First report of human immunodeficiency virus transmission via an RNA‐screened blood donation

Delwart, Eric; Kalmin, N. D.; Jones, T. Stephen; Ladd, Daniel; Foley, Brian; Tobler, Leslie H.; Tsui, Rose; Busch, Michael P.

doi:10.1111/j.0042-9007.2004.00416.x

Cited by 93 publications

(83 citation statements)

References 15 publications

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“…Prior to the use of MP-NAT, HIV was transmitted via window-stage donations at significant rates (5,22). Although very rarely, HIV has been transmitted by window period blood donations that were determined to have Յ150 vRNA copies/ml even after the adoption of MP-NAT (9,11,35,36). The occurrence of rare HIV transmission events by donations with no evidence of anti-HIV antibodies and very low vRNA levels is consistent with our findings.…”

Section: Discussionsupporting

confidence: 88%

“…For practical and economic reasons, NAT is often performed using minipools (MP), consisting of pooled specimens derived from different donors, with follow-up testing of individual donors from positive MP. Even after the implementation of NAT, HIV has been transmitted by transfusions of blood obtained from donations that were determined to have viral loads of fewer than 100 to 500 vRNA copies/ml, the sensitivity limit of MP-NAT assays (9). These MP-NAT breakthrough transmission cases have led to recommendations to move to individual-donation NAT (sensitivity limits, 5 to 30 vRNA copies/ml) and/or to implement pathogen reduction and/or inactivation procedures to eliminate the infectivity of low-level viremic units missed by NAT and serological screening.…”

Section: Cd4mentioning

confidence: 99%

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High Specific Infectivity of Plasma Virus from the Pre-Ramp-Up and Ramp-Up Stages of Acute Simian Immunodeficiency Virus Infection

Zhong

Stone

Piatak

et al. 2009

J Virol

116

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To define the ratio of simian immunodeficiency virus (SIV) RNA molecules to infectious virions in plasma, a ramp-up-stage plasma pool was made from the earliest viral RNA (vRNA)-positive plasma samples (collected approximately 7 days after inoculation) from seven macaques, and a set-point-stage plasma pool was made from plasma samples collected 10 to 16 weeks after peak viremia from seven macaques; vRNA levels in these plasma pools were determined, and serial 10-fold dilutions containing 1 to 1,500 vRNA copies/ml were made. Intravenous (i.v.) inoculation of a 1-ml aliquot of diluted ramp-up-stage plasma containing 20 vRNA copies infected 2 of 2 rhesus macaques, while for the set-point-stage plasma, i.v. inoculation with 1,500 vRNA copies was needed to transmit infection. Further, when the heat-inactivated set-point-stage plasma pool was mixed with ramp-up-stage virions, infection of inoculated macaques was blocked. Notably, 2 of 2 animals inoculated with 85 ml of a pre-ramp-up plasma pool containing <3 SIV RNA copies/ml developed SIV infections characterized by high levels of viral replication, demonstrating that "vRNA-negative" plasma collected from macaques in the pre-ramp-up stage is infectious. Furthermore, there is a high ratio of infectious virions to total virions in ramp-up-stage plasma (between 1:1 and 1:10) and a lower ratio in set-point-stage plasma (between 1:75 and 1:750). Heat-inactivated chronic-stage plasma can "neutralize" the highly infectious ramp-up-stage virions. These findings have implications for the understanding of the natural history of SIV and human immunodeficiency virus infection and transmission.

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Section: Discussionsupporting

confidence: 88%

Section: Cd4mentioning

confidence: 99%

High Specific Infectivity of Plasma Virus from the Pre-Ramp-Up and Ramp-Up Stages of Acute Simian Immunodeficiency Virus Infection

Zhong

Stone

Piatak

et al. 2009

J Virol

116

View full text Add to dashboard Cite

show abstract

“…However, minipool NAT screening used in this case was clearly inefficient to detect one infectious unit of red blood cells from a donor during the pre-seroconversion window. To our knowledge, at least one other case of HIV transmission with units of red blood cells collected from a donor during the infectious pre-seroconversion period despite minipool NAT screening has been reported [Delwart et al, 2002]. Retrospective study of one other case of HIV transmission by blood components during the pre-seroconversion period showed that the viral load in the implicated donation was estimated to be less than 40 copies/ml of plasma [Ling et al, 2000].…”

Section: Discussionmentioning

confidence: 91%

Failure and success of HIV tests for the prevention of HIV‐1 transmission by blood and tissue donations

Najioullah

Barlet

Renaudier

et al. 2004

Journal of Medical Virology

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French blood banks recently implemented nucleic acid testing (NAT) of all blood donations to reduce the risk of HIV transmission during the pre-seroconversion period. For tissue donation, HIV infection screening relies on HIV p24 antigen and anti-HIV-1 and 2 antibody detection. In this report, two related cases of infectious donations are described from a cornea donor during the preseroconversion window who was infected by an HIV antibody and NAT negative blood donor. After investigation, the blood donor was found to be herself in the preseroconversion window. Two months after donation, she was found to be HIV positive. The residual risk of HIV infectious blood donations since NAT has been introduced is estimated to be lower than one out of 2.5 millions. Individual NAT instead of minipool testing would not increase significantly the blood transfusion safety. In contrast, introduction of NAT should be considered to increase tissue donation safety as soon as such screening will be possible technically.

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“…Stochastically positive TMA results have been previously reported for samples with very low HCV and human immunodeficiency virus viral loads. [28][29][30] Sixty of 67 initially aviremic seropositive donors therefore remained aviremic over an average of 2.5 years, and of the 7 donors that became viremic, only 1 donor had a viral load Ͼ 100 RNA copies/mL. These 7 seropositive subjects may reflect low-level plasma viral load fluctuations near the limit of detection or, in the case of the high viral load follow-up sample, possible reinfection with another HCV strain.…”

Section: Resultsmentioning

confidence: 99%

Clearance of hepatitis C virus RNA from the peripheral blood mononuclear cells of blood donors who spontaneously or therapeutically control their plasma viremia

et al. 2008

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We determined whether hepatitis C virus (HCV) RNA could be detected associated with peripheral blood mononuclear cells (PBMC) of seropositive blood donors who had spontaneously or therapeutically cleared their plasma viremia. Blood donor plasma viremia status was first determined with a highly sensitive transcription-mediated amplification (TMA) test performed in duplicate assays. PBMC from 69 aviremic and 56 viremic blood donors were then analyzed for the presence of HCV RNA with TMA adapted to detect viral RNA in PBMC and with a reverse transcription-nested polymerase chain reaction assay. PBMCassociated HCV RNA was detected in none of the 69 aviremic donors, including all 6 subjects with a sustained viral response following antiviral therapy. PBMC-associated HCV RNA was detected in 43 of the 56 viremic donors. The 13 viremic donors with no detectable PBMCassociated HCV RNA all had very low viral loads (6 positive only in 1 of 2 duplicate plasma TMA assays, 6 with viral loads below 100 HCV RNA copies/mL, and 1 with a viremia of 2700 HCV RNA copies/mL). The absence of detectable PBMC HCV RNA detection in all 69 aviremic donors reported here contrasts with prior studies, possibly as a result of the higher sensitivity of the TMA assay used to test for plasma viremia. Conclusion: Our results indicate that PBMC are unlikely to serve as a long-lived reservoir of HCV in aviremic subjects.

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First report of human immunodeficiency virus transmission via an RNA‐screened blood donation

Abstract: Even following the introduction of MP-NAT, a preseroconversion donation with a viral load of

Cited by 93 publications

References 15 publications

High Specific Infectivity of Plasma Virus from the Pre-Ramp-Up and Ramp-Up Stages of Acute Simian Immunodeficiency Virus Infection

High Specific Infectivity of Plasma Virus from the Pre-Ramp-Up and Ramp-Up Stages of Acute Simian Immunodeficiency Virus Infection

Failure and success of HIV tests for the prevention of HIV‐1 transmission by blood and tissue donations

Clearance of hepatitis C virus RNA from the peripheral blood mononuclear cells of blood donors who spontaneously or therapeutically control their plasma viremia

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