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PubMed2003

Human immunodeficiency virus-1 RNA levels and CD4 lymphocyte counts, during treatment for active tuberculosis, in South African patients.

During 6 months of treatment, we measured human immunodeficiency virus (HIV)-1 virus loads, CD4 T cell counts, and immune activation markers, in 111 HIV-1-infected patients with active tuberculosis (TB). The median virus load (baseline, 5.58 log(10) copies/mL) significantly increased at 1 month (5.71 log(10) copies/mL), then returned to near-baseline levels at 3 months (5.40 log(10) copies/mL) and at 6 months (5.36 log(10) copies/mL). In contrast, the median CD4 counts increased at 1 month (186/mm(3)), at 3 months (238/mm(3)), and at 6 months (239/mm(3)). CD4 counts and virus loads did not change during therapy. Expression of CD38 and HLA-DR remained high throughout treatment, whereas plasma levels of interleukin-6 decreased over time.

AIDS-Related Opportunistic Infections↗
PubMed2003

Ethnicity and discordance in plasma HIV-1 RNA viral load and CD4+ lymphocyte count in a cohort of HIV-1-infected individuals.

BACKGROUND: Guidelines for commencing therapy for HIV infection have been based upon HIV-1 RNA and CD4 lymphocyte thresholds. The influence of confounding factors such as gender, ethnicity and co-infections is unproven. OBJECTIVES: To analyse ethnic discordance in plasma HIV-1 viral load (VL) and CD4+ count and its potential clinical significance in Black and Caucasian groups. STUDY DESIGN: Retrospective, cross-sectional, observational study of 537 antiretroviral nai;ve HIV-1-positive individuals attending two East London clinics. Baseline data were obtained from individuals who registered at the clinic from November 1996 to August 1999. An analysis was performed comparing ethnic differences in plasma HIV-1 VL, CD4+ count, CD8+ count, co-infections, CDC disease category, AIDS-defining illnesses and mode of transmission. RESULTS: Plasma HIV-1 VL was significantly lower in Blacks (4.5 copies/ml versus 4.7 copies/ml; P<0.05) despite lower baseline CD4+ counts and similar rates of disease progression to Caucasian groups. This association remained for patients with less advanced disease after stratification for CD4+ count (CD4+ 200-500, VL 4.5 copies/ml versus 4.7 copies/ml, P<0.01; CD4+ >500, VL 3.4 copies/ml versus 4.3 copies/ml, P<0.001) and disease category (non-AIDS, 4.4 copies/ml versus 4.7 copies/ml; P<0.005). On multivariate analysis, the association persisted following adjustment for gender, age, co-infections, CD4+ count and mode of transmission. CONCLUSIONS: These results suggest that plasma HIV-1 VL is discordantly low in Black compared with Caucasian groups stratified for CD4+ count, in this cohort of antiretroviral nai;ve HIV-1-positive individuals living in London. Although there are a number of possible explanations for this finding, it has considerable clinical relevance for the management of Black HIV-1-infected patients within UK, with significant implications for the decision about when to commence antiretroviral or immune-based therapies.

Adult↗
PubMed1998

Pleural tuberculosis in Harare, Zimbabwe: the relationship between human immunodeficiency virus, CD4 lymphocyte count, granuloma formation and disseminated disease.

OBJECTIVE: To elucidate the relationship between HIV, CD4+ count and pleural TB. METHOD: In a prospective study, 94 patients presenting at two large Harare hospitals with clinically suspected pleural TB were enrolled over a 10-month period. All underwent standardized evaluation, closed pleural aspiration and biopsy. Patients receiving directly observed anti-TB therapy were followed-up. RESULTS: Pleural TB was diagnosed in 90 individuals (median age 33 years; range 18-65; 64 males); the seroprevalence of HIV was 85%. HIV-positive patients were older than HIV-negative individuals (median age 33 vs 23 years, P = 0.013) and had a significantly lower median CD4+ count (191 vs 1106 x 10(6)/l respectively, P = 0.004). A CD4+ count of <200 x 10(6)/l was associated with a length of illness >30 days (65% vs 37%; P = 0.05), a positive pleural fluid smear (37% vs 0%; P = 0.0006) and a positive pleural biopsy Ziehl-Neelsen stain (35% vs 7%; P = 0.021). However, a relationship between CD4+ count and either pleural granuloma formation or radiological evidence of disseminated disease was not observed. CONCLUSION: In sub-Saharan Africa, TB pleural effusions have become associated with older age, a chronic onset, and an increased mycobacterial load. These data emphasize the complex relationship between pleural TB, HIV infection and a low CD4+ count.

Adult↗
PubMedDate not supplied

Response to hepatitis B vaccination in a primary care setting: influence of HIV infection, CD4+ lymphocyte count and vaccination schedule.

Factors affecting the response to hepatitis B vaccination in a primary care setting were examined by means of a review of case notes of patients attending 22 sexually transmissible disease services. Where not available from the notes, presence of antibody to hepatitis B surface antigen (anti-HBs) was determined by testing available stored serum. One hundred and ninety-five patients completed a course of 3 injections and had an anti-HBs assay performed. The highest response rate (anti-HBs > or = 10 IU/L) was found in human immunodeficiency virus (HIV)-negative heterosexual women (16 of 17, 94.1%) followed by HIV-negative heterosexual men (11 of 12, 91.7%); HIV-negative homosexual men (105 of 120, 87.5%); and HIV-positive homosexual men (6 of 14, 42.9%). (For HIV-positive vs HIV-negative homosexual men, P = 0.0003). Eleven of 14 (78.6%) homosexual men of unknown HIV status responded to vaccination. There was a trend to lower CD4+ lymphocyte counts among HIV-infected patients who responded to hepatitis B vaccination (mean 482 cells/cm2) when compared to those that did not respond (632 cells) but this difference was not statistically significant (P = 0.330). Neither the type of vaccine (recombinant, plasma-derived or mixed) nor the length of vaccination course (mean 6.2 months; range 2 to 18) affected response. This study confirmed that vaccination against hepatitis B is much less effective in HIV-infected homosexual men and marginally less effective for HIV-negative homosexual men, though the mechanism for this reduced response is uncertain. Reassuringly vaccine response was not affected by common variables in primary care settings such as vaccine type or delays in the vaccine schedule.

Adult↗
PubMed1998

Mathematical modeling of the interrelationship of CD4 lymphocyte count and viral load changes induced by the protease inhibitor indinavir.

While CD4 cell counts are widely used to predict disease progression in human immunodeficiency virus (HIV)-infected patients, they are poorly explanatory of the progression to AIDS or death after the introduction of chemotherapy. Changes in HIV load (as measured by RNA PCR) have been shown to be a much better predictor of the risk of disease progression. Since the interrelationship of these markers is of great clinical interest, we modeled the time-averaged return of CD4 cell count and change in viral load subsequent to therapy with the HIV protease inhibitor indinavir. We found that CD4 cell return was significantly related to both the baseline CD4 count (r2 = 0.86, P < 0.001) and the decline in HIV RNA PCR-determined viral load (also referred to in this work as the HIV RNA PCR decline) (r2 = 0.60, P < 0.01). Simultaneously modeling both influences in a linked nonlinear model (r2 = 0.93, P < 0.001) demonstrated that (i) the starting number of CD4 cells accounted for the majority of the change in CD4 cell return and (ii) the return of CD4 cells attributable to viral load decrease was 50% of maximal with only a decrease of approximately 0.2 log of HIV RNA as modeled from the first 12 weeks of therapy. Much greater viral inhibition beyond that necessary for maximal CD4 cell return is possible. Given that HIV RNA PCR decline is more strongly linked to ultimate clinical course in HIV disease, our findings indicate that CD4 return is potentially misleading as an indicator of antiviral effect, since it is determined more by the starting CD4 value than by viral load decline and since near-maximal changes occur with minimal antiviral effect.

Acquired Immunodeficiency Syndrome↗
PubMed1998

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

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

Acquired Immunodeficiency Syndrome↗
PubMed1999

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

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

Adult↗
PubMed2000

Immunomodulating effects of surgical intervention in tumors of the head and neck.

The immunomodulating effect of primary surgical intervention in 33 patients with squamous cell carcinoma of the oral cavity, pharynx, and larynx was analyzed prospectively. An operation time of longer than 7 hours was significantly associated with a decrease of total lymphocyte counts, CD4(+) T lymphocytes, and CD8(+) T lymphocytes. The CD4/CD8 ratio as a marker for the downregulation of the cellular immune response was slightly decreased but still in the normal range. CD4(+) lymphocyte counts increased within 7 days, and CD8(+) lymphocytes increased 4 weeks after the operation. The in vitro stimulation of the lymphocytes was impaired for 1 to 4 weeks. Release of interleukins, interferon-gamma, and tumor necrosis factor-alpha remained low despite the surgical trauma. The decreased lymphocyte counts, especially CD4(+) and CD8(+) lymphocytes, were significantly associated with duration of operation and volume of blood loss. Extension of trauma, age, type of anesthesia, and type of intensive care intervention were not associated with specific immunomodulating effects. However, these factors might be responsible for suppression of the immune system, which is expressed by lymphocyte depletion, lymphocyte dysfunction, and impaired upregulation of cytokine secretion.

Adult↗
PubMed1999

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

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

Adult↗
PubMedDate not supplied

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

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

Acquired Immunodeficiency Syndrome↗
PubMed2003

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

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

Adult↗
PubMed2006

Monitoring antiretroviral therapy in HIV/AIDS patients in resource-limited settings: CD4 counts or total lymphocyte counts?

OBJECTIVE: In order to improve the monitoring of disease progression and therapeutic effectiveness in the management of HIV/AIDS in a resource-limited setting, this study was carried out to establish a correlation between total lymphocyte counts (TLC) and CD4 lymphocyte counts in HIV-1 infected/AIDS adults in Yaoundé, Cameroon. METHODS: Full blood counts, differential white, and CD4 counts were measured in 149 patients using standard methods. The correlation coefficient established correlation between values. Sensitivity, specificity, and positive predictive values were calculated as required. RESULTS: The mean TLC, CD4 count, and CD4% as well as CD4/CD8 ratios were 1.932+/-0.895 x 10(9)/L, 268+/-183 cells/mm(3), 14.51+/-15.9%, and 0.34+/-0.25, respectively. Only a weak correlation was observed between TLC and CD4 counts (r=0.41, p=0.05). As a predictor of CD4 count, TLC cut-offs <2.0 and <1.0 x 10(9)/L were unable to predict these values reliably, but showed that at TLC cut-offs of <1.0 x 10(9)/L there was a high chance of CD4 counts being under 200 cells/mm(3). CONCLUSIONS: These data suggest that TLC are of limited value in predicting CD4 counts and should not be substituted for CD4 counts whenever possible. However, TLC may be reliably used in designing algorithms and programs for initiating patient management and follow-up in this setting.

Acquired Immunodeficiency Syndrome↗