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CD4 lymphocyte count as a predictor of the duration of highly active antiretroviral therapy-induced suppression of human immunodeficiency virus load.

The association between CD4 cell count and duration of virus load suppression was investigated in 558 patients in the Frankfurt HIV Clinic Cohort who had begun highly active antiretroviral therapy and who had virus load declines to </=500 copies/mL. The Kaplan-Meier method estimated viral rebound in 42.5% of patients by 24 weeks and in 64.3% by 84 weeks. Risk of viral rebound was independently associated with baseline and changes from baseline CD4 cell count. The achieved CD4 cell count was the most important factor for prediction of viral rebound (relative hazard, 5.4 for an updated CD4 cell count of <20 vs. >500 copies/mL; P=.0001). Baseline virus load was not associated with virus load rebound. Lower baseline CD4 cell counts were associated with increased risk of viral rebound; however, this risk was significantly reduced in persons with low baseline CD4 cell counts who experienced substantial increases in CD4 cell counts during follow-up.

Adult↗

Human immunodeficiency virus infection in haemophiliacs in Taiwan: the importance of CD4 lymphocyte count in the progression to acquired immunodeficiency syndrome.

From July 1984 to December 1996, we tested and studied 303 haemophilic patients for the infection of the human immunodeficiency virus (HIV). Among the 261 haemophilia A patients 44 were HIV positive (16.9%), while none of the haemophilia B patients was HIV positive. The mean age of the 44 HIV-seropositive patients in 1984 was 20.6 years (2-37 years). Seven who had known seroconversion dates and 29 whose first seropositive dates were known seroconverted before 1986. Acquired immunodeficiency syndrome (AIDS) has developed in 16 patients, nine of whom presented with Pneumocystis carinii pneumonia, three with tuberculosis infection, and 13 had died. The Kaplan-Meier estimate of the progression rate to AIDS after the date of first seropositive test is about 30% at the 10th year. The median survival time after development of AIDS obtained from the Kaplan-Meier estimate of the survival curve was 11.7 months. Statistical analysis for the covariate effects on the risk of developing AIDS by the Cox proportional hazards model revealed that there was a statistically significant negative association of the risk for progression to AIDS with the logarithm of initial CD4 cell counts (P = 0.027) and the rate of decline of CD4 cell counts (P = 0.040), but not with age (P = 0.650). In conclusion, the clinical characteristics of AIDS haemophiliacs in Taiwan were not different from that observed in western countries. Low initial CD4 cell count and sharp decline in CD4 cell counts, but not age, increased the risk of progression to AIDS.

Acquired Immunodeficiency Syndrome↗

Both serum HIV type 1 RNA levels and CD4+ lymphocyte counts predict clinical outcome in HIV type 1-infected subjects with 200 to 500 CD4+ cells per cubic millimeter. AIDS Clinical Trials Group Study 175 Virology Study Team.

To evaluate HIV-1 RNA and CD4+ cell responses to therapy as predictors of clinical progression and to evaluate levels and trends of these markers prior to clinical failure, HIV-1 RNA measurements were retrospectively obtained on subjects who progressed to AIDS or death and a random sample of subjects who did not. Samples were taken from AIDS Clinical Trials Group Study 175, a randomized trial comparing nucleoside analog therapies in subjects with CD4+ cell counts of between 200 and 500 cells/mm3. HIV-1 RNA and CD4+ cell count independently predicted clinical progression. Risk of subsequent progression is best captured by the change to the last measured value for CD4+ cell count and the area under the curve minus baseline, a measure of viral replication over time, for HIV-1 RNA. Subjects who failed had lower CD4+ cell counts, greater rates of CD4+ cell decline, and higher HIV-1 RNA levels, but not greater rates of HIV-1 RNA increase than subjects who did not. Subjects who maintained more than 200 CD4+ cells/mm3 and fewer than 10,000 copies of HIV-1 RNA per milliliter had low risk of progression. During the first few months of therapy, treatments are best monitored by regular HIV-1 RNA and less frequent CD4+ cell measurements. Thereafter, both markers should be monitored on a similar schedule to identify rapidly declining CD4+ cell counts, or adverse levels of either. These results further delineate the prognostic significance of HIV-1 RNA and CD4+ cell count and should help to better define their utility in the practice setting.

Adult↗

Relations among CD4 lymphocyte count nadir, antiretroviral therapy, and HIV-1 disease progression: results from the EuroSIDA study.

BACKGROUND: The effect of previous CD4 cell count nadir on clinical progression in patients with increases in CD4 cell counts has not been investigated. OBJECTIVE: To assess risk for progression of HIV disease in patients with CD4 counts of at least 200 cells/mm3 (stratified by the lowest previous CD4 count) and compare the rate of progression in patients with CD4 counts less than 50 cells/mm3 with that in patients whose CD4 counts rebounded from less than 50 cells/mm3 to at least 200 cells/mm3. DESIGN: Prospective, observational multicenter study. SETTING: 52 HIV outpatient clinics in Europe. PATIENTS: Two groups were identified: those with CD4 counts of at least 200 cells/mm3 (group A) and those with CD4 counts less than 50 cells/mm3 (group B). Group A was stratified according to the lowest previous CD4 count: at least 150 cells/mm3 (stratum 1), 100 to 149 cells/mm3 (stratum 2), 50 to 99 cells/mm3 (stratum 3), and 1 to 50 cells/mm3 (stratum 4). MEASUREMENTS: Patients were followed until a progression event occurred (first AIDS-defining event, new AIDS-defining event, or death) or until the CD4 count decreased to less than 200 cells/mm3 (group A) or increased to more than 50 cells/mm3 (group B). Incidence rates were based on a patient-years analysis and reported as events per 100 patient-years of follow-up; the relative hazards for progression were based on Cox proportional hazards models. RESULTS: The overall rate of disease progression in group A was 3.9 per 100 patient-years (95% CI, 3.5 to 4.3 per 100 patient-years), whereas in group B it was much higher (72.9 per 100 patient-years [CI, 69.0 to 76.8 per 100 patient-years]). In group A, the rate increased in patients with previous low CD4 cell count nadirs, resulting in a significant increase in the relative hazard for progression. The relative hazards for strata 2, 3, and 4 were 2.29 (CI, 1.30 to 4.03), 3.65 (CI, 1.94 to 6.85), and 2.94 (CI, 1.44 to 6.00), respectively. CONCLUSIONS: Increases in CD4 counts from very low levels to at least 200 cells/mm3 are associated with a much reduced rate of disease progression. However, a previously low CD4 cell count nadir remains associated with a moderately higher risk for disease progression among patients with CD4 counts of at least 200 cells/mm3.

Adult↗

[Extension of reporting AIDS cases in Catalonia: study based on requests for CD4 lymphocyte count and prescription of antiretroviral drugs].

BACKGROUND: To ascertain the degree to which AIDS is officially reported in Catalunya. METHOD: The request for T CD4+ white blood cell counts and the prescribing of antiretroviral drugs in seven university hospitals in Catalunya from January 1, 1994 to June 31, 1994 were used as data-comparison sources. A case was considered to not have been reported when the clinical history showed a diagnosis of AIDS (according to the Europe 93 definition) and the case in question did not show up on the AIDS Registry for Catalunya. RESULTS: Of the 1,370 cases studied, 50 unreported AIDS cases were found. In all, 98.6% of all cases were found to have been reported, for a 95% confidence interval (95% CI): 98.2-99.0. Most of the unreported cases were males (72%) averaging 37.3 years of age (HCA: 11.8), 52% of whom were injected drug users (IDU's), extrapulmonary tuberculosis being the disease most often diagnosed (16%), 81.4% having been found to have a T CD4+ white blood cell count of 200 WBC/mm3 or below. 92% of these cases were detected based on T CD4+ white blood cell counts. CONCLUSIONS: The degree of completeness found is considered to be adequate. It is recommended that the white blood cell count records being used for this type of studies.

Acquired Immunodeficiency Syndrome↗

Lymphocyte counting by cell size distribution analysis of leucocytes compared with conventional blood film differential count.

The fourteen parameter Coulter Counter S-Plus IV automated haematology analyser includes the innovative capability of calculating the percentage and number of lymphocytes in the leucocyte population. These features have been evaluated. The percentage of lymphocytes ( LYP ) correlates well to that of the conventional blood film differential count (CDC) and the reproducibility and linearity is excellent. The reproducibility exceeds that of the CDC and it is proposed that with a few safeguards the accuracy also is superior. The reason for possible erroneous LYPs are discussed and the safeguards to detect them are described. It is suggested that in cases where information on the percentage of lymphocytes (or granulocytes) is sufficient the CC LYP may replace the CDC. Use of LYP may reduce the number of CDCs to be performed by 50-75%.

Autoanalysis↗

Fluctuations in HIV-1 viral load are correlated to CD4+ T-lymphocyte count during the natural course of infection.

Viral load fluctuates during the natural course of asymptomatic HIV-1 infection. It is often assumed that these fluctuations are random around a set point or underlying growth trend. Using longitudinal data, we tested whether fluctuations in viral load can be better explained by changes in CD4+ T-cell count than by a set point or trend of exponential growth. The correspondence between viral load and CD4+ T-cell count could be described by a simple mathematical relation. Using a bootstrapping approach, the hypothesis that viral load fluctuations are random around a set point was rejected with p < .00005. The hypothesis that viral load fluctuations are random around a trend of exponential growth was rejected with p < .005. Viral load data was explained better by changes in CD4+ T-cell counts than by a set point or by a trend of exponential growth. The implications of this finding for improved prognostication are discussed.

CD4 Lymphocyte Count↗

Systemic and lung protein changes in sarcoidosis. Lymphocyte counts, gallium uptake values, and serum angiotensin-converting enzyme levels may reflect different aspects of disease activity.

BAL lymphocyte percentages, quantitated gallium-67 lung uptake, and SACE levels have all been proposed as measures of disease activity in sarcoidosis. We analyzed 32 paired sera and BAL fluids from sarcoidosis patients by high-resolution agarose electrophoresis to look for protein changes characteristic of systemic or local inflammation and compared the results with those from the above tests. Nine patients (group 1) had serum inflammatory protein changes and increased total protein, albumin, beta 1-globulin (transferrin), and gamma-globulin levels in fluid recovered by BAL. Thirteen patients (group 2) had normal protein levels in sera but abnormal protein levels in BAL specimens. Ten patients (group 3) had normal protein levels in sera and in BAL specimens. Patients in groups 1 and 2 had a disproportionate increase in beta 1-globulin (transferrin) and gamma-globulin levels in their BAL specimens. The BAL lymphocyte percentage changes paralleled the BAL protein level changes, suggesting relationships among the immunoregulatory role of these cells, increased local immunoglobulin synthesis, and the pathogenesis of altered alveolar permeability. Gallium-67 uptake was highest in patients with serum inflammatory protein changes. Thus, systemic inflammation may facilitate pulmonary gallium-67 uptake, possibly by changes in BAL fluid or serum transferrin saturation and/or kinetics. SACE levels showed no relationship to changes in the levels of serum or BAL proteins. These data suggest that the various proposed measures of disease activity reflect different aspects of inflammation in sarcoidosis.

Blood Protein Electrophoresis↗

CD4 lymphocyte counts and mortality in AIDS patients requiring mechanical ventilator support due to Pneumocystis carinii pneumonia.

OBJECTIVE: To evaluate CD4 counts as a predictor of mortality in AIDS patients with respiratory failure due to Pneumocystis carinii pneumonia (PCP). DESIGN: Retrospective chart review. SETTING: Urban university medical center. PATIENTS: Forty-eight patients admitted to the medical ICU from January 1993 to August 1996 with diagnosis of HIV/AIDS, PCP, CD4 count <200 cells per cubic millimeter, who required mechanical ventilation for respiratory failure. INTERVENTIONS: Medical records were reviewed and age, CD4 count, lactate dehydrogenase, room air (RA) PaO2, coinfections, and day of admission to day of intubation (DOA-DOI) data were recorded. RESULTS: All 48 patients (12 women and 36 men) were treated with corticosteroids and IV trimethoprim-sulfamethoxazole. Age ranged from 21 to 65 years; CD4, 1 to 180, RA PaO2, 27 to 93 mm Hg; and DOA-DOI, 0 to 20 days. Mortality varied significantly depending on CD4 counts: CD4 0 to 10 (100%); CD4 11 to 50 (88%); CD4 51 to 100 (50%); and CD4 >100 (25%). There were no significant difference in mortality between the groups with DOA-DOI <5 days (82%) vs >5 days (80%) or between the groups with PaO2 <60 mm Hg (85%) vs PaO2 >60 mm Hg (73%). CONCLUSION: Even though overall mortality was 81%, the mortality rate was significantly different among the four groups. Most striking was the progressive increase in mortality as CD4 cells decreased from >100 (25% mortality) to <10 (100% mortality). Survivors had significantly higher CD4 cell counts than those who died. The CD4 cell count within 2 weeks of admission has significant prognostic value and may be helpful when counseling patients, families, and healthcare surrogates in end-of-life decision making.

Acquired Immunodeficiency Syndrome↗

Reliability and validity of self-reported CD4 lymphocyte count and viral load test results in people living with HIV/AIDS.

Self-reporting is a common, convenient, and inexpensive method for collecting health status information in HIV/AIDS research, but the reliability and validity of these data remain suspect. HIV-positive persons (n=174) completed self-report measures of demographics, health status, and health literacy, and provided permission to collect CD4 cell counts and viral load results from provider charts. Clinically meaningful categories of CD4 cell counts were reliably and validly assessed using self-report measures. Self-reported viral load, however, demonstrated only marginally acceptable reliability and validity, with the greatest validity occurring for recall of undetectable viral load. Self-reported health status was most reliable and valid for persons with higher levels of education and literacy. CD4 cell counts can therefore be reliably and validly assessed through self-reporting, particularly when collected in clinically meaningful units from persons with higher education. Self-reported viral load should be interpreted with caution and is most reliable when dichotomized into detectable/undetectable categories.

Adult↗

[Quantitative evaluation of Vibrio cholerae colonization and lymphocyte count in small intestine villi of rabbits immunized with vibrio and cholera toxin].

The influence of parenteral immunization with live virulent vibrios and lipopolysaccharide-containing choleragen toxoid and oral immunization with liver avirulent vibrios on the interaction of V. eltor and the mucous membrane was studied on the ligated loops of the small intestine in 164 rabbits. Protection from enterotoxigenicity (the accumulation of fluid) was compared with the suppressive effect on the adhesion and colonization of vibrios. The coefficient of immunization efficacy was determined microbiologically, as the ratio of the adhesion index (i. e. the percentage of the number of vibrios in the media inoculated with the homogenized matter of the washed intestinal wall from the sum of this number and the amount of vibrios in the contents) in the control rabbits to the adhesion index in the immunized ones, and histologically, as the ratio of the average number of vibrios attached to the epithelial number of vibrios attached to the epithelial cells of one intestinal villus in the control rabbits to the corresponding number in the immunized animals. Protection from the enterotoxigenicity of vibrios resulted from the suppression of their adhesion and colonization, lipopolysaccharide being, probably, the factor of adhesiveness. Effective protection was accompanied by an increase in the number of lymphocytes (especially "granular" lymphocytes with lysosome-like granules) between intestinal villi and the number of lymphoid and plasmic cells in the lamina propria of the villi, which indicates the role of lymphocytes in cholera-induced immunity.

Adhesiveness↗

Factors associated with a reduced CD4 lymphocyte count response to HAART despite full viral suppression in the EuroSIDA study.

OBJECTIVES: To describe the prevalence and risk factors of poor CD4 count rise despite a good virological response on highly active antiretroviral treatment (HAART). METHODS: The patients from the EuroSIDA study who started HAART with a baseline CD4 count of <350 cells/microL and where all viral load (pVL) measures remained below 500 HIV-1 RNA copies/mL between 6 and 12 months after the start of HAART were included. The risk factors for poor CD4 count rise were analyzed by multiple regression. RESULTS: Seven hundred and eighty patients were included. A low CD4 count response was observed in 225 patients (29%). The risk factors for this condition were older age, lower CD4 count at baseline, higher increase from the nadir to baseline CD4 count and lower pVL at baseline. Patients taking > or =one drug from each of the three antiviral classes were more likely to have a good CD4 response but a minority of the study participants was taking this treatment regimen (3.1%) and the confidence interval was large. CONCLUSIONS: A poor immune reconstitution despite a good virological control is frequent after initiation of HAART among patients with a baseline CD4 count of <350 cells/microL. The underlying mechanisms leading to this condition seems mainly driven by the age and the baseline immunological and virological status of the patients.

Adult↗

Prognostic factors in human immunodeficiency virus-positive patients with a CD4+ lymphocyte count < 50/microL.

This analysis investigated variability of survival time in a cohort of 553 human immunodeficiency virus type 1 (HIV-1)-infected homosexual or bisexual men with < 50 CD4+ cells/microL. Median survival after the first CD4+ cell count < 50/microL was 1.34 years; 25% survived > or = 2 years. Multivariate analysis showed longer survival with concurrent acyclovir and zidovudine use, hemoglobin > or = 12 g/dL, and full-time employment (P < .0001). Other significant covariates associated with longer survival included African-American race, no prior AIDS illness, weight loss < 4.5 kg, and zidovudine use (with or without concurrent acyclovir) after CD4+ cells fell to < 50/microL. An easily derived score identified Multicenter AIDS Cohort Study subjects likely to survive > 2 years after CD4+ cell count was < 50/microL. Survival once CD4+ cell count fell below 50/microL may be longer for persons with a good performance status and specific clinical markers. Health care providers should consider these variables in decision-making strategies and design of clinical trials.

Acyclovir↗

Interleukin-2 dose, blood monocyte and CD25+ lymphocyte counts as predictors of clinical response to interleukin-2 therapy in patients with renal cell carcinoma.

The purpose of this study was to determine immunological parameters in the peripheral blood that correlate with the clinical effect of interleukin-2 (IL-2) in patients with metastatic renal cell cancer. A group of 26 patients with metastatic renal cell cancer underwent IL-2 treatment using a 36-day schedule with continuous intravenous IL-2 infusion (3 x 10(6) units m-2 day-1) administered from days 1 to 5 and days 12 to 16. The white blood cell count and the absolute and relative number of neutrophils, lymphocytes, eosinophils and monocytes were recorded six times in peripheral blood during the treatment. Also the blood counts of T cell and NK cell subsets and cells expressing the T cell activation markers IL-2R alpha and VLA-1 were measured. The lymphokine-activated killer (LAK) cell cytotoxicity was measured either with or without additional in vitro stimulation by IL-2. Multivariate statistical analysis showed that the clinical responses were related to the administered dose of IL-2, to a low number of blood cells expressing IL-2 receptors and to a reduction in the blood monocyte count (P less than 0.05).

Adult↗

[Value of HIV-1 viral load and CD4 lymphocyte count as determinants of progression to AIDS and survival].

BACKGROUND: HIV-1 viral load is regarded as a better surrogate marker for progression and death than CD4+ cell counts. Both markers are analysed in a cohort of patients with unknown seroconversion date and advanced HIV infection. PATIENTS AND METHODS: Retrospective cohort analysis of 421 patients, most on antiretroviral therapy, with a median initial CD4+ cell count of 209 x 10(6)/l and a median initial viral load of 4.7 log copies/ml. One thousand two hundred and eighty-six samples were analysed. Univariate and bivariate analysis were performed with initial and sequential CD4+ cell counts and viral load values to estimate the risk of progression and death by Cox regression models. RESULTS: After a median follow up of 763 days, 124 patients developed AIDS and 117 died. Relative risks of progression related to the group that maintained viral load values always < 35,000 copies/ml were: 5-fold (95% CI: 1.4-17.0; p < 0.05) for patients with any viral load value > 35,000 copies/ml but always < 200,000 copies/ml; and 13.6 fold (95% CI: 5.4-34.2; p < 0.0001) for patients who could not maintain viral load < 200.000 copies/ml. CD4+ counts = 100 x 10(6)/l and viral load = 220,000 copies/ml were the threshold values that best fitted to estimate the probability of survival by a bivariate analysis. CONCLUSIONS: The maintenance of sequential viral load values < 35.000 copies/ml is associated with a lower risk of progression. The maintenance of sequential viral load values < 150,000 copies/ml is associated with higher short-term survival rates.

Acquired Immunodeficiency Syndrome↗

Declining CD4+ T-lymphocyte counts are associated with increased risk of enteric parasitosis and chronic diarrhea: results of a 3-year longitudinal study.

From January 1991 through September 1994, we observed people who were infected with HIV to assess the impact of enteric parasite-associated diarrhea. Respondents answered comprehensive questionnaires covering clinical and epidemiologic information and provided stool specimens monthly, which were examined unstained as well as stained with trichrome, chromotrope 2R, and with Kinyoun carbol-fuchsin, and with indirect immunofluorescence for Cryptosporidium. In all, 602 participants, who were interviewed, provided stool specimens at 3254 monthly visits. Parasites were associated with 50 of 354 (14.1%) acute diarrheal episodes (lasting < or = 28 days) and with 97 of 279 (34.8%) chronic episodes (lasting > 28 days). A parasite was associated with 31 of 222 (14.0%) episodes that occurred when CD4+ counts were > or = 200 cells/microl and with 150 of 566 (26.5%) episodes that occurred when CD4+ counts were < 200 cells/microl. The most commonly identified parasite was C. parvum, which was associated with 18 of 354 (5.1%) acute episodes and 36 (12.9%) of the 279 chronic episodes of diarrhea. In this patient population, enteric protozoan parasites were commonly associated with illness, particularly as immunosuppression worsened, and were more likely to be associated with chronic rather than acute diarrhea.

AIDS-Related Opportunistic Infections↗