Progressive multifocal leukoencephalopathy as an AIDS-defining condition in a patient with high CD4+ T-lymphocyte count

We present the case of a 31-year-old man with acute manifestation of progressive multifocal leukoencephalopathy (PML) as an AIDS-defining disease. The patient presented with a three-day history of neurological disease, brain lesions without mass effect or contrast uptake and a slightly increased protein concentration in cerebrospinal fluid. A serological test for HIV was positive and the CD4+ T-cell count was 427/mm³. Histological examination of the brain tissue revealed abnormalities compatible with PML. The disease progressed despite antiretroviral therapy, and the patient died three months later. PML remains an important cause of morbidity and mortality among HIV-infected patients.

Sleep deprivation reduces the lymphocyte count in a non-obese mouse model of type 1 diabetes mellitus

The objective of the present study was to determine whether sleep deprivation (SD) would promote changes in lymphocyte numbers in a type 1 diabetes model (non-obese diabetic, NOD, mouse strain) and to determine whether SD would affect female and male NOD compared to Swiss mice. The number of lymphocytes in peripheral blood after 24 and 96 h of SD (by multiple platform method) or equivalent period of time in home-cage controls was examined prior to the onset of diabetes. SD for 96 h significantly reduced lymphocytes in male Swiss mice compared to control (8.6 ± 2.1 vs 4.1 ± 0.7 10³/µL; P < 0.02). In male NOD animals, 24- and 96-h SD caused a significant decrease of lymphocytes compared to control (4.4 ± 0.3 vs 1.6 ± 0.5; P < 0.001 and 4.4 ± 0.3 vs 0.9 ± 0.1 10³/µL; P < 0.00001, respectively). Both 24- and 96-h SD induced a reduction in the number of lymphocytes in female Swiss (7.5 ± 0.5 vs 4.5 ± 0.5, 4.4 ± 0.6 10³/µL; P < 0.001, respectively) and NOD mice (4 ± 0.6 vs 1.8 ± 0.2, 1.2 ± 0.4 10³/µL; P < 0.01, respectively) compared to the respective controls. Loss of sleep induced lymphopenia in peripheral blood in both genders and strains used. Since many cases of autoimmunity present reduced numbers of lymphocytes and, in this study, it was more evident in the NOD strain, our results suggest that SD should be considered a risk factor in the onset of autoimmune disorders.

The association between CD4+ lymphocyte count and measures of body composition in HIV-infected men

Purpose. This project was designed to describe the association between wasting and CD4 cell counts in HIV-infected men in order to better understand the role of wasting in progression of HIV infection.^ Methods. Baseline and prevalence data were collected from a cross-sectional survey of 278 HIV-infected men seen at the Houston Veterans Affairs Medical Center Special Medicine Clinic, from June 1, 1991 to January 1, 1994. A follow-up study was conducted among those at risk, to investigate the incidence of wasting and the association between wasting and low CD4 cell counts. Wasting was described by four methods. Z-scores for age-, sex-, and height-adjusted weight; sex-, and age-adjusted mid-arm muscle circumference (MAMC); and fat-free mass; and the ratio of extra-cellular mass (ECM) to body-cell mass (BCM) $>$ 1.20. FFM, ECM, and BCM were estimated from bioelectrical impedance analysis. MAMC was calculated from triceps skinfold and mid-arm circumference. The relationship between wasting and covariates was examined with logistic regression in the cross-sectional study, and with Poisson regression in the follow-up study. The association between death and wasting was examined with Cox's regression.^ Results. The prevalence of wasting ranged from 5% (weight and ECM:BCM) to almost 14% (MAMC and FFM) among the 278 men examined. The odds of wasting, associated with baseline CD4 cell count $<$200, was significant for each method but weight, and ranged from 4.6 to 12.7. Use of antiviral therapy was significantly protective of MAMC, FFM and ECM:BCM (OR $\approx$ 0.2), whereas the need for antibacterial therapy was a risk (OR 3.1, 95% CI 1.1-8.7). The average incidence of wasting ranged from 4 to 16 per 100 person-years among the approximately 145 men followed for 160 person-years. Low CD4 cell count seemed to increase the risk of wasting, but statistical significance was not reached. The effect of the small sample size on the power to detect a significant association should be considered. Wasting, by MAMC and FFM, was significantly associated with death, after adjusting for baseline serum albumin concentration and CD4 cell count.^ Conclusions. Wasting by MAMC and FFM were strongly associated with baseline CD4 cell counts in both the prevalence and incidence study and strong predictors of death. Of the two methods, MAMC is convenient, has available reference population data, may be the most appropriate for assessing the nutritional status of HIV-infected men. ^

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio are Predictors of Heart Failure

Abstract Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inflammatory markers used as prognostic factors in various diseases. The aims of this study were to compare the PLR and the NLR of heart failure (HF) patients with those of age-sex matched controls, to evaluate the predictive value of those markers in detecting HF, and to demonstrate the effect of NLR and PLR on mortality in HF patients during follow-up. Methods: This study included 56 HF patients and 40 controls without HF. All subjects underwent transthoracic echocardiography to evaluate cardiac functions. The NLR and the PLR were calculated as the ratio of neutrophil count to lymphocyte count and as the ratio of platelet count to lymphocyte count, respectively. All HF patients were followed after their discharge from the hospital to evaluate mortality, cerebrovascular events, and re-hospitalization. Results: The NLR and the PLR of HF patients were significantly higher compared to those of the controls (p < 0.01). There was an inverse correlation between the NLR and the left ventricular ejection fraction of the study population (r: -0.409, p < 0.001). The best cut-off value of NLR to predict HF was 3.0, with 86.3% sensitivity and 77.5% specificity, and the best cut-off value of PLR to predict HF was 137.3, with 70% sensitivity and 60% specificity. Only NLR was an independent predictor of mortality in HF patients. A cut-off value of 5.1 for NLR can predict death in HF patients with 75% sensitivity and 62% specificity during a 12.8-month follow-up period on average. Conclusion: NLR and PLR were higher in HF patients than in age-sex matched controls. However, NLR and PLR were not sufficient to establish a diagnosis of HF. NLR can be used to predict mortality during the follow-up of HF patients.

CD4+ T cell count recovery in HIV type 1-infected patients is independent of class of antiretroviral therapy.

BACKGROUND: In recent years, treatment options for human immunodeficiency virus type 1 (HIV-1) infection have changed from nonboosted protease inhibitors (PIs) to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and boosted PI-based antiretroviral drug regimens, but the impact on immunological recovery remains uncertain. METHODS: During January 1996 through December 2004 [corrected] all patients in the Swiss HIV Cohort were included if they received the first combination antiretroviral therapy (cART) and had known baseline CD4(+) T cell counts and HIV-1 RNA values (n = 3293). For follow-up, we used the Swiss HIV Cohort Study database update of May 2007 [corrected] The mean (+/-SD) duration of follow-up was 26.8 +/- 20.5 months. The follow-up time was limited to the duration of the first cART. CD4(+) T cell recovery was analyzed in 3 different treatment groups: nonboosted PI, NNRTI, or boosted PI. The end point was the absolute increase of CD4(+) T cell count in the 3 treatment groups after the initiation of cART. RESULTS: Two thousand five hundred ninety individuals (78.7%) initiated a nonboosted-PI regimen, 452 (13.7%) initiated an NNRTI regimen, and 251 (7.6%) initiated a boosted-PI regimen. Absolute CD4(+) T cell count increases at 48 months were as follows: in the nonboosted-PI group, from 210 to 520 cells/muL; in the NNRTI group, from 220 to 475 cells/muL; and in the boosted-PI group, from 168 to 511 cells/muL. In a multivariate analysis, the treatment group did not affect the response of CD4(+) T cells; however, increased age, pretreatment with nucleoside reverse-transcriptase inhibitors, serological tests positive for hepatitis C virus, Centers for Disease Control and Prevention stage C infection, lower baseline CD4(+) T cell count, and lower baseline HIV-1 RNA level were risk factors for smaller increases in CD4(+) T cell count. CONCLUSION: CD4(+) T cell recovery was similar in patients receiving nonboosted PI-, NNRTI-, and boosted PI-based cART.

Low postseroconversion CD4 count and rapid decrease of CD4 density identify HIV+ fast progressors.

CD4 expression in HIV replication is paradoxical: HIV entry requires high cell-surface CD4 densities, but replication requires CD4 down-modulation. However, is CD4 density in HIV+ patients affected over time? Do changes in CD4 density correlate with disease progression? Here, we examined the role of CD4 density for HIV disease progression by longitudinally quantifying CD4 densities on CD4+ T cells and monocytes of ART-naive HIV+ patients with different disease progression rates. This was a retrospective study. We defined three groups of HIV+ patients by their rate of CD4+ T cell loss, calculated by the time between infection and reaching a CD4 level of 200 cells/microl: fast (<7.5 years), intermediate (7.5-12 years), and slow progressors (>12 years). Mathematical modeling permitted us to determine the maximum CD4+ T cell count after HIV seroconversion (defined as "postseroconversion CD4 count") and longitudinal profiles of CD4 count and density. CD4 densities were quantified on CD4+ T cells and monocytes from these patients and from healthy individuals by flow cytometry. Fast progressors had significantly lower postseroconversion CD4 counts than other progressors. CD4 density on T cells was lower in HIV+ patients than in healthy individuals and decreased more rapidly in fast than in slow progressors. Antiretroviral therapy (ART) did not normalize CD4 density. Thus, postseroconversion CD4 counts define individual HIV disease progression rates that may help to identify patients who might benefit most from early ART. Early discrimination of slow and fast progressors suggests that critical events during primary infection define long-term outcome. A more rapid CD4 density decrease in fast progressors might contribute to progressive functional impairments of the immune response in advanced HIV infection. The lack of an effect of ART on CD4 density implies a persistent dysfunctional immune response by uncontrolled HIV infection.

Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study.

OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients were included who had genotypic resistance tests performed on plasma samples collected while antiretroviral therapy naive. TDR was defined as at least one resistance mutation from a list proposed for genotypic TDR surveillance. Multivariable logistic regression was used to analyze factors associated with detection of TDR, with virological (viral load<500 copies/mL) and CD4 count response (>or=50% increase) to combination antiretroviral therapy at months 6-12. RESULTS: The overall prevalence of TDR was 11.4%, which was stable over 1996-2004. There were no significant differences in virological suppression (those resistant to at least one drug prescribed versus susceptible), adjusted odds ratio: 0.68 (95% confidence interval: 0.27 to 1.71; P=0.408) or CD4 count response, adjusted odds ratio: 1.65 (95% confidence interval: 0.73 to 3.73; P=0.231). CONCLUSIONS: Prevalence of TDR in antiretroviral-naive patients was found to be in line with other European studies. No significant differences were found in virological and CD4 count response after initiation of first-line combination antiretroviral therapy between resistant and susceptible patients, possibly due to the small number of patients with resistance and consequently low power.

CD4(+) T cell count decreases by ethnicity among untreated patients with HIV infection in South Africa and Switzerland.

BACKGROUND: Estimates of the decrease in CD4(+) cell counts in untreated patients with human immunodeficiency virus (HIV) infection are important for patient care and public health. We analyzed CD4(+) cell count decreases in the Cape Town AIDS Cohort and the Swiss HIV Cohort Study. METHODS: We used mixed-effects models and joint models that allowed for the correlation between CD4(+) cell count decreases and survival and stratified analyses by the initial cell count (50-199, 200-349, 350-499, and 500-750 cells/microL). Results are presented as the mean decrease in CD4(+) cell count with 95% confidence intervals (CIs) during the first year after the initial CD4(+) cell count. RESULTS: A total of 784 South African (629 nonwhite) and 2030 Swiss (218 nonwhite) patients with HIV infection contributed 13,388 CD4(+) cell counts. Decreases in CD4(+) cell count were steeper in white patients, patients with higher initial CD4(+) cell counts, and older patients. Decreases ranged from a mean of 38 cells/microL (95% CI, 24-54 cells/microL) in nonwhite patients from the Swiss HIV Cohort Study 15-39 years of age with an initial CD4(+) cell count of 200-349 cells/microL to a mean of 210 cells/microL (95% CI, 143-268 cells/microL) in white patients in the Cape Town AIDS Cohort > or =40 years of age with an initial CD4(+) cell count of 500-750 cells/microL. CONCLUSIONS: Among both patients from Switzerland and patients from South Africa, CD4(+) cell count decreases were greater in white patients with HIV infection than they were in nonwhite patients with HIV infection.

Fungal infection as a risk factor for HIV disease progression among patients with a CD4 count above 200/microl in the era of cART.

The identification of clinical risk factors for AIDS in patients with preserved immune function is of significant interest. We examined whether patients with fungal infection (FI) and CD4 cell count >or=200/microl were at higher risk of disease progression in the era of cART. 11,009 EuroSIDA patients were followed from their first CD4 cell count >or=200/microl after 1 January 1997 until progression to any non-azoles/amphotericin B susceptible (AAS) AIDS disease, last visit or death. Initiation of antimycotic therapy (AMT) was used as a marker of FI and was modelled as a time-updated covariate using Poisson regression. After adjustment for current CD4 cell count, HIV-RNA, starting cART and diagnosis of AAS-AIDS, AMT was significantly associated with an increased incidence of non-AAS-AIDS (IRR=1.55, 95% CI 1.17-2.06, p=0.0024). Despite low incidence of AIDS in the cART era, FI in patients with a CD4 cell count >or=200/microl is associated with a 55% higher risk of non-AAS-AIDS (95% confidence interval 1.17-2.06, p=0.0024). These data suggest that patients with FI are more immune compromized than would be expected from their CD4 cell count alone. FI can be used as a clinical marker for disease progression and indirect indicator for initiation/changing cART in settings where laboratory facilities are limited.

Gut intraepithelial lymphocyte counts in neonates, infants and children

Intraepithelial lymphocyte (IEL) counts were histologically assessed in the jejunum, ileum and appendix of 39 neonates (0-28 days), 32 infants (1-9 months) and 13 children (1-9 years). Small intestinal mucosa samples were obtained from 73 autopsies, and from 8 surgical and 3 aspirative biopsies. IEL counts of specimens from the jejunum, ileum and appendix gave similar results in the same patient. The number of IEL counts was significantly lower in neonates for all three segments. The difference between infants and children was more marked in the jejunum than in the ileum, although this was not significant. In the appendix, there was no difference between the different age groups. Our results indicate that postnatal expansion of IEL occurs homogeneously along the gut after the neonatal period.

Impact Of Pharmacist Interventions On Drug-related Problems And Laboratory Markers In Outpatients With Human Immunodeficiency Virus Infection.

Substantial complexity has been introduced into treatment regimens for patients with human immunodeficiency virus (HIV) infection. Many drug-related problems (DRPs) are detected in these patients, such as low adherence, therapeutic inefficacy, and safety issues. We evaluated the impact of pharmacist interventions on CD4+ T-lymphocyte count, HIV viral load, and DRPs in patients with HIV infection. In this 18-month prospective controlled study, 90 outpatients were selected by convenience sampling from the Hospital Dia-University of Campinas Teaching Hospital (Brazil). Forty-five patients comprised the pharmacist intervention group and 45 the control group; all patients had HIV infection with or without acquired immunodeficiency syndrome. Pharmaceutical appointments were conducted based on the Pharmacotherapy Workup method, although DRPs and pharmacist intervention classifications were modified for applicability to institutional service limitations and research requirements. Pharmacist interventions were performed immediately after detection of DRPs. The main outcome measures were DRPs, CD4+ T-lymphocyte count, and HIV viral load. After pharmacist intervention, DRPs decreased from 5.2 (95% confidence interval [CI] =4.1-6.2) to 4.2 (95% CI =3.3-5.1) per patient (P=0.043). A total of 122 pharmacist interventions were proposed, with an average of 2.7 interventions per patient. All the pharmacist interventions were accepted by physicians, and among patients, the interventions were well accepted during the appointments, but compliance with the interventions was not measured. A statistically significant increase in CD4+ T-lymphocyte count in the intervention group was found (260.7 cells/mm(3) [95% CI =175.8-345.6] to 312.0 cells/mm(3) [95% CI =23.5-40.6], P=0.015), which was not observed in the control group. There was no statistical difference between the groups regarding HIV viral load. This study suggests that pharmacist interventions in patients with HIV infection can cause an increase in CD4+ T-lymphocyte counts and a decrease in DRPs, demonstrating the importance of an optimal pharmaceutical care plan.

Prevalence, Incidence Density, and Genotype Distribution of GB Virus C Infection in a Cohort of Recently HIV-1-Infected Subjects in Sao Paulo, Brazil

Background: The results of previous studies elsewhere have indicated that GB virus C (GBV-C) infection is frequent in patients infected with the human immunodeficiency virus type 1 (HIV-1) due to similar transmission routes of both viruses. The aim of this study was to determine the prevalence, incidence density and genotypic characteristics of GBV-C in this population. Methodology/Principal Findings: The study population included 233 patients from a cohort primarily comprised of homosexual men recently infected with HIV-1 in Sao Paulo, Brazil. The presence of GBV-C RNA was determined in plasma samples by reverse transcriptase-nested polymerase chain reaction and quantified by real-time PCR. GBV-C genotypes were determined by direct sequencing. HIV viral load, CD4+ T lymphocyte and CD8+ T lymphocyte count were also tested in all patients. The overall prevalence of GBV-C infection was 0.23 (95% CI: 0.18 to 0.29) in the study group. There was no significant difference between patients with and without GBV-C infection and Glycoprotein E2 antibody presence regarding age, sex, HIV-1 viral load, CD4+ and CD8+ T cell counts and treatment with antiretroviral drugs. An inverse correlation was observed between GBV-C and HIV-1 loads at enrollment and after one year. Also, a positive but not significant correlation was observed between GBV-C load and CD4+ T lymphocyte. Phylogenetic analysis of the GBV-C isolates revealed the presence of genotype 1 and genotype 2, these sub classified into subtype 2a and 2b. Conclusion/Significance: GBV-C infection is common in recently HIV -1 infected patients in Sao Paulo, Brazil and the predominant genotype is 2b. This study provides the first report of the GBV-C prevalence at the time of diagnosis of HIV-1 and the incidence density of GBV-C infection in one year.

Role of upper endoscopy in diagnosing opportunistic infections in human immunodeficiency virus-infected patients

Highly active antiretroviral therapy (HAART) has dramatically decreased opportunistic infections (OIs) in human immunodeficiency virus (HIV)-infected patients. However, gastrointestinal disease continues to account for a high proportion of presenting symptoms in these patients. Gastrointestinal symptoms in treated patients who respond to therapy are more likely to the result of drug-induced complications than OI. Endoscopi evaluation of the gastrointestinal tract remains a cornerstone of diagnosis, especially in patients with advanced immunodeficiency, who are at risk for OI. The peripheral blood CD4 lymphocyte count helps to predict the risk of an OI, with the highest risk seen in HIV-infected patients with low CD4 count (< 200 cells/mm(3)). This review provides an update of the role of endoscopy in diagnosing OI in the upper gastrointestinal tract in HIV-infected patients in the era of HAART. (C) 2009 The WJG Press and Baishideng. All rights reserved.

Factors influencing wound healing after surgery for metastatic disease of the spine

Study Design, The study group consisted of 53 patients who underwent 75 operations for spine metastases. Patient and tumor demographic factors, preoperative nutritional status, and perioperative adjunctive therapy were retrospectively reviewed. Objective, To determine the risk factors for wound breakdown and infection in patients undergoing surgery for spinal metastases. Summary of Background Data. Spinal Fusion using spine implants may be associated with an infection rate of 5% or more. Surgery for spine metastases is associated with an infection rate of more than 10%. Factors other than the type of surgery performed may account for the greater infection rate. Methods. Data were obtained by reviewing patient records. Age, sex, and neurologic status of the patient; tumor type and site; and surgical details were noted. Adjunctive treatment with corticosteroids and radiotherapy was recorded, Nutritional status was evaluated by determining serum protein and serum albumin concentrations and by total lymphocyte count. Results. Wound breakdown and Infection occurred in 75 of 75 wounds. No patient or tumor demographic factors other than intraoperative blood loss (P < 0.1) were statistically associated with infection; The correlation between preoperative protein deficiency (P < 0.01) or perioperative corticosteroid administration (P < 0.10) and wound infection was significant. There was no statistical correlation between lymphocyte count or perioperative radiotherapy and wound infection. Conclusions, The results indicate that preoperative protein depletion and perioperative administration of corticosteroids are risk factors for wound infection in patients undergoing surgery for spine metastases, Perioperative correction of nutritional depletion and cessation of steroid therapy may reduce wound complications.

Incidence, Risk Factors, and Outcome of Herpes Zoster in Systemic Lupus Erythematosus

Background: The incidence and outcome of Herpes zoster (HZ) in systemic lupus erythematosus (SLE) are not completely defined as well as the relevance to HZ of disease and therapy factors. Objective: To determine HZ features in SLE. Patients and Methods: SLE patients ( 1997 update of the American College of Rheumatology classification criteria) with definitive HZ infection were identified from our Lupus Clinic computerized database of 1145 patients. Results: HZ was diagnosed in 51 SLE patients (4.45%) with an annual incidence rate of 6.4 events/1000 patient-years. At HZ diagnosis, mean disease duration was 9.78 +/- 8.37 years, median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 1, and only 17.6% had SLEDAI >= 8. Frequency of manifestations and immunosuppressor use were similar between patients with and without HZ. Forty-two patients (82.5%) with HZ were under prednisone with concomitant immunosuppressive therapy in 66.7%. Thirty-five patients (68.6%) were using immunosuppressors: azathioprine (39.2%), cyclophosphamide (9.8%), and mycophenolate mofetil ( 9.8%). The mean lymphocyte count was 1219 +/- 803/mm(3) (43.1% < 1000/mm(3) and 17.6% < 500/mm(3)). Only patients using azathioprine and cyclophosphamide had lymphocyte counts < 500/mm(3) (15% and 40%). All patients received acyclovir, 19.6% had postherpetic neuralgia, and recurrence occurred in only 7.8%. Thoracic nerves were the most involved site (56.8%) followed by lumbar (23.5%). Bacterial suprainfection occurred in 11.7% but was not associated with therapy, lymphocyte count, or SLEDAI scores ( P > 0.05). Conclusion: This is the largest cohort to determine that HZ is a late SLE complication with some peculiar features, such as good prognosis and typical dermatomal distribution. In addition, we have identified that the major trigger factor for this viral infection in SLE is therapy, particularly the concomitant use of corticosteroid and immunosuppressors, and not active disease.