Monitoring the activity of antiviral therapy for HIV infection using a polymerase chain reaction method coupled with reverse transcription

Kojima, Eiji; Shirasaka, Takuma; Anderson, Barry; Chokekijchai, Sudhichai; Sei, Shizuko; Yarchoan, Robert; Mitsuya, Hiroaki

doi:10.1097/00002030-199311002-00019

Cited by 15 publications

(5 citation statements)

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“…Our data provide strong epidemiologic evidence that drugs or biologic agents that can prevent high viral loads early after HCT may reasonably be expected to have an impact on mortality, even if they cannot completely prevent viremia or the initiation of preemptive antiviral therapy. In 1993, Kojima and colleagues predicted that using PCR to measure HIV-1 RNA copy number in the plasma of infected patients was “likely to be built into every clinical trial of anti-HIV-1 therapy in the near future.” 20 It has been twenty years since the landmark papers correlating HIV-1 viral load with disease progression were published 21 – 23 changing the regulatory environment to allow the use of a virologic endpoint, and thereby fostering the development of dozens of new antiretroviral agents.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study

Green

Leisenring

Xie

et al. 2016

The Lancet Haematology

344

289

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SummaryBackgroundWhile CMV viral load (CMV-VL) is commonly used to guide preemptive therapy in the post-transplant setting, there is little data correlating viremia with clinical endpoints. We therefore investigated the association of CMV-VL with mortality in the first year after hematopoietic cell transplantation (HCT).MethodsThis cohort study included patients who received an allogeneic HCT between 01 January 2007 and 28 February 2013, were CMV seropositive or had a seropositive donor, and underwent weekly plasma CMV monitoring by PCR through day 100 post-transplant. Cox proportional hazards models were used to estimate the association of CMV-VL at different thresholds with overall by 1 year post-transplant, adjusting for the use of preemptive therapy and other factors such as neutropenia, and graft-versus-host disease. Secondary endpoints were non-relapse mortality and CMV end organ disease by 1 year post-transplant.FindingsAmong 926 patients, the cumulative overall mortality was 30·0% (95% CI 26·9–33·0) by 1 year. CMV-VL of ≥250 IU/ml was associated with increased risk of early (day 0–60 post-transplant) death (adjusted HR 18·1, 95% CI 8·8–37·4). The risk was attenuated after day 60 (adjusted HR 1·8, 95% CI 1·4–2·4). Similar associations were observed for higher CMV-VL thresholds. CMV-VL was also associated with increased risk of non-relapse mortality and demonstrated a dose-response relationship. The adjusted HR (95% CI) for CMV-VL of any positive CMV-VL below 500, 501–1000, and >1000 IU/ml were 1·4 (0·9–2·1), 2·6 (1·3–4·9), and 5·0 (3·1–8·1), respectively.InterpretationCMV viremia is associated with increased risk of overall and non-relapse mortality in the first year after HCT, independent of the use of preemptive therapy and with evidence of a postitive dose-response relationship. These data establish the suitability of viral load as a surrogate clinical endpoint for clinical trials for CMV vaccines, biologics, and drugs.FundingMerck & Co., Inc., National Institute of Health (K23-AI097234, K24HL093294, HL088021, CA78902, CA18029, HL122173)

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Section: Discussionmentioning

confidence: 99%

Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study

Green

Leisenring

Xie

et al. 2016

The Lancet Haematology

344

289

View full text Add to dashboard Cite

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“…Quantitative analyses of viral load in vivo have been shown to be useful in the evaluation of several human viral infections (4,5,14,16,21,28,36). QC-PCR has been tested as a means of evaluating antiviral therapy and assessing disease progression, and for some infections, the quantitation of viral DNA can be necessary to distinguish between dormant and active infection (4,5,14,16,21,30). This is not the case for HSV infection of the central nervous system (CNS), in which the qualitative detection of the HSV genome in CSF samples has a high correlation with active disease and is presently the best noninvasive method for the diagnosis of HSE.…”

Section: Discussionmentioning

confidence: 99%

Application of Competitive PCR to Cerebrospinal Fluid Samples from Patients with Herpes Simplex Encephalitis

Domingues¹,

et al. 1998

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The purpose of the present study was to determine if the quantity of herpes simplex virus (HSV) DNA in the cerebrospinal fluid (CSF) of patients with herpes encephalitis would be useful in establishing the prognosis of the disease and to determine the effect of antiviral therapy on the clearance of viral DNA from the CSF. Quantitation of HSV DNA was done by constructing an internal standard (IS) from the glycoprotein B amplicon which had a 25-bp deletion between primer annealing sites. Each CSF specimen was coamplified with the IS and the ratio of the amount of HSV/amount of IS was compared to the ratios on a standard curve constructed with the same IS plus known amounts of HSV DNA. CSF specimens were available from 16 patients who were treated with intravenous acyclovir, and the amount of HSV DNA ranged from <25 to 18,000 copies per μl in CSF obtained before or within 4 days of the initiation of acyclovir therapy. Patients with >100 copies of HSV DNA per μl were older, were found by computed tomography to have lesions, and had poorer outcomes than patients with <100 copies. Follow-up CSF specimens were available from seven patients. In six of these seven patients, the HSV DNA levels decreased during therapy. One patient had a twofold increase in HSV DNA levels after 1 week of therapy and died on day 8. The application of this assay may be helpful in establishing the prognosis and in the monitoring of patients with herpes simplex encephalitis.

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“…A relationship between HIV-1 RNA levels in plasma and clinical progression has been found by these assays (12,30,33,35). Moreover, several investigators reported a decrease in plasma RNA levels in patients starting antiretroviral therapies, suggesting that this viral surrogate marker may be useful for predicting the clinical response to therapy, although it is not yet known how the results obtained by these assays correlate with the clinical outcome (3,7,11,13,17,22,24,25,40).…”

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confidence: 99%

Comparative evaluation of NASBA HIV-1 RNA QT, AMPLICOR-HIV monitor, and QUANTIPLEX HIV RNA assay, three methods for quantification of human immunodeficiency virus type 1 RNA in plasma

et al. 1996

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Three commercial assays for quantifying plasma human immunodeficiency virus type 1 (HIV-1) RNA were evaluated. The assays differed in their sample volumes, the means of preparing samples, and methods of amplification and detection. Plasma samples were obtained from 36 HIV-1-infected patients representing all stages of HIV-1 infection and were analyzed as coded specimens. Measurement of HIV-1 RNA baseline levels revealed no significant difference in sensitivity between the three assays. The assays were also applied to the quantitation of HIV-1 RNA levels in the plasma of patients who were changing their antiretroviral therapy. The changes measured in HIV-1 RNA levels in plasma in response to therapy were comparable by the three assays. No close correlation was found between the amount of HIV-1 RNA and the CD4 T-cell count;HIV-1 RNA assays were more sensitive than p24 antigen assays as an indicator of plasma viremia. Overall, the study demonstrates that all three quantitative assays for HIV-1 RNA can be used to measure the HIV-1 RNA copy number representing the HIV-1 viremia status in patients with HIV-1 infection. Since this copy number is likely to be useful in monitoring the effectiveness of antiviral therapy, these quantitative assays for HIV-1 RNA are ready to be built into clinical trials.

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Monitoring the activity of antiviral therapy for HIV infection using a polymerase chain reaction method coupled with reverse transcription

Cited by 15 publications

References 0 publications

Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study

Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study

Application of Competitive PCR to Cerebrospinal Fluid Samples from Patients with Herpes Simplex Encephalitis

Comparative evaluation of NASBA HIV-1 RNA QT, AMPLICOR-HIV monitor, and QUANTIPLEX HIV RNA assay, three methods for quantification of human immunodeficiency virus type 1 RNA in plasma

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