Absolute CD4 Lymphocyte Count Research Articles

HIV-infection in the Russian Federation: current diagnostic trends

The aim of the study: to analyse diagnostic trends of HIV-infection in the Russian Federation in the period 2017–2022. Materials and methods. The study used data obtained from reports from the Federal Register of persons infected with the human immunodeficiency virus (FRHIV). The circumstances in HIV diagnosis and clinical and epidemiological characteristics of newly diagnosed patients, including CD4+ T-lymphocyte counts, were analysed. A likely time window between presumed infection and confirmation of HIV diagnosis was also determined. Categorical data evaluated in the study were presented as proportions and caparisoned using the chi-square test (χ2). In case of multiple comparisons, the Bonferroni correction for multiplicity was used. Quantitative data were tested for normality using the Kolmogorov-Smirnov criterion. In most cases, nonparametric characteristics of distributions — median and interquartile range — were applied, as well as the Mann-Whitney criteria for comparison of two independent groups and the Kraskell-Wallis criteria for comparison more than two groups, followed by pair wise comparisons using the Mann-Whitney criterion with Bonferroni multiplicity correction. A p-value<0.05 was considered statistically significant. Data analysis and graphical visualization was performed using the statistical software R version 4.1.1 and its libraries.Results and discussion. The results showed an increase in HIV detection through voluntary testing, preventive medical examination, and clinical indications. The proportion of injecting drug users (IDUs) decreased over time, while the involvement of women in the epidemic process and heterosexual transmission increased. Additionally, there was an increase in the proportion of patients aged 35 years and older. The analysis of CD4-cell counts revealed significant differences among gender and age subgroups. Women had higher absolute CD4-lymphocyte counts throughout the follow-up period. Patients aged 0–14 years had the highest proportion of CD4-lymphocytes over 500 cells/μL, while patients over 50 years old had the highest proportion of CD4-lymphocytes less than 200 cells/μL. Men who have sex with men and people infected through mother-to-child transmission had the highest mean baseline CD4-cell counts. IDUs and heterosexuals had a statistically significant decrease in CD4-cell counts over the follow-up period and also had the longest median time from infection to disease detection — 24 and 20 months, respectively.Conclusion: Thus, this study helps identify the most significant risk groups of HIV-infected individuals in Russia at present.

Once Monthly Elotuzumab and Lenalidomide Plus Dexamethasone for Multiple Myeloma: A Multicenter Observation Study

Introduction: Elotuzumab and lenalidomide plus dexamethasone (ERd) is a standard salvage chemotherapy for multiple myeloma, and elotuzumab is commonly administered every 2 weeks after cycle 3 (conventional ERd). Alternatively, elotuzumab may often be used every 4 weeks (monthly ERd) in real-world practice. The purpose of this multicenter observational study was to investigate the efficacy and tolerability of monthly ERd. Methods: We investigated the efficacy and tolerability between conventional and monthly ERd regimens for the myeloma patients in six institutes retrospectively. Results: Seventy-five patients were included in this study. The median patient age was 68 years. The median number of prior chemotherapies was two (1–5). The number of patients with prior lenalidomide exposure was 57 (76.0%). The numbers of progressive disease (PD) and non-PD before ERd were 23 (30.7%) and 52 (69.3%), respectively. The frequency of PD before ERd was significantly lower in the monthly ERd group than in the conventional ERd group. In 26.9 months of median follow-up period, the 2-year progression-free survival (PFS) rate in the monthly ERd group was significantly longer than that in the conventional ERd group (95.0% and 62.0%, hazard ratio 0.082, p = 0.002). However, no significant difference in PFS between these two ERd groups was found using multivariate analysis. The complete response rates were similar between the monthly and conventional ERd groups (55.0% and 32.7%, p = 0.109). There was no significant difference in the incidence of adverse events between the monthly and conventional ERd groups (35.0% and 54.5%, p = 0.192). There was no significant difference in the kinetics of the mean absolute lymphocyte count, CD4, CD8, CD16, CD56, and CD57 positive lymphocyte counts, and CD4 to CD8 ratio between the monthly and conventional ERd groups. Discussion: The efficacy and tolerability of monthly ERd were similar to those of conventional ERd. Thus, monthly ERd might be a reasonable option, considering the quality of life of patients and convenience.

Prevalence of Cryptococcus gattii in Ugandan HIV-infected patients presenting with cryptococcal meningitis.

IntroductionCryptococcal meningitis (CM) is a life threatening disease and leading cause of opportunistic fungal-related mortality in HIV/AIDS. Most CM infections are caused by C. neoformans species complexes but the prevalence of Cryptococcus gattii species complexes in Uganda is unknown however, it is known in a few other parts of Africa. We estimated the prevalence of C. gattii in patients living with HIV and a diagnosis of cryptococcal meningitis in Uganda.MethodsCryptococcus isolates (n = 200) obtained from cerebrospinal fluid of patients with CM recruited at the Infectious Diseases Institute, Kampala, Uganda, were tested by phenotypic methods. The Cryptococcus isolates were sub-cultured on Sabouraud Dextrose Agar plates for 48 hours. The yeast colonies were examined by India ink stain, urea hydrolysis, and C. gattii was identified by blue pigmentation on CGB agar. The results were analyzed for frequency of C. gattii. Patient demographic characteristics were collected from the case record forms.ResultsFrom the 200 patients’ case record forms, 87 (43.5%) were female and 113 (56.5%) were male. The median age was 35 (19–64) years. Most patients, 93% (187/200) were from Central Uganda in the districts of Kampala and Wakiso. 97.51% (157/161) of the patients had absolute CD4 lymphocyte counts of less than 200 cells per cubic millimeter; 1.86% (3/161) 200–350 cells per cubic millimeter and 0.62% (1/161) above 500 cells per cubic millimeter. 45.4% (74/163) were not yet on HAART and 54.6% (89/163) were on HAART. 66.7% (58/87) had poor adherence to HAART treatment and 33.3% (29/87) had reported good adherence to HAART treatment. A total of 200 clinical isolates of Cryptococcus isolates were tested. No (0% (0/200) C. gattii was identified among the Cryptococcus isolates.ConclusionIn this study among patients living with HIV and a diagnosis of cryptococcal meningitis in Uganda, we found no C. gattii infections.

ABNORMAL TREC RESULTS ON THE OHIO NEWBORN SCREEN IN CHILDREN WITH CARTILAGE-HAIR HYPOPLASIA

Introduction While newborn screening (NBS) using T-cell receptor excision circle (TREC) analysis was introduced primarily to screen for severe combined immunodeficiency (SCID), it also identifies T-cell lymphopenia or low naive T-cell numbers due to other etiologies. Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder caused by mutations in the RMRP gene that result in short limbed skeletal dysplasia and a range of immunologic deficits involving both cellular and humoral immune function. The immune defect can range from minor abnormalities to a SCID phenotype. Methods We analyzed the NBS TREC results performed in Ohio between July 2013 and July 2018. We reviewed the results of the immunologic workup in patients with abnormal TREC results who were later confirmed to have CHH. Results A total of 693,706 unique infants had NBS performed between July 2013 and July 2018, with 192 (0.027%) having abnormal TREC results. Eight infants with abnormal TREC results were diagnosed with CHH. This included 6 cases of non-SCID T-cell lymphopenia and 2 children with SCID phenotypes. In the children with abnormal screening and a diagnosis of CHH, the absolute CD4 lymphocyte counts on initial immunophenotyping ranged from 76 – 757 cells/mm3 (median = 552 cells/mm3). The two CHH patients with SCID received bone marrow transplants. Conclusions CHH is a rare genetic disorder associated with widely varying levels of T-cell lymphopenia ranging from clinically insignificant to SCID. The T-cell lymphopenia may cause an abnormal result on the NBS TREC analysis, allowing for early diagnosis of a significant immunodeficiency and institution of life-saving therapies.

The Difference of CD4 Count Between HIV Positive Patients With Cognitive Decline and Without Cognitive Decline

The relationship between low absolute CD4 lymphocyte count and neurological complications is well established in the era preceding highly active antiretroviral therapy (HAART). The aims of this study to assess the proportion of cognitive decline among HIV outclinic patient Sardjito General Hospital Yogyakarta and to determine whether the difference of CD4 count between HIV positive patients with cognitive decline and without cognitive decline. A cross sectional study with consecutive sampling. Subject eligible were 15-50 years of age, without a history of stroke, brain injury, CNS tumor and Parkinson’s disease wich devided into 2 groups (CD4 > 200 cel/mm3 and d”200 cel/mm3). Cognitive function was measured by using MMSE and specified for each domain. Digit span and Trail Making Test B were added to further analyze short term memory and motor processing speed and they perform CD4 count in their blood. Ninety six patients fulfill inclution and exclution criteria. Proportion of cognitive decline was 33.3% among HIV patient. Univariate analysis showed significant difference of CD4 count between HIV positive patients with cognitive decline and without cognitive decline (p=0.02). CD4 count was significantly different in the decline of all cognitive domain on MMSE, also in the decline of short term memory and processing speed. There are high of cognitive decline among HIV outclinic patient Sardjito General Hospital Yogyakarta. CD4 count are difference between HIV positive patients with cognitive decline and without cognitive decline.

Description of the cascade of care and factors associated with attrition before and after initiating antiretroviral therapy of HIV infected children in a cohort study in India

In low- and middle-income countries, the attrition across the continuum of care of HIV infected children is not well known. The aim of this study was to investigate predictors of mortality and loss to follow up (LTFU) in HIV infected children from a cohort study in India and to describe the cascade of care from HIV diagnosis to virological suppression after antiretroviral therapy (ART) initiation. Multivariable analysis was performed using competing risk regression. The cumulative incidence of attrition due to mortality or LTFU after five year of follow-up was 16% from entry into care to ART initiation and 24.9% after ART initiation. Of all children diagnosed with HIV, it was estimated that 91.9% entered into care, 77.2% were retained until ART initiation, 58% stayed in care after ART initiation, and 43.4% achieved virological suppression on ART. Approximately half of the attrition occurred before ART initiation, and the other half after starting ART. Belonging to socially disadvantaged communities and living >90 min from the hospital were associated with a higher risk of attrition. Being >10 years old and having higher 12-month risk of AIDS (calculated using the absolute CD4 lymphocyte count and the age) were associated with an increased risk of mortality. These findings indicate that we should consider placing more emphasis on promoting research and implementing interventions to improve the engagement of HIV infected children in pre-ART care. The results of this study can be used by HIV programmes to design interventions aimed at reducing the attrition across the continuum of care of HIV infected children in India.

Reactivity of white blood cell flux to hyperoxia in patients infected with human immunodeficiency virus

The aetiology of the apparently vasoocclusive phenomena in human immunodeficiency virus (HIV)-related retinopathy is not well understood. Several hypotheses, including infectious damage of the retinal vasculature and altered retinal haemodynamics, have been postulated. Direct measurement of oxygen tension in the retina is not possible in vivo and indirect methods have to be employed. The objective of this study was to investigate the retinal vascular response to 100% oxygen breathing in patients with HIV. Twelve patients infected with HIV and 12 healthy individuals, matched for age, sex and smoking habits, were studied in an open study using the blue-field entoptic technique for the measurement of retinal white blood cell (WBC) flux. Reactivity in retinal blood flow during 100% O(2) breathing over 15 min was measured and expressed as percentage change over baseline. WBC velocity during oxygen inhalation decreased over baseline by 9.0 ± 5.8% in HIV-infected patients and by 18.6 ± 5.4% in healthy participants (p < 0.04 between groups, ANOVA). The decrease in WBC velocity was paralleled by a decrease in WBC density. This decrease tended to be more pronounced in healthy participants (13.6 ± 7.9%) than in HIV-infected patients (8.0 ± 10.8%), but the difference was not statistically significant (p = 0.1 between groups, ANOVA). WBC flux decrease was 16.2 ± 11.4% in HIV-infected patients and 29.5 ± 9.5% in the control group and was significant between groups (p = 0.007 between groups, ANOVA). Our results indicate a reduced reactivity of WBC flux to systemic hyperoxia in patients with HIV. Whether abnormal retinal haemodynamics in HIV-infected persons contributes to the pathogenesis of HIV-related microvascular diseases or is a consequence of the structural changes associated with the disease is unknown.

Absolute lymphocyte count as a marker for Cd4 T-lymphocyte count: criterion for initiating antiretroviral therapy in HIV infected Nigerians

Few laboratories in resource-constrained countries can afford to perform laboratory-monitoring tests required for the implementation of HIV therapy. In this case control study, we have investigated the relevance of absolute lymphocyte count as a surrogate marker for CD4 lymphocyte count as a criterion for initiating HAARTin HIV-infected Nigerians. A total of 100 consecutive recruited HIV-infected, previously antiretroviral naive persons and 30 HIV-negative individuals blood samples were run for absolute lymphocyte and CD4 lymphocyte counts and results were compared by a model of linear regression analysis. An overall modest correlation was observed between absolute lymphocyte count and CD4 lymphocyte (r = 0.51) and at CD4 lymphocyte threshold relevant for clinical management of HIV-infected; <200, 200-350 and >350 cells/microL (r = 0.41, 0.30 and 0.21) respectively. Mean absolute lymphocyte count of 1.60 +/- 0.77 x 10(9)/L, 1.88 +/- 1.11 x 10(9)/L and 2.04 +/- 0.54 x 10(9)/L was equivalent respectively to CD4 of <200, 200-350 and >350 cells/microL. This study indicates a modest correlation between absolute and CD4 lymphocyte counts of HIV-infected Nigerians and at CD4 lymphocyte count threshold significant for clinical management of HIV-infected. Absolute lymphocyte count can become a minimal inexpensive alternative to CD4 lymphocyte count in conjunction with WHO staging and clinical status of patient in determining the optimal time to initiate therapy particularly in resource limited settings where other expensive methods of CD4 enumeration are unavailable.

CD4&lt;sup&gt;+&lt;/sup&gt; lymphocyte reference ranges in healthy adults in Port Harcourt, Nigeria

Aims and Objectives : Reference values are essential for the interpretation of data in clinical practice and research studies. The aim of this study was to establish reference ranges for CD4 lymphocytes in healthy HIV-negative Nigerians. Methodology : 200 healthy Human Immunodeficiency Virus (HIV) antibody free individuals constituted the subjects for this study. 150 HIV-infected without AIDS-defining illness and 150 HIV-infected with AIDS-defining illness were included as controls. Results : Participants were aged 18-63years (mean age 34 ± 9.2years). the CD4 lymphocyte count of healthy Nigerians mean SD 685 ± 99, 95% CI 487 883 was twice that of HIV-infected subjects without AIDS-defining illness (314 ± 45, 95% CI 224 404). The CD4 lymphocyte count of HIV-infected with AIDS-defining illness was one fourth or less (148 ± 30, 95% CI 88 208). The mean AIDS-defining CD4 lymphocyte count was (148 30 cells/ul). Healthy women had significantly higher mean absolute CD4 lymphocyte count (729 ± 87, 95% CI 555 to 903) compared to men (647 ± 93, 95% CI 460 to 833) (p Conclusion : Caucasian CD4 lymphocyte reference values are not applicable to Nigerians, as it does not reflect the Nigerian CD4 lymphocyte population. Keywords : CD4 lymphocyte count, reference ranges, Port Harcourt, Nigerians Sahel Medical Journal Vol. 8(3) 2005: 71-75

CD4 Lymphoctye Percentage versus Absolute CD4 Lymphocyte Count in Predicting HIV Disease Progression: An Old Debate Revisited

CD4 Lymphoctye Percentage versus Absolute CD4 Lymphocyte Count in Predicting HIV Disease Progression: An Old Debate Revisited

Cladribine therapy in a patient with an aleukemic subvariant of mast cell leukemia

Dear Sir, We present the case of a patient with an aleukemic subvariant of mast cell leukemia (MCL) with a very good partial response to cladribine therapy. MCL is very rare and is characterized by neoplastic mast cell (MC) proliferation that may lead to myelofibrosis with hemopoietic insufficiency, organ dysfunction, bleeding and death after a median survival time of 6–7 months. Imatinib is ineffective in cases where the activating mutation of the tyrosine kinase receptor c-kit affects its enzymatic site (D816V) [2, 3, 6]. Recently, promising treatment results were published using cladribine (2-CDA) in patients with systemic mastocytosis [1, 4, 5]. However, there are no reports on 2-CDA in patients with MCL. A 65-year-old white male presented in his usual symptom-free state of health in September 2002 for assessment of hepatosplenomegaly, mild normochromic–normocytic anemia (hemoglobin level 110 g/l) and thrombocytopenia (125,000/mm), with normal total and differential white blood cell counts. Radiographic studies revealed abdominal lymphadenopathy as well as osteoblastic and osteolytic bone lesions. Bone marrow biopsy showed osteomyelosclerosis and infiltration with atypical MC accounting for 30% of all nucleated cells. The level of the serum tryptase was 10.1 ng/ml (normal 200 ng/ ml), chymase, CD2, CD25, and CD117 (KIT). The characteristic point mutation of the c-kit proto-oncogene in codon 816 (Asp-816-Val) was detected in DNA from bone marrow, while the karyotype was normal. However, circulating MCs were not found in the peripheral blood. An aleukemic subvariant of MCL was diagnosed according to the WHO classification of tumors [7]. Pegylated interferon α-2b given initially had no therapeutic effect whatsoever. Due to the patient’s deteriorating condition, we started continuous intravenous infusion of 2-CDA (0.1 mg/kg body weight) for 5 days and repeated monthly. This led to only a moderate reduction of absolute CD4 lymphocyte counts, and prophylaxis with cotrimoxazole was thus not considered necessary. All six courses of 2-CDA therapy were given on time without severe (grades 3–4) hematological toxicity or infectious complications. Mediator-related symptoms (night sweats, pruritus, arthralgia, diarrhea) began to improve after 1 week and disappeared completely within 2 months. The spleen size had decreased from 23 cm (maximum diameter) before 2-CDA therapy to 12 cm post-treatment. The serum tryptase level dropped to 29 ng/ml and the degree of bone marrow MC infiltration was reduced to 10–15%. The patient regained a 90–100% Karnofsky performance status, reflected by his ability to hike 10 miles/day. However, radiological evaluations were performed after treatment and revealed no significant changes in bone lesions. In contrast to the other 15 cases of proven MCL in the literature, this patient does not show a progressive course on 2-CDA 30 months after the diagnosis of MCL. In conclusion, 2-CDA has demonstrated an excellent therapeutic index in this patient with MCL and warrants further investigations of this infrequent entity. O. Penack (*) . E. Thiel . M. Notter Department of Hematology, Oncology, and Transfusion Medicine, Charite-Campus Benjamin Franklin, Berlin, Germany e-mail: olaf.penack@charite.de

Predictors of proteinuria and renal failure among women with HIV infection

Glomerular disease with proteinuria and renal failure are complications of human immunodeficiency virus (HIV) infection. While studies suggest risk factors for both include black race and lower CD4 lymphocyte count, they have not been established in population-based cohorts. This study examines the risk factors for proteinuria and renal failure in a large cohort of HIV-infected women not selected for the presence of renal disease. This prospective cohort includes 2059 women enrolled in the Women's Interagency HIV study (WIHS). WIHS is a longitudinal study of the clinical course of HIV infection in which subjects are followed biannually with a detailed exam including urine analysis, serum creatinine, CD4 lymphocyte count, and HIV RNA level. Proteinuria was defined as > or =+1 on urine dipstick exam on at least two consecutive urine analyses, and renal failure was defined as a doubling of serum creatinine. Multivariable logistic regression was used to estimate the associations between clinical variables and the presence of proteinuria on initial evaluation in a cross-sectional analysis. Cox proportional hazards regression was used to estimate the associations between clinical variables and time to renal failure among study participants with proteinuria in a prospective longitudinal analysis. Of 2057 HIV-positive women, 32% (N=671) had proteinuria on initial evaluation. Predictors of proteinuria include increasing (log) HIV RNA level [odds ratio (OR)=1.05], black race (OR=2.0), absolute CD4 lymphocyte count < or =200 cells/mm3 (OR=1.41), and the presence of hepatitis C antibody (OR=1.27; all P < 0.0001). Absolute CD4 lymphocyte count < or =200 cells/mm3 [hazard ratio (HR)=3.57, P=0.001], detectable HIV RNA level (HR=2.33, P=0.02), increasing systolic blood pressure (HR=1.02, P=0.002), and decreasing albumin (HR=3.33, P=0.0001) and increasing creatinine (1.67, P=0.0001) were all associated with the development of renal failure. This analysis establishes the associations between both increasing HIV RNA level and decreasing CD4 lymphocyte count with the presence of proteinuria and occurrence of renal failure. Additionally, it demonstrates an association between proteinuria and a positive hepatitis C antibody. To lessen the presence and progression of renal disease among HIV-infected patients, future research should focus on suppression of the HIV RNA level and improvement in CD4 lymphocyte count.

Predictors of operative outcome in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome

Background: Plasma viral load has recently been associated with clinical outcome in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We hypothetized that, in addition to CD4 lymphocytes, plasma HIV-1 RNA counts are predictive of postoperative outcome. Methods: HIV-infected and AIDS patients admitted to a major teaching hospital requiring invasive or surgical procedures were retrospectively analyzed for postoperative outcome. Preoperative and postoperative immune cell counts including plasma HIV-1 RNA counts were recorded. Chi-square analysis, Fisher’s exact test, and multivariate regression were performed with statistical significance P ≤0.05. Results: Fifty-five consecutive patients between 14 and 62 years of age were admitted in a 1-year period and underwent 64 diagnostic and therapeutic procedures. Fourteen (22%) postoperative infections and 18 (28%) complications other than infection, with an overall mortality of 11%, were documented. Total preoperative white blood cell count ([WBC] P <0.01), preoperative percent lymphocyte count ( P <0.01), absolute postoperative CD4 lymphocyte count ( P <0.01), and postoperative plasma viral load ( P <0.0001) are associated with mortality. Multivariate regression indicated that postoperative percent CD4 lymphocyte count is an independent predictor of both postoperative infection and other complications ( P <0.05, R = 0.848, power = 0.9911), while the decrement in percent CD4 lymphocyte count is an independent predictor of postoperative complications other than infection ( P <0.05, R = 0.596, power = 0.7838). Conclusions: In accordance with the medical literature for clinical outcome in HIV-infected and AIDS patients, both immune cell counts and HIV-1 RNA counts were found to associate with postoperative mortality. However, the postoperative and decrement in percent CD4 lymphocyte proved to be the independent predictors of postoperative complications.

Microvolume fluorimetry for the determination of absolute CD4 and CD8 lymphocyte counts in patients with HIV: a comparative evaluation

This study compared CD4 and CD8 lymphocyte counts obtained by microvolume fluorimetry (MVF) with those derived by flow cytometry (FC). Samples from 192 patients with known or suspected HIV were analysed, and the distribution of CD4 counts for these samples ranged from 0 and 1,279/microl, with 142/192 (74%) of the samples having CD4 values of less than 400/microl. Good agreement between FC and MVF CD4 counts was found (MVF = 0.98 x FC + 7.30) although there was a minor constant inter-method bias of approximately +7 cells/microl for the MVF data. For CD8 counts there was a constant bias between the two methods of approximately +23 cells/microl for FC. Most outliers were associated with higher FC CD8 counts. Supplementary analyses showed a high level of agreement between FC and MVF methods for the CD4:CD8 ratios (MVF = 0.98 x FC). This suggests that observed discrepancies between FC and MVF methods were almost certainly a result of the influence of the absolute lymphocyte counts obtained from the haematology analyser. The results confirm that the IMAGN 2000 microvolume fluorimeter system can be used as an alternative to conventional flow cytometry for the enumeration of CD4 and CD8 counts.

Human immunodeficiency virus status and delayed-type hypersensitivity skin testing in Ugandan children.

In previous studies, delayed-type hypersensitivity (DTH) skin testing has been shown to be affected by several factors including nutritional status, intercurrent infection, host immune status, and previous exposure to the antigen being used. To determine the effect of human immunodeficiency virus type 1 (HIV-1) status on DTH skin testing in a cohort of HIV-1-infected and noninfected Ugandan children followed prospectively from birth. Nested case-control study. Primary care clinic serving study participants at Mulago Hospital, Makerere University, Kampala, Uganda. Thirty HIV-1-infected children and 30 age-matched, HIV-1-noninfected children. After completion of history and physical, each child underwent Mantoux skin testing with both Candida and purified protein derivative (PPD). Results of skin testing were read in 48 to 72 hours. Complete chart reviews were performed on all children. CD4 lymphocyte counts were obtained on all HIV-1-infected children at the time the skin testing was read. The average age of participants was 67 months (range, 51-92 months). HIV-1-infected children (mean CD4 lymphocyte count, 1069 mL-1; range, 86-3378 mL-1), compared with noninfected, age-matched peers, developed significantly smaller PPD reaction size (mean, 1.18 mm +/- 4.3 vs 3.6 mm +/- 7.6, respectively). Candida responses were not different between the two groups of children. Among HIV-1-infected children, there was a larger Candida reaction size in children who had recently received chloroquine treatment. There was no significant correlation between Candida reactivity and PPD reactivity, progressive HIV-1 disease, or CD4 lymphocyte count. The six children diagnosed clinically with active tuberculosis had lower absolute CD4 lymphocyte counts than children without tuberculosis. Lack of reaction to PPD was associated with lower CD4 lymphocyte counts and progressive HIV-1 disease. In HIV-1-infected Ugandan children, DTH skin testing was influenced by the choice of antigen selected, HIV-1 infection, and recent treatment with chloroquine. Based on these findings, we believe that further prospective, longitudinal investigation into the role of chloroquine in HIV-1-infected children is needed. We emphasize the limitations of DTH skin testing in HIV-infected children as an adjunct in the diagnosis of active tuberculosis.

Mycobacterial lymphadenitis associated with the initiation of combination antiretroviral therapy.

To characterize the impact of combination antiretroviral therapy on the clinical and laboratory features of mycobacterial lymphadenitis, we conducted a retrospective chart review of HIV-related mycobacterial lymphadenitis at St. Paul's hospital between 1989 and 1997. Among 52 evaluable patients, 12 presented within 12 weeks of initiating combination antiretroviral therapy (group 1, n = 12); the others developed lesions while receiving no antiretrovirals, monotherapy, or a stable combination regimen of >12 weeks duration (group 2, n = 40). Group 1 patients had higher absolute CD4 lymphocyte counts (median, 150 versus 20 cells/mm3, respectively; p = .001) and hemoglobin levels (median, 113 versus 88 g/L, respectively; p = .002) at the time of mycobacterial diagnosis. Clinical comparison showed that group 1 patients were more likely to develop a draining sinus (50% versus 0%; p < .001), but less often to have weight loss (17% versus 74%; p < .0001) or disease which was disseminated (25% versus 70%; p = .04) or caused by Mycobacterium tuberculosis (0% versus 33%; p = .04). Mycobacterial lymphadenitis developing within 12 weeks of initiating combination antiretroviral therapy is often localized Mycobacterium avium complex disease, associated with a relatively high CD4 count. The clinical course is often complicated by the development of a draining sinus. The close temporal association suggests that such treatment may unmask subclinical infection by enhancing the immune response to mycobacterial antigens.

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.

Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy

In previous natural history studies and clinical trials, AIDS-related cytomegalovirus (CMV) retinitis has occurred primarily in patients with absolute CD4 counts of 50 cells/microL or less (0.05 x 10(9)/L) at the time of diagnosis. We report five patients identified from our clinical practices who were diagnosed with CMV retinitis while their CD4 counts were above 195 cells/microL. We also analysed, based on CD4 counts, 76 AIDS patients with newly diagnosed CMV retinitis whose CD4 lymphocyte enumerations were done in laboratories that maintained certification in a common external quality control programme. 5-24 weeks before retinitis was diagnosed, all five patients had had absolute CD4 lymphocyte counts of less than 85 cells/microL, and 4-7 weeks before diagnosis, all five patients had started taking highly active antiretroviral treatment (HAART) regimens. Only one (4%) of 27 patients enrolled in the trial between July, 1995, and February, 1996, had an absolute CD4 count of more than 50 cells/microL, and none of 27 had an absolute CD4 count of more than 100/microL on entry to the trial. However, from March, 1996 (when indinavir and ritonavir were approved by the FDA for marketing in the USA), to August, 1996, 14 (29%) of 49 patients had CD4 counts of more than 50/microL and seven (14%) of 49 had a CD4 count of more than 100 cells/microL on entry. These findings suggest that the early immunological effects of HAART may not provide sufficient protection to prevent CMV retinitis in patients who have very low CD4 counts when therapy is started. Clinicians should note that CMV retinitis may now occur in patients who have CD4 counts of more than 100 cells/microL.

Symptomatology of HIV-Related Illness and Community-Acquired Illness in an HIV-Infected Emergency Department Population

Study objective: Community-acquired infections and non–AIDS-related illnesses are a significant proportion of the final diagnoses in HIV-infected patients presenting to an emergency department. We hypothesized that emergency physicians overdiagnose opportunistic infections in the HIV-infected patient. We also hypothesized that the absolute CD4 lymphocyte level could be used to stratify patients by likelihood of HIV related disease. Methods: We retrospectively reviewed ED logbooks and medical records to find all ED patients with self-reported HIV seropositivity during a 19-month period. Age, sex, insurance status, chief complaint(s), ED assessment, and disposition were recorded from the ED logs; absolute CD4 lymphocyte counts, risk factors, and final diagnoses were recorded from the medical records. HIV-related disease was evaluated with the use of established Centers for Disease Control and Prevention criteria. Data were evaluated with the use of the χ 2 test, the χ 2 test for trend, and κ-proportions. Results: Analysis of 344 ED visits demonstrated that decreasing absolute CD4 lymphocyte counts were associated with increasing incidence of HIV-related disease ( P<.001), even when noninfectious causes were excluded. Only 34% of visits were related to HIV-associated illness. Emergency physicians exhibited high sensitivity (72.9%) and specificity (95.5%) in diagnosing HIV-related disease and conducted appropriate visit disposition. Conclusion: ED visits by HIV-infected individuals are often not made for reasons of opportunistic infection, and the absolute CD4 lymphocyte count is inversely related to HIV-related disease. [Hafner JW Jr, Brillman JC: Symptomatology of HIV-related illness and community-acquired illness in an HIV-infected emergency department population. Ann Emerg Med January 1997;29:151-157.]

Reference intervals of CD3, CD4, CD8, CD4/CD8, and absolute CD4 values in Asian and Non-Asian populations.

A study to determine reference intervals in normal Asian and non-Asian populations for CD3 (T cells), CD4 (T helper/inducer cells), CD8 (T suppressor/cytotoxic cells), and for the CD4/CD8 ratio and absolute CD4 lymphocyte count was performed. Coulter Clone/Cytostat reagents were used. The samples were lysed using the Coulter Q-Prep and analyzed on the Coulter Profile II flow cytometer. The Asian population appeared to have a lower mean percentage of CD3 and CD4 cells, a lower CD4/CD8 ratio, and lower absolute CD4 lymphocytes. These findings indicate that race should be a consideration in determining reference intervals for immunophenotyping for CD3, CD4, and CD8.