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At least 217 records · Page 12Linked to original sources

It is safe to stop antiretroviral therapy in patients with preantiretroviral CD4 cell counts >250 cells/microL.

OBJECTIVE: To study clinical, immunologic, and virologic outcomes in patients who stop antiretroviral therapy (ART) with relatively preserved CD4 cell counts. DESIGN AND METHODS: Patients with a documented CD4 cell count >250 cells/microL who stopped ART for any reason for at least 5 weeks were studied. Relevant clinical and laboratory data were collected using a standardized data collection form. MAIN OUTCOME MEASURES: Patients were monitored for outcomes including Centers for Disease Control (CDC) category B or C events, time to restarting ART, and time to reaching a CD4 cell count of < or = 250 cells/microL. RESULTS: A total of 107 patients were included. The median time on ART was 45 months and median number of antiretroviral medications was 4. The median pre-ART CD4 cell count and HIV viral load were 463 cells/microL and 4.35 log copies/mL, respectively. The median CD4 cell at time of ART stop was 739 cell/microL. The slope of the CD4 decrease was 65 cells/mo in the first 2 months, which was greater than the subsequent decline of 8 cells/mo thereafter (P < 0.01). Similarly the median viral load increase was 2.54 log copies/mL in the first 2 months after stopping and was unchanged after that point. Two patients experienced the retroviral rebound syndrome after ART cessation but no CDC category B or C events were observed during 10 months of follow-up. The median time from stopping ART to reaching the combined endpoint of CD4 <250 or restarting ART was 8.9 months. In multivariate analysis, pre-ART CD4 cell count >250 was protective of reaching the combined endpoint (odds ratio = 0.156, P = 0.03). Other predictors of reaching the combined endpoint in multivariate analysis were older age and number of prior ART agents. Patients who restarted ART had a favorable virologic and immunologic response. CONCLUSIONS: Patients with relatively high CD4 cell counts prior to starting ART did well after stopping ART. Pre-ART CD4 cell count can be used to predict outcomes after ART cessation.

Adult↗

Long-term CD4+ T-cell response to highly active antiretroviral therapy according to baseline CD4+ T-cell count.

Current treatment guidelines for HIV infection recommend a relatively late initiation of highly active antiretroviral therapy (HAART). Nevertheless, there is still a concern that immune recovery may not be as complete once CD4+ T cells have decreased below a certain threshold. This study addressed the long-term response of CD4+ T-cell counts in patients on HAART and analyzed the influence of baseline CD4+ T-cell counts, baseline viral load, and age. An observational analysis of evolution of CD4+ T cells in 861 antiretroviral therapy-naive chronic HIV-1-infected patients who started treatment consisting of at least 3 drugs in or after 1996 was performed. Patients were classified in 4 groups according to baseline CD4+ T cells: <200 cells/mm3, 200-349 cells/mm3, 350-499 cells/mm3, and >or=500 cells/mm3. The main outcome measures were proportion of patients with CD4+ T cells <200/mm3 and >500/mm3 at last determination and rate of CD4+ T-cell recovery. Patients were followed-up for a median of 173 weeks (interquartile range [IQR], 100-234). There were no differences in follow-up between the 4 groups. CD4+ T cells increased in the whole cohort from a median of 214 cells/mm3 (IQR, 90-355) to 499 cells/mm3 (IQR, 312-733) (P<0.001). Compared with the group with a baseline CD4+ T-cell count of >or=500/mm3, the relative risk of having a last determination of CD4+ T-cell counts >200 cells/mm3 was 0.79 (95% CI, 0.75-0.83), 0.92 (95% CI, 0.89-0.96) and 1 for baseline CD4+ T cells <200 cells/mm3, 200-349 cells/mm3, and 350-499 cells/mm3, respectively. The relative risk of having a last determination of CD4+ T-cell counts >500 cells/mm3 was 0.32 (95% CI, 0.27-0.39, P<0.001), 0.69 (95% CI, 0.60-0.79, P<0.001), and 0.94 (95% CI, 0.83-1.06, P=0.38) for baseline CD4+ T-cell counts <200 cells/mm3, 200-349 cells/mm3, and 350-0499 cells/mm3, respectively, compared with a baseline CD4+ T-cell count of >or=500 cells/mm3. The increase in CD4+ T cells from baseline was statistically significant and was maintained for up to 4 years of follow-up. This increase seemed to slow down after approximately 3 years and reached a plateau after 4-5 years of follow-up even in patients who achieved and maintained viral suppression in plasma. Long-term immune recovery is possible regardless of baseline CD4+ T-cell count. However, patients who start therapy with a CD4+ T-cell count <200 cells/mm3 have poorer immunologic outcome as measured by the proportion of patients with CD4+ T cells <200/mm3 or >500/mm3 at last determination. It seems that the immune recovery slows down after approximately 3 years of HAART and reaches a plateau after 4-5 years of HAART.

Acquired Immunodeficiency Syndrome↗

White blood cell counts and differential in synovial fluid of aseptically failed total knee arthroplasty.

A cell count and differential was obtained on synovial fluid samples from 79 total knee arthroplasties undergoing revision for aseptic failure over a 5-year period. The mean white blood cell count (WBC) was 782/mL (range, 11-7,200/mL). The mean percentage of monocyte cells was 87%, and the mean polymorphonuclear leukocyte (PML) cell count was 13%. Eight patients (10.4%) had leukocyte cell counts >2,000. Five knees in 4 patients with rheumatoid arthritis had PML counts >50%. There was a single postoperative infection. In patients with osteoarthritis as a primary diagnosis, a synovial WBC of <2,000 and a differential with <50% PMLs had a 98% negative predictive value for the absence of infection. Key words: synovial fluid, cell count and differential, failed total knee arthroplasty, revision total knee arthroplasty.

Adult↗

"Discordant" increases in CD4 cell count relative to plasma viral load in a closely followed cohort of patients initiating antiretroviral therapy.

BACKGROUND: In HIV-positive persons receiving antiretroviral therapy, CD4 cell responses are associated with optimal suppression of viral replication. However, increases in CD4 cell counts in the absence of viral suppression have been reported. We characterized plasma viral load (pVL) and CD4 cell count increases in closely followed patients to evaluate determinants and the prevalence of CD4 cell responses at a populational level. METHODS: All HIV-positive patients in the province of British Columbia, Canada, who were antiretroviral naive and initiated therapy between August 1996 and May 1998 were eligible for the study. The selection criteria were that patients had to have CD4 cell counts and pVLs measured at baseline and at least once during eight 16-week periods after the initiation of therapy. We characterized CD4 cell responses and sought patients who had a "discordant" increase at 1 year, which was defined as an increase in CD4 cell count of >or=50/mm3 with a <1 log10 decrease in pVL. We also evaluated adherence and antiretroviral use. RESULTS: Overall, when baseline and 1-year pVLs and CD4 cell counts were compared, 6.2% of patients had CD4 cell count increases without pVL decreases of >or=1 log10. However, when all pVLs before 1 year were considered, 92% of the discordant increases could be attributed to prior transient or partial viral suppression. Furthermore, although substantial increases in CD4 cell counts were observed in transient virologic responders, the cumulative number of antiretroviral agents used by this group was significantly higher than that used by full virologic responders (p <.001). CONCLUSIONS: Our results demonstrate that virtually all CD4 cell count increases can be attributed to transient or partial pVL suppression. Unmeasured pVL suppression likely explains discordant responses that have been previously reported. Similarities between transient and full virologic responders also appear to be time limited and are often associated with greater cumulative use of antiretroviral therapy by transient virologic responders.

Adult↗

The impact of adherence on CD4 cell count responses among HIV-infected patients.

BACKGROUND: There have been concerns that irreversible immune damage may result if highly active antiretroviral therapy (HAART) is initiated after the CD4 cell count declines to below 350 cells/microL; however, the role of antiretroviral adherence on CD4 cell count responses has not been well evaluated. METHODS: We evaluated CD4 cell count responses of 1522 antiretroviral-naive patients initiating HAART who were stratified by baseline CD4 cell count (<50, 50-199, and >or=200 cells/microL) and adherence. RESULTS: Among patients starting HAART with <50 cells/microL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 200 cells/microL (interquartile range [IQR]: 130-290) for adherent patients versus 60 cells/microL (IQR: 10-130) for nonadherent patients. Similarly, among patients starting HAART with 50 to 199 cells/microL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 300 cells/microL (IQR: 180-390) versus 125 cells/microL (IQR: 40-210) for nonadherent patients. In Cox regression analyses, adherence was the strongest independent predictor of the time to a gain of >or=50 cells/microL from baseline (relative hazard [RH] = 2.88, 95% confidence interval [CI]: 2.46-3.37). Among patients with baseline CD4 cell counts <200 cells/microL, adherence was the strongest independent predictor of the time to a CD4 cell count >200 cells/microL (RH = 4.85, 95% CI: 3.15-7.47). CONCLUSIONS: These data demonstrate that substantial CD4 gains are possible among highly advanced adherent patients and should contribute to the ongoing debate over the optimal time to initiate HAART.

Acquired Immunodeficiency Syndrome↗

Factors associated with the development of opportunistic infections in HIV-1-infected adults with high CD4+ cell counts: a EuroSIDA study.

BACKGROUND: Limited data exist on factors predicting the development of opportunistic infections (OIs) at higher-than-expected CD4(+) cell counts in human immunodeficiency virus (HIV) type 1-infected adults. METHODS: Multivariate Poisson regression models were used to determine factors related to the development of groups of OIs above their respective traditional upper CD4(+) cell count thresholds: group 1 (>or=100 cells/ microL), OIs caused by cytomegalovirus, Mycobacterium avium complex, and Toxoplasma gondii; group 2 (>or=200 cells/ microL), Pneumocystis pneumonia and esophageal candidiasis; and group 3 (>or=300 cells/ microL), pulmonary and extrapulmonary tuberculosis. RESULTS: In groups 1, 2, and 3, 71 of 9,219, 125 of 7,934, and 36 of 7,838 patients, respectively, developed >or=1 intragroup OI. The strongest predictor of an OI in groups 1 and 2 was current CD4(+) cell count (for group 1, incidence rate ratio [IRR] per 50% lower CD4(+) cell count, 5.37 [95% confidence interval {CI}, 3.71-7.77]; for group 2, 4.28 [95% CI, 2.98-6.14]). Injection drug use but not current CD4(+) cell count predicted risk in group 3. Use of antiretroviral treatment was associated with a lower incidence of OIs in all groups, likely by reducing HIV-1 RNA levels (IRR per 1-log(10) copies/mL higher HIV-1 RNA levels for group 1, 1.50 [95% CI, 1.15-1.95]; for group 2, 1.68 [95% CI, 1.40-2.02]; and for group 3, 1.89 [95% CI, 1.40-2.54]). CONCLUSION: Although the absolute incidence is low, the current CD4(+) cell count and HIV-1 RNA level are strong predictors of most OIs in patients with high CD4(+) cell counts.

AIDS-Related Opportunistic Infections↗

Dental disease, fibrinogen and white cell count; links with myocardial infarction?

Plasma fibrinogen and white blood cell count were compared in fifty patients aged 25-50 years with periodontal disease and in fifty age-matched controls with relatively healthy periodontal tissues. Patients had significantly higher levels of fibrinogen and white cell count, and dental indices correlated significantly with these two cardiovascular risk factors on multivariate analyses. We suggest that inflammatory dental disease may be a determinant of fibrinogen level and white cell count in the general population, and that fibrinogen and white cell count may be two mediators of the link between dental disease and myocardial infarction.

Adult↗

Mast cell count in surgically resected appendices.

Two hundred appendices were studied for mucosal and submucosal mast cell counts. In histologically normal appendices mucosal mean mast cell count (47.63/sq mm) was more than submucosal mean mast cell count (44.27/sq mm). Those patients who were aged under 15 and above 46 years showed more mean mucosal mast cell count compared to others. In acute appendicitis both mucosal and submucosal mast cells were decreased and in subacute appendicitis their count was found to be intermediate between normal and acute appendicitis.

Adolescent↗

An unbiased correction factor for cell counts in histological sections.

It is common procedure to correct raw counts of cells (or nuclei or other such particles) in histological sections by multiplying them by a 'correction factor', to allow for sectioned particles being counted more than once. However, the derivation of the standard formulae assumes that the particles to be counted are of uniform size. Therefore, these formulae may be biased in practical situations. Here, a more general correction factor (C) not depending on this restrictive assumption is derived: C = sigma i = 1 m T/(T - h(i))/sigma i = 1 m (T - R - S + h(i))/(T - h(i)) where T is section thickness, h(i) is the height of particle i measured perpendicular to the section plane, R and S are the heights, assumed constant, of the upper and lower 'lost caps', and the summation is performed over m (about 20) particles sampled randomly from among those lying wholly within individual sections. It is proposed that h(i) be measured by a differential focusing method; the formula will then be valid for particles of variable shape as well as size.

Bias↗

Long-term survival without clinical AIDS after CD4+ cell counts fall below 200 x 10(6)/l.

OBJECTIVE: Quantify and study cofactors of long-term survival without AIDS in HIV-1-infected individuals with CD4+ cell counts < 200 x 10(6)/l. DESIGN: Comparison of 579 participants who could be longitudinally evaluated for at least 3 years after the earliest date of first reaching a CD4+ cell count < 200 x 10(6)/l or an AIDS-defining illness (1987 Centers for Disease Control and Prevention definition). SETTING: Ongoing 9-year cohort study with data collected at 6-month intervals. PATIENTS: HIV-1-infected homosexual men. MEASUREMENTS AND MAIN RESULTS: Of the men, 20% did not develop an AIDS illness within 3 years following a confirmed CD4+ cell count < 200 x 10(6)/l; 29 and 28% were diagnosed with a first clinical AIDS illness from 1-3 and < 1 years, respectively, beyond their first CD4+ cell count < 200 x 10(6)/l; 23% were diagnosed with a clinical AIDS illness prior to their first CD4+ cell count < 200 x 10(6)/l. Slower decline of CD4+ cell count (P < 0.001) and presence of higher body-mass index during the period prior to the first CD4+ cell count < 200 x 10(6)/l (P < 0.001) predicted longer time to an AIDS illness once this threshold was reached. Most men had rapid loss of CD4+ cells, total T cells, and hemoglobin during the period after CD4+ cells declined below 200 x 10(6)/l. However, those remaining free of AIDS illnesses the longest arrested their decline in CD4+ cell counts and hemoglobin levels and increased total T cells during this period. Although antiretroviral therapy and Pneumocystis carinii prophylaxis extend AIDS-free survival, 45% of the group who were AIDS-free > or = 3 years after CD4+ cells fell below 200 x 10(6)/l had not used these treatments. CONCLUSIONS: Significant numbers of individuals remain free of illnesses and AIDS symptoms > or = 3 years after CD4+ cell counts drop below 200 x 10(6)/l. This occurs even in the absence of treatment. The associations seen here suggest that host and viral factors play important roles. Thus, further studies are needed to determine the biological basis of long-term survival without AIDS illnesses in HIV-1-immunosuppressed patients.

Acquired Immunodeficiency Syndrome↗

Malignancy-related ascites: a diagnostic pitfall of spontaneous bacterial peritonitis by ascitic fluid polymorphonuclear cell count.

To define patients with an ascitic fluid polymorphonuclear cell count > or = 250 cells/mm3 or > or = 500 cells/mm3 but without spontaneous bacterial peritonitis, 166 patients with sterile cirrhotic ascites, 46 patients with spontaneous bacterial peritonitis, 123 patients with hepatocellular carcinoma, 67 patients with peritoneal carcinomatosis or massive liver metastasis and 12 patients with other miscellaneous diseases were studied. The sensitivity, specificity and accuracy of the diagnosis of spontaneous bacterial peritonitis were 100, 86 and 88% with the cut-off value of an ascitic fluid polymorphonuclear cell count > or = 250 cells/mm3; and were 93, 91 and 92% with that value > or = 500 cells/mm3, respectively. With the cut-off value > or = 250 cells/mm3 or > or = 500 cells/mm3, the prevalence was 18% or 14% in hepatocellular carcinoma; and 30% or 19% in peritoneal carcinomatosis or massive liver metastasis. The ascitic fluid lactate concentration was insensitive and nonspecific. Among the patients with an ascitic fluid polymorphonuclear cell count greater than the cut-off values, an ascitic fluid erythrocyte count > or = 10,000 cells/mm3, a ratio of ascitic fluid erythrocyte to total leukocyte count > or = 100, and the ratio of ascitic fluid polymorphonuclear cell to total leukocyte count < or = 75% indicated hepatocellular carcinoma, while serum to ascites albumin gradient < or = 1.1 g/dl and a ratio of ascitic fluid polymorphonuclear cell to total leukocyte count < or = 75% indicated peritoneal carcinomatosis or massive liver metastasis.

Ascites↗

Use of induced sputum cell counts to investigate airway inflammation in asthma.

BACKGROUND: Airway inflammation is considered to be important in asthma but is relatively inaccessible to study. Less invasive methods of obtaining sputum from patients unable to produce it spontaneously should provide a useful investigational tool in asthma. METHODS: A method to induce sputum with inhaled hypertonic saline was modified for use in 17 asthmatic patients and 17 normal subjects who could not produce sputum spontaneously. The success rate and safety of the method, the reproducibility of cell counts, and differences in cell counts between the asthmatic and normal groups were examined. Hypertonic saline solution 3-5% was inhaled for up to 30 minutes after inhalation of salbutamol. Subjects were asked to expectorate sputum every five minutes. The quality of the sample was scored on the volume of plugs and the extent of salivary contamination. Plugs from the lower respiratory tract were selected for a total cell count and for differential cell counts of eosinophils and metachromatic cells (mast cells and basophils) in direct smears. RESULTS: Adequate samples from the lower respiratory tract were obtained in 76% of first attempts. The mean fall in the forced expiratory volume in one second (FEV1) during inhalation of saline was 5.3% and the maximum fall 20%. Eosinophil and metachromatic cell counts were reproducible (reliability coefficient 0.8 and 0.7 respectively). When compared with sputum from normal subjects sputum from asthmatic patients contained a significantly higher proportion of eosinophils (mean 18.5% (SE 3.8%) v 1.9% (0.6%)) and metachromatic cells (0.50% (0.18%) v 0.039% (0.014%)). In the asthmatic group the differential eosinophil count correlated with the baseline FEV1. CONCLUSION: Induced sputum is capable of detecting differences in cell counts between normal and asthmatic subjects and merits further development as a potential means of assessing airway inflammation in asthma.

Adolescent↗

A clinical trial of three-part electronic differential white blood cell counts.

Three-part white blood cell differential counts (diffs), performed during electrical impedance counting of blood cells, can accurately classify lymphocytes, granulocytes, and mononuclear cells in 85% of specimens, with an error rate not exceeding that of conventional diffs. To assess the clinical utility of the new test, we tried it for three months on a medical unit. Conventional diffs were no better than three-part diffs or total white blood cell counts in signaling clinical changes, and the same decisions would have been made in 78% of instances if only three-part diffs were available. The three-part diff is as reliable a clinical index for monitoring most inpatients as the conventional diff or white blood cell count. Although its use could effect significant cost savings, acceptance of the new test seems unlikely unless enforced by administrative flat.

Clinical Trials as Topic↗