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Results for “Disease progression prediction”

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At least 19 recordsLinked to original sources

PubMed2005

The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system.

BACKGROUND: The objective of this study was to compare the accuracy of disease progression prediction of the molecular genetics and morphometry-based Endometrial Intraepithelial Neoplasia (EIN) and World Health Organization 1994 (WHO94) classification systems in patients with endometrial hyperplasias. METHODS: A multicenter, multivariate analysis was conducted on 477 patients with endometrial hyperplasia who were required to have a 1-year minimum disease-free interval from the time of the index biopsy (1-18 years of follow-up). The results from that analysis were compared with the results from 197 patients who had < 1 year of follow-up. RESULTS: Twenty-four of 477 hyperplasias (5.0%) progressed to malignant disease over an average of 4 years (maximum, 10 years). According to the WHO94 classification, 16 of 123 atypical hyperplasias (13%) and 8 of 354 nonatypical hyperplasias (2.3%) progressed (hazard ratio [HR] = 7). Twenty-two of 118 EINs (19%) and 2 of 359 non-EINs (0.6%) progressed (HR = 45). EIN was prognostic within each WHO94 subcategory. Progression rates were 3% in simple hyperplasias, 22% in complex hyperplasias, 17% in simple atypical hyperplasias, and 38% in complex atypical hyperplasias with EIN, compared with progression rates of 0.0-2.0% in all hyperplasias if EIN was absent. EIN detected precancerous lesions (sensitivity, 92%) better than WHO94 atypical hyperplasias collectively (67%) or complex atypical hyperplasias alone (46%). In a Cox regression analysis, EIN was the strongest prognostic index of future endometrial carcinoma. The same was true for patients with < 1 year of follow-up (HR for EIN, atypical hyperplasia, and complex atypical hyperplasia: 58, 7, and 8, respectively). CONCLUSIONS: The EIN classification system predicted disease progression more accurately than the WHO94 classification and identified many women with benign changes that would have been regarded as high risk according to the WHO94 classification system.

Adult↗

PubMed2001

Deletions on chromosome 8p22 may predict disease progression as well as pathological staging in prostate cancer.

PURPOSE: A recent report demonstrated that the deletion of chromosome 8p22 could predict disease progression in stage III (capsular penetrating) prostate cancer. We studied if the status of chromosomal deletions of 8p22 could reflect pathological stage as well as patient prognosis, thereby serving as a diagnostic tool to optimize the treatment strategy in prostate cancer. EXPERIMENTAL DESIGN: A total of 97 patients (41 Japanese and 56 Swedish) were studied by the fluorescence in situ hybridization technique. Seventy-seven patients (23 pT2, 18 pT3, and 36 pN+ tumors) underwent surgery (radical prostatectomy or lymph node dissection). The specimens were prepared by touch biopsy. From another 20 cases, fine-needle aspiration biopsies were obtained. RESULTS: 8p22 deletions were detected in 47 (61%) and 11 (55%) specimens of 77 touch biopsies and 20 fine-needle aspiration biopsies, respectively. No significant difference was found in the frequency of 8p22 deletion between different preparations of specimens, as well as between different races (Japanese versus Swedish). The frequency of 8p22 deletion was statistically higher in patients with pT3 or more than in those with pT2 (P < 0.01). Disease progression was evaluated in 57 patients. The Cox proportional hazards model revealed 8p22 deletion to be the strongest parameter to predict disease progression (hazards ratio = 5.75; P = 0.0001). CONCLUSIONS: Studies on chromosomal deletions of 8p22 by fluorescence in situ hybridization technique may serve as a genetic marker to optimize the treatment strategy in patients with prostate cancer to the optimal treatment.

Aged↗

PubMed1996

The significance of tumour grade in predicting disease progression in stage Ta transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To determine the significance of tumour grade in predicting disease progression in stage Ta transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: From August 1975 to January 1991, 140 patients (121 men and 19 women, mean age 64.2 years, range 30-83) with stage Ta TCC of the urinary bladder were treated at the Veterans General Hospital-Taipei by transurethral resection and post-operative adjuvant intravesical chemotherapy. There were 48 patients (34%) with grade 1, 78 patients (56%) with grade 2 and 14 patients (10%) with grade 3 tumours. Disease progression and muscle invasion were assessed during a mean follow-up of 74.3 months and related to grade, urine cytology and the number and location of tumours. RESULTS: A total of 10 patients (7%) had tumour recurrence which invaded the muscle, of whom one had grade 1, six had grade 2 and three had grade 3 tumours. The patient with a grade 1 tumour developed muscle invasion within 16 months of surgery. The mean interval to the development of muscle invasion was 49.2 months in patients with grade 2 and 39.4 months with grade 3 tumour. In patients with stage Ta TCC, a grade 3 tumour was more likely to progress to muscle invasion (21%) than was a grade 1 (2.1%; P < 0.05) or grade 2 (7.7%; P < 0.05) tumour. One patient with a grade 2 and one patient with grade 3 tumour developed distant metastases without muscle invasion. Overall, the disease progression rate was 8.6% (12/140) in stage Ta TCC. Disease progression was more common with grade 3 (28.5%) than with grade 2 (9.0%; P < 0.05) and grade 1 (2.1%; P < 0.05) tumours. CONCLUSION: Tumour grade may be used to predict disease progression after resection of stage Ta urinary bladder cancer. A higher grade of tumour was associated with a higher incidence of disease progression.

Administration, Intravesical↗

PubMed2005

Serum proteomic fingerprinting discriminates between clinical stages and predicts disease progression in melanoma patients.

PURPOSE: Currently known serum biomarkers do not predict clinical outcome in melanoma. S100-beta is widely established as a reliable prognostic indicator in patients with advanced metastatic disease but is of limited predictive value in tumor-free patients. This study was aimed to determine whether molecular profiling of the serum proteome could discriminate between early- and late-stage melanoma and predict disease progression. PATIENTS AND METHODS: Two hundred five serum samples from 101 early-stage (American Joint Committee on Cancer [AJCC] stage I) and 104 advanced stage (AJCC stage IV) melanoma patients were analyzed by matrix-assisted laser desorption/ionisation (MALDI) time-of-flight (ToF; MALDI-ToF) mass spectrometry utilizing protein chip technology and artificial neural networks (ANN). Serum samples from 55 additional patients after complete dissection of regional lymph node metastases (AJCC stage III), with 28 of 55 patients relapsing within the first year of follow-up, were analyzed in an attempt to predict disease recurrence. Serum S100-beta was measured using a sandwich immunoluminometric assay. RESULTS: Analysis of 205 stage I/IV serum samples, utilizing a training set of 94 of 205 and a test set of 15 of 205 samples for 32 different ANN models, revealed correct stage assignment in 84 (88%) of 96 of a blind set of 96 of 205 serum samples. Forty-four (80%) of 55 stage III serum samples could be correctly assigned as progressors or nonprogressors using random sample cross-validation statistical methodologies. Twenty-three (82%) of 28 stage III progressors were correctly identified by MALDI-ToF combined with ANN, whereas only six (21%) of 28 could be detected by S100-beta. CONCLUSION: Validation of these findings may enable proteomic profiling to become a valuable tool for identifying high-risk melanoma patients eligible for adjuvant therapeutic interventions.

Disease Progression↗

PubMed1996

Estramustine-binding protein to dihydrotestosterone ratio in human prostatic carcinoma: a new marker for predicting disease progression.

OBJECTIVE: To elucidate the clinical significance of estramustine-binding protein (EMBP) in human prostatic carcinoma (PC) as an indicator for predicting disease progression. PATIENTS AND METHODS: EMBP concentrations in prostate tissue samples taken from 35 patients with benign prostatic hyperplasia (BPH), 33 patients with prostatic carcinoma (PC) taken before treatment, and from nine patients with hormone-refractory PC (hr-PC) were measured by radioimmunoassay using an antibody raised against rat EMBP. The dihydrotestosterone (DHT), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA) and zinc levels in the tissue were also measured. RESULTS: The EMBP concentration in well differentiated PC (W-PC) samples was no higher than in samples of BPH tissue, whereas concentrations in moderately differentiated PC (M-PC) and poorly differentiated PC (P-PC) were significantly higher (P < 0.01 and P < 0.005, respectively); the highest levels were those in tissue from hr-PC (P < 0.001). Levels of PAP, PSA and zinc were significantly lower in tissue from PC than from BPH, while the differences in levels between W-PC, M-PC and P-PC were not significant. The EMBP to DHT ratio in the tissue increased significantly from W-PC through M-PC to P-PC and was greatest in hr-PC tissue. Conversely, the PAP:DHT, PSA:DHT and zinc:DHT ratios did not correlate with the progress of histological grade. In addition, the pre-treatment EMBP:DHT and zinc:DHT ratios in 14 patients who developed hr-PC within 3 years after the administration of estramustine phosphate were significantly higher when compared with the remaining 19 patients (P < 0.001 and P = 0.0184, respectively), whereas the PAP:DHT and PSA:DHT ratios showed no significant difference between the groups. Moreover, patients with a high EMBP:DHT ratio (> or = 82) had a low progression-free probability compared to those with a lower ratio. CONCLUSION: The androgen-dependent property of EMBP tends to decline with the transformation of prostatic tissue into biologically more malignant disease. The tissue EMBP:DHT ratio before treatment may be a good indicator of the individual malignant potential of PCs.

Aged↗

PubMed2004

Does hypervascularity of liver metastases as detected on MRI predict disease progression in breast cancer patients?

OBJECTIVE: The aim of our study was to evaluate the association of the vascularity of liver metastases, as characterized by MRI, and disease progression in breast cancer patients. MATERIALS AND METHODS: Sixteen breast cancer patients with liver metastases who underwent MRI before and after systemic therapy were retrospectively identified. On the basis of comparison of each MRI examination with the previous examination, disease status of the patients was classified as complete response, partial response, stable disease, or progressive disease. Liver metastases were characterized as hyper- or hypovascular on the basis of the degree of enhancement in the arterial, portal, and interstitial phases of imaging after administration of a contrast agent. Fisher's exact test and ordinal logistic regression models, including the type of systemic therapy, presence of multiple metastases, and hormone receptor status, were used to estimate the unadjusted and risk-adjusted association between the presence of hypervascular liver metastases and disease progression. RESULTS: All patients in our sample (n = 16) were women and most (12/16, 75%) were white. Their median age was 51.5 years. In unadjusted analyses, the association between the presence of hypervascular liver metastases and disease progression was statistically significant (p < 0.0001). In multiple logistic regression analyses, hypervascular liver metastases were found to be an independent predictor of disease progression. Patients with hypervascular liver lesions were 20.5 times more likely to experience disease progression than patients without hypervascular metastases (odds ratio, 20.5; 95% confidence interval, 5.1-83.5; p < 0.0001). CONCLUSION: Our analysis provides suggestive evidence that disease progression can be predicted through MRI assessment of the vascularity of liver metastases in patients with breast cancer.

Adult↗

PubMed2005

CD4 lymphocyte percentage predicts disease progression in HIV-infected patients initiating highly active antiretroviral therapy with CD4 lymphocyte counts >350 lymphocytes/mm3.

BACKGROUND: The optimal timing of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients with > or = 200 absolute CD4 lymphocytes/mm3 is unknown. CD4 lymphocyte percentage could add prognostic information. METHODS: Persons who initiated HAART between 1 January 1998 and 1 January 2003, received > or = 30 days of therapy, and had baseline CD4 lymphocyte data available were included in the study. The log-rank test for time to event and Cox proportional hazards models were used to determine predictors of a new acquired immunodeficiency syndrome-defining illness or death. RESULTS: A total of 788 patients met the inclusion criteria. At baseline, subjects had a median of 225 CD4 lymphocytes/mm3 and 17% CD4 lymphocytes. Subjects with < 17% CD4 lymphocytes had earlier disease progression, compared with subjects with > or = 17%, both in the entire cohort (P<.0001) and of those subjects with > 350 absolute CD4 lymphocytes/mm3 at baseline (P=.03). CD4 lymphocyte percentage < 17% was the strongest predictor of disease progression among subjects in this latter group (hazard ratio, 3.57; P=.045). CONCLUSIONS: In this cohort, CD4 lymphocyte percentage predicted disease progression in HIV-infected subjects who initiated therapy with > 350 CD4 lymphocytes/mm3. This information may help identify persons who will derive the greatest benefit from initiation of HAART.

Adolescent↗

PubMed2003

The role of chromosome 8p22 deletion for predicting disease progression and pathological staging in prostate cancer.

The natural course of human prostate cancer is highly variable, and we still lack reliable tools to predict the patient's outcome. Recent publications suggest that the deletion of chromosome 8p22 has an important role for tumor progression in prostate cancer. Totally, 97 patients (41 Japanese and 56 Swedish) were studied to detect the status of chromosome 8p22 deletion by the fluorescence in situ hybridization (FISH) technique. Seventy-seven underwent surgery (59 radical prostatectomies or 18 lymph node dissections), and the specimens were prepared by touch biopsy. Fine-needle aspiration biopsies (FNAB) were obtained from another non-operative 20 cases. Disease progression was evaluated in 57 patients with a median follow-up of 59 months. 8p22 deletions were detected in 58 (60 %) of all cases. The frequency of 8p22 deletion did not significantly differ between different preparations of specimens (touch biopsy vs. FNAB) as well as between different races (Japanese vs. Swedish). Cases with more than pT3 tumors had a significantly higher frequency of 8p22 deletion than those with pT2 (p < 0.01). Multivariate analysis demonstrated that 8p22 deletion was the strongest parameter to predict disease progression (hazard ratio = 5.75; p = 0.0001). Studies on chromosomal deletions of 8p22 by the FISH technique may serve as a universal genetic marker to optimize the treatment strategy in patients with prostate cancer.

Aged↗

PubMed1998

Predicting disease progression in childhood cerebellar astrocytoma.

Pediatric cerebellar astrocytomas are frequently curable by complete surgical resection. However, even incompletely resected tumors may lie dormant indefinitely or spontaneously involute, and tumors thought to be completely excised have reappeared in the same location several years later. Because of the unpredictable nature of some cerebellar astrocytomas, this study was designed to analyze several variables for their potential value in predicting disease progression. The charts of 78 children treated at a children's hospital between 1966 and 1993 were reviewed; 62 tumors were pilocytic, 13 were fibrillary, and 3 were mixed oligoastrocytomas. Four children had the additional diagnosis of neurofibromatosis type 1, and those children were considered separately. Of the remaining 74 children, 48 underwent postoperative contrast-enhanced computerized tomography or magnetic resonance imaging. Of those 48 children, 17 had residual disease, and in 15 cases the tumor volume could be measured. Frequently the surgeon's report conflicted with the postoperative scan regarding the presence of residual disease. However, the surgeon's report of brainstem infiltration correlated highly with residual disease on postoperative imaging. On univariate Cox analysis, sex, age, tumor location, and tumor morphology did not show prognostic significance. In spite of their differences, the surgeon's report of residual tumor and the presence of residual disease on postoperative imaging were similar in their correlation with disease progression. However, on multivariate analysis, the volume of residual tumor was most closely linked with disease progression. Only the presence of fibrillary histology significantly complemented the volume of residual tumor as a negative prognostic indicator.

Adolescent↗

PubMed2006

The chemokine CCL5 as a potential prognostic factor predicting disease progression in stage II breast cancer patients.

PURPOSE: The aim of this study was to determine the prognostic value of the chemokine CCL5, considered as a promalignancy factor in breast cancer, in predicting breast cancer progression and to evaluate its ability to strengthen the prognostic significance of other biomarkers. EXPERIMENTAL DESIGN: The expression of CCL5, alone and in conjunction with estrogen receptor (ER)-alpha, ER-beta, progesterone receptor (PR), and HER-2/neu (ErbB2), was determined in breast tumor cells by immunohistochemistry. The study included 142 breast cancer patients, including individuals in whom disease has progressed. RESULTS: Using Cox proportional hazard models, univariate analysis suggested that, in stage I breast cancer patients, CCL5 was not a significant predictor of disease progression. In contrast, in stage II patients, the expression of CCL5 (CCL5(+)), the absence of ER-alpha (ER-alpha(-)), and the lack of PR expression (PR(-)) increased significantly the risk for disease progression (P = 0.0045, 0.0041, and 0.0107, respectively). The prognostic strength of CCL5, as well as of ER-alpha(-), improved by combining them together (CCL5(+)/ER-alpha(-): P = 0.0001), being highly evident in the stage IIA subgroup [CCL5(+)/ER-alpha(-) (P = 0.0003); ER-alpha(-) (P = 0.0315)]. In the stage II group as a whole, the combinations of CCL5(-)/ER-alpha(+) and CCL5(-)/PR(+) were highly correlated with an improved prognosis. Multivariate analysis indicated that, in stage II patients, ER-alpha and CCL5 were independent predictors of disease progression. CONCLUSIONS: CCL5 could be considered as a biomarker for disease progression in stage II breast cancer patients, with the CCL5(+)/ER-alpha(-) combination providing improved prediction of disease progression, primarily in the stage IIA subgroup.

Adult↗

PubMed1997

Low-level increases in serum C-reactive protein are present in early osteoarthritis of the knee and predict progressive disease.

OBJECTIVE: To examine the role of low-grade inflammation in the etiology and progression of early osteoarthritis (OA) of the knee. METHODS: We used a new, high-sensitivity, automated monoclonal antibody immunoassay for the classic acute-phase protein, C-reactive protein (CRP), in serum. Anteroposterior radiographs of the knee with weight bearing were obtained on 845 women (ages 44-67) on entry into a population-based study of OA in Chingford, North London. In those defined radiologically as "cases," the knee radiographs were repeated after 4 years. RESULTS: Levels of CRP were higher in 105 women with knee OA defined radiologically as Kellgren-Lawrence grade 2+ (median 2.4 mg/liter, interquartile range [IQR] 1.0-5.1), compared with 740 women without OA (median 0.7 mg/liter, IQR 0.3-1.8) (P < 0.001). Median levels of CRP were higher in the 31 women whose disease progressed at least 1 Kellgren-Lawrence grade (median 2.6 mg/liter, IQR 1.9-4.6), compared with the 39 whose disease did not (median 1.3 mg/liter, IQR 0.6-2.4) (P = 0.006) . The significance of these differences persisted after adjustment for age, weight, height, smoking, knee pain, or injury. Classifying disease by the presence of joint space narrowing or osteophytes alone produced similar results. CONCLUSION: CRP levels are modestly but significantly increased in women with early knee OA, and higher levels predict those whose disease will progress over 4 years, suggesting that low-grade inflammation may be a significant aspect of early OA and may be amenable to therapeutic intervention and secondary prevention.

Adult↗

PubMed1995

Human immunodeficiency virus type 1 cellular RNA load and splicing patterns predict disease progression in a longitudinally studied cohort.

We report the results of a longitudinal study of RNA splicing patterns in 31 early-stage human immunodeficiency virus disease patients with an average follow-up time of 3 years. Eighteen patients showed no evidence for disease progression, whereas 13 patients either showed a > or = 50% reduction in baseline CD4 count or developed opportunistic infections. Levels of unspliced, tat, rev, and nef mRNAs in peripheral blood mononuclear cells were measured by a reverse transcriptase-quantitative, competitive PCR assay. Viral RNA was detected in all patients at all time points. All 13 rapid progressors had viral RNA loads that were > or = 1 log unit greater than those of the slow progressors. In addition, seven of the rapid progressors showed a reduction of more than threefold in the ratio of spliced to unspliced RNA over the 3 years of follow-up. Conversely, two slow progressors with intermediate levels of viral RNA showed no splicing shift. These results confirm earlier observations that viral RNA is uniformly expressed in early-stage patients. We further show that cellular RNA viral load is predictive of disease progression. Importantly, the shift from a predominately spliced or regulatory viral mRNA pattern to a predominately unspliced pattern both is associated with disease progression and adds predictive utility to measurement of either RNA class alone.

AIDS Vaccines↗

PubMed2000

Linear estimates of disease progression predict survival in patients with amyotrophic lateral sclerosis.

We have shown that linear estimates of rates of disease progression (LEP), derived from isometric myometry [grip or foot dorsiflexion (FD) strength] and forced vital capacity (FVC%), are clinically and statistically significant predictors of survival of patients with amyotrophic lateral sclerosis (ALS) from date of disease onset and, except those based on grip strength, of survival from the date of measurement. We tested these results in 2 additional groups of patients: 1) those who participated in a previously reported Protropin (GH) study; and 2) those enrolled in two other clinical trials (group 2). The LEP were derived and tested as predictors of survival. In a Cox proportional hazards model, LEP based on all measures predicted survival from disease onset in both groups of patients. Using cutoff points determined within the original group to stratify patients in the validation groups into faster and slower progressing subgroups resulted in statistically significant separation of survival curves from disease onset in group 2 for all LEP and in group 1 (the GH group) for LEP derived from FD strength; and, for survival from date of measurement in group 2, when stratified by LEP based on FD strength or FVC%. LEP based on data generated by myometry or pulmonary function studies have now been shown to predict survival in 3 unrelated groups of patients with ALS entering clinical trials. Their precise use in clinical trial design needs to be explored further.

Adult↗

PubMed2003

Prostate-specific antigen doubling time predicts disease progression and survival.

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Disease Progression↗

PubMed2000

Maternal and infant factors predicting disease progression in human immunodeficiency virus type 1-infected infants. Women and Infants Transmission Study Group.

BACKGROUND: Infants with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection have widely variable courses. Previous studies showed that a number of maternal and infant factors, when analyzed separately, are associated with infant HIV-1 disease progression. In this study, clincal, virologic, and immunologic characteristics in the mothers and infants were examined together to determine the predictors of disease progression by 18 months of age and the associations with rapid progression during the first 6 months of life. METHODS: One hundred twenty-two HIV-1-infected women whose infants were HIV-1 infected were identified from the Women and Infants Transmission Study (WITS) cohort. WITS is a longitudinal natural history study of perinatal HIV-1 infection carried out in 6 sites in the continental United States and in Puerto Rico. The women were enrolled during pregnancy and their infants were enrolled at the time of delivery and followed prospectively by a standardized protocol. Virologic and immunologic studies were performed in laboratories certified by National Institutes of Health-sponsored quality assurance programs. Maternal factors in pregnancy were used as potential predictors of infant disease progression (progression to Centers for Disease Control and Prevention [CDC] Clinical Class C disease or death by 18 months of age) or as correlates of progression at <6 months of age. Infant factors defined during the first 6 months of life were used as potential predictors of progression during 6 to 18 months of age and as correlates of progression at <6 months of age. RESULTS: Progression by 18 months of age occurred in 32% of infants and by 6 months of age in 15%. Maternal characteristics that, by univariate analysis, were significant predictors of infant disease progression by 18 months of age were elevated viral load, depressed CD4(+)%, and depressed vitamin A. CD8(+)%, CD8(+) activation markers, zidovudine (ZDV) use, hard drug use, and gestational age at delivery were not. When examined in a combined multivariate analysis of maternal characteristics, only vitamin A concentration independently predicted infant progression. Infant characteristics during the first 6 months of life that, by univariate analysis, were associated with disease progression included elevated mean viral load at 1 to 6 months of age, depressed CD4(+)%, CDC Clinical Disease Category B, and growth delay. Early HIV-1 culture positivity (<48 hours), CD8(+)%, CD8(+) activation markers, and ZDV use during the first month of life did not predict progression. Multivariate analysis of infant characteristics showed that the only independent predictors were progression to CDC Category B by 6 months of age (odds ratio [OR], 5.80) and mean viral load from 1 to 6 months of age (OR, 1.99). The final combined maternal and infant analysis included the significant maternal and infant characteristics in a multivariate analysis. It showed that factors independently predicting infant progression by 18 months of age were progression to CDC Category B by 6 months of age (OR, 5.80) and elevated mean HIV-1 RNA copy number at 1 to 6 months of age (OR, 1.99). The characteristics associated with rapid progression to CDC Category C disease or death by 6 months of age were also examined. The only maternal characteristic associated with progression by 6 months in multivariate analysis was low maternal CD4(+)%. The infant characteristics associated with progression by 6 months of age in multivariate analysis were depressed mean CD4(+)% from birth through 2 months and the presence of lymphadenopathy, hepatomegaly, or splenomegaly by 3 months. Infant ZDV use was not assocciated with rapid progression. CONCLUSION: The strongest predictors of progression by 18 months are the presence of moderate clinical symptoms and elevated RNA copy number in the infants in the first 6 months of life. In contrast, progression by 6 months is associated with maternal and infant immun

Analysis of Variance↗

PubMed1996

Plasma viral RNA load predicts disease progression in accelerated feline immunodeficiency virus infection.

Viral RNA load has been shown to indicate disease stage and predict the rapidity of disease progression in human immunodeficiency virus type 1 (HIV-1)-infected individuals. We had previously demonstrated that feline immunodeficiency virus (FIV) RNA levels in plasma correlate with disease stage in infected cats. Here we expand upon those observations by demonstrating that plasma virus load is 1 to 2 logs higher in cats with rapidly progressive FIV disease than in long-term survivors. Differences in plasma FIV RNA levels are evident by 1 to 2 weeks after infection and are consistent throughout infection. We also evaluated humoral immune responses in FIV-infected cats for correlation with survival times. Total anti-FIV antibody titers did not differ between cats with rapidly progressive FIV disease and long-term survivors. These findings indicate that virus replication plays an important role in FIV disease progression, as it does in HIV-1 disease progression. The parallels in virus loads and disease progressions between HIV-1 and FIV support the idea that the accelerated disease model is well suited for the study of therapeutic agents directed at reducing lentiviral replication.

Animals↗

PubMed1994

Human immunodeficiency virus type 1 mRNA expression in peripheral blood cells predicts disease progression independently of the numbers of CD4+ lymphocytes.

To address the significance of human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cells (PBMCs), we have used reverse transcriptase-initiated PCR to measure HIV-1 mRNA expression in PBMC specimens collected from a cohort of HIV-infected individuals during a long-term prospective study. We found dramatic differences in HIV mRNA expression among individuals with very similar clinical and laboratory indices, and this variation strongly correlated with the future course of the disease. No evidence of viral replication was detected in PBMCs from asymptomatic individuals who, thereafter, had normal levels of CD4+ cells for at least 5 years. Irrespective of whether the CD4+ cell numbers were normal at the time of sampling, abundant expression of HIV-1 mRNA in PBMCs predicted accelerated disease progression within the next 2 years. Thus, independently of what may be the rate of HIV replication in other viral reservoirs, such as lymphatic tissue, the amount of HIV mRNA in PBMCs appears to reflect the subsequent development of HIV disease. We have also used the reverse transcriptase-initiated PCR assay to demonstrate a transient response to 3'-azido-3'-deoxythymidine treatment. Determination of HIV-1 mRNA expression in the PBMCs of infected individuals could, therefore, have significant clinical utility as a prognostic indicator and as a means to guiding and monitoring antiviral therapies.

CD4-Positive T-Lymphocytes↗

PubMed2005

Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection.

BACKGROUND: CD4+ T lymphocyte (CD4) counts and plasma human immunodeficiency virus (HIV) type 1 RNA concentrations predict clinical outcome in HIV-1 infection. Our objective was to assess the independent prognostic value for disease progression of soluble markers of immune system activation. METHODS: This retrospective marker-validation study utilized previously obtained clinical and laboratory data, including CD4+ cell counts, and made use of stored frozen serum samples to assay for levels of beta2-microglobulin, neopterin, endogenous interferon, triglycerides, interleukin-6, soluble tumor necrosis factor- alpha receptor II, and HIV-1 RNA, and to determine HIV genotypic reverse-transcriptase inhibitor resistance. The 152 patients who participated in this study represented a subsample of participants in AIDS Clinical Trials Group (ACTG) 116B/117, a randomized trial that demonstrated the clinical benefit of didanosine over zidovudine monotherapy in persons with advanced HIV-1 infection. Marker data were analyzed in relation to protocol-defined clinical disease progression, using Cox proportional hazards models. RESULTS: The median duration of follow-up was 344 days. Elevated baseline values for neopterin (P=.0009), endogenous interferon (P=.00039) and interleukin-6 (P=.0007) were each associated with greater subsequent risk of clinical disease progression. In a head-to-head comparison that was adjusted for CD4+ cell count (P=.0165) and HIV-1 RNA level (P=.1220), we found that elevated values for neopterin (P=.0002) and, to a lesser extent, endogenous interferon (P=.0053) were the strongest predictors of increased risk of clinical disease progression 6 months later. CONCLUSIONS: Soluble markers of immune activation add prognostic information to CD4 counts and viral load for risk of disease progression in advanced HIV-1 infection. The robust performance of neopterin, an inexpensive and reliably measured serum marker, supports its potential suitability for patient monitoring, particularly in resource-limited settings.

Anti-HIV Agents↗