Ewa Siwak

The cyclophilin inhibitor Debio‐025 shows potent anti–hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus

Debio‐025 is an oral cyclophilin (Cyp) inhibitor with potent anti–hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double‐blind, placebo‐controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log10 after a 14‐day oral treatment with 1200 mg twice daily (P < 0.0001) with an effect against the 3 genotypes (1, 3, and 4) represented in the study. In addition, the absence of viral rebound during treatment indicates that Debio‐025 has a high barrier for the selection of resistance. In Debio‐025–treated patients, cyclophilin B (CypB) levels in peripheral blood mononuclear cells decreased from 67 ± 6 (standard error) ng/mg protein (baseline) to 5 ± 1 ng/mg protein at day 15 (P < 0.01). Conclusion: Debio‐025 induced a strong drop in CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti–hepatitis C drugs. (HEPATOLOGY 2008;47:817–826.)

Intestinal fatty acid binding protein (I-FABP) as a possible biomarker of ileitis in patients with ulcerative colitis.

BACKGROUND One of nine types of FABP, intestinal fatty acid binding protein (I-FABP) is primarily limited to the mature enterocytes of the small intestine, with only trace amounts identified in the stomach and large intestine. The aim of this study was to investigate the use of I-FABP as a possible plasma marker of intestinal injury in patients with ulcerative colitis (UC). MATERIAL AND METHODS The study group consisted of 42 patients (11 females and 31 males) with active ulcerative colitis (UC), aged from 24 to 74 years (mean age: 41.8+/-3.5 years). Plasma I-FABP concentrations and hsCRP were compared using endoscopic pictures scored according to the system developed by Meyers et al., and analysed in the context of inflammatory process extension: pancolitis, or distal or left side colitis. RESULTS The mean serum I-FABP concentration /mL), whereas individuals with left-side colitis had a mean I-FABP concentration of 61.8+/-8.5 pg/mL. Significant serum I-FABP elevation was observed in UC patients with a severe form of the disease, in contrast to the serum I-FABP concentration in patients with the mild form (260.5+/-60.6 vs. 61.5+/-7.9 pg/mL). CONCLUSION The elevated serum I-FABP concentration in patients with UC may indicate ileitis. I-FABP may be a useful marker of the extended inflammatory process.

Changes in the trends of the HIV/AIDS epidemic, based on surveillance data of Warsaw cohort

Summary HIV infection remains one of the major public health concern, with evidence of increasing, even in several developed countries. The article provides an overview of HIV surveillance data of patients from outpatient clinic in Warsaw. In Poland the first HIV infection was detected in 1985, and the first case of AIDS one year later. In the period between 1990–2000y among HIV infected patients approximately 70% were intravenous drug users. In the next decade the shift of predominant mode of transmission for HIV infection is observed. From 2001 onward, the increasing number of persons infected through sexual contacts, without the past history of intravenous drug using has been noticed. Since 2005, among newly reported HIV infected adolescents the sexual contact between men followed by heterosexual contact has been the main route of transmission. The significant increase of this mode of transmission was noticed in 2008. The deaths rate remains relatively low, even decreases.

Identifying pre-existing Ns3 and Ns5a resistance-associated variants and transmission chains in the Polish Hiv/hcv genotype 1 epidemic: impact on prevention and treatment

Background: Hepatitis C virus (HCV) resistance–associated variants (RAVs) have been shown to adversely affect treatment response of direct-acting antivirals. Identifying pre-existing RAVs and transmission networks among HIV/HCV genotype 1 (G1)–infected patients from Poland will assist in shaping surveillance strategies for HCV. Methods: NS3 and NS5A sequences were obtained from samples of 112 direct-acting antiviral–naive G1 patients (45 G1a and 67 G1b), of which 74 were chronically infected and 38 were diagnosed with acute hepatitis C (AHC). RAVs were identified using geno2pheno, and 98 concatenated NS3/NS5A alignments were constructed to identify transmission clusters using a maximum likelihood approach. Results: G1a was notably more prevalent compared with G1b among men-having-sex-with-men (MSM) (60.0% vs. 31.3%, P = 0.004), AHC cases (46.7% vs. 25.4%, P = 0.019), and patients diagnosed with syphilis (52.2% vs. 24.5%, P = 0.009). The overall NS3/NS5A RAVs frequency was 14.3% with variants occurring more often in G1a compared with G1b (27.5% vs. 5.2%, P = 0.005), mostly for NS3 due to the high prevalence of polymorphism Q80K. NS5A RAVs were only found in 2.9% of sequences. Significant clustering was observed for 73.5% of the Polish sequences, however, more common in G1a MSM compared with G1b (50.0% vs. 25.9%, P = 0.02). The identified clusters contained sequences originating from up to 5 Polish cities, located within a mean distance of 370 km. Conclusions: Close clustering of Polish strains suggests the presence of compartmentalized epidemics of MSM that fuel the spread of G1a variants. Particularly patients with AHC form a national transmission network, including clusters enriched with the NS3 Q80K polymorphism.

“Efficacy and safety of nucleoside‐sparing regimen based on raltegravir and ritonavir‐boosted darunavir in HIV‐1‐infected treatment‐experienced patients”

To assess the efficacy and tolerability of dual therapy containing raltegravir (RAL) and ritonavir boosted darunavir (DRV/r) in HIV‐1‐infected treatment‐experienced patients.

Slowly progressing cutaneous T-cell lymphoma in HIV infected individual

Summary We present a case of HIV-infected individual on HAART diagnosed with mycosis fungoides (MF) – a variant of cutaneus T-cell lymphoma (CTCL), in which the prominent increase of peripheral blood CD4+ count was noted although the haematological form of this lymphoproliferative disease – Sezary syndrome (SS) was not confirmed.

Serum concentrations of α-defensins in patients with different stages of HIV-infection

Summary In our study we demonstrated significantly higher serum concentrations of HNP, IL-22 and hsCRP in the HIV-infected group, compared to the control group. The levels of HNP in the HIV-infected group differed significantly according to the stage of the disease as determined by CDC classification (Kruskal-Wallis ANOVA test, H = 15.80084, p = 0.0004).

Dual therapy based on raltegravir and boosted protease inhibitors – the experience of Polish centers

Introduction The aim of the study was to present the experience of Polish centers regarding dual therapy based on the integrase inhibitor raltegravir (RAL) and ritonavir-boosted protease inhibitors (PI/r) for treating treatment-naïve and -experienced HIV-infected patients. Material and methods The paper concerns a retrospective multicenter study. The medical databases of six main Polish HIV centers from January 2009 to December 2014 were analyzed for the use of combined antiretroviral treatment consisting of RAL + PI/r. This study included 126 HIV-infected patients receiving RAL + PI/r therapy, of whom 17 patients were treatment-naive and 109 patients were treatment-experienced. Results In treatment-experienced patients, the most common reasons for the introduction of a RAL + PI/r regimen were virologic failure and impaired renal function (45 of 109 patients). In the treatment-naïve group kidney disease was the cause of the RAL + PI/r regimen in 3 of 17 participants. In treatment-experienced patients, 80% of individuals still were on RAL + PI/r treatment after 12 months, 65% after 24 months and 53% of subjects after 60 months. In both groups, the simplification of the antiretroviral regimen was the most common reason for discontinuation of RAL + PI/r based therapy. Conclusions In antiretroviral-experienced patients the dual therapy based on RAL + PI/s is safe and effective. In antiretroviral-naïve patients the RAL + PI/r regimen is rarely used in Poland.

Comparison of effectivness of different methods of prevention of mother-to-child hiv transmission

Summary HIV infection among pregnant women is related to the risk of infection transmission to a newborn. The rate of mother-to-child HIV transmission without any prevention may exceed 30% and it increases to about 45% when children are breastfed. First international preventive program based upon ACTG-076 study started in 1994 and caused substantial decrease of frequency of HIV mother-to-child transmission. In Poland almost 25% of HIV infected population are women, and 150 children born in the country have been HIV diagnosed since the very beginning of HIV history. Analyzed group consisted of pregnant women registered in out-patient clinic for HIV patients in Warsaw. There were 718 women registered in the clinic between 1991–2008 and 196 pregnancies were observed in this period. Group was divided according to age group (under 20, 20–30 and over 30 years old), drug abuse status (active user, former user, methadone substitution, never used) and method of prevention (group 1 – none, 2 – ACTG076, 3 – HAART). Most of women were 20–30 years old (76,4%) and majority of them were drug abusers in periods preceding pregnancy (51%). Mother-to-child transmission rate ranged from 34,6% in group 1, 3,96% in group 2 and 0,95% in group 3. The lowest rate, 0% was observed in 60 patients in the group of caesarean section and HAART. Performed analysis confirms that HAART is the most effective method of prevention of mother-to-child HIV transmission.

Efficacy and safety of boosted atazanavir in HIV-infected, ARV-naive patients — results from 48/96 weeks Castle study

Summary Antiretroviral regimens based on human immunodeficiency virus-1 protease inhibitors are the cornerstone of combination antiretroviral therapy because of their antiviral efficacy and high genetic barrier. Protease inhibitor – containing regimens are complicated by a number of side effects, mainly diarrhea, dyslipidemia, an increased risk of myocardial infarction, diabetes and lipodystrophy. Atazanavir (ReyatazTM) is the first, originally designed as once-daily HIV-1 protease inhibitor that offers a more convenient and safer PI-containing management of HIV infection. The antiviral efficacy of atazanavir has been proven in both treatment-experienced and treatment-naive patients. In July 2008 boosted atazanavir has received registration for use in antiretroviral-naive HIV-infected population. This specific registration was based on results from 48 weeks of the Castle (BMS AI424138) study.