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PubMed1992

The relationship of total lymphocyte count to CD4 lymphocyte counts in patients infected with human immunodeficiency virus.

A simple, inexpensive alternative to CD4 counts would facilitate the management of asymptomatic and early symptomatic patients with HIV infection. In this report, a high correlation was found between CD4 counts and total lymphocyte counts calculated from complete blood counts in a cohort of ambulatory HIV-infected patients. Using these data, patients with CD4 counts above and below 500 cells/mm3, 200 cells/mm3, and those with and without symptoms can be identified with a high degree of predictive value. The availability and lower cost of lymphocyte counts make them an attractive alternative to CD4 counts in managing asymptomatic and early symptomatic patients with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Acquired immunodeficiency syndrome (AIDS) risk in recent and long-standing human immunodeficiency virus type 1 (HIV-1)-infected patients with similar CD4 lymphocyte counts.

The loss of CD4 lymphocytes is known to be an important component of human immunodeficiency virus type 1 (HIV-1) pathogenesis. It remains unclear, however, whether the importance of the CD4 lymphocyte count is such that individuals who have been infected for widely different lengths of time, but for whom the CD4 lymphocyte count is the same, have the same risk of developing acquired immunodeficiency syndrome (AIDS). The authors directly addressed this question for 111 HIV-1-infected hemophiliacs who had been followed for up to 12 years from seroconversion and for whom a median of 16 CD4 lymphocyte counts had been made. Thirty-eight patients had developed AIDS by January 1, 1992. As of August 1, 1985, the time from seroconversion to AIDS ranged from 3 weeks to almost 6 years. The risk of AIDS increased with time from seroconversion (relative hazard = 1.25 per year; p = 0.09). CD4 lymphocyte count was strongly related to time from seroconversion and also to the risk of AIDS (relative hazard = 3.25 per 100/mm3; p < 0.00005). In a bivariate Cox regression model, the relative hazard for time from seroconversion fell markedly towards unity (1.05; p = 0.7), while that for CD4 lymphocyte count remained unchanged. This suggests that time from seroconversion is a relevant factor in HIV-1 infection only insofar as it provides information as to the probable degree of loss of CD4 lymphocytes. If the number of these cells is known, time from seroconversion seems to be of little additional value in assessing the risk of AIDS. This finding has implications for the clinical assessment of individual patient prognosis, for the design of epidemiologic studies of HIV-1 infection, and for our understanding of how HIV-1 causes disease.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Comparison of absolute CD4+ lymphocyte counts determined by enzyme immunoassay (TRAx CD4 test kit) and flow cytometry.

Currently, CD4+ lymphocyte counts are one of the most widely used surrogate markers for monitoring disease progression in and initiating therapy for human immunodeficiency virus-infected individuals. However, the process of obtaining lymphocyte subset counts can be complex and expensive, often rendering the test inaccessible to many patients. In contrast to standard laser-based flow cytometry, the TRAx CD4 Test Kit utilizes an enzyme-linked immunoassay format to provide CD4+ lymphocyte counts by a simple and more cost-effective means. In order to evaluate the utility of the TRAx CD4+ assay in comparison with flow cytometry, heparinized blood samples were drawn from 188 infected and uninfected adult patients and 24 infected pediatric patients and evaluated by both assays. The correlation coefficient for all adult individuals tested was 0.94, and the mean absolute counts (in cells per milliliter, +/- standard deviation) were 510 +/- 358 for TRAx and 480 +/- 361 for flow cytometry. The correlation for the pediatric group was 0.93, with mean absolute counts of 956 +/- 767 for TRAx and 1,521 +/-a 1,438 for flow cytometry. Overall the TRAx CD4 Test Kit performed well in comparison to flow cytometry, and its lower cost and ease of use make it an encouraging alternative for the routine determination of CD4+ lymphocyte counts.

Adult↗
PubMed1991

Serial CD4 lymphocyte counts and development of AIDS.

Low CD4 lymphocyte counts are associated with increased risk of progression to AIDS in human immunodeficiency virus (HIV) infection. We investigated the extent to which the timing of progression to AIDS can be explained solely in terms of decline of the CD4 lymphocyte count in 111 haemophiliacs followed for up to 11 years since infection with HIV. A median of 10 CD4 lymphocyte counts were made per patient. By applying a simple linear model for the decline in CD4 lymphocyte counts over time, we estimated the date of development of AIDS in 96 patients who had at least 5 determinations. 84% (81 of 96) of patients were correctly classified as to development of AIDS before Jan 1, 1990 (p less than 0.0001), with this model. The results suggest that differences in the time at which patients with HIV will progress to AIDS can largely be explained by differences in rates of decline of CD4 lymphocyte counts.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Correlation between total and CD4 lymphocyte counts in HIV infection: not making the good an enemy of the not so perfect.

The aim of this study was to assess the correlation and average cost of total lymphocyte count compared with CD4 count as a broad estimate of immunosuppression in HIV-1 infected individuals. Spearman's partial rank correlation were calculated between total lymphocyte count, absolute CD4 count and CD4 per cent stratified by stage of HIV-1 infection for routinely collected samples. Data were collected prospectively from a T cell-subset register combined with clinical data obtained retrospectively from case notes of HIV-infected patients managed at St Mary's Hospital, London 1982-1991. Costing data were obtained through a survey of the departments of haematology and immunology (1989/90 prices). The correlation between 1534 paired absolute lymphocyte count and CD4 lymphocyte count was found to be high (R = 0.76). When analysed by stage of HIV infection, the correlation increased from R = 0.64 for asymptomatic patients, to R = 0.72 for patients with symptomatic non-AIDS HIV infection and R = 0.73 for AIDS patients. Correlations between absolute lymphocyte count and CD4 per cent were considerably weaker: R = 0.41 all paired counts; R = 0.32 for asymptomatic patients; R = 0.25 for symptomatic non-AIDS patients; R = 0.32 for AIDS patients. Average cost was pounds 8 per full blood count compared with pounds 38 per T-cell subset analysis. The high correlation between total and CD4 lymphocyte counts, especially for patients with symptomatic HIV disease, demonstrates the suitability of the use of total lymphocyte count in the absence of CD4 counts. Given the considerably lower prices of total lymphocyte counts compared with T-cell subset analysis, this is particularly relevant for developing countries.

CD4 Lymphocyte Count↗
PubMed1995

Quantification of the variation due to laboratory and physiologic sources in CD4 lymphocyte counts of clinically stable HIV-infected individuals.

We have conducted a study to quantify the amount of variation in the CD4 lymphocyte counts of HIV-infected individuals due to laboratory and physiological factors. Thirty HIV-infected male volunteers had blood drawn on six occasions: three times in each of 2 weeks, 4 weeks apart. Two tubes of blood were drawn at each visit, and duplicate measurements were obtained from one of the tubes of blood. Differences between duplicate measurements from a single tube of blood and between CD4 counts obtained from two tubes of blood drawn on the same day were attributed to laboratory factors. Differences between CD4 counts obtained on different days were attributed to a combination of laboratory factors and physiologic factors, which included the effects of exercise, tobacco, and the consumption of alcohol and caffeine. The mean absolute CD4 count at the first visit was 450 (range 86-1,081). The short-term coefficient of variation of CD4 count was 13.7 (95% CI: 12.9, 14.6). Physiologic and laboratory factors accounted for 85% and 15% of the variation in CD4 counts, respectively. Variation in the absolute white blood cell count, lymphocyte percentage, and CD4 percentage accounted fo 52%, 29%, and 19% of the physiologic variation in CD4 counts, respectively. Our results confirm a high degree of short-term variability of CD4 counts among HIV-infected individuals, which can be largely attributed to physiological factors. This variability can be minimized more effectively by repeating CD4 counts over time than by repeating measurements at a single visit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Prediction of progression to AIDS by analysis of CD4 lymphocyte counts in a haemophilic cohort.

Serial CD4 lymphocyte counts were recorded in 112 anti-HIV-positive haemophiliacs who were followed for up to 8 years after seroconversion. The patients remained at low risk of developing AIDS until their CD4 lymphocyte count fell to 0.25 X 10(9)/l. From this point, the risk increased as their count approached zero. Using this result and on the assumption (which is evaluated) that the underlying trend over time in CD4 lymphocyte counts is linear, the predicted rate of progression to AIDS was calculated for the cohort. It was estimated that 73% (95% confidence limits 60-86%) of the cohort will develop AIDS within 15 years of HIV-seropositivity. During 8 years of follow-up, this cohort had shown similar rates of progression to AIDS to other cohorts--haemophilic and otherwise--suggesting that this estimate may well have general applicability. The method described could be used to plan the provision of health-care resources for groups of anti-HIV-positive patients as it allows the number of new cases of AIDS to be predicted year by year, even when the patients' dates of seroconversion are unknown.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Risk of reactivation of tuberculosis in the course of human immunodeficiency virus infection.

OBJECTIVES: To establish, in a longitudinal study, whether reactivation of latent tuberculous infection takes place below an identifiable immunological threshold in subjects with human immunodeficiency virus (HIV) infection. METHODS: We followed up for 2 years 44 subjects with HIV infection who had a positive intradermal reaction to tuberculin. All subjects were asymptomatic at enrollment. End points of the study were the development of active tuberculosis or the final evaluation (24 months since the beginning) for those who did not develop tuberculosis over the study period. Total lymphocyte count, CD4+ lymphocyte count and beta-2 microglobulin serum levels were measured at baseline, during the period of observation (every 3-6 months) and at the end point. Multiple Antigen Skin Testing and purified protein derivative (PPD) testing were also performed at baseline and end point, as well as in intermediate phases of the study (every 6 and 12 months respectively). RESULTS: Ten subjects (22.7%) developed tuberculosis during the study period. Both baseline and end point values of the parameters investigated differed significantly between subjects who developed tuberculosis and those who did not. Cox's model showed that total and CD4+ lymphocyte counts as well as beta-2 microglobulin levels had a prognostic value at a univariate analysis; CD4+ and beta-2 microglobulin retained statistical significance in a multivariate evaluation. CD4+ lymphocyte count was the parameter most strongly associated with the development of tuberculosis. CONCLUSIONS: Tuberculosis in this setting most often reactivates only when immune surveillance has fallen to an identifiable level. Planners of antituberculous chemoprophylactic policies should consider the downgrading tendency of immune function in these subjects in order to choose the most appropriate time to intervene in the course of HIV infection. Starting prophylaxis in HIV-infected subjects only when CD4+ cells have dropped below the value of 500/mm3 seems to be a more fruitful option than the currently adopted strategy, which recommends time-limited (12 months) administration of daily isoniazid to all PPD+ HIV-infected subjects regardless their immunological status.

Adult↗
PubMed1998

Decline in total T cell count is associated with onset of AIDS, independent of CD4(+) lymphocyte count: implications for AIDS pathogenesis.

We previously reported that blind T cell homeostasis, in which the total T cell count is maintained but the CD4(+) and CD8(+) subset composition of the T cells can vary, fails approximately 1.5 to 2.5 years before the onset of AIDS. The present study was premised on the hypothesis that if failure of T cell homeostasis (i.e., a decline in total T cell counts) is important in the pathogenesis of AIDS, it should be a significant predictor of AIDS after controlling for the CD4(+) lymphocyte count. Data from 1556 homosexual men with sufficient sequential T cell subset measurements were evaluated, representing 11,988 person-visits in men with known clinical outcomes over a period of more than 10 years. Using regression models that incorporated CD4(+) lymphocyte count and HIV-related symptoms (fever, thrush), it was determined that a yearly decline of more than 300 T cells/microliter of peripheral blood was an independent predictor of the onset of AIDS for subjects with CD4(+) lymphocyte counts of <500 cells/microliter. The results support an important role for failure of T cell homeostasis in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗
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↗
PubMedDate not supplied

Interpretation of chest radiographs in AIDS patients: usefulness of CD4 lymphocyte counts.

Specific infections and neoplasms that are complications of acquired immunodeficiency syndrome (AIDS) occur within various CD4 lymphocyte count ranges. Knowledge of how these counts correlate with radiographic appearances of these entities can limit the differential diagnosis because certain conditions are uncommon above a specific count. In patients with CD4 lymphocyte counts above 200 cells/mm3 and radiographic findings of cavitary and noncavitary consolidation, bacterial pneumonia and Mycobacterium tuberculosis are the major diagnostic considerations. As the CD4 lymphocyte count falls, these infections are still common; however, cavitation is seen less frequently with Mycobacterium tuberculosis, and unusual bacterial infections, including those caused by Rhodococcus equi and Nocardia asteroides, should be considered. In patients with counts below 200 cells/mm3, Pneumocystis carinii pneumonia is the most common infection, usually manifesting radiographically as a reticular interstitial pattern. At CD4 lymphocyte counts of 50-200 cells/mm3, disseminated fungal infection and Kaposi sarcoma become prevalent. In patients with advanced AIDS and counts below 50 cells/mm3, radiographic nodular or reticular patterns may indicate AIDS-related lymphoma and cytomegalovirus and Mycobacterium avium-intracellulare infections. When CD4 lymphocyte counts are applied to interpretation of chest radiographs in AIDS patients, the working differential diagnosis of a radiographic pattern can be tailored to the clinical situation of a given patient.

AIDS-Related Opportunistic Infections↗
PubMed1990

Predicting progression to AIDS: combined usefulness of CD4 lymphocyte counts and p24 antigenemia.

PURPOSE: To investigate the combined usefulness of CD4 lymphocyte counts and human immunodeficiency virus type 1 (HIV-1) p24 antigen in predicting progression to the acquired immunodeficiency syndrome (AIDS). PATIENTS AND METHODS: CD4 lymphocyte counts and HIV-1 p24 antigen status were evaluated over a 4-year period in 518 HIV-1-seropositive men enrolled in the Multicenter AIDS Cohort Study in Chicago. RESULTS: Twenty-six percent (134 of 518) of the HIV-1-seropositive cohort had detectable p24 antigen during the study period. Men with p24 antigenemia experienced a more rapid decline in CD4 lymphocyte counts than men who were persistently p24 antigen-negative (p less than 0.01). Mean CD4 lymphocyte counts at first detection of p24 antigen were 406 and 455 cells/microL for men with incident and prevalent antigenemia, respectively. Antigen was detected in 61% (63 of 103) of the men who progressed to AIDS and in only 17% (71 of 415) of the men who did not (p less than 0.0001). The 4-year estimated cumulative AIDS incidence was 86%, 63%, and 21% for men with entry CD4 counts less than 200, 200 to 399, and 400 or more cells/microL, respectively. Presence of p24 antigenemia was strongly associated with more rapid disease progression within each of these CD4 groupings (p less than 0.0001). CONCLUSION: Our data indicate that p24 antigenemia can first be detected with moderate CD4 cell depletion, is associated with a more rapid decline in the CD4 lymphocyte population, and combined with CD4 lymphocyte counts is useful in identifying individuals at significantly greater risk of disease progression. Our findings provide important information for assessing HIV-1 disease prognosis over a 4-year period.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Decrease in CD4 lymphocyte counts with rest; implications for the monitoring of HIV infection.

Measurement of the CD4 lymphocyte count is widely used as a prognostic marker and guide for the institution of antiretroviral therapy in patients infected with HIV (human immunodeficiency virus). CD4 counts are known to fluctuate with strenuous physical activity and diurnal variation but there is no information on the effects of rest or normal daily activity. We investigated the effects of rest on the absolute CD4 lymphocyte count in 20 healthy laboratory workers. Blood samples were obtained in 20 subjects upon arrival in the laboratory (CD4 0), following 30 and 60 min rest (CD4 30 and CD4 60 respectively) and 8 h into a normal working day (CD4 8). A significant decrease in the CD4 lymphocyte count was observed following 60 min rest; mean CD4 count at 0 min 1060 x 10(6)/L, mean CD4 count at 60 min 660 x 10(6)/L (P = 0.0017). These results demonstrate a significant effect of rest on CD4 lymphocyte counts in healthy volunteers. This biological variation may be important in HIV-infected patients and needs to be addressed by further studies.

Activities of Daily Living↗
PubMed1993

Relationship between CD4 lymphocyte count and AIDS mortality, 1986-1991.

OBJECTIVE: To determine the relationship between CD4 lymphocyte count and short-term AIDS mortality, and to determine whether this relationship changed during 1986-1991. DESIGN: A retrospective analysis of CD4 lymphocyte counts in patients dying with AIDS and estimation of median survival in patients with a CD4 count < .50 x 10(6)/l. METHODS: Absolute CD4 lymphocyte count in the 6 months before death was available for 178 patients. The terminal CD4 count was compared in five cohorts of patients dying in 12-month periods from July 1986. Kaplan-Meier survival curves were constructed using survival from date of first absolute CD4 count < 50 x 10(6)/l in 271 patients and compared for each yearly cohort. RESULTS: The median terminal CD4 lymphocyte count for all patients was 10 x 10(6)/l. The median terminal CD4 counts for each yearly cohort were: 1986/1987, 100 (n = 13); 1987-1988, 10 (n = 27); 1988-1989, 10 (n = 30); 1989/1990, 20 (n = 59); 1990-1991, 10 (n = 58). There was a significant difference in the terminal CD4 count in the 1986-1987 period compared with all other years combined, but no further changes after 1987-1988. The median survival of all patients from date of first CD4 count < 50 x 10(6)/l was 11.9 months. There was no significant difference in median survival in each yearly cohort. CONCLUSIONS: There is a close correlation between CD4 lymphocyte count and short-term mortality in AIDS. Therapeutic advances over the past 5 years are not reflected by changes in CD4 count before death or improved survival in patients with very low CD4 counts.

Acquired Immunodeficiency Syndrome↗
PubMed1995

CD4+ lymphocyte count in African patients co-infected with HIV and tuberculosis.

The objectives of this study were (a) to compare the CD4+ lymphocyte profiles over time of two groups of patients hospitalized for tuberculosis (TB) treatment [a group of patients with TB only (TB group) and a group dually infected by HIV and TB (HIV/TB group)] and (b) to assess the usefulness of the total lymphocyte count (TLC) as a surrogate of the CD4+ lymphocyte count in the HIV/TB group. A total of 345 patients were enrolled in the study of whom 104 (29.8%) were HIV seropositive (HIV/TB). On admission, the CD4+ lymphocyte counts of the HIV/TB cohort were significantly lower than the TB group with medians of 230 (interquartile range, 90-475) and 630 (500-865), respectively (p < 0.0001). The CD4+ lymphocyte count increased significantly in both cohorts on routine TB treatment. A TLC of 1,300-1,500 cells/mm3 was found to be predictive of a CD4+ lymphocyte count of < or = 200 cells/mm3 both on admission and after 1 month of TB therapy. We conclude from this study that the positive influence of TB therapy on the CD4+ lymphocyte count strongly suggests an additional avenue of influence on the course of HIV infection, whereas the usefulness of the TLC as a surrogate estimation of CD4+ lymphocyte count in HIV/TB patients has important implications for the developing world.

AIDS-Related Opportunistic Infections↗
PubMed1997

Modeling of the change in CD4 lymphocyte counts in patients before and after administration of the human immunodeficiency virus protease inhibitor indinavir.

We investigated the relationships between changes in CD4 lymphocytes counts over 24 weeks after the initiation of therapy with indinavir at dosages of > or = 2.4 g/day (n = 15) in human immunodeficiency virus-positive patients and compared them to the baseline values. Starting CD4 count were linked to the time-weighted average CD4 cell count (return) through a nonlinear effect model. The diminution of destruction of CD4 cells after the initiation of indinavir therapy was estimated by fitting simultaneous differential equations to the data by using a linked lymph node (LN)-blood (BL) (two-compartment) system in which there is a constant rate of generation (R), first-order transfer rate constants (KLN-BL and KBL-LN) of compartment exchange, and first-order rate constants of CD4 destruction in the absence and presence of indinavir (KLN-OUT1 and KLN-OUT2). The half-life of CD4 lymphocytes was calculated from the rate constants by standard two-compartment methods. The CD4 lymphocyte counts at the start and return were linked in a sigmoid-Emax model were the maximal effect (Emax) was at 574.6 cells/microliters and 50% of the effect occurred at 157.1 cells/microliters (r2 = 0.94; P < 0.001). The mean +/- standard deviation (median) KLN-OUT2 was 0.574 +/- 0.202 (0.589), indicating that indinavir decrease the destruction of CD4 cells by circa 41 to 42%. The mean (median) CD4 half-life was 11.5 +/- 5.72 day (10.3 days). In multivariate analysis, KLN-OUT2 was significantly correlated with starting the CD4 cells count and the change in the CD4 cell count on therapy. The relationship between CD4 lymphocyte half-life and the starting CD4 lymphocyte count was hyperbolic, with a rapid increase in half-life as the CD4 count decreased. On the basis of the calculated half-life, the average production (destruction) of CD4 lymphocytes was approximately 3 x 10(9) cells/day, with an individual variation of 44-fold. These findings suggest that (i) the CD4 lymphocyte cell count at the start is significantly correlated to both the decrease in the destruction rate of CD4 cells and the degree of change in the CD4 lymphocytes on therapy, (ii) the lower the initial CD4 lymphocyte count, the higher the amount of CD4 lymphocyte turnover and the lower the ability of the immune system to increase absolute CD4 lymphocyte levels after viral suppression, consistent with a decreased regenerative capacity with progression of disease; and (iii) the increase in CD4 lymphocytes is likely secondary to the expansion of proliferating pool of cells since our determinations are based on 24 weeks of effect.

Anti-HIV Agents↗
PubMed1994

Predictive value of repeated measurements of CD4 lymphocyte counts on progression to AIDS.

OBJECTIVE: Description of the relationship between repeated measurements of CD4 lymphocyte count and development of AIDS in asymptomatic HIV-infected patients. DESIGN: Repeated measurements of CD4 lymphocyte counts over an AIDS-free period in asymptomatic HIV-infected patients, and follow-up of the cohort to record subsequent clinical progression to AIDS. METHODS: The cohort was studied in a double-blind randomized clinical trial. CD4 lymphocyte counts were measured on three occasions over 8 months in 851 patients. RESULTS: Eighty subsequent clinical progressions to AIDS were recorded during a median follow-up period of 15.3 months. Each of the three measurements of CD4 lymphocyte count were separately predictive of subsequent progression to AIDS. However, when the three measurements were included simultaneously in a predictive model only the last measurement showed a significant predictive value. Change in individual CD4 count was also related to the risk of developing AIDS, but was no longer significant when the most recent measurement was included in the model. CONCLUSION: These results indicate the closeness of the relationship between the actual state of the immune system and subsequent progression to AIDS.

Acquired Immunodeficiency Syndrome↗