Mortality and morbidity related to AIDS have decreased among HIV-infected patients taking highly active anti-retroviral therapy (HAART), but previous studies may have been confounded by other changes ...in treatment.
To assess the benefit of HAART in patients with advanced AIDS and anemia.
Prospective, multicenter cohort study.
The Viral Activation Transfusion Study (VATS), with enrollment from August 1995 through July 1998 and follow-up through June 1999.
528 HIV-infected patients with cytomegalovirus (CMV) seropositivity or disease who were receiving a first red blood cell transfusion for anemia.
In a person-year analysis of follow-up before and after initiation of HAART, Poisson regression was used to calculate crude rate ratios and rate ratios adjusted for CD4 count, HIV RNA level, calendar period, time on study, sex, ethnicity, and injection drug use.
At baseline, patients had a median CD4(+) lymphocyte count of 0.015 x 10(9) cell/L, median plasma HIV RNA level of 4.8 log(10) copies/mL, and median hemoglobin concentration of 73 g/L. Use of HAART increased from 1% of active patients in January 1996 to 79% of active patients in January 1999. The crude death rate was 0.24 event/person-year among patients taking HAART and 0.88 event/person-year among those not taking HAART (rate ratio, 0.26; adjusted rate ratio, 0.38; P < 0.001 for both comparisons). Rates of non-CMV disease were 0.15 event/ person-year after HAART and 0.45 event/person-year before HAART (crude rate ratio, 0.34 P < 0.001; adjusted rate ratio, 0.66 P < 0.05). Rates of CMV disease were 0.10 event/person-year after HAART and 0.25 before HAART (crude rate ratio, 0.42 P < 0.01; adjusted rate ratio, 1.01 P > 0.2). Results were similar in patients with baseline CD4(+) lymphocyte counts less than 0.010 x 10(9) cells/L.
The data support an independent reduction in mortality and opportunistic events attributable to HAART, even in patients with very advanced HIV disease. However, patients with CMV infection or disease may not have a reduction in new CMV events due to HAART.
BACKGROUND: As part of assessing the possibility of transfusion transmission of human herpesvirus 8 (HHV‐8 or Kaposi's sarcoma‐associated herpesvirus), HHV‐8 seroprevalence was estimated among US ...blood donors, the performance of HHV‐8 serologic tests was compared, and the presence of HHV‐8 DNA was tested for in donated blood.
STUDY DESIGN AND METHODS: Replicate panels of 1040 plasma specimens prepared from 1000 US blood donors (collected in 1994 and 1995) and 21 Kaposi's sarcoma patients were tested for antibodies to HHV‐8 in six laboratories. HHV‐8 PCR was performed on blood samples from 138 donors, including all 33 who tested seropositive in at least two laboratories and 22 who tested positive in at least one.
RESULTS: The estimated HHV‐8 seroprevalence among US blood donors was 3.5 percent (95% CI, 1.2%‐9.8%) by a conditional dependence latent‐class model, 3.0 percent (95% CI, 2.0%‐4.6%) by a conditional independence latent‐class model, and 3.3 percent (95% CI, 2.3%‐4.6%) by use of a consensus‐derived gold standard (specimens positive in two or more laboratories); the conditional dependence model best fit the data. In this model, laboratory specificities ranged from 96.6 to 100 percent. Sensitivities ranged widely, but with overlapping 95 percent CIs. HHV‐8 DNA was detected in blood from none of 138 donors evaluated.
CONCLUSIONS: Medical and behavioral screening does not eliminate HHV‐8‐seropositive persons from the US blood donor pool, but no viral DNA was found in donor blood. Further studies of much larger numbers of seropositive individuals will be required to more completely assess the rate of viremia and possibility of HHV‐8 transfusion transmission. Current data do not indicate a need to screen US blood donors for HHV‐8.
An ELISA was developed for detection of antibodies to GB virus C (GBV-C)using a recombinant E2 protein expressed in CHO cells. Seroconversion to anti-E2 positivity was noted among several persons ...infected with GBV-C RNA-positive blood through transfusion. Of6 blood recipients infected by GBV-C RNA-positive donors, 4 (67%)became anti-E2 positive and cleared their viremia. Thus, anti-E2 seroconversion is associated with viral clearance. The prevalence of antibodies to E2 was relatively low (3.0%–8.1%) in volunteer blood donors but was higher in several other groups, including plasmapheresis donors (34.0%), intravenous drug users (85.2%),and West African subjects (13.3%), all of whom tested negative by GBV-C reverse-transcription polymerase chain reaction (RT-PCR). These data demonstrate that testing for anti-E2 should greatly extend the ability of RTPCR to define the epidemiologyand clinical significance of GBV-C.
Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus (HIV) hyperimmune immunoglobulin (HIVIG) infusions administered monthly ...during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin (IVIG) without HIV antibody. Subjects had baseline CD4 cell counts ⩽500/μL (22% had counts <200/μL) and required zidovudine for maternal health (24% received zidovudine before pregnancy). Transmission was associated with lower maternal baseline CD4 cell count (odds ratio, 1.58 per 100-cell decrement; P = .005; 10.0% vs. 3.6% transmission for count <200 vs. ⩾200/μL) but not with time of zidovudine initiation (5.6% vs. 4.8% if started before vs. during pregnancy; P = .75). The Kaplan-Meier transmission rate for HIVIG recipients was 4.1% (95% confidence interval, 1.5%–6.7%) and for IVIG recipients was 6.0% (2.8%–9.1%) (P = .36). The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission.
Injection drug use (IDU) is a known risk factor for hepatitis C virus (HCV) infection, but the strength of other parenteral and sexual risk factors is unclear. In 1997, we performed a case‐control ...study of 2,316 HCV‐seropositive blood donors and 2,316 seronegative donors matched on age, sex, race/ethnicity, blood center, and first‐time versus repeat‐donor status. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Questionnaires were returned by 758 (33%) HCV+ and 1,039 (45%) control subjects (P = .001). The final multivariate model included only the following independent HCV risk factors: IDU (OR = 49.6; 95% CI: 20.3‐121.1), blood transfusion in non‐IDU (OR = 10.9; 95% CI: 6.5‐18.2), sex with an IDU (OR = 6.3; 95% CI: 3.3‐12.0), having been in jail more than 3 days (OR = 2.9; 95% CI: 1.3‐6.6), religious scarification (OR = 2.8; 95% CI: 1.2‐7.0), having been stuck or cut with a bloody object (OR = 2.1; 95% CI: 1.1‐4.1), pierced ears or body parts (OR = 2.0; 95% CI: 1.1‐3.7), and immunoglobulin injection (OR = 1.6; 95% CI: 1.0‐2.6). Although drug inhalation and a high number of lifetime sex partners were significantly more common among HCV seropositives, they were not associated with HCV after controlling for IDU and other risk factors. IDU, blood transfusion among non‐IDU, and sex with an IDU are strong risk factors for HCV among United States blood donors. Weaker associations with incarceration, religious scarification, being stuck or cut with a bloody object, pierced ears or body parts, and immunoglobulin injection must be interpreted with caution.
The causes of post-transfusion non-A, non-B hepatitis are still not fully defined, nor is it clear how accurate the tests are that are used to screen blood donors for hepatitis C virus (HCV) and to ...diagnose post-transfusion hepatitis caused by infected blood.
We used two first-generation enzyme-linked immunoassays (EIAs) and one second-generation immunoassay to test for anti-HCV antibodies in serum samples collected between 1976 and 1979 in the Transfusion-Transmitted Viruses Study (from 1247 patients who underwent transfusion and 1235 matched control subjects who did not receive transfusions). We tested serum collected before and after infection from the patients in whom non-A, non-B hepatitis developed, serum from their blood donors, and serum from 41 of the control subjects who had hepatitis unrelated to transfusion.
Of the 115 patients in whom post-transfusion non-A, non-B hepatitis developed, the initial serum samples of 111 were anti-HCV-negative; after hepatitis developed in these 111 patients, the first-generation EIAs detected anti-HCV in 51 (46 percent), and the second-generation assay detected anti-HCV in an additional 16 (14 percent), for a total of 60 percent. Of 40 controls, 37 were anti-HCV-negative initially, and none seroconverted after hepatitis developed. If the 3 percent rate of non-A, non-B, non-C hepatitis among the controls (37 of 1235) was applied to the 1247 transfusion recipients, only 74 of the 111 cases of hepatitis were attributable to the transfusion. Thus, 91 percent (67 of 74) of the cases of post-transfusion hepatitis were caused by HCV. Of the 99 donors, 60 were HCV-positive (9 on second-generation tests only) and 39 were not.
Nearly all cases of non-A, non-B post-transfusion hepatitis are caused by HCV. Screening with a second-generation assay improves the rate of detection of HCV infection in patients with post-transfusion hepatitis and in blood donors. The use of this test showed a 3.6 percent risk of non-A, non-B, non-C hepatitis, which was not significantly different from the rate in the controls (3.0 percent).
BACKGROUND: An ongoing issue in transfusion medicine is whether newly identified or emerging pathogens can be transmitted by transfusion. One method to study this question is through the use of a ...contemporary linked donor‐recipient repository.
STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study Allogeneic Donor and Recipient (RADAR) repository was established between 2000 and 2003 by seven blood centers and eight collaborating hospitals. Specimens from consented donors were collected, components from their donations were routed to participating hospitals, and recipients of these units gave enrollment and follow‐up specimens for long‐term storage. The repository was designed to show that zero transmissions to enrolled recipients would indicate with 95 percent confidence that the transfusion transmission rate of an agent with prevalence of 0.05 to 1 percent was lower than 25 percent.
RESULTS: The repository contains pre‐ and posttransfusion specimens from 3,575 cardiac, vascular, and orthopedic surgery patients, linked to 13,201 donation specimens. The mean number of RADAR donation exposures per recipient is 3.85. The distribution of components transfused is 77 percent red cells, 13 percent whole blood–derived platelet concentrates, and 10 percent fresh frozen plasma. A supplementary unlinked donation repository containing 99,906 specimens from 84,339 donors was also established and can be used to evaluate the prevalence of an agent and validate assay(s) performance before accessing the donor‐recipient–linked repository. Recipient testing conducted during the establishment of RADAR revealed no transmissions of human immunodeficiency virus, hepatitis C virus, or human T‐lymphotropic virus.
CONCLUSIONS: RADAR is a contemporary donor‐recipient repository that can be accessed to study the transfusion transmissibility of emerging agents.
Disease associations of human T lymphotropic virus types I and II (HTLV-I and -II) infection were studied in 154 HTLV-I-infected, 387 HTLV-II-infected, and 799 uninfected blood donors. Adjusted odds ...ratios (ORs) and 99% confidence intervals (CIs) were derived from logistic regression models controlling for demographics and relevant confounders. All subjects were human immunodeficiency virus type 1-seronegative. HTLV-II was significantly associated with a history of pneumonia (OR, 2.6; 99% CI, 1.2–5.3), minor fungal infection (OR, 2.9; 99% CI, 1.2–7.1), and bladder or kidney infection (OR, 1.6; 99% CI, 1.0–2.5) within the past 5 years and with a lifetime history of tuberculosis (OR, 3.9; 99% CI, 1.3–11.6) and arthritis (OR, 1.8; 99% CI, 1.2–2.9). Lymphadenopathy (⩾1 cm) was associated with both HTLV-I (OR, 6.6; 99% CI, 2.2–19.2) and HTLV-II (OR, 2.8; 99% CI, 1.1–7.1) infection, although no case of adult T cell leukemia/lymphoma was diagnosed. Urinary urgency and gait disturbance were associated with both viruses. This new finding of increased prevalence of a variety of infections in HTLV-II-positive donors suggests immunologic impairment.
PDF
