Steven Kleinman

The natural history of transfusion-associated infection with human immunodeficiency virus. Factors influencing the rate of progression to disease

Patients infected by the human immunodeficiency virus (HIV) as a result of blood transfusions are unique in that their dates of infection are well defined and their medical conditions before infection are known. To characterize the natural history of transfusion-associated HIV infection, we studied 694 recipients of blood from 112 donors in whom AIDS later developed and from 31 donors later found to be positive for HIV antibody. Of the recipients tested, 85 were seronegative, 116 were seropositive, and 19 had AIDS. Of 101 HIV-seropositive recipients followed for a median of 55 months after infection, 54 had Centers for Disease Control Class IV disease, including 43 with AIDS. Life-table analysis suggested that AIDS will develop in 49 percent of infected recipients (95 percent confidence limits, 36 to 62 percent) within seven years after infection. As compared with recipients without AIDS, the 43 recipients with AIDS had received more transfusions at the time of infection (median, 21 vs. 7; P = 0.01). HIV-infected blood donors in whom AIDS developed were grouped according to whether AIDS developed within 29 months (the median) after donation (Group 1) or 29 or more months after donation (Group 2). As compared with the 31 recipients of blood from Group 2 blood donors, the 31 recipients of blood from Group 1 donors were more likely to have AIDS four years after infection (49 percent vs. 4 percent; P = 0.005) and illnesses resembling acute retroviral syndrome (14 of 24 vs. 5 of 22; P = 0.03). We conclude that most recipients of HIV-infected blood become seropositive, that AIDS develops in about half these recipients within seven years, and that the risk may be higher when AIDS develops in the blood donor soon after donation.

Duration of time from onset of human immunodeficiency virus type 1 infectiousness to development of detectable antibody

Background: For persons newly infected with the human immunodeficiency virus type 1 (HIV‐1), the time from the onset of infectivity to the development of detectable HIV‐1 antibody is unknown. Persons who donate blood during this period account for nearly all instances of HIV‐1 transmission from HIV‐1 antibody‐screened blood transfusions.

Follow‐up testing and notification of anti‐HIV Western blot atypical (indeterminant) donors

ABSTRACT: We conducted anti‐HIV testing on follow‐up samples obtained at a mean interval of 20 weeks from 150 blood donors who had previously tested anti‐HIV ELISA positive and Western blot atypical. Of 93 donors who demonstrated reactivity to HIV core protein p24, 4 progressed to positive Western blots. Most of the remaining donors showed a persistent p24 reactivity on Western blot and had no risk factors for HIV infection. Immunofluorescence testing of the initial sample from 93 donors could not definitively separate seroconverters from those with persistent p24 reactivity. Of 57 donors with p18 reactivity, none were positive on follow‐up anti‐HIV testing. Our findings suggest policies and strategies for notifying donors of atypical anti‐HIV Western blot results.

Impact of changes in viral marker screening assays

BACKGROUND : Monitoring the performance of routinely used infectious disease serologic tests is necessary to evaluate their effectiveness in identifying true‐positive units and erroneously disqualifying safe blood donors.

HIV seroconverting donors delay their return: screening test implications

BACKGROUND: The yield of HIV p24 antigen testing implemented in March 1996 has been lower than projected. One possible explanation is that HIV seroconverting donors delay their return because of the recent practice of risk behaviors and/or signs and symptoms associated with primary infection.

Detection of West Nile virus RNA and antibody in frozen plasma components from a voluntary market withdrawal during the 2002 peak epidemic.

BACKGROUND: The US West Nile virus (WNV) epidemic in the summer and fall of 2002 included the first documented cases of transfusion‐transmitted WNV infection. In December 2002, the FDA supported a voluntary market withdrawal by the blood banking community of frozen blood components collected in WNV high‐activity areas. At the time, the prevalence of viremia and serologic markers for WNV in the blood supply was undefined.

In vitro activation of T lymphocytes from human immunodeficiency virus (HIV)-seropositive blood donors. I: Soluble interleukin 2 receptor (IL2R) production parallels cellular IL2R expression and DNA synthesis

We investigated the relationship of soluble interleukin 2 receptor (sIL2R) production to cellular IL2R expression and DNA synthesis by mitogen-stimulated mononuclear cells from blood donors seropositive for human immunodeficiency virus (HIV). SIL2R was measured using an enzyme-linked immunosorbent assay which employed 2 anti-IL2R monoclonal antibodies recognizing distinct IL2R epitopes. Decreased phytohemagglutinin-induced DNA synthesis and cellular IL2R expression were accompanied by decreased levels of sIL2R in cell culture supernatants. Similar findings were observed for pokeweed mitogen-induced responses. There was no detectable spontaneous secretion of sIL2R into culture supernatants by unstimulated mononuclear cells from either HIV-seropositive or control seronegative donors. These findings indicate that thein vitro T-cell activation defects which characterize HIV infection include decreased sIL2R production, as well as decreased cellular IL2R expression and DNA synthesis. Further, they show that assessment of supernatant sIL2R levels can be used as a valid, reliable assay for T-cell activation.

Comparison of demographic and donation profiles and transfusion-transmissible disease markers and risk rates in previously transfused and nontransfused blood donors

BACKGROUND:  Increasing concern about transfusion transmission of variant Creutzfeldt‐Jakob disease has resulted in indefinite deferral of transfused donors in France and the UK. Little is known, however, about the impact of indefinite deferral of transfused donors on blood safety and availability in the US.

Relative specificity of enzyme‐linked immunosorbent assays for antibodies to human T‐cell lymphotrophic virus, type III, and their relationship to Western blotting

Abstract: A population of 73 donor samples was assembled on the basis of reactive results in routine screening with three different licensed human T‐lymphotrophic virus type III (HTLV‐III) antibody enzyme‐linked immunosorbent assay (ELISA) procedures. The samples were retested by a number of licensed and developmental tests and by Western blot analysis. Our data indicate that nonspecific results are generated by ELISA tests and that many of these reactions appear to be directed against the cell substrate used to grow the virus. These findings suggest that combinations of currently licensed ELISA tests, based upon HTLV‐III grown in H‐9 cells, cannot be used to confirm the specificity of reactive samples.

Duration of Dengue Viremia in Blood Donors and Relationships Between Donor Viremia, Infection Incidence and Clinical Case Reports During a Large Epidemic

BACKGROUND Dengue viruses (DENV-1-4) pose a transfusion-transmission risk. This study estimated the dengue RNA detection period in asymptomatic blood donors and relationships between donor viremia and dengue incidence during a large epidemic. METHODS Donor samples from the 2012 dengue transmission season in Rio de Janeiro, Brazil, were tested for DENV RNA by a transcription-mediated amplification (TMA) assay, with DENV types and viral loads determined by polymerase chain reaction. Samples collected during the first and last weeks of enrollment were tested for DENV immunoglobulin (Ig) G and IgM to estimate incidence during the study period, which was analyzed relative to nucleic acid amplification technology (NAT) yield to estimate the duration of NAT-detectable viremia and compared with reported clinical dengue cases in Rio. RESULTS Samples from 16 241 donations were tested; 87 (0.54%) were confirmed as DENV-4 RNA positive. Dengue IgM-positive/IgG-positive reactivity increased from 2.8% to 8.8%, indicating a 6.2% incidence (95% confidence interval [CI], 3.2%-9.1%) during the study period. Based on these data, we estimated a 9.1-day period (95% CI, 4.4-13.9 days) of RNA detectable with TMA. With 100 475 reported cases of clinical dengue, 1 RNA-positive donation was identified per 800 DENV cases. CONCLUSIONS These parameters allow projections of dengue incidence from donor NAT yield data and vice versa, and suggest that viremic donations will be rare relative to clinical disease cases.