ABSTRACT
OBJECTIVES: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. METHODS: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. RESULTS: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/µL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/µL], independent of age, while a CD4 count < 200 cells/µL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40-4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5-5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2-7.2) per 1000 person-years over the same period. CONCLUSIONS: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost-benefit of screening for IURMs in HIV-infected populations.
Subject(s)
AIDS-Related Opportunistic Infections/complications , Aging , HIV Infections/complications , Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Prospective StudiesABSTRACT
OBJECTIVES: Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals. METHODS: Mixed models were used to analyse the natural history of HCV RNA changes over time in HIV-positive patients with chronic HCV infection. RESULTS: A total of 1541 individuals, predominantly White (91%), male (73%), from southern (35%) and western central Europe (23%) and with HCV genotype 1 (58%), were included in the analysis. The median follow-up time was 5.0 years [interquartile range (IQR) 2.8 to 8.3 years]. Among patients not on combination antiretroviral therapy (cART), HCV RNA levels increased by a mean 27.6% per year [95% confidence interval (CI) 6.1-53.5%; P = 0.0098]. Among patients receiving cART, HCV RNA levels were stable, increasing by a mean 2.6% per year (95% CI -1.1 to 6.5%; P = 0.17). Baseline HCV RNA levels were 25.5% higher (95% CI 8.8 to 39.1%; P = 0.0044) in individuals with HCV genotype 1 compared with HCV genotypes 2, 3 and 4. A 1 log HIV-1 RNA copies/mL increase in HIV RNA was associated with a 10.9% increase (95% CI 2.3 to 20.2%; P = 0.012) in HCV RNA. CONCLUSIONS: While HCV RNA levels increased significantly in patients prior to receiving cART, among those treated with cART HCV RNA levels remained stable over time.
Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/complications , HIV Infections/drug therapy , Hepacivirus/isolation & purification , Hepatitis C, Chronic/virology , Viral Load , Adult , Antiretroviral Therapy, Highly Active/methods , Cohort Studies , Europe , Female , Humans , Male , Prospective Studies , RNA, Viral/bloodABSTRACT
BACKGROUND: ESPRIT, is a phase III, open-label, randomized, international clinical trial evaluating the effects of subcutaneous recombinant interleukin-2 (rIL-2) plus antiretroviral therapy (ART) versus ART alone on HIV-disease progression and death in HIV-1-infected individuals with CD4+ T-cells > or =300 cells/microL. OBJECTIVES: To describe the baseline characteristics of participants randomized to ESPRIT overall and by geographic location. METHOD: Baseline characteristics of randomized participants were summarized by region. RESULTS: 4,150 patients were enrolled in ESPRIT from 254 sites in 25 countries. 41%, 27%, 16%, 11%, and 5% were enrolled in Europe, North America, South America, Asia, and Australia, respectively. The median age was 40 years, 81% were men, and 76%, 11%, and 9% were Caucasian, Asian, and African American or African, respectively. 44% of women enrolled (n = 769) were enrolled in Thailand and Argentina. Overall, 55% and 38% of the cohort acquired HIV through male homosexual and heterosexual contact, respectively. 25% had a prior history of AIDS-defining illness; Pneumocystis jirovecii pneumonia, M. tuberculosis, and esophageal candida were most commonly reported. Median nadir and baseline CD4+ T-cell counts were 199 and 458 cells/muL, respectively. 6% and 13% were hepatitis B or C virus coinfected, respectively. Median duration of antiretroviral therapy (ART) was 4.2 years; the longest median duration was in Australia (5.2 years) and the shortest was in Asia (2.3 years). 17%, 13%, and 69% of participants began ART before 1995, between 1996 and 1997, and from 1998 onward, respectively. 86% used ART from two or more ART classes, with 49% using a protease inhibitor-based regimen and 46% using a nonnucleoside reverse transcriptase inhibitor-based regimen. 78% had plasma HIV RNA below detection (<500 cp/mL). CONCLUSION: ESPRIT has enrolled a diverse population of HIV-infected individuals including large populations of women and patients of African-American/African and Asian ethnicity often underrepresented in HIV research. As a consequence, the results of the study may have wide global applicability.
Subject(s)
Anti-HIV Agents/therapeutic use , Data Collection/statistics & numerical data , HIV Infections/drug therapy , HIV-1 , Interleukin-2/analogs & derivatives , Randomized Controlled Trials as Topic/statistics & numerical data , Adult , Antiretroviral Therapy, Highly Active , Ethnicity/statistics & numerical data , Female , Global Health , HIV Infections/complications , Hepatitis B/complications , Hepatitis C/complications , Humans , Injections, Subcutaneous , Interleukin-2/administration & dosage , Interleukin-2/therapeutic use , Male , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Sexual Behavior/statistics & numerical data , Treatment Outcome , Women's HealthABSTRACT
BACKGROUND: Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies. AIM: To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions. METHODS: Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT. RESULTS: A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients. CONCLUSIONS: The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting.
Subject(s)
Anilides/administration & dosage , Carbamates/administration & dosage , Hepatitis C, Chronic/drug therapy , Macrocyclic Compounds/administration & dosage , Ribavirin/administration & dosage , Ritonavir/administration & dosage , Sulfonamides/administration & dosage , Uracil/analogs & derivatives , 2-Naphthylamine , Adult , Anilides/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Carbamates/adverse effects , Cyclopropanes , Diarrhea/chemically induced , Drug Therapy, Combination , Hepacivirus/drug effects , Hepatitis C, Chronic/diagnosis , Humans , Lactams, Macrocyclic , Liver Cirrhosis/diagnosis , Liver Cirrhosis/drug therapy , Macrocyclic Compounds/adverse effects , Male , Middle Aged , Proline/analogs & derivatives , Ribavirin/adverse effects , Ritonavir/adverse effects , Sulfonamides/adverse effects , Treatment Outcome , Uracil/administration & dosage , Uracil/adverse effects , ValineABSTRACT
BACKGROUND: Since the introduction of highly active antiretroviral therapy (HAART), little is known about whether changes in HIV-1 mortality and morbidity rates have been sustained. We aimed to assess possible changes in these rates across Europe. METHODS: We analysed data for 9803 patients in 70 European HIV centres including ones in Israel and Argentina. Incidence rates of AIDS or death were calculated for overall and most recent CD4 count in 6-monthly periods and in three treatment eras (pre-HAART, 1994-1995; early-HAART, 1996-1997; and late-HAART, 1998-2002). FINDINGS: The incidence of AIDS or death fell after September, 1998, by 8% per 6-month period (rate ratio 0.92, 95% CI 0.88-0.95, p<0.0001). When AIDS and death were analysed separately, the incidence of all deaths during the late-HAART era was significantly lower than that during the early-HAART era in patients whose latest CD4 count was 20 cells/microL or less (0.43, 0.35-0.53, p<0.0001), but at higher CD4 counts, did not differ between early-HAART and late-HAART. Incidence of AIDS was about 50% lower in late-HAART than in early-HAART, irrespective of latest CD4 count (p<0.0001). In multivariate Cox's models, with early-HAART as the reference, there was an increased risk of AIDS (relative hazard 1.39; 95% CI 1.16-1.67, p=0.0004) and all deaths (1.29; 1.08-1.56, p=0.0065) in the pre-HAART era, and a reduced risk of AIDS (0.62; 0.50-0.77, p<0.0001) and all deaths (0.66; 0.53-0.82, p=0.0002) in the late-HAART era. INTERPRETATION: The initial drop in mortality and morbidity after the introduction of HAART has been sustained. Potential long-term adverse effects associated with HAART have not altered its effectiveness in treating AIDS.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/epidemiology , Antiretroviral Therapy, Highly Active , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/mortality , Antiretroviral Therapy, Highly Active/adverse effects , CD4 Lymphocyte Count , Female , HIV-1 , Humans , Incidence , Male , Prospective StudiesABSTRACT
In the advanced stages of human immunodeficiency virus (HIV) infection the defective interferon (IFN) responses have been observed. Persisting high lebels of the acid-labile interferons (al-IFNs) have been found in sera of the patients with AIDS. The combined antiretroviral therapy, that included the reverse transcriptase and viral protease inhibitors, resulted in a significant improvement of the clinical state of the majority of HIV-infected patients. In this report we describe the levels of IFNs in 41 HIV patients subjected to the combined treatment. High IFN levels (median 84, up to 576 U/ml) were found in sera of patients classified as the stage C2 or C3 of AIDS before the treatment. The combined therapy resulted in the decrease of IFN levels (median 7.5, up to 24 U/ml) that approached the levels of IFNs detected in the HIV+, A1-A3 stage patients (median 4, up to 36 U/ml). In contrast, the unsuccessful therapy connected with the worsening of the clinical state and the decrease of CD4+ cell count had no effect on the IFNs levels (median 48, up to 96 U/ml). Thus, the measurements of IFN activity in sera may be useful for monitoring the effects of the antiretroviral combined therapy. In sera of the AIDS patients, subjected to the antiviral bioassays, the mixture of the acid-labile and acid-stable form of IFN-alpha, with the prevailing al-IFN-alpha, have been detected.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/administration & dosage , HIV Infections/drug therapy , Interferon-alpha/blood , Acquired Immunodeficiency Syndrome/blood , Adolescent , Adult , Drug Therapy, Combination , Female , HIV Infections/blood , HIV Protease Inhibitors/administration & dosage , Humans , Male , Middle Aged , Reverse Transcriptase Inhibitors/administration & dosageABSTRACT
Impairment of interferon (IFN) system in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) became a basis for searching IFN responses to monitor the disease progression. For detailed investigations 16 HIV+/AIDS patients with at least 4 successively taken blood samples available for IFN determinations were selected. IFN responses were tested in two ways. Firstly, IFN level in plasma was measured. Secondly, capacity of IFN production by leukocytes was evaluated. The latter was determined in the whole blood assay, in which Newcastle disease virus (NDV) and phytohemagglutinin (PHA) were used as IFN-alpha and IFN-gamma inducers, respectively. The levels of IFN induced in whole blood leukocytes varied considerably in all individuals that had been tested. Nevertheless, two patterns of IFN responses were observed. In pattern I, patients had low levels of IFN in plasma and high levels of induced IFN-alpha and IFN-gamma. It was characteristic for 8 patients in good clinical condition. On the contrary, severe disease found in 2 patients was correlated with high levels of IFN in plasma and low levels of induced IFNs (pattern II). In 6 patients IFN responses were classified as intermediate pattern I/II suggesting transition from pattern I to pattern II. A variation of pattern I was found in the case of a patient defined as long-term survivor having relatively low levels of all IFN tested. The results suggested that interferon measurements reflected clinical condition of HIV+ patients showing not only past but also current immune changes.
Subject(s)
Acquired Immunodeficiency Syndrome/blood , HIV Seropositivity/blood , Interferon-alpha/blood , Interferon-gamma/blood , Adult , CD4 Lymphocyte Count , Cells, Cultured , Disease Progression , Female , Follow-Up Studies , Humans , Interferon Inducers/pharmacology , Interferon-alpha/biosynthesis , Interferon-gamma/biosynthesis , Leukocytes/drug effects , Leukocytes/metabolism , Male , Newcastle disease virus/physiology , Phytohemagglutinins/pharmacologyABSTRACT
The blood samples taken from 31 HIV+ and AIDS patients were used to study interferon (IFN) and tumor necrosis factor (TNF) responses. The IFN and TNF levels in plasma were determined. In the whole blood assay (whole blood diluted 1:10 with culture medium) Newcastle disease virus (NDV) and phytohemagglutinin (PHA) were used as cytokine inducers. Blood leukocytes of HIV+ patients produced significantly less IFN-alpha after NDV stimulation than the cells of healthy (HIV-) individuals. On the other hand, the production of IFN-gamma in response to PHA was impaired only in AIDS patients with stage CDC IV and CD4+ cell number < 200/microliters. These patients had also increased IFN levels in plasma. Particularly, the high level of IFN in plasma was frequently detected in patients with progressing AIDS with CD4+ cell number < 50/microliters. This type of IFN was identified as a mixture of acid-labile and acid-stable IFN-alpha. The IFN responses of HIV+ patients may be considered as markers for monitoring progression of AIDS and therapy.
Subject(s)
Acquired Immunodeficiency Syndrome/blood , HIV Infections/blood , Interferons/blood , Tumor Necrosis Factor-alpha/metabolism , Acquired Immunodeficiency Syndrome/immunology , Adolescent , Adult , Biomarkers/blood , CD4 Lymphocyte Count , Disease Progression , Female , HIV Infections/immunology , Humans , Interferon Inducers/pharmacology , Interferons/biosynthesis , Leukocytes/drug effects , Leukocytes/metabolism , Leukocytes/virology , Male , Middle Aged , Newcastle disease virus , Phytohemagglutinins/pharmacology , Reference Values , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
Human ehrlichiosis is transmitted by ticks. For the first time it was described in 1987. The ethiologic agent is Ehrlichia chaffeenisis. The course of the disease may be mild, self-limited or sometimes severe finishing with dead. The main symptoms are: fever, leucopenia, thrombocytopenia, or pancytopenia. Tetracyclines are mostly efficient in the treatment.
Subject(s)
Ehrlichiosis/transmission , Ticks , Animals , Ehrlichia chaffeensis/isolation & purification , Ehrlichiosis/drug therapy , Ehrlichiosis/microbiology , Humans , Tetracycline/therapeutic useABSTRACT
BACKGROUND: Planning clinical-endpoint trials in patients with HIV remain difficult as long-term follow-up of many patients is required. Cohort studies of patients with HIV can provide key estimates of the likely disease progression, required sample size and follow-up. OBJECTIVES: To verify the assumptions used in designing ESPRIT, a large randomized clinical trial assessing the clinical benefit of interleukin-2 treatment in patients with HIV infection, to use EuroSIDA to mimic the inclusion criterion of ESPRIT in order to compare the observed event rate in ESPRIT with the projected rate in EuroSIDA, and to project the required length of ESPRIT. METHODS: Patients in EuroSIDA who satisfied the ESPRIT recruitment criteria were selected. Patients were followed from baseline to new AIDS or death. RESULTS: The incidence of clinical progression in the selected EuroSIDA patients (N = 4482) was 1.5 per 100 PYFU (95% CI 1.3-1.7), and did not increase with increasing time from baseline, contrary to what was assumed in the design of the ESPRIT trial. In ESPRIT (N = 4150), for which the comparative data remain blinded, the incidence was 1.1 per 100 PYFU (95% CI 0.9-1.3), with no increase over time. The average follow-up required to complete ESPRIT and accrue the 320 events required by protocol would be seven years, 10 months using the projected rates from the EuroSIDA study, and seven years, 11 months if the observed event rate in ESPRIT continued unchanged. LIMITATIONS: Differences between patients recruited to observational studies or clinical trials cannot always be adjusted for. CONCLUSIONS: Event rates in EuroSIDA were similar in the first two years to those used in the design of ESPRIT, but did not increase over time, leading to an increase in the expected duration of ESPRIT. Clinical endpoint trials in HIV infection remain feasible, and large cohort studies are critical to the planning and ongoing assessment of design assumptions in such trials. The underlying assumptions of the clinical trial should be re-examined to ensure the original trial assumptions remain valid.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Antiretroviral Therapy, Highly Active , Clinical Trials as Topic/standards , Acquired Immunodeficiency Syndrome/mortality , Feasibility Studies , Follow-Up Studies , HIV Infections/drug therapy , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as TopicABSTRACT
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.
Subject(s)
AIDS-Related Opportunistic Infections/epidemiology , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Humans , Mycoses/epidemiology , Mycoses/etiology , Pneumonia, Pneumocystis/epidemiology , Pneumonia, Pneumocystis/etiology , Poland/epidemiology , Tuberculosis/epidemiology , Tuberculosis/etiology , Viral LoadABSTRACT
We assessed the prevalence of anti-hepatitis C virus (anti-HCV) antibodies and markers of hepatitis B virus (HBV) infection in patients of three haemodialysis centres before initiating anti-HBV vaccinations. Of the 94 patients, 39 (41.5%) were anti-HCV positive (+) and 81 (86.2%) were anti-hepatitis B core antigen (HBc) positive. There was a high rate of anti-HBc positivity among anti-HCV (+) patients (92.3%), although the presence of anti-HCV and anti-HBc antibodies were not significantly related to each other. Multiple blood transfusions (> 5 units) was a risk factor for development of HCV infection (P < 0.02), while none of our patients admitted intravenous drug abuse. Although 53.8% of anti-HCV (+) patients have had moderate serum alanine aminotransferase (ALT) elevations during the study period, none has had considerable liver disease, nor did the increased ALT correlate with the presence of anti-HCV. Only two of 17 staff members participating in the survey were anti-HCV (+), though almost every one gave a history of accidental needlestick exposure. All the study subjects were human immunodeficiency virus (HIV) negative. Our results, obtained with the second-generation, highly specific enzyme immunoassay and verified by the immunoblot assay for anti-HCV antibodies, support a recent suggestion that earlier reports might have underestimated the true prevalence of anti-HCV antibodies in haemodialysis patients.
Subject(s)
Hepacivirus/immunology , Hepatitis Antibodies/blood , Hepatitis C/epidemiology , Renal Dialysis/adverse effects , Adult , Alanine Transaminase/blood , Female , Hemodialysis Units, Hospital , Hepatitis C/etiology , Hepatitis C Antibodies , Humans , Male , Middle Aged , Poland/epidemiology , PrevalenceABSTRACT
The aim of this study was the assessment the efficacy and safety of therapy with interferon alpha (Intron A) administered s.c. 3 MU x 3/week for 12 weeks for patients with HBV related liver cirrhosis (Child's class A). Fifteen patients completed therapy and 12 months follow-up. At the end of follow-up sustained response to the therapy, defined by clearance of HBV-DNA, normalization of ALAT activity in serum and improvement in the liver histology was achieved in 46.6% of treated patients. Moreover, among few patients from group of nonresponders (patients without sustained clearance of HBV-DNA) decrease of HBV-DNA level, ALAT activity in serum and improvement in the liver histology were observed. Adverse effects of IFN alpha therapy were typical, but in any case were no necessity terminate the therapy.