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Absolute lymphocyte count as surrogate for CD4+ cell count in monitoring response to antiretroviral therapy.

The objective of the study is to determine whether Absolute Lymphocyte Count (ALC) can serve as a surrogate for CD4 T-lymphocyte Cell Count (CCC) in HIV infected Nigerians on Lamivudine/Zidovudine anti-retroviral therapy. 32 adult Nigerians infected with HIV were recruited into the study. They were assessed clinically and categorised into three clinical stages A, B and C according to CDC criteria. They all received lamivudine 150 mg b.d and Zidovodine 300 mg b.d for six months. Blood specimens were taken on enrollment and at four weekly intervals for paired ALC and CCC determination. ANOVA statistics was used to determine whether ALC and CCC (separately) change significantly with increasing duration of therapy. Paired ALC and CCC values were tested for correlation. Sensitivity and specificity of low ALC values in predicting low CCC values were also calculated. The 32 patients comprised 18 males and 14 females aged between 16 and 49 years. The mean age (SD) was 36.1 (+/-7.85) years. The mean ALC value rose from 2485/l and 2352/microl before commencement of therapy to 3026/microl and 3151/microl four weeks after for males and females respectively. These changes were not significant, P>0.05. No further changes were noted over the next 24 weeks. However, the mean CCC values increased from 233/microl before therapy through 339/microl at four weeks, 362/microl at eight weeks to 398/micro1 at 12 weeks. It then fluctuated between 372/microl and 310/microl for the remaining part of the study. These changes were not significant: F: ratio = 1.28 (df = 6,181), P>0.05. A weak but significant positive correlation was established between ALC and CCC. Correlation coefficient was 0.25, P<0.05. The sensitivity and specificity of ALC 2000/microl as a predictor of CCC 200/microl were 57% and 72% respectively. ALC correlates weakly with CCC in patients undergoing antiretroviral therapy and it may not serve as a perfect surrogate for CCC as a monitor of immunological response to therapy.

Adolescent↗

FTY 720A mediates reduction of lymphocyte counts in human renal allograft recipients by an apoptosis-independent mechanism.

The novel immunosuppressive compound FTY 720A posseses a mode of action which is different from all other immunosuppressive drugs. The most prominent feature is a reversible decrease in peripheral lymphocyte counts observed in animal experiments. We investigated in the first human trial (phase 1) whether FTY 720A induces apoptosis of peripheral blood mononuclear cells (PBMC) in stable renal allograft recipients. Monitoring of lymphocyte counts revealed a significant and dose-dependent decrease within 6 h post-FTY 720A dose: placebo 5.1%; 0.25 mg 36.4%; 0.5 mg 40.8%; 0.75 mg 39.4%; 1 mg 45.8%; 2 mg 67.2%; 3.5 mg 64.9%. PBMC apoptosis rates did not change, as determined before intake of FTY 720A and 2 h, 6 h, 24 h and 96 h post-FTY 720A dose. We detected no significant difference in apoptosis rates between patients who received placebo or FTY 720A. However, in vitro experiments showed that high concentrations of FTY 720 A induced apoptosis in human PBMC.

Apoptosis↗

Increased serum lipids are associated with higher CD4 lymphocyte count in HIV-infected women.

OBJECTIVE: Highly active antiretroviral therapy (HAART) has been associated with dyslipidaemia; however, the roles of immune status and non-HIV-disease risk factors remain unclear. METHODS: A cross-sectional analysis of fasting lipids was carried out for 231 women, of whom 132 were HIV-infected and 99 were uninfected. The concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B (apo B) were measured. CD4 lymphocyte count, hepatitis C status, demographics, diet, and anthropometrics were also assessed. RESULTS: A total of 132 women were HIV-infected [30 were antiretroviral-naive, 68 were on protease inhibitors (PIs), and 34 were on non-PI HAART]. HIV infection was associated with higher triglycerides, lower HDL-C, and, among obese women, higher total cholesterol and LDL-C. Non-PI and PI HAART were each independently associated with higher total cholesterol, LDL-C, and apo B, compared with being ART-naive. Among HIV-infected women, after adjustment for HAART use, women with a CD4 lymphocyte count > or =500 cells/microL had total cholesterol 41.8 mg/dL (P = 0.002) and LDL-C 28.8 mg/dL (P = 0.01) higher, on average, than women with a CD4 count <200 cells/microL. Women with a CD4 count of 200-499 cells/microL had total cholesterol 26.31 mg/dL higher, on average, than those with a CD4 count <200 cells/microL (P = 0.04), although differences in LDL-C did not reach significance (15.51 mg/dL; P = 0.12). A higher CD4 count was also associated with higher apo B (P < 0.001). Active hepatitis C infection was associated with lower total cholesterol, LDL-C, triglycerides, and apo B. CONCLUSIONS: Higher CD4 lymphocyte counts were associated with higher lipid levels, suggesting that immune competence may independently affect the dyslipidaemia seen in the HAART era. In addition, it is important that hepatitis C status be assessed in studies of dyslipidaemia in the HIV-infected population.

Adult↗

The peripheral lymphocyte count as an aid in the clinical staging of lung cancer.

The association between disease staging and peripheral lymphocyte count (PLC) was studied in 178 patients with histologically verified lung cancer. Mean PLC varied inversely with the stage of disease (p less than .01). The mean values were 2821, 2217, and 1594 for Stages I, II and III respectively. Thoretical normal distributions were generated about the mean peripheral lymphocyte count for each stage. Relative frequencies of lung cancer staging based on the PLC are estimated utilizing these curves.

Adenocarcinoma↗

Delayed cutaneous hypersensitivity ad peripheral blood lymphocyte counts in gastrointestinal cancer.

Cell-mediated immune responses as expressed by delayed cutaneous hypersensitivity (DCH) reactions to specific recall antigens (PPD and BCG) and non-specific contact antigen (DNCB), and peripheral blood lymphocyte counts were studied in 60 patients of gastrointestinal cancer and 20 control subjects. The pattern of these immune responses in gastrointestinal cancer was significantly different from tumour-free control subjects of comparable age and sex distribution and apparently indicates a depressed immunologic function in cancer patients. Our study suggests that DNCB skin testing and peripheral blood lymphocyte counts are relatively simple and reliable investigations for predicting the advanced stage of gastrointestinal cancer (and BBY implication prognosis).

Adult↗

Improvement in CD4 lymphocyte count in HIV-Reiter's syndrome after treatment with sulfasalazine.

OBJECTIVE: To describe an observed improvement in CD4 lymphocytes in patients with Reiter's syndrome (RS) and human immunodeficiency virus (HIV) infection, after treatment with sulfasalazine (SFSZ). METHODS . Care series. We analyzed CD4 lymphocyte counts in 4 consecutive patients with RS and HIV disease before and after treatment with SFSZ. RESULTS: CD4+ lymphocyte counts increased from a mean of 315 +/- 179 before treatment to 542 +/- 231 x 10(6)/l on followup (p < 0.03), in the absence of antiretroviral therapy. The significance of these observations is discussed. CONCLUSION: Treatment of RS with SFSZ in HIV disease appears to be associated with an improvement in CD4 count.

Adult↗

Dinitrochlorobenzene skin sensitization and peripheral lymphocyte count: predictors of survival in head and neck cancer.

Dinitrochlorobenzene (DNCB) is a simple chemical useful to evaluate both afferent (sensitizing) and efferent (reacting) limbs of the delayed, cell-mediated immune system. This system invokes the small lymphocyte (T cell) and is apparently part of the host defense against cancer. Severnty-two patients with new primary squamous cell carcinomas of the larynx, hypopharynx and oropharynx were sensitized to DNCB by contact application, and delayed cutaneous hypersensitivity tested. The T cells were also assessed in this study by lymphocyte count. All patients were treated for cure. Ninety-one percent of DNCB reactors were alive and tumor-free at two years. Forty-five percent of negative reactors had recurrent tumor and died of carcinoma. Cases grouped by site among glottic, supraglottic and inferior hypopharynx showed identical results. Lymphocyte counts showed a trend in the same direction. On statistical analysis, all differrences were significant. Eighty-five percent of recurrent tumors occurred in patients who were nonresponders. The present data suggest DNCB reactivity is helpful in predicting outcome after surgery, or combined radiation and surgery, for mucosal squamous carcinoma of the head and neck.

Adult↗

Four-color flow cytometric immunophenotypic determination of peripheral blood CD4+ T-lymphocyte counts: a comparison of validity and cost-effectiveness with a two-color method.

The clinical usefulness of monitoring CD4+ T-lymphocyte counts in patients infected with HIV is now well established. The need for accurate, rapid, and cost-effective methods for making these determinations is evident. Recent technologic advances have allowed for the development of a system for the determination of CD4+ T-lymphocyte counts by simultaneous 4-color flow cytometry. A new 4-color 2-tube flow cytometric method for analyzing CD4+ T-lymphocyte subsets in whole blood was compared with a standard 2-color 5-tube method. The new method provides results almost identical to those of the well-established 2-color method used in our clinical laboratory. Statistical analyses indicate very low variability in CD4+ counts between the 2 methods, strongly supporting the usefulness of this new procedure. In addition, the 4-color procedure provides a 15% reduction in the materials cost per test compared with the 2-color method, as well as a marked reduction in the time expenditure of flow cytometry technologists.

Adult↗

Reduction of absolute lymphocyte count in children with recurrent medulloblastoma.

The complete blood cell (CBC) count with differential cell counts of 36 children with medulloblastoma showed a substantial reduction of the absolute lymphocyte count at recurrence. The preoperative value of the CBC count with differential cell counts failed to predict the survival of patients with medulloblastoma. A prospective study with serial measurement of the CBC count with differential cell counts will be needed to determine sensitivity and specificity of the CBC count with differential cell counts to clinical application for early detection of recurrence of medulloblastoma.

Adolescent↗

Quality control of the total lymphocyte count parameter obtained from routine haematology analyzers, and its relevance in HIV management.

Lylmphocyte subsets/CD4 T Helper cell enumeration in HIV care and treatment in resource constrained settings can be difficult to ascertain as a result of the lack of the necessary instrumentation, capacity and infrastructure. However. it is imperative to gain such information for patient monitoring in HIV. The Total Lymphocyte Count (TLC) is useful as a surrogate marker for CD4 count as recommended by the World Health Organisation (WHO) and to calculate CD4% for pacdiatric use. This study therefore sets out to determine and compare the accuracy of the total lymphocyte counts obtained from three haematology analysers designated A. B and C. that are in regular use for routine haemnatological parameters at the main referral hospital in Barbados. West Indies. The TLC of 263 HIV treatment naive individuals attending the HIV Reference Unit in Barbados were enumnerated on the three haematology analysers. The lymphosumn (Sum of lymphocyte subsets: T-helper cell. T-cytotoxic cells. B lymphocytes and Natural killer cells) should be equal to the TLC. and is derived by immunophenotypic analysis on a 4-colour flowcytometer. Machine C had the highest positive correlation between the TLC and the lymphosumn with and R' of 0.9031 compared to machine A with an R values of 0.7119 and Machine B with R(2) values of 0.637. These results show that there can be dramatic inaccuracies when using routine haematology analysers for both routine use. as a surrogate marker of CD4 or for derivation of CD4% in HIV management. It further demonstrates that all haematology analyzers require some form of Quality control. The possible lack of accuracy of the TLC by haematology analysers should be taken into consideration when following the recommendations of the WHO in resource poor settings or using it as a denominator for calculating CD4%.

Biomarkers↗

Pulmonary tuberculosis in HIV infection: radiographic appearance is related to CD4+ T-lymphocyte count.

SETTING: An adult HIV outpatient clinic in Cape Town, South Africa. OBJECTIVE: To investigate the relationship between the radiographic appearance of pulmonary tuberculosis (PTB) in HIV infected patients and CD4+ T-lymphocyte count. DESIGN: Pretreatment radiographs of 150 patients with newly diagnosed PTB were reviewed. CD4+ T-lymphocyte count was used as a marker of HIV disease progression. RESULTS: Upper zone infiltrate typical of PTB reactivation was present in 18 patients. This pattern was associated with early HIV infection (mean CD4+ T-cell count 389) and had 78% positive predictive value for identifying patients with > 200 CD4+ T-lymphocytes/microL. Pleural effusion was present in 32 patients and occurred over a wide intermediate range of CD4+ T-cell counts (mean 185). Lower or midzone infiltrates, adenopathy, interstitial pattern or normal radiograph occurred in 136 patients and were associated with advanced HIV disease (mean CD4+ T-cell count 105). These patterns had 84%, 89%, 89% and 100% positive predictive value, respectively, for identifying patients with < 200 CD4+ T-cell/microL. CONCLUSION: Pulmonary tuberculosis in African HIV-positive patients presents with a spectrum of radiographic abnormalities predictive of stage of HIV disease progression. In patients dually infected with HIV and PTB, chest radiographs are a useful adjunct to clinical staging.

Adolescent↗

Correspondence between the effect of zidovudine plus lamivudine on plasma HIV level/CD4 lymphocyte count and the incidence of clinical disease in infected individuals. North American Lamivudine HIV Working Group.

OBJECTIVES: To investigate whether apparently beneficial changes in plasma HIV RNA level and CD4 lymphocyte count that are induced by antiretroviral therapy are associated with a corresponding clinical benefit. METHODS: For 620 patients in two randomized, double-blind trials of lamivudine (3TC) and zidovudine (ZDV) plasma HIV RNA and CD4 lymphocyte count changes were compared in patients randomized to 3TC plus ZDV and patients randomized to other treatment arms. The effect of therapy on the HIV RNA level and CD4 count was compared with the effect of therapy on clinical endpoints over the same time period. RESULTS: Median baseline values for all subjects were 42 420 copies/ml for HIV RNA and 277 x 10(6)/l for CD4 count. During the trial a significantly lower HIV RNA level and higher CD4 count was sustained in the ZDV/3TC group compared with the other group, with a difference in the median area under the curve from baseline per month of follow-up of 0.38 log10 copies/ml HIV RNA and 0.18 log2 x 10(6)/l CD4 cells (P < 0.001 in each case). For patients who were initially asymptomatic or in CDC stage B, the adjusted relative hazard (RH) of AIDS for a twofold lower CD4 count was 3.14 [95% confidence interval (CI), 1.44-6.83] and for a 10-fold higher HIV RNA level was 3.22 (1.20-8.59). The RH progression to AIDS expected with ZDV/3TC compared with the control treatments, given the observed effects of treatment on CD4 cell counts and HIV RNA levels, is 0.52, whereas the observed value was 0.16 (0.03-0.74). After adjustment for HIV RNA and CD4 changes over time the observed RH of progression to AIDS for ZDV/3TC treatment compared with controls was increased to 0.36 and was no longer significant (95% CI, 0.07-1.85). CONCLUSION: In this analysis of two trials, the effects of ZDV/3TC in reducing plasma HIV RNA and raising peripheral blood CD4 counts were associated with concurrent clinical benefits and the effect of treatment on these markers could account for at least part of the clinical benefits of therapy that were observed.

Anti-HIV Agents↗

Lymphocyte counts and functions in arterial and venous splenic blood of patients with Hodgkin's disease. Evidence for elimination of spontaneously DNA synthesizing cells in the spleen.

Lymphocyte counts and functional competence of lymphocytes from arterial and venous splenic blood were studied in six patients with Hodgkin's disease subjected to splenectomy. One patient was untreated, four were tested after mantle field treatment and a sixth patient had a splenic relapse after total nodal radiotherapy. The percentage of E binding cells in splenic venous blood was lower than that of arterial blood though no significant differences were found in total lymphocyte or E binding cell counts. The spontaneous lymphocyte DNA synthesis was lower in venous than in arterial splenic lymphocytes in all patients. Pokeweed mitogen (PWM)-induced DNA synthesis was much lower in lymphocytes from splenic venous blood than in those from arterial blood in two patients and marginally decreased in another two. The pattern of concanavalin A response was similar to that of PWM. The elimination of lymphocytes over the spleen could not be related to the presence of lymphocytotoxic serum factors or to splenic weight or histologically verified tumour involvement. The results support the notion that some facets of the blood lymphocyte abnormalities in Hodgkin's disease may be explained by removal of functionally active lymphocyte subpopulations in the spleen. It is also concluded that spontaneously activated lymphoid cells are detained in the spleen.

Adult↗

CD4 and total lymphocyte counts as predictors of HIV disease progression.

CD4+ T-lymphocyte (CD4) counts are a standard laboratory marker of disease progression in HIV infection, but expense precludes their use in large parts of the world. Total lymphocyte counts (TLC), in contrast, are widely available. We compared CD4 and TLC counts as predictors of developing AIDS or death in 831 HIV-positive out-patients (582 males and 249 females with both homosexual (males, n = 316) and heterosexual (n = 515) transmission patterns. The first CD4 count < 200/microliter and first TLC < 1250/microliter predicted similar (p = 0.52) survival, irrespective of clinical stage. For each clinical stage, a significant difference in progression to AIDS and mortality was predicted by TLC above or below 1250/microliter (p < 0.03). Survival and progression to AIDS occurred at similar rates in patients with a TLC < 1250/microliter or a CD4 count < 200/microliter (p > 0.1), and patients with a TLC > 1250/microliter or a CD4 count > 200/microliter (p > 0.5). A TLC < 1250/microliter preceded the development of Pneumocystis carinii pneumonia or cerebral toxoplasmosis in 76% of patients. In this longitudinal study, TLC and CD4 counts were equal predictors of disease progression. A TLC < 1250/microliter could be considered an indication for commencing cotrimoxazole prophylaxis.

Acquired Immunodeficiency Syndrome↗

Pneumocystis carinii pneumonia in a term newborn infant with a transiently depressed T lymphocyte count, primarily of cells carrying the CD4 antigen.

A term infant without infection by human immunodeficiency virus had pneumocystis pneumonia at 17 days of life. Initial counts of T lymphocytes carrying the CD4 antigen were approximately 50% of the lower limits of normal; later the counts of T lymphocytes carrying the CD3 and CD8 antigens decreased as well. By 7 weeks after resolution of the pneumonia, CD3+, CD4+ and CD8+ cell counts had returned to normal. These observations suggest that a primary transient deficiency of T cell production or maturation, especially involving CD4+ cells, may occur in otherwise normal newborn infants.

CD4 Antigens↗

Immunodeficiency and elevated CD4 T lymphocyte counts in two patients coinfected with human immunodeficiency virus and human lymphotropic virus type I.

We describe two patients who were coinfected with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus (HTLV) type I. They had clinical evidence of immunodeficiency (anergy, oral candidiasis, and disseminated herpes zoster) despite having elevated CD4 T lymphocyte counts (range, 2,450-5,292/mm3). We conclude that CD4 lymphocyte counts may not be reliable markers of immunologic competence in patients coinfected with HIV and HTLV-I.

Adult↗