1 from the univariable models.ResultsA total of 110 persons were diagnosed as HIV-positive: 91% lived in central Poland, 5% were female and 71% were men who have sex with men (MSM). Forty-seven (42%) persons were LTC, seven of whom did not collect their enzyme-linked immunosorbent assay (ELISA) test result. Of those who registered, 75% registered within 1 month from HIV diagnosis, and 54% were late presenters. LTC individuals were more likely to have heterosexual or bisexual orientation, to have > 20 sexual partners, to not be in a relationship with an HIV-positive partner, to not use condoms, and to be taking their first HIV test. In a logistic regression model, after adjusting for these factors, using condoms in a stable relationship decreased the odds of LTC by 72% (odds ratio 0.28; confidence interval 0.11−0.67).Conclusions
Integration into care after HIV diagnosis requires improvement. Our results suggest that broadening awareness and counselling about sexual risks may have a positive impact.
[Show abstract][Hide abstract] ABSTRACT: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.
[Show abstract][Hide abstract] ABSTRACT: Hypervariable region 1 (HVR1) contained within envelope protein 2 (E2) gene is the most variable part of HCV genome and its translation product is a major target for the host immune response. Variability within HVR1 may facilitate evasion of the immune response and could affect treatment outcome. The aim of the study was to analyze the impact of HVR1 heterogeneity employing sensitive ultra-deep sequencing, on the outcome of PEG-IFN-alpha (pegylated interferon alpha) and ribavirin treatment.
[Show abstract][Hide abstract] ABSTRACT: Hepatitis C virus (HCV) highly conserved IRES (internal ribosome entry site) sequence, localized within the 5(')-untranslated region (5(')UTR), may determine viral properties like replication efficiency and cell tropism. The aim of the present study was to characterize newly emerging 5(')UTR variants in serum and peripheral blood mononuclear cells (PBMC) in chronic hepatitis C patients treated with interferon (IFN) and ribavirin and to identify their effect on IRES secondary structures. The study group consisted of 87 patients infected with genotype 1b from whom serum and PBMC samples were collected at 9 time points (before, during, and after treatment). New 5(')UTR variants developed in 9 patients. Out of the overall 14 new variants, 9 (64%) were found in PBMC. HCV variants with decreased thermodynamic stability were identified only in PBMC and C183U mutation was the most common one in this compartment. In conclusion, antiviral treatment may favor emergence of new 5(')UTR variants both in blood and in PBMC compartments. However, variants developing in the latter compartment were predicted to have lower thermodynamic stability of the IRES secondary structures compared to serum strains. C-U change in position 183, which has not been described previously, might indicate viral adaptation to lymphoid cells.
BioMed Research International 07/2014; 2014:175405. · 2.71 Impact Factor
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[Show abstract][Hide abstract] ABSTRACT: Background
Despite an increase in number of new drugs in the last few years, the clinical options are limited due to cross resistance and adverse effects of cART. We explored reasons for treatment discontinuation and effectiveness of first-line LPV/r containing regimen.
The study is a retrospective analysis of data collected in POLCA cohort study. Patients were cART naïve and continued LPV/r based regimen for 24 months. Effectiveness analyses included CD4 count and proportion of patients with durable HIV VL suppression. Safety analyses included changes in selected parameters: metabolic (total cholesterol, LDL, HDL, triglycerides, glucose), hepatic (ALT, AST, GGT, total bilirubin) and renal (creatinine, urea).
The median CD4 count increased at all time points till 24 months and the largest difference was in group with CD4 < 100 cells/μl at baseline. After 24 months from starting cART 60.8% of patients achieved HIV RNA below 40 copies/ml. Twenty patients (10.6%) developed virological failure.
Substantial part of patients had abnormal lipid tests results: TCh, HDL-ch, LDL-ch, TG before starting cART (21%, 29%, 40%, 46%, respectively). An increasing proportion of abnormal results of TCh and TG have been observed during cART with only 41% and 46% of normal results at 24 months. Serum creatinine level was normal in approximately 91% patients at baseline and proportion decreased to 86% between 12 and 24 months of treatment.
In POLCA cohort 24 months treatment with LPV/r-based regimen was safe and effective. Gastrointestinal side effects and lipids disorders were quite common but rarely led to treatment discontinuation.