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PubMed2006

CD4 percentages and total lymphocyte counts as early surrogate markers for pediatric HIV-1 infection in resource-limited settings.

The early diagnosis of pediatric HIV-1 infection is a critical issue in resource-limited settings to prioritize eligibility for antiretroviral therapy among HIV-1-infected children. A case-control study was performed within the ANRS 1201/1202 Ditrame Plus cohort (Abidjan, Côte d'Ivoire) to assess the usefulness of CD4+ T-cell percentage (CD4%) and total lymphocyte count (TLC) measured early in life in African children born to HIV-1-infected mothers. Using plasma HIV-1 RNA testing at 4 weeks of life as gold standard, CD4% and TLC were determined at month 3 and 6 in all 33 children HIV-1-infected in utero or intrapartum/early postpartum (cases) born to mothers receiving peripartum antiretroviral prophylaxis. Controls were 66 HIV-1-uninfected children from the same cohort. At month 3, the median CD4% was significantly lower in HIV-1-infected children (17.7%, 95% percentiles, 7.1-27.4) than in uninfected controls (34.8%, 18.5-45.3) (P < 0.001). A comparable difference was also observed at month 6. At the same time points, no significant difference was measurable for TLCs. The best threshold differentiating HIV-infected and uninfected children at month 3 was 25% CD4+. Compared to HIV-1 RNA results, sensitivity of this marker was 87.1% (95% confidence interval, 70.2-96.4) at month 3 and 88.9% (70.8-97.6) at month 6. Specificity was 78.3% (63.6-89.0) and 88.3% (77.4-95.2), respectively. Early CD4% measurement allows one to classify adequately the vast majority of exposed children according to their HIV status. CD4% should be further evaluated under field conditions for the diagnosis of pediatric HIV-1 infection and the monitoring of pediatric antiretroviral therapy.

CD4 Lymphocyte Count↗
PubMed2000

Multisite comparison of CD4 and CD8 T-lymphocyte counting by single- versus multiple-platform methodologies: evaluation of Beckman Coulter flow-count fluorospheres and the tetraONE system. The NIAID DAIDS New Technologies Evaluation Group.

New analytic methods that permit absolute CD4 and CD8 T-cell determinations to be performed entirely on the flow cytometer have the potential for improving assay precision and accuracy. In a multisite trial, we compared two different single-platform assay methods with a predicate two-color assay in which the absolute lymphocyte count was derived by conventional hematology. A two-color method employing lymphocyte light scatter gating and Beckman Coulter Flow-Count fluorospheres for absolute counting produced within-laboratory precision equivalent to that of the two-color predicate method, as measured by coefficient of variation of replicate measurements. The fully automated Beckman Coulter tetraONE System four-color assay employing CD45 lymphocyte gating, automated analysis, and absolute counting by fluorospheres resulted in a small but significant improvement in the within-laboratory precision of CD4 and CD8 cell counts and percentages suggesting that the CD45 lymphocyte gating and automated analysis might have contributed to the improved performance. Both the two-color method employing Flow-Count fluorospheres and the four-color tetraONE System provided significant and substantial improvements in between-laboratory precision of absolute counts. In some laboratories, absolute counts obtained by the single-platform methods showed small but consistent differences relative to the predicate method. Comparison of each laboratory's absolute counts with the five-laboratory median value suggested that these differences resulted from a bias in the absolute lymphocyte count obtained from the hematology instrument in some laboratories. These results demonstrate the potential for single-platform assay methods to improve within-laboratory and between-laboratory precision of CD4 and CD8 T-cell determinations compared with conventional assay methods.

CD4-CD8 Ratio↗
PubMedDate not supplied

[Simplified CD4+ T-lymphocyte count in patients with HIV/AIDS in Mexico].

OBJECTIVE: To study the correlation between ALC and CD4 cell counts and to find alternative ways of counting CD4+ T-lymphocytes. MATERIAL AND METHODS: The double positivity for CD3/CD4 antibodies was measured in 175 consecutive HIV-positive patients using flow cytometry; in these cases a difference was made between counting cells that were positive for both antibodies vs those that were positive only to CD4. ALC and CD4 counts were also compared among 500 subjects infected with HIV, using linear regression analysis and comparing the number of dissimilar cases for counts below 200 cells/microliters and ALC counts lower than 1 500 and 2000 cells/microliters. RESULTS: In the 175 cases measured by the CD3/CD4 antibody combination the mean percent was 13.8% and for total CD4 cells 14.2% (p = NS); the mean difference was 0.4% and the median 0.2%. For the 500 patients the mean ALC was 1 700 cells/microliters and the mean CD4 count was 219 cells/microliters; the correlation coefficient was 0.59. CONCLUSIONS: These data suggest a poor correlation of ALC and CD4 cell counts, thus it is impossible to predict CD4 on the basis of ALC. This is the reason why it is necessary to measure CD4 cells separately. The difference between measuring double positive CD3/CD4 cells vs only CD4 positive cells was not significant. Our data suggest that the use of a single CD4 antibody may cut costs and still produce clinically useful information.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Impact of early HIV-1 RNA and T-lymphocyte dynamics during primary HIV-1 infection on the subsequent course of HIV-1 RNA levels and CD4+ T-lymphocyte counts in the first year of HIV-1 infection. Sydney Primary HIV Infection Study Group.

Plasma HIV-1 RNA and CD4+ T-cell counts after HIV-1 seroconversion are important independent markers that predict the clinical course of HIV-1 infection. The prognostic significance of these parameters during primary HIV-1 infection, however, remains largely unknown. In a cohort of 53 male study subjects (age, 33 +/- 7 years), who consecutively presented with primary HIV-1 infection, we analyzed the relationship between early plasma HIV-1 RNA, CD4+ and CD8+ T-cell counts, beta2-microglobulin, and p24-antigen levels determined in the first 3 months and subsequent plasma HIV-1 RNA levels and CD4+ T-cell counts 6 to 12 months after onset of primary symptoms. Peak, nadir, and median HIV-1 RNA levels in the first 30 days were already significantly associated with HIV-1 RNA levels at 6 to 12 months (p = .02, p < .0001, and p = .01, respectively). Similarly, early nadir and median CD4+ T-lymphocyte counts in the first 30 days showed a significant relationship with CD4+ T-cell counts at 6 to 12 months (p = .009 and p = .0008, respectively). Study subjects with an early decline of CD4+ counts to <500 cells/microl had an eightfold higher risk that CD4+ counts were <500 cells/microl at 1 year. Of all evaluated virologic parameters, only nadir HIV-1 RNA at 76 days predicted CD4+ counts at 6 to 12 months (p = .006). Early HIV-1 RNA levels and CD4+ counts are already associated with the time course of those parameters 6 to 12 months after onset of symptoms. Nadir viral load was the strongest predictor of HIV-1 RNA levels as well as of CD4+ counts at 6 to 12 months. An early decline of CD4+ T lymphocytes may be a useful clinical prognostic marker for rapid disease progression.

Adult↗
PubMed1998

[Neurophysiological parameters and CD4 lymphocyte count in patients infected by human immunodeficiency virus].

INTRODUCTION AND OBJECTIVE: The human immunodeficiency virus (HIV) causes serious, irreversible, progressive deterioration of the immune and nervous systems. The main target cells are the 'helper' T lymphocytes and monocyte-macrophage cells with CD4 molecules on the surface acting as virus receptors. In this study we attempt to find whether the immune state and the nervous system are involved in parallel, or whether, on the contrary, HIV neurotropism is such that it leads to early nerve involvement, out of proportion to that of the immune system. PATIENTS AND METHODS: We studied a total of 66 persons, 30 seronegative and 36 seropositive, with different CD4 lymphocyte counts. In all cases motor and sensory conduction studies were done in the arms and legs, namely auditory, visual and somatosensory evoked potentials and also endogenous potentials (mainly P300). CONCLUSIONS: There are neurophysiological parameters which give pathological figures, even when immunity is maintained (figures of CD4 greater than 500/mm3) especially with regard to the figures for sensitivity of the legs, somatosensory evoked potentials and P300. Moreover, these are increased and others added at the same time as the CD4 count falls as the disease advances.

Adult↗
PubMed1983

The level of some serum proteins and lymphocyte count in persons exposed to the action of lead during work. Report I.

80 persons, aged 22 to 62, were examined clinically. Tests were made to determine the levels of total protein, immunoglobulins IgG, IgM and IgA, leukocytes and lymphocytes. The group included 20 persons exposed to the action of lead for a number of years, with biochemical traits of lead poisoning, 30 persons exposed to the action of lead but with no biochemical traits of lead poisoning, and 30 healthy persons not exposed to the action of lead during work. The levels of serum immunoglobulins G and M and lymphocyte count were reduced in the first group compared with the remaining two groups. The differences were statistically significant. According to the author, the process described indicates a suppressive lead action on the immunological response of the body. Besides other components of the immunological system, B and T lymphocyte are probably involved in the process.

Adult↗
PubMedDate not supplied

Total lymphocyte count: a promising prognostic index of mortality in patients on CAPD.

OBJECTIVE: In view of the limitations of albumin in peritoneal dialysis (PD), we set out to evaluate whether total lymphocyte counts (TLC) could serve as a better prognostic indicator. We were also interested in how these parameters might differ between PD and hemodialysis (HD) patients. DESIGN: In a retrospective study, we reviewed 113 charts from our dialysis unit. All laboratory analyses were performed by the Department of Clinical Pathology of the Nassau County Medical Center, using standard procedures. Intact parathyroid hormone (PTH) was sent out to Nichols Laboratories. SETTING: All patients originated from the renal clinic at Nassau County Medical Center, a 612 bed public hospital. PATIENTS: The 38 PD and 75 HD patients selected had been receiving dialysis for at least 12 months and up to 3 years. The PD patients received either continuous ambulatory and/or cycler PD. For the survivors, the averages of their routine chemical analyses were considered their representative values. For the nonsurvivors, the most recent laboratory values prior to their end point were considered. MAIN OUTCOME MEASURES: Mortality or apparent malnutrition leading to transfer to HD represented the end points for PD patients. Mortality alone was used as the end point for HD patients. RESULTS: Within the PD population, serum albumin was not significantly lower in nonsurvivors compared to survivors, while the TLC was significantly lower in nonsurvivors (1277 +/- 146/mm3 vs 2249 +/- 236/mm3, p = 0.0036). The HD population demonstrated a significant difference in both TLC and serum albumin levels between its two prognostic groups; albumin was the better discriminator. Nonsurvivors had a 20% lower serum albumin than did the survivors (27.0 +/- 1.6 g/L vs 34.0 +/- 0.5 g/L, p = 0.0001). Patients on PD had a higher TLC than those on HD (p = 0.0001). CONCLUSIONS: In the HD population, but not in the PD population, both serum albumin and TLC were significantly higher in the group that survived. Serum albumin is a more powerful discriminator of mortality in the HD population, while TLC is a better discriminator of mortality in the PD population. For uncertain reasons, PD patients have a higher TLC than those on HD.

Female↗
PubMed2005

Use of total lymphocyte count and hemoglobin concentration for monitoring progression of HIV infection.

BACKGROUND: Prognostic markers for HIV monitoring are needed for resource-limited regions. Prior research has demonstrated rapid declines in total lymphocyte count (TLC) and hemoglobin levels before AIDS, but the prognostic accuracy of these declines has not been examined prospectively. METHODS: Longitudinal TLC and hemoglobin data from men in the Multicenter AIDS Cohort Study (MACS) before the introduction of potent HIV therapy were used to identify the first time when the TLC was 33% per year, and hemoglobin declined by >11.6% per year. The prognostic value of these declines for AIDS was evaluated by Cox regression models and Kaplan-Meier survival curves. RESULTS: Rapid declines in TLC or hemoglobin were associated with progression to AIDS (relative hazard [RH]=4.70, 95% confidence interval [CI]: 3.23-6.86 for TLC; RH=5.55, 95% CI: 3.69-8.36 for hemoglobin). The World Health Organization criterion for initiating therapy, a TLC 1200 cells/mm, a rapid decline in TLC or hemoglobin was strongly associated with progression to AIDS (RH=2.53, 95% CI: 1.56-4.10 for TLC; RH=5.28, 95% CI: 3.11-8.97 for hemoglobin). CONCLUSIONS: In the MACS, rapid declines in TLC or hemoglobin concentration indicated an increased likelihood of progression of HIV infection to AIDS. These results support the potential utility of these markers for monitoring HIV-infected people in resource-limited regions, but critical levels and rates of decline of markers for such regions remain to be defined.

Biomarkers↗
PubMed2004

HIV therapy after treatment interruption in patients with multiple failure and more than 200 CD4+ T lymphocyte count.

The aim of the study was to investigate the safety and efficacy of a salvage therapy initiated after interrupting treatment in patients with virological failure and more than 200 CD4(+) T lymphocyte count. In this prospective study, 77 patients who received failing regimens had stopped completely all medication for 3 months before starting an optimised regimen consisting of 3-5 drugs. Patients were tested for HIV resistance before and after treatment interruption. Discontinuation of therapy for 3 months was associated with a median increase in HIV RNA of 1.1 log(10), a median decrease in CD4(+) T cell count of 136 x 10(6)/L and five clinical events related to HIV, but no AIDS-defining event. Eighty-seven percent of patients showed a shift from a drug resistant genotype to a wild-type genotype based on the major resistance mutations. Forty-seven percent of patients with a genotype shift reached fewer than 200 HIV RNA copies/ml of plasma 6 and 12 months after treatment resumption whereas none of those without a genotype shift did so (P = 0.03). However, the genotypic shift was not associated with a sustained virological response by multivariate analysis. The use of a new therapeutic class of compound in the salvage regimen was the only predictor of the sustained virological response. Salvage therapy with 3-5 drugs after interrupting treatment for 3 months can be a safe and effective strategy provided the HIV disease is not too advanced. Randomised trials in this population are needed to assess the clinical benefit of this strategy.

AIDS-Related Opportunistic Infections↗
PubMed1993

CD4 lymphocyte counts within 24 months of human immunodeficiency virus seroconversion. Findings in the US Navy and Marine Corps. The Navy Retroviral Working Group.

BACKGROUND: Although CD4 lymphocytes are the primary target of the human immunodeficiency virus (HIV), few studies have evaluated CD4 cell counts in a large population of seroconverters with known dates of seroconversion. This study reports an analysis of CD4 lymphocyte counts and CD4 cells as a percentage of all lymphocytes within 24 months of estimated date of HIV seroconversion in 1046 HIV seroconverters. METHODS: Study participants included all Navy and Marine Corps seroconverters (1023 men, 23 women) from 1987 through 1991 with a previous negative HIV test. CD4 lymphocyte counts and percentages were obtained for blood drawn from HIV seroconverters during initial clinical evaluations carried out at Naval Medical Centers in Bethesda, Md; Oakland, Calif; Portsmouth, Va; and San Diego, Calif. The seroconversion date was estimated as the midpoint between the last negative test date and the first positive test date. RESULTS: Nearly 40% of seroconverters presented with initial CD4 lymphocyte counts lower than 0.50 x 10(9)/L (500/microL) and 3% with counts lower than 0.20 x 10(9)/L (200/microL). Approximately half the seroconverters presented with fewer than 29% CD4 cells, and 5% presented with fewer than 14% CD4 cells. There were no significant differences in CD4 counts according to sex, race, or estimated duration of HIV infection. CONCLUSIONS: Little difference in CD4 lymphocyte counts or percentages by duration of infection within 24 months was evident on initial clinical evaluation of HIV seroconverters. The high percentage of seroconverters presenting with low CD4 counts or percentages suggests a population of seroconverters with rapid depletion of CD4 lymphocytes following seroconversion.

Adolescent↗
PubMed2001

Modeling changes in CD4-positive T-lymphocyte counts after the start of highly active antiretroviral therapy and the relation with risk of opportunistic infections: the Aquitaine Cohort, 1996-1997.

After initiation of a treatment for human immunodeficiency virus type 1 infection containing a protease inhibitor, immune restoration associated with increases in CD4-positive (CD4+) T lymphocyte count may be delayed. In a sample of patients who had been prescribed protease inhibitors for the first time, the authors tested to see whether there was a minimal duration of CD4+ cell count increase before the increase had an impact on the occurrence of opportunistic infections. The evolution (difference between time t and baseline) of CD4+ cell count was modeled using a mixed effects linear model. Changes in CD4+ count estimated by this model were then included as time-dependent covariates in a proportional hazards model. Finally, the authors tested for the existence of a CD4+ change x time interaction. The authors used a sample of 553 French patients first prescribed protease inhibitors in 1996 and followed for a median of 16 months. During the first 120 days, there was no association between CD4+ change and the rate of opportunistic infections. After 120 days, each 50-cell/mm3 increase in CD4+ count was associated with a 60% (95% confidence interval: 45, 72) reduction in the incidence of opportunistic infections. These results, based on modeling of CD4+ cell response, at least indirectly reinforce the concept of a delayed but possible immune recovery with the use of protease inhibitors. The findings support the potential for interruption of certain types of prophylaxis against opportunistic infections under reasonable conditions of duration of antiretroviral therapy and sustained CD4+ cell response.

AIDS-Related Opportunistic Infections↗
PubMed2000

Changes in CD4 lymphocyte counts after interruption of therapy in patients with viral failure on protease inhibitor-containing regimens. Royal Free Centre for HIV Medicine.

OBJECTIVE: To describe the short-term changes in CD4 lymphocyte counts after the interruption of antiretroviral HIV therapy in order to increase the understanding of CD4 lymphocyte dynamics, and so that appropriate monitoring strategies can be designed. METHODS: We studied 35 HIV-infected patients with late-stage disease who had therapy interruptions leading to high viral load levels, median greater than 750 000 RNA log10 copies/ml, and in whom two CD4 cell counts (median 28 days apart) were available before beginning a salvage regimen. RESULTS: Overall, there was a substantial decline in CD4 cell counts from a median of 125 to 83 cells/mm3 in the average 28 day period, with median proportionate and absolute losses of 26% and 24 cells/mm3 per month, respectively (P < 0.008). This tended to be greater in individuals studied sooner after interrupting therapy (P = 0.03) and in those with CD4 cell counts above the pre-therapy baseline (P = 0.06). There was a strong negative correlation between the proportionate increase in viral load and the absolute change in CD4 cell count (-0.66, P = 0.0002). CONCLUSION: Patients with relatively advanced HIV infection interrupting antiretroviral therapy after failing a protease inhibitor-containing regimen require frequent monitoring because CD4 cell counts appear to fall quite rapidly, at least in the first few weeks after interruption.

Adult↗
PubMed2002

The relative lymphocyte count predicts death in patients receiving implantable cardioverter defibrillators.

Although the survival benefit conveyed by the automatic defibrillator has been well established for several subsets of patients, some patients who receive the device still die early. The relative lymphocyte count (%L), a portion of the white blood cell count differential, which is decreased in states of excess systemic stress, has prognostic value in patients with coronary artery disease and advanced heart failure. This study assessed the association of %L with survival in patients receiving automatic defibrillators. A total of 136 consecutive patients (81% men; mean age 64 +/- 12 years) who were using automatic defibrillators were followed for 29.6 months. The mean ejection fraction was 0.36 +/- 0.17, the mean %L was 22.7 +/- 8%, and 55 (40%) patients had decreased %L (< 20.3%). There were 20 deaths, for a 4-year survival of 71.5%. The association of %L with time to death was assessed by Cox proportional hazards analysis. Ejection fraction (P = 0.005), %L (P = 0.01), and diagnosis (P = 0.03) were independently associated with time to death on multivariate analysis. One-year and 4-year survival rates were 93% and 54%, respectively, for the 55 patients with abnormal %L, compared with 99% and 84%, respectively, for the 81 with normal %L (P = 0.03). This suggests that the %L is a readily accessible prognostic marker in patients using automatic defibrillators. This association is independent of age, sex, diagnosis, and ejection fraction.

Aged↗
PubMedDate not supplied

[T- and B-lymphocyte count of thyroid pathology patients].

Absolute and relative content of the peripheral blood T-, B- and "zero" cells was studied in 204 patients with thyroid pathology (154 subjects with toxic and 32 with non-toxic goiter, 12 with hypothyrosis and 6 with Hashimoto thyroiditis) by means of spontaneous and complementary rosette-forming method. Patients, suffering from thyroid diseases, mainly from moderate and severe goiter, hypothyrosis and Hashimoto goiter, developed changes in T- and B-lymphocyte system, manifesting in significant fall of the blood absolute and relative T-cell number and B-lymphocyte count increase. Frequency and extent of these alterations depend on severity of toxic goiter, ophthalmopathy and chronic infection presence. T- and B-lymphocyte system does not return to normal in the nearest periods after the drug treatment.

Adolescent↗
PubMed2002

The effect of N-acetylcysteine supplementation upon viral load, CD4, CD8, total lymphocyte count and hematocrit in individuals undergoing antiretroviral treatment.

Individuals infected with the human immunodeficiency virus (HIV-1) present with decreased CD4, a progressive increase in viral load, compromised cell immune defense, and hematologic alterations. The aim of this study was to assess the serum viral load, CD4, CD8, lymphocyte count and hematocrit at the beginning of antiretroviral therapy in individuals who were supplemented with N-acetylcysteine (NAC). Twenty volunteers participated in this double-blind, placebo-controlled 180-day study. Ten participants received 600 mg of NAC per day (NAC group) and the other ten serving as a control group received placebo. The above mentioned parameters were determined before treatment, and after 60, 120 and 180 days. In NAC-treated patients hematocrit remained stable and an increase in CD4 cell count took place earlier than that in the control group.

Acetylcysteine↗
PubMed1994

Relationship of CD4 lymphocyte counts to survival in a cohort of hemophiliacs infected with HIV. Multicenter Hemophilia Cohort Study.

Although CD4 positive lymphocyte counts are important predictors of clinical events in persons infected with human immunodeficiency virus (HIV), little is known about their predictive value for survival. We analyzed CD4 counts obtained regularly since 1983 with regard to survival in a multicenter cohort study of 921 HIV-infected hemophiliacs of whom 177 have died. Dates of seroconversion were determined from stored serum samples. Cumulative mortality and actuarial survival rates were calculated from the first time the mean of two consecutive CD4 counts decreased from levels of > 500 to 200-499, 100-199, 50-99, and < 50 cells/microliter. The death rate per 100 patient years of observation was 0.87 (95% CI 0.27, 1.47) for those with CD4 counts of > 500 cells/microliter and increased progressively to 26.23 (95% CI 21.29, 31.17) for those with CD4 counts of < 50/microliter. HIV-related deaths occurred in 50 of 58 who died with CD4 counts of < 300/microliter compared to 0 of 6 who died with CD4 counts of > 500/microliter. The median CD4 count most proximal to death was 39.5 (range, 1-945). The 10-year actuarial estimate of survival from seroconversion was 77.3 +/- 2% for 546 persons who seroconverted at age > or = 18 years compared to 90.5 +/- 2% for 375 persons who seroconverted at age < 18. Survival decreased at each CD4 level to a median of 27 months at CD4 counts of < 50/microliter. At each CD4 level, younger patients survived longer than older patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2004

Total lymphocyte count and femoral bone mineral density in postmenopausal women.

In vitro studies showed that several cytokines produced by the immune system can play a relevant role in modulating bone turnover, thus affecting the health of bone tissue. Our aim was to evaluate the association between total lymphocyte count (TLC) and femoral bone mineral density (BMD) in a sample of postmenopausal women. We studied 114 out of 124 consecutive, caucasian, home-dwelling, apparently healthy postmenopausal women referred for osteodensitometry by general practitioners. Femoral BMD was measured by dual-energy X-ray absorptiometry at five sites. A significant positive correlation (p < 0.001) was observed between TLC and BMD (T score) measured the five sites: total proximal femur ( r = 0.45), trochanter (r = 0.43), intertrochanteric region (r = 0.38), femoral neck (r = 0.49), and Ward's triangle (r = 0.42). With a linear multiple regression model, TLC adjusted for age, weight, height, body mass index, and erythrocyte sedimentation rate showed a significant association with femoral BMD assessed at each of the five sites. The R(2) values ranged from 0.33 with BMD measured at Ward's triangle to 0.51 with BMD measured at the trochanter. The significance of the association between TLC and BMD ranged from P < 0.001 with BMD measured at the femoral neck to P < 0.05 with BMD measured at the intertrochanteric area. The results were similar when BMD was expressed as either a Z score (in the 110 of the 114 women aged 84 years or younger) or as absolute values. Our data show a positive association between TLC and femoral BMD in a sample of apparently healthy, postmenopausal women, supporting the view of a close connection between the immune system and bone tissue.

Absorptiometry, Photon↗