Home-based versus clinic-based care for patients starting antiretroviral therapy with low CD4⁺ cell counts: findings from a cluster-randomized trial.

OBJECTIVES: African health services have shortages of clinical staff. We showed previously, in a cluster-randomized trial, that a home-based strategy using trained lay-workers is as effective as a clinic-based strategy. It is not known whether home-based care is suitable for patients with advanced HIV disease. METHODS: The trial was conducted in Jinja, Uganda. One thousand, four hundred and fifty-three adults initiating ART between February 2005 and January 2009 were randomized to receive either home-based care or routine clinic-based care, and followed up for about 3 years. Trained lay workers, supervised by clinical staff based in a clinic, delivered the home-based care. In this sub-analysis, we compared survival between the two strategies for those who presented with CD4⁺ cell count less than 50 cells/μl and those who presented with higher CD4⁺ cell counts. We used Kaplan-Meier methods and Poisson regression. RESULTS: Four hundred and forty four of 1453 (31%) participants had baseline CD4⁺ cell count less than 50 cells/μl. Overall, 110 (25%) deaths occurred among participants with baseline CD4⁺ cell count less than 50  cells/μl and 87 (9%) in those with higher CD4⁺ cell count. Among participants with CD4 cell count less than 50  cells/μl, mortality rates were similar for the home and facility-based arms; adjusted mortality rate ratio 0.80 [95% confidence interval (CI) 0.53-1.18] compared with 1.22 (95% CI 0.78-1.89) for those who presented with higher CD4⁺ cell count. CONCLUSION: HIV home-based care, with lay workers playing a major role in the delivery of care including providing monthly adherence support, leads to similar survival rates as clinic-based care even among patients who present with very low CD4⁺ cell count. This emphasises the critical role of adherence to antiretroviral therapy

Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia.

BACKGROUND: HAART efficacy was evaluated in a real-life setting in Phnom Penh (Médecins Sans Frontières programme) among severely immuno-compromised patients. METHODS: Factors associated with mortality and immune reconstitution were identified using Cox proportional hazards and logistic regression models, respectively. RESULTS: From July 2001 to April 2005, 1735 patients initiated HAART, with median CD4 cell count of 20 (inter-quartile range, 6-78) cells/microl. Mortality at 2 years increased as the CD4 cell count at HAART initiation decreased, (4.4, 4.5, 7.5 and 24.7% in patients with CD4 cell count > 100, 51-100, 21-50 and < or = 20 cells/microl, respectively; P < 10). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained < or = 200 and < or = 100 cells/microl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/microl at 6 months) was 46.3%; it was lower in patients with previous ART exposure [odds ratio (OR), 0.16; 95% confidence interval (CI), 0.05-0.45] and patients developing a new opportunistic infection/immune reconstitution infection syndromes (OR, 0.71; 95% CI, 0.52-0.98). Similar efficacy was found between the stavudine-lamivudine-nevirapine fixed dose combination and the combination stavudine-lamivudine-efavirenz in terms of mortality and successful immune reconstitution. No surrogate markers for CD4 cell change could be identified among total lymphocyte count, haemoglobin, weight and body mass index. CONCLUSION: Although CD4 cell count-stratified mortality rates were similar to those observed in industrialized countries for patients with CD4 cell count > 50 cells/microl, patients with CD4 cell count < or = 20 cells/microl posed a real challenge to clinicians. Widespread voluntary HIV testing and counselling should be encouraged to allow HAART initiation before the development of severe immuno-suppression

CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

BACKGROUND: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. METHODS AND FINDINGS: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30-0.40) for counts <200 cells/µl, 0.81 (0.71-0.92) for counts 200 to <350 cells/µl, 0.74 (0.66-0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. CONCLUSIONS: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl

Impact Of Hepatitis C Co-Infection On CD4 Cell Count In HIV Infected Subjects

Background: Human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) co-infection is reported to be common among HIV infected subjects due to share routes of transmission. The fact that HCV infection may act as cofactor for HIV disease progression has been suggested.\ud Objective: To determine if HCV and HIV co-infection affect the immunocompetence (CD4) of the infected subjects and response to Highly Active Anti Retroviral therapy.\ud Subjects and methods: Fifty HIV/HCV co-infected and fifty HIV monoinfected adults were retrospectively studied. Their baseline CD4 cell counts were done using Dynal beads technique before commencement of HAART and repeated after six months.\ud Results: The CD4 cell counts of co-infected subjects were lower than the mono-infected subjects. Sixty eight percent of the co-infected subjects had CD4 cell count less than 200cells/uL, and they responded poorly to HAART therapy than the mono-infected subjects (P<0.05). Those with CD4 cell count greater than 200cells/uL responded better to treatment than those with CD4 cell count less than 200cells/uL (P<0.001)\ud Conclusion: HCV/HIV co-infection affects the immunocompetence of the patients and HCV may acts as cofactor for HIV disease progression. It is needful to screen all HIV positive subjects for HCV antibody as this will improve their clinical management and outcome

Differential leukocyte count method for bovine low somatic cell count milk

Whereas many differential leukocyte count methods for high somatic cell count (SCC) milk from mastitic cows are available, only a few have been developed for low SCC milk. We have developed a flow cytometric differential leukocyte count method for low SCC milk. The procedure consists of 1) 1.5 ml of diluted milk sample (30%, vol/vol dilution with PBS), 2) centrifugation, 3) leukocyte labeling with SYTO 13 and 4) flow cytometric analysis. Four major leukocyte populations can be clearly identified in the green fluorescence-side scatter dot plot: lymphocytes and monocytes (LM), polymorphonuclear neutrophils (PMN), mature macrophages (MO), and cells with apoptotic features based on chromatin condensation and nuclear fragmentation. The optimal processing temperature was 20degreesC. Significant differences among samples with similar differential leukocyte counts were found. Storage of milk samples during 2 d at 7degreesC had no effect on differential leukocyte count. Using the new method, differential leukocyte count was performed in low SCC milk samples from cows in early, mid, and late lactation. In accordance with previous studies, PMN and M P percentages were lower and LM percentages were higher in early lactation than in the other stages of lactation. The percentage of cells with apoptotic features was higher in early lactation than in mid and late lactation. In conclusion, a rapid, simple, accurate, and reproducible standard procedure was developed to determine the differential leukocyte count (MO, PMN, LM, and cells with apoptotic features) of bovine low SCC milk

The VIMOS Public Extragalactic Redshift Survey (VIPERS): On the correct recovery of the count-in-cell probability distribution function

We compare three methods to measure the count-in-cell probability density function of galaxies in a spectroscopic redshift survey. From this comparison we found that when the sampling is low (the average number of object per cell is around unity) it is necessary to use a parametric method to model the galaxy distribution. We used a set of mock catalogues of VIPERS, in order to verify if we were able to reconstruct the cell-count probability distribution once the observational strategy is applied. We find that in the simulated catalogues, the probability distribution of galaxies is better represented by a Gamma expansion than a Skewed Log-Normal. Finally, we correct the cell-count probability distribution function from the angular selection effect of the VIMOS instrument and study the redshift and absolute magnitude dependency of the underlying galaxy density function in VIPERS from redshift $0.5$ to $1.1$. We found very weak evolution of the probability density distribution function and that it is well approximated, independently from the chosen tracers, by a Gamma distribution.Comment: 14 pages, 11 figures, 2 table

Quantifying tumour-infiltrating lymphocyte subsets : a practical immuno-histochemical method

Background: Efficient histological quantification of tumour-infiltrating T and B lymphocyte (TIL) subsets in archival tissues would greatly facilitate investigations of the role of TIL in human cancer biology. We sought to develop such a method. Methods: Ten ×40 digital images of 4 μ sections of 16 ductal invasive breast carcinomas immunostained for CD3, CD4, CD8, and CD20 were acquired (a total of 640 images). The number of pixels in each image matching a partition of Lab colour space corresponding to immunostained cells were counted using the ‘Color range’ and ‘Histogram’ tools in Adobe Photoshop 7. These pixel counts were converted to cell counts per mm2 using a calibration factor derived from one, two, three or all 10 images of each case/antibody combination. Results: Variations in the number of labelled pixels per immunostained cell made individual calibration for each case/antibody combination necessary. Calibration based on two fields containing the most labelled pixels gave a cell count minimally higher (+ 5.3%) than the count based on 10-field calibration, with 95% confidence limits − 14.7 to + 25.3%. As TIL density could vary up to 100-fold between cases, this accuracy and precision are acceptable. Conclusion: The methodology described offers sufficient accuracy, precision and efficiency to quantify the density of TIL sub-populations in breast cancer using commonly available software, and could be adapted to batch processing of image files

Characteristics, Determinants, and Clinical Relevance of CD4 T Cell Recovery to <500 Cells/µL in HIV Type 1—Infected Individuals Receiving Potent Antiretroviral Therapy

Background. The CD4 T cell count recovery in human immunodeficiency virus type 1 (HIV-1)—infected individuals receiving potent antiretroviral therapy (ART) shows high variability. We studied the determinants and the clinical relevance of incomplete CD4 T cell restoration. Methods. Longitudinal CD4 T cell count was analyzed in 293 participants of the Swiss HIV Cohort Study who had had a plasma HIV-1 RNA load .05). Older age (adjusted odds ratio [aOR], 1.71 per 10-year increase; 95% confidence interval [CI], 1.21-2.43), lower baseline CD4 T cell count (aOR, 0.37 per 100-cell increase; 95% CI, 0.28-0.49), and longer duration of HIV infection (aOR, 2.39 per 10-year increase; 95% CI, 1.19-4.81) were significantly associated with a CD4 T cell count <500 cells/µL at 5 years. The median increases in CD4 T cell count after 3-6 months of ART were smaller in incomplete responders (P < .001) and predicted, in conjunction with baseline CD4 T cell count and age, incomplete response with 80% sensitivity and 72% specificity. Conclusion. Individuals with incomplete CD4 T cell recovery to <500 cells/µL had more advanced HIV-1 infection at baseline. CD4 T cell changes during the first 3-6 months of ART already reflect the capacity of the immune system to replenish depleted CD4 T lymphocyte