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Biomedical subjects

A Horban

Publications and source records attributed to A Horban.

At least 19 recordsLinked to original sources
PubMed2006

Opportunistic infections and other AIDS-defining illnesses in Poland in 2000-2002.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) led to a decreased incidence of the most severe opportunistic infections (OIs) in HIV-infected patients. In Poland, HAART became widely used in 1998. MATERIALS AND METHODS: This study was based on data from medical records data collected in the years 2000-2002 from medical centers for HIV-infected patients in Poland. The aim of the study was to determine the incidence of opportunistic infections (OIs) and other AIDS defining illnesses (ADIs). The chi(2) test was used to determine any significant trends. RESULTS: The incidence of ADIs was 6.8, 6.5 and 4.8/100 persons/year in 2000-2002, respectively. The most common diagnosed OIs were: fungal infections, tuberculosis, recurrent pneumonia, PCP and toxoplasmosis. In patients receiving HAART (HAART+) the incidence of ADIs was significantly lower than in non-ARV-treated as well as in all HIV+ (p < 0.02, p < 0.001, p < 0.001, respectively). A significant decrease in the incidence of ADIs in HAART+ patients between 2000 and 2002 (p < 0.0001) was observed. From 25% to 30% of ADIs among HAART+ patients were diagnosed within the first 3 months of antiretroviral therapy. In HAART+ patients the most common ADIs were fungal infections and tuberculosis. The diagnosis of ADIs resulted in the recognition of HIV status in 8.7-8.9% of patients. CONCLUSIONS: Five years after the introduction of HAART the incidence of ADIs had declined. Fungal infections and tuberculosis were the most common OIs in HIV+ patients in Poland.

AIDS-Related Opportunistic Infections↗
PubMed2006

Effects of nandrolone decanoate compared with placebo or testosterone on HIV-associated wasting.

Objectives Current research is unclear about the most effective pharmacological agents for managing the loss of weight and fat-free mass common in HIV/AIDS. The aim of this study was to compare nandrolone decanoate with placebo and testosterone. Methods The study was a multicentre randomized double-blind placebo-controlled trial. Three hundred and three adult HIV-positive male patients with a weight loss of 5-15% in the last 12 months, or a body mass index of 17-19 kg/m(2), or a body cell mass/height ratio lower than 13.5 kg/m, were randomly assigned to receive nandrolone decanoate (150 mg), testosterone (250 mg) or placebo intramuscularly every 2 weeks for 12 weeks. Fat-free mass, weight, immune markers and perception of treatment were the main outcome measures. Results Treatment with nandrolone resulted in significantly greater increases in fat-free mass [mean increase 1.34 kg; 95% confidence interval (CI) 0.60; 2.08 kg] and in weight (mean increase 1.48 kg; 95% CI 0.82; 2.14 kg) compared with placebo. The mean increase in weight with nandrolone of 1.00 kg (95% CI 0.27; 1.74 kg) when compared with testosterone was significant, although the difference in fat free mass did not reach significance (mean increase 0.69 kg; 95% CI-0.13; 1.51 kg). Patient perception of benefit was significantly greater in the nandrolone group when compared with both the placebo and the testosterone groups. Conclusions Treatment with nandrolone decanoate increased body weight when compared with placebo and testosterone. Nandrolone decanoate treatment resulted in greater increases in fat-free mass than placebo and demonstrated a trend for a significant increase when compared with testosterone.

Adult↗
PubMed2005

Comparison of gastrointestinal tolerability and patient preference for treatment with the 625 mg and 250 mg nelfinavir tablet formulations.

OBJECTIVES: To compare gastrointestinal (GI) tolerability and patient preference for the new 625 mg formulation of nelfinavir (NFV) and the marketed 250 mg tablets (Viracept) in HIV-1-infected patients. METHODS: Virologically controlled patients (n=126) treated with a nelfinavir (NFV) 250 mg-containing regimen for > or =8 weeks completed a stool diary for 14 days to assess baseline bowel function. After switching to the NFV 625 mg formulation [1250 mg twice a day (bid)] for 28 days, patients continued their stool diaries and at study completion answered a questionnaire regarding formulation preferences. RESULTS: The incidence and mean weekly duration of GI upset over a 2-week period were lower with NFV 625 mg than with NFV 250 mg (79.8% vs. 84.9% of patients and 2.1 vs. 3.0 days, respectively). Fewer patients experienced moderate or severe diarrhoea with NFV 625 mg (6.5% vs. 11.1%), and the incidence of investigator-assessed diarrhoea also decreased with NFV 625 mg. Importantly, there was a significant improvement overall in the incidence of diarrhoea (any grade) when patients switched to NFV 625 mg [38 of 124 (31%) improving, 69 of 124 (56%) stable and 17 of 124 (14%) worsening on NFV 625 mg; P<0.01]. At study completion, most patients expressed a preference to continue treatment with NFV 625 mg [112 of 122 (91.8%); P<0.0001], with only one patient (0.8%) preferring to resume treatment with NFV 250 mg. The new formulation was well tolerated with no new safety concerns. CONCLUSIONS: The new NFV 625 mg formulation is better tolerated and preferred by patients switching from NFV 250 mg tablets. By reducing the daily pill count and improving GI tolerability, the NFV 625 mg formulation may enhance patient adherence to NFV-containing antiretroviral regimens and thus potentially improve virological outcomes.

CD4 Lymphocyte Count↗
PubMed2004

Time to virological failure of 3 classes of antiretrovirals after initiation of highly active antiretroviral therapy: results from the EuroSIDA study group.

OBJECTIVE: The purpose of the present study was to determine the prevalence and incidence of virological triple drug-class failure (TCF) and to summarize the clinical outcome for patients who started receiving highly active antiretroviral therapy (HAART). METHODS: The present study is an observational longitudinal study of 3496 treatment-experienced (TE) and treatment-naive (TN) patients monitored from the time they started receiving HAART (baseline) until TCF occurred (as determined on the basis of viral loads), until AIDS was newly diagnosed, or until death. RESULTS: Four hundred forty-five patients (12.7%) had TCF; 370 (16.6%) of 2230 patients were TE, and 75 (5.9%) of 1266 patients were TN. At 6 years after starting HAART, 21.4% of TE and 11.2% of TN patients had TCF (P<.0001). The prevalence of TCF at or after 2002 was 15.5% in TE patients and 4.8% in TN patients. TN patients had a 32% annual increase in the incidence of TCF (95% confidence interval [CI], 14%-54%; P<.0001); at 5 years after starting HAART, the rate was comparable for TE and TN patients (3.3 and 3.4 cases/100 person-years of follow-up [PYFU], respectively). The incidence of new cases of AIDS or death was 2.7 cases/100 PYFU in patients who did not experience TCF and 5.0 cases/100 PYFU in patients who did experience TCF, an estimated 36% increase with each category of TCF (95% CI, 19%-56%; P<.0001). CONCLUSION: The prevalence of TCF was low after patients started receiving HAART, particularly among TN patients. Despite the influx of patients who had started receiving HAART more recently, the prevalence of TCF increased over calendar time. Patients with TCF had a higher incidence of newly diagnosed AIDS or death. Treatment of patients with TCF deserves further investigation.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study.

BACKGROUND: The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz. METHODS: In this multicentre, open-label, randomised trial, 1216 antiretroviral-therapy-naive patients were assigned nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine, for 48 weeks. The primary endpoint was the proportion of patients with treatment failure (less than 1 log(10) decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards, disease progression [new Centers for Disease Control and Prevention grade C event or death], or change of allocated treatment). Analyses were by intention to treat. FINDINGS: Treatment failure occurred in 96 (43.6%) of 220 patients assigned nevirapine once daily, 169 (43.7%) of 387 assigned nevirapine twice daily, 151 (37.8%) of 400 assigned efavirenz, and 111 (53.1%) of 209 assigned nevirapine plus efavirenz. The difference between nevirapine twice daily and efavirenz was 5.9% (95% CI -0.9 to 12.8). There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 (p=0.193) or the increases in CD4-positive cells (p=0.800). Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events, and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz. Of 25 observed deaths, two were attributed to nevirapine. INTERPRETATION: Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy, so triple-drug regimens with either NNRTI are valid for first-line treatment. There are, however, differences in safety profiles. Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events.

Adult↗
PubMed2004

Updated European recommendations for the clinical use of HIV drug resistance testing.

In most European countries, HIV drug resistance testing has become a routine clinical tool. However, its practical implementation in a clinical context is demanding. The European HIV Drug Resistance Panel was established to make recommendations to clinicians and virologists on this topic and to propose quality control measures. The panel recommends resistance testing for the following indications: i) drug-naive patients with acute or recent infection; ii) therapy failure, including suboptimal treatment response, when treatment change is considered; iii) pregnant HIV-1-infected women and paediatric patients with detectable viral load when treatment initiation or change is considered; and iv) genotype source patient when post-exposure prophylaxis is considered. In addition, for drug-naive patients with chronic infection in whom treatment is to be started, the panel suggests that resistance testing should be strongly considered and recommends testing the earliest sample for drug resistance if suspicion of resistance is high or prevalence of resistance in this population exceeds 10%. The panel does not favour genotyping over phenotype, however it is anticipated that genotyping will be used more often because of its greater accessibility, lower cost and faster turnaround time. For the interpretation of resistance data, clinically validated systems should be used to the greatest extent possible. It is mandatory that laboratories performing HIV resistance tests take regular part in quality assurance programs. Similarly, it is necessary that HIV clinicians and virologists take part in continuous education and meet regularly to discuss problematic clinical cases. Indeed, resistance test results should be used in the context of all other clinically relevant information for predicting therapy response. The panel also encourages the timely collection of epidemiological information to estimate the impact of transmission of resistant HIV and the prevalence of HIV-1 non-B subtypes in the different European countries.

Anti-HIV Agents↗
PubMed2002

High prevalence of genotypic resistance to nucleoside reverse transcriptase inhibitors among therapy-naive individuals from the Warsaw cohort.

BACKGROUND: The purpose of this study was to recognize nucleoside reverse transcriptase inhibitor (NRTI)-resistant HIV-1 strains among a group of therapy-naive patients, and subsequently to guide the choice of antiretroviral therapy. PATIENTS AND METHODS: HIV strains present in sera of 128 antiretroviral therapy-naive patients were tested for NRTI resistance-associated mutations. The RT-PCR amplified HIV rt regions were analyzed with an INNI-LiPA-HIV-1 RT assay. The number and pattern of resistance-associated mutated codons were determined and interpreted as resistance to particular drugs. RESULTS: Mutated codons were detected in 66 (51.5%) out of 128 tested samples. In 54 (81.8%) out of 66 samples, a K70R mutation was identified, which was followed by an M184V mutation in 22 cases (33.3%). For a majority of these samples, mixed wild/mutant populations were recognized in 44 (66.6%) cases. The interpretation of hybridization data revealed drug-resistant strains in 37 (28.9%) out of all samples tested. The determined resistance to particular drugs was as follows: 20 strains were resistant to zidovudine (ZDV), ten to lamivudine (3TC) and six to didanosine (ddI)/zalcitabine (ddC)/abacavir (ABC). In one case, a ZDV/3TC-resistant HIV strain was found. CONCLUSION: The prevalence of mutations associated with NRTI resistance was high in the tested cohort. The key reasons for that were most probably needle and drug sharing within the group of intravenous drug users (IVDUs) and the use of ZDV in monotherapeutic regimes in the early 1990s.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Nevirapine-containing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile.

BACKGROUND: Protease inhibitor-containing antiretroviral therapy for the treatment of HIV-1 infection is associated with elevated triglyceride and low-density lipoprotein (LDL)-cholesterol levels which may expose patients to an increased risk of coronary artery disease (CAD). We report the lipid and lipoprotein profiles of a representative subset of treatment-naive patients included in the Atlantic Study. This study compares patients treated with stavudine and didanosine plus the random addition of either the non-nucleoside reverse transcriptase inhibitor nevirapine (NVP), the protease inhibitor indinavir or the nucleoside reverse transcriptase inhibitor lamivudine. METHODS: Lipids and lipoproteins were quantified from prospectively collected and cryopreserved plasma samples obtained at weeks 0, 6 and 24. RESULTS: We observed a striking increase in high-density lipoprotein (HDL)-cholesterol (49%), apolipoprotein AI (19%), lipoprotein AI (38%) and HDL particle size (3%) in the NVP-treated patients (n = 34) at week 24. Much less pronounced changes in these parameters were seen to a similar extent both in patients receiving lamivudine (n = 39) and indinavir (n = 41). LDL-cholesterol also increased significantly both in the NVP and indinavir arms, but only in the NVP arm was this offset by a significant reduction (14%) in total over HDL-cholesterol ratio. Using a multivariate linear regression model, adjusting for CD4 cell count and plasma HIV RNA both at baseline and during treatment, randomization to the NVP-containing arm remained significant in explaining the observed changes in HDL-cholesterol and other HDL-related parameters. CONCLUSIONS: In HIV-1 infected patients treated with a regimen of stavudine, didanosine and NVP we found changes in lipids and lipoproteins which are associated with a sharp decrease in risk for CAD in other settings. If confirmed in larger studies, these findings both may influence the initial choice of therapy for HIV-1 infection, and might lead to novel approaches targeted at raising HDL-cholesterol for CAD prevention.

Adult↗
PubMed2001

Prednisolone does not prevent hypersensitivity reactions in antiretroviral drug regimens containing abacavir with or without nevirapine.

OBJECTIVES: To determine the effect of adjuvant prednisolone use on the development of abacavir (ABC)- and nevirapine (NVP)-associated hypersensitivity reactions (HSR). METHODS: Randomized open-label study in antiretroviral-naive adult HIV-1 infected patients using a factorial design in which NVP and/or hydroxyurea (HU) and/or prednisolone are added to a regimen of ABC, zidovudine and lamivudine. Prednisolone (40 mg once daily) was added for the first 2 weeks of treatment. As it was difficult to distinguish ABC-associated HSR from NVP-associated HSR, these events were treated as a composite endpoint. The odds ratio (OR) of developing HSR for prednisolone-use was calculated with and without stratification by NVP and/or HU. Logistic regression was performed to identify risk factors for developing HSR. RESULTS: Of the 229 patients 115 were randomized to prednisolone and 114 to no-prednisolone; 19 (17%) and 11 (10%) patients, respectively, developed HSR. The expected prevention of HSR by prednisolone use was not observed. In fact use of prednisolone showed an increased risk for HSR although this did not reach statistical significance [OR, 1.82; 95% confidence interval (CI), 0.82-4.03]. There was a higher incidence of HSR in the NVP group than in the non-NVP group (20% versus 6%; P = 0.002). An additional risk factor identified in a multivariate logistic model was a high baseline CD4 cell count (OR, 1.26 per 100 x 10(6) cells/l increase; 95% CI, 1.06-1.51). CONCLUSIONS: The simultaneous start of ABC and NVP in first-line antiretroviral regimens should be avoided because of a high (20%) incidence of HSR. Short-term therapy with prednisolone did not prevent HSR in patients using ABC with or without NVP.

Adult↗
PubMed2001

[Tuberculosis and mycobacteriosis important opportunistic disease in AIDS patients].

OBJECTIVE: The aim of the search was investigation of tuberculosis in AIDS patients. Each year 8-9 mln people fall ill of tuberculosis and one third of them die. To the infection of tuberculosis and fast development into active state are especially exposed people with AIDS. MATERIAL AND METHODS: 696 people were examined on tuberculosis most of which were AIDS patients hospitalized and cured in Hospital of Infection Diseases and Prison Hospital. 159 patients were women and 537 were men. The average age was between 25 and 45 (70%). The investigated population was characterized according to age, social and living conditions, using drugs and former contact with tuberculosis. All patients suspected of tuberculosis had chest X-rayed, sputum, BAL and pleural liquor were taken to bacteriological examination when extrapulmonary tuberculosis was suspected. The material was taken adequately to the disease process: CSF, urine, lymph nodes, peritoneal fluids, blood, stool, swabs and other. Bacteriological investigations have been carried out by fast cultivating method since 1998 and rapid genetic method since 1999. Apart from modern, fast diagnostic methods, routine bacteriological procedures were applied in tuberculosis diagnosis. RESULTS: More than 30% of the examined population were from bad social-living conditions, 78% had risk factors, 65% were drug users. The analysis of the tuberculosis illness from 1997 to July 2001 shows growing tendency. Nowadays it is 20% cases proved by bacteriological diagnosis. The structure of falling ill with tuberculosis has changed. Considerable increase of extrapulmonary tuberculosis was observed, 20 patients died due to tuberculosis and 8 patients due to mycobacteriosis. Resistance of M.tub.complex occurred within the range of 10% cases.

AIDS-Related Opportunistic Infections↗
PubMed2001

[Nested PCR in the diagnosis of Pneumocystis carinii pneumonia (PCP) in AIDS patients].

The studies were undertaken to evaluate the usefulness of a nested PCR assay in the diagnosis of Pneumocystis carinii pneumonia (PCP) in AIDS patients. To achieve the end, 51 excretions samples from the respiratory tract were collected from HIV-infected patients with respiratory symptoms, and examined for the presence of specific DNA. A portion of the mitochondrial large-subunit rRNA gene of Pneumocystis carinii was amplified with outer primers pair pAZ 102E, pAZ 102H and internal primers pAZ 102X, pAZ 102Y. Positive nested PCR results were obtained with 36 out of 51 examined samples. Some 52.8% of the positive results were obtained with samples collected from patients without clinical diagnosis of PCP. It was concluded, that the nested PCR method, being too sensitive, is not suitable for the routine diagnosis of PCP in AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed2000

Hepatitis C virus in lymphoid cells of patients coinfected with human immunodeficiency virus type 1: evidence of active replication in monocytes/macrophages and lymphocytes.

It has been reported that hepatitis C virus (HCV) may be lymphotropic in the setting of human immunodeficiency virus type 1 (HIV-1) coinfection. The present study was undertaken to determine the phenotype of lymphoid cells harboring replicating HCV in HIV-1-positive subjects. By means of highly strand-specific thermostable enzyme Tth-based reverse-transcriptase polymerase chain reaction, the presence of viral RNA-negative strand was sought in different subpopulations of peripheral blood mononuclear cells from 10 HIV-positive patients. HCV RNA-negative strand was most commonly present in monocytes/macrophages (4 cases), followed by CD8+ and CD4+ lymphocytes (2 cases) and CD19+ cells (1 case). In 2 cases that were further analyzed, viral-negative strand remained detectable in monocytes/macrophages cultured for 3 weeks. Moreover, monocyte/macrophage- and serum-derived viral sequences differed in the 5' untranslated region. These findings imply that, in HIV-infected subjects, HCV may replicate in the same cells as HIV-1, which raises the possibility of direct interactions between these pathogens.

5' Untranslated Regions↗
PubMed1998

[Humoral response to HBV antigens in acute and chronic hepatitis B].

Sera of patients with acute and chronic hepatitis B and antigenemia were tested for the presence of anti-HBe and anti-HBs antibodies, free or bound in immune complexes. The possible occurrence of immune complexes of HBcAg in these sera was also investigated. Immune complexes were identified by antigen specific enzyme immunoassay, in which polyclonal antibodies against synthetic fragments of proteins S and C of HBV and mono- and polyclonal anti-HBc antibodies were used as a solid phase. Free and/or antigen bound anti-HBe antibodies were detected in 100% of patients with acute (81% HBeAg positive) and in 37% of patients with chronic hepatitis, all HBeAg positive. Anti-HBs antibodies or their immune complexes were found in 83% and 37% of patients, respectively. In not any patient circulating complexes of HBcAg could be identified. The results obtained support the observations that humoral immune response to HBeAg and HBsAg can be detected earlier than generally accepted; they also suggest that the detection of anti-HBs in a single sample of serum should not be considered as the evidence of elimination of infection.

Acute Disease↗
PubMed1998

[Antiretroviral therapy in pregnant women with HIV].

Antiretroviral therapy decreases rates of maternal-infant HIV transmission when given ante and intrapartum to the pregnant women and post partum to the infant. The use of zidovudine (AZT) in pregnant women and newborn is well tolerated and reduces the maternal-infant transmission of HIV even though the complete protocol has not been used. Combination therapy leads to a sustained undetectable viral load in mother blood and does not have detrimental effects on the newborn. The use of combination antiretroviral therapy is now recommended in pregnancy, although limited data currently exists on the impact of this regimen on newborns. In future, there is a clear need to assemble larger population-based cohorts of HIV+ parturients and their offspring to explore the safety of antiviral therapy in pregnancy.

Anti-HIV Agents↗
PubMed1997

Correlation between function and proto-oncogene expression in isolated working rat hearts under various overload conditions.

In isolated perfused working rat hearts we have studied the effects of norepinephrine (NE) and of pressure as well as volume overload alone, and in combination on heart function and expression of the proto-oncogenes c-fos and c-myc. This preparation was functionally stable over the observation period of 120 min. NE (3x10(-8) M) induced an immediate and sustained increase in aortic and coronary flow as well as in cardiac output. Volume overload was established by increasing left atrial filling pressure (preload) from 8-16 cm H2O and resulted in a marked increase in aortic flow and cardiac output which subsided somewhat over time. Pressure overload was created by elevation of afterload from 80-100 cm H2O and induced a decrease in aortic flow and a slight increase in coronary flow. Using specific cDNA clones, the mRNAs of c-fos and c-myc were measured by Northern blots and quantified with densitometry. In all three conditions, c-fos mRNA was increased first, after 30 min. It was more pronounced and of longer duration in the NE-stimulated hearts. The increase in c-myc-mRNA occurred after 60 or 90 min. After 120 min, all signals were normal, although heart function was still altered in a manner specific for the respective intervention. Combination of NE with preload and afterload elevation as well as combination of preload and afterload elevation led first to an increase in cardiac output which was followed by a decline to various degrees. In all these combinations, the c-fos mRNA signal appeared earlier, after 15 min, and persisted for a longer period of time compared with the effect of a single stimulus. The c-myc mRNA was increased later, after 30 or 60 min. This increase persisted throughout the entire observation period, showing a further progressive rise. These results show that stimuli which cause cardiac hypertrophy in vivo induce a transient and sequential increase in proto-oncogene expression in the isolated working rat heart. Combination of two hypertrophy-inducing stimuli elicit an earlier, more pronounced and longer-lasting expression of the proto-oncogenes c-fos and c-myc, while functional parameters deteriorate.

Analysis of Variance↗
PubMed1996

[Initial evaluation of the diagnostic usefulness of tuberculin tests among the patients of the Center of Diagnosis and Treatment of AIDS].

Tuberculin and Candida skin tests were done on 98 HIV(+) and 42 control HIV(-) patients of AIDS Diagnosis and Therapy Center in Warsaw. Prevalence of the positive Tuberculin tests in the control group was 29% and it was not significantly different from those groups of patients HIV(+) whose CD4 cell count was higher than 350. For those with CD4 cell count 350 or below, tests were positive only in two cases both of the patients with active tuberculosis. The prevalence of positive Candida tests was in the control group only 12% and such result did not differ significantly from any other group of HIV positive patients with different CD4 cell counts. It is concluded that routine Tuberculin skin tests might be of value due to low initial prevalence among patients of the AIDS Center and that those persons who undergo conversion into positive tests will be under high suspicion of TB asymptomatic infection. Low prevalence and rather random distribution of positive Candida skin tests shows their insufficiency as single reference tests in anergy panel.

Acquired Immunodeficiency Syndrome↗