Viral DNA and mRNA expression correlate with the stage of human immunodeficiency virus (HIV) type 1 infection in humans: evidence for viral replication in all stages of HIV disease

Michael, N L; Vahey, Maryanne; Burke, Donald S.; Redfield, Robert

doi:10.1128/jvi.66.1.310-316.1992

Cited by 161 publications

(54 citation statements)

References 19 publications

(22 reference statements)

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“…Viral burden was measured in serum samples from the early-stage HIV-infected patients by quantitation of HIV gag RNA amplified by reverse transcriptase linked PCR using a modification of the method of Michael et al (43,60).…”

Section: Viral Burdenmentioning

confidence: 99%

Measurement of CD69 induction in the assessment of immune function in asymptomatic HIV-infected individuals

et al. 1997

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Peripheral blood mononuclear cells from many asymptomatic HIV‐infected patients exhibit defects in cytokine production and impaired proliferative responses in vitro but the mechanisms underlying this subclinical immune deficiency are controversial. To determine whether abnormalities in the earliest events following receptor engagement may help to explain the in vitro immune dysfunction, we measured the inducibility of the early activation marker CD69 in T cells from asymptomatic HIV‐infected individuals in response to stimulation with anti‐CD2 or anti‐CD3 mAb. In a whole blood assay, we found that induction of CD69 was markedly impaired in CD4+ T cells from later‐stage HIV‐infected patients (CD4 counts 200–400/mm3) compared to uninfected controls. Among early stage patients (CD4 > 400/mm3), a subset (29%) had impaired CD69 induction. CD69 responses were equally depressed after stimulation through the CD3 or CD2 receptor pathways. Survey of a panel of immunophenotypic markers and propensity for apoptosis demonstrated a significant association between depressed induction of CD69 and decreased percentages of CD4+CD26+ and CD4+CD95+ cells but no association with the level of apoptosis. These data indicate that defects in T lymphocyte activation through CD3 and CD2 can be measured within hours of receptor stimulation in asymptomatic HIV‐infected individuals and might be useful to monitor as an indicator of immune function in these patients. Cytometry 30:1–9, 1997. © 1997 Wiley‐Liss, Inc.

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Section: Viral Burdenmentioning

confidence: 99%

Measurement of CD69 induction in the assessment of immune function in asymptomatic HIV-infected individuals

et al. 1997

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“…Initially, most of the HIV-1 RNA quantification assays were performed with in-house polymerase chain reaction (PCR)based methods [1][2][3][4][5]. In general, these methods were laborious and lacked proper quality assurance and quality control.…”

Section: Introductionmentioning

confidence: 99%

Blinded, multicenter quality control study for the quantification of human immunodeficiency virus type 1 RNA in plasma by the Belgian AIDS reference laboratories

Muyldermans

Debaisieux

Fransen

et al. 2000

Clinical Microbiology and Infection

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Since interlaboratory variability never reached 0.5 log10 copies/mL and each of the laboratories was able to detect four-fold differences in plasma HIV-1 RNA levels, the Amplicor assay can be used in multicenter studies without a centralized analysis of samples. Furthermore, this well-characterized proficiency panel of spiked plasma samples could be used as a standard in the study of interassay comparisons.

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“…Studies reported in the last 3 years [24][25][26] have shown that in most asymptomatic patients there is no real viral latency, but that viral turnover is continuous throughout the course of infection [27,28]. The high error rate of the reverse transcriptase enzyme in the synthesis of the cDNA could be responsible for the generation of high genetic variability and the appearance of mutations that give rise to viruses with reduced sensitivity to ZDV.…”

Section: Discussionmentioning

confidence: 99%

Rate of development of mutation at codon 215 of HIV‐1 reverse transcriptase and its predictive factors at the time of initiation of zidovudine therapy

Leal¹,

Rey

Torres

et al. 1996

Eur J Clin Investigation

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The objective of the present study was to determine the rate of development of mutation at codon 215 of HIV-1 reverse transcriptase and to identify baseline characteristics associated with this mutation following initiation of zidovudine therapy. To achieve such a purpose, 80 HIV-1-infected patients starting zidovudine therapy have been submitted to clinical, immunological and virological monitoring at entry and every 12 weeks. The critical end point of the study was time to development of mutation at codon 215. The association of key baseline characteristics (CD4+ counts, clinical stage, HIV-1 p24 antigen, CD8+ counts, serum beta 2-microglobulin and virus phenotype) with the mutation at codon 215 was also investigated. A total of 38 subjects (48%) developed mutation at codon 215 during follow-up. The estimated Kaplan-Meier probability of remaining with wild genotype at 24, 48 and 96 weeks (96% CI) was 0.82 (0.73-0.90), 0.70 (0.60-0.80) and 0.53 (0.41-0.66) respectively. Univariate analysis showed that time to the development of mutation at codon 215 was positively associated with baseline p24 positivity, C clinical stage, low CD4+ count and high beta 2-microglobulin level. Only p24 antigenaemia and CD4+ count remained significantly independent predictive factors for the development of mutation at codon 215 in the Cox proportional hazard stepwise regression analysis [risk ratio (95% CI): 3.67 (1.75-7.70), P = 0.0007; 2.89 (1.17-6.72), P = 0.0073 respectively]. Thus, a continuous emergence of mutation at codon 215 was observed and HIV-1 p24 antigenaemia should be considered an independent predictor for faster development of zidovudine resistance.

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Viral DNA and mRNA expression correlate with the stage of human immunodeficiency virus (HIV) type 1 infection in humans: evidence for viral replication in all stages of HIV disease

Cited by 161 publications

References 19 publications

Measurement of CD69 induction in the assessment of immune function in asymptomatic HIV-infected individuals

Measurement of CD69 induction in the assessment of immune function in asymptomatic HIV-infected individuals

Blinded, multicenter quality control study for the quantification of human immunodeficiency virus type 1 RNA in plasma by the Belgian AIDS reference laboratories

Rate of development of mutation at codon 215 of HIV‐1 reverse transcriptase and its predictive factors at the time of initiation of zidovudine therapy

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