Quantitation of Human Cytomegalovirus DNA from Peripheral Blood Cells of Human Immunodeficiency Virus-Infected Patients Could Predict Cytomegalovirus Retinitis

Rasmussen, Lucy; Morris, Shannon R.; Zipeto, Donato; Fessel, Jeffrey; Wolitz, Richard A.; Dowling, Anna; Tc, Merigan

doi:10.1097/00006982-199515040-00024

Cited by 23 publications

(40 citation statements)

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“…Patients with CD4 ϩ T cell counts !100 cells/mL and detectable levels of HCMV DNA in the blood may be at increased risk of developing HCMV diseases [16,18,[21][22][23]26]. We believe that our method can be used to predict the risk of developing HCMV diseases.…”

Section: Discussionmentioning

confidence: 90%

“…PCR analysis of several blood fractions, including whole blood [18,19], plasma [16,[20][21][22], leukocytes [20,21,[23][24][25], and polymorphonuclear leukocytes [17,19,26], have been used to measure the HCMV DNA loads of patients infected with HIV. However, it has not been known which fraction is the most appropriate material for diagnosis of HCMV disease in patients infected with HIV [26].…”

Section: Discussionmentioning

confidence: 99%

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Diagnosis and Monitoring of Human Cytomegalovirus Diseases in Patients with Human Immunodeficiency Virus Infection by Use of a Real‐Time PCR Assay

et al. 2001

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We used a real-time PCR assay to measure human cytomegalovirus (HCMV) DNA load in whole blood and plasma of 70 patients who were infected with human immunodeficiency virus type 1. Break points of copies/mL in whole blood and copies/mL in plasma were well-correlated with the existence 3 33.0 ϫ 10 1.0 ϫ 10 of definite HCMV disease (sensitivity, 93% and 86%; specificity, 89% and 85%; positive predictive value, 70% and 63%; and negative predictive value, 98% and 95%, respectively). In patients with !50 cells/mL of CD4 + T lymphocytes, positive predictive values increased to 78% and 71%, respectively. The viral loads of all patients who received anti-HCMV therapy declined to copies/mL in parallel with the improvement of 2 р 2.0 ϫ 10 clinical symptoms. These findings show that the HCMV DNA load quantified with our method is a useful tool for diagnosis of HCMV diseases and for monitoring the disease activity in patients infected with HIV-1.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Diagnosis and Monitoring of Human Cytomegalovirus Diseases in Patients with Human Immunodeficiency Virus Infection by Use of a Real‐Time PCR Assay

et al. 2001

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“…However, the concurrent rise and fall in anti-HIV-1 and anti-CMV CD8 ϩ T-cell reactivity during the natural progression of HIV-1 infection was unexpected. It could be a response to an increased burden of CMV antigen with progressive immunosuppression, although major elevations in systemic CMV load only appear late in HIV-1 infection (39). Alternatively, it is possible that the increases in the number of anti-CMV CD8 ϩ T cells are due to a bystander effect where these cells are signaled to expand by cytokines produced in response to other, possibly HIV-1-specific stimuli (48).…”

Section: Cd45romentioning

confidence: 99%

Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8⁺T-Lymphocyte Reactivity during Combination Antiretroviral Therapy in HIV-1-Infected Patients with Advanced Immunodeficiency

Rinaldo

Huang²,

Zheng³

et al. 2000

J Virol

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The long-term efficacy of combination antiretroviral therapy may relate to augmentation of anti-human immunodeficiency virus type 1 (HIV-1) CD8؉ T-cell responses. We found that prolonged treatment of latestage HIV-1-infected patients with a protease inhibitor and two nucleoside reverse transcriptase inhibitors failed to restore sustained, high levels of HIV-1-specific, HLA class I-restricted, cytotoxic-T-lymphocyte precursors and gamma interferon (IFN-␥) production by CD8 ؉ T cells. In some patients, particularly those initiating three-drug combination therapy simultaneously rather than sequentially, there were early, transient increases in the frequency of anti-HIV-1 CD8 ؉ T cells that correlated with decreases in HIV-1 RNA and increases in T-cell counts. In the other patients, HIV-1-specific T-cell functions either failed to increase or declined from baseline during triple-drug therapy, even though some of these patients showed suppression of plasma HIV-1 RNA. These effects of combination therapy were not unique to HIV-1 specific T-cell responses, since similar effects were noted for CD8 ؉ T cells specific for the cytomegalovirus pp65 matrix protein. The level and breadth of CD8؉ cell reactivity to HLA A*02 HIV-1 epitopes, as determined by IFN-␥ production and HLA tetramer staining after combination therapy, were related to the corresponding responses prior to treatment. There was, however, a stable, residual population of potentially immunocompetent HIV-1-specific T cells remaining after therapy, as shown by tetramer staining of CD8 ؉ CD45RO ؉ cells. These results indicate that new strategies will be needed to target residual, immunocompetent HIV-1-specific CD8 ؉ T cells to enhance the effectiveness of antiretroviral therapy in patients with advanced immunodeficiency.

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“…Specifically, cross-sectional and longitudinal studies have indicated the importance of monitoring HCMV load in congenitally infected infants, 19 renal transplant recipients [20][21][22] and HIV infected patients. 23,24 There is, however, a paucity of information on longitudinal fluctuations in cytomegalovirus load in the bone marrow transplant patient. 25 Previous studies in our laboratory have used a quantitative-competitive PCR assay for HCMV to show that HCMV load in the urine of renal transplant recipients and in the blood of liver-transplant patients is a significant risk factor for HCMV disease independent of other risk factors.…”

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confidence: 99%

Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, acute GVHD and CMV disease

Gor

Sabin

Prentice

et al. 1998

Bone Marrow Transplant

170

119

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Summary:Quantitative competitive PCR was used to monitor the quantity of cytomegalovirus (HCMV) in 1647 blood samples from 110 BMT recipients. DNAemia was detected in 49/110 (45%) of the patients, of whom 15/49 experienced HCMV disease. Peak virus load during surveillance was elevated in symptomatic (median 4.5 log 10 genomes/ml) vs asymptomatic patients (median 3.6 log 10 genomes/ml, P = 0.002) and was also significantly elevated in HCMV seropositive recipients of seronegative marrow, (R+D−, median 5.0 log 10 ), compared to those in the R−D− and R+D+ groups (P Ͻ 0.01 and Ͻ0.005). Odds ratios for disease per 0.25 log 10 increase in viral load, recipient seropositivity and aGVHD were 1.43 (P = 0.004), 6.60 (P = 0.05) and 3.17 (P = 0.08), respectively. In multivariate logistic regression analysis only elevated viral load remained a significant risk factor for HCMV disease. The computed disease probability viral load curve showed a rapid increase in disease risk at viral loads between 3.8 and 5.5 log 10 genomes/ml in blood, and odds ratios for disease were determined for different threshold viral loads. These data demonstrate the central role of viral load in the pathogenesis of HCMV in BMT recipients and provide an additional marker for targeting and monitoring therapy.

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Quantitation of Human Cytomegalovirus DNA from Peripheral Blood Cells of Human Immunodeficiency Virus-Infected Patients Could Predict Cytomegalovirus Retinitis

Cited by 23 publications

References 0 publications

Diagnosis and Monitoring of Human Cytomegalovirus Diseases in Patients with Human Immunodeficiency Virus Infection by Use of a Real‐Time PCR Assay

Diagnosis and Monitoring of Human Cytomegalovirus Diseases in Patients with Human Immunodeficiency Virus Infection by Use of a Real‐Time PCR Assay

Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8⁺T-Lymphocyte Reactivity during Combination Antiretroviral Therapy in HIV-1-Infected Patients with Advanced Immunodeficiency

Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, acute GVHD and CMV disease

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Quantitation of Human Cytomegalovirus DNA from Peripheral Blood Cells of Human Immunodeficiency Virus-Infected Patients Could Predict Cytomegalovirus Retinitis

Cited by 23 publications

References 0 publications

Diagnosis and Monitoring of Human Cytomegalovirus Diseases in Patients with Human Immunodeficiency Virus Infection by Use of a Real‐Time PCR Assay

Diagnosis and Monitoring of Human Cytomegalovirus Diseases in Patients with Human Immunodeficiency Virus Infection by Use of a Real‐Time PCR Assay

Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8+T-Lymphocyte Reactivity during Combination Antiretroviral Therapy in HIV-1-Infected Patients with Advanced Immunodeficiency

Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, acute GVHD and CMV disease

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Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8⁺T-Lymphocyte Reactivity during Combination Antiretroviral Therapy in HIV-1-Infected Patients with Advanced Immunodeficiency