SPEAK OUT

HIV
POST EXPOSURE PROPHYLAXIS / ANTIRETROVIRAL

Even a blood transfusion of HIV blood can be stopped by PEP.

Annals of Internal Medicine © 2000
American College of Physicians, 4 July 2000 pp 31-34

Failure To Develop HIV Infection after Receipt of HIV-Contaminated Blood and Postexposure Prophylaxis
by Katzenstein, Terese L. MD, PhD; Dickmeiss, Ebbe MD, DrMedSci; Aladdin, Hassan MSc; Hede, Adam MD; Nielsen, Claus MSc, PhD; Nielsen, Helle BA; Jørgensen, Louise B. MSc, PhD; Gerstoft, Jan MD, DrMedSci, National University Hospital Rigshospitalet and State Serum Institute, Copenhagen, Denmark.

Terese L. Katzenstein; terese@rh.dk
Barbara Hudson, Reprints Coordinator; bhudson@mail.acponline.org

Use of HIV-antibody screening of blood donated for transfusions has reduced the risk for HIV transmission. However, because of the lag time between acquisition of HIV infection and development of antibodies (the window period), some HIV-infected blood donors escape detection. Currently, the window period is estimated to be 3 weeks. We report a case in which transfusion of HIV RNA-positive, HIV-seronegative blood did not lead to infection in the recipient, most likely because potent postexposure antiretroviral therapy was initiated promptly and followed thoroughly.

Case Report

Patient D-1 developed fever and a follicular confluent rash. No exposure to HIV could be identified; the patient had had no extramarital contacts or intravenous drug use. He had, however, been involved in a bloody altercation at a gay bar 25 days earlier. During the altercation, the patient head-butted another guest. Substantial bleeding occurred, but the patient did not recall blood exchange. The patient was transferred to care in the Department of Infectious Diseases at Rigshospitalet, Copenhagen, Denmark, with a diagnosis of primary HIV infection. He had a high HIV RNA load (2 × 106 copies/mL). Antiretroviral therapy with zidovudine, lamivudine, and ritonavir was initiated.

On admission to the ward, the patient disclosed that he had donated blood 1 week earlier. As is routine, the whole-blood donation had been divided into red blood cells in additive solutions (buffy coat removed), buffy coat, and fresh frozen plasma. The red blood cells were used for transfusion and the buffy coat was discarded. The fresh frozen plasma was still in stock and was immediately tested for HIV RNA and HIV p24 antigen. Although p24 antigen was not detected, the plasma tested positive for HIV RNA at about 11 000 copies/mL . A 13-year-old recipient (RSS) underwent transfusion with the packed red blood cells 2 days before the donation was tested and found to be positive for HIV RNA. The recipient also received 1 unit of platelets, 3 units of fresh frozen plasma, and 5 units of red cells during corrective orthopaedic surgery. Postexposure prophylaxis (child dosing) with zidovudine (200 mg twice daily), lamivudine (150 mg twice daily), and indinavir (600 mg three times daily) was immediately initiated. Because of extensive side effects, indinavir was replaced with ritonavir after 1 day; ritonavir was in turn replaced with nelfinavir (500 three times daily) the next day. The recipient took postexposure prophylaxis for 9 months; the treatment was planned to last for 1 year but was discontinued because of persistent intolerable side effects.

During postexposure prophylaxis, the recipient underwent 11 analyses for HIV RNA and HIV DNA, 5 analyses for HIV antibody, and 2 analyses for HIV p24 antigen. Before cessation of therapy, HIV culture was performed. After discontinuation of treatment, HIV analyses (DNA, RNA and antibodies) were performed three times weekly for the first 3 weeks, once weekly for the subsequent 6 weeks, and once monthly thereafter until therapy had been discontinued for 6 months.

Samples from the recipient were analyzed for HIV antibodies (enzyme-linked immunosorbent assay anti-HIV 1/2, Chiron Diagnostics, Emeryville, California, and ICE HIV-1.0/2, Murex Biotech Ltd., Dartford, Kent, United Kingdom), HIV DNA (Amplicor HIV-1 test, Roche Diagnostic Systems, Branchburg, New Jersey), and HIV RNA (Amplicor HIV-1 Monitor, Roche Diagnostic Systems; lower limit of detection, 20 copies/mL). Some samples were reanalyzed by using an optimized HIV RNA method (lower limit of detection, 3 copies/mL) (5). Culture for HIV using peripheral blood mononuclear cells was performed with and without phytohemagglutinin stimulation. The recipient's CCR5 genotype was ascertained. In addition, HIV RNA from the donor was analyzed for antiretroviral resistance. In the recipient, all tests for HIV RNA (lower limit of detection, 20 copies/mL), HIV DNA, HIV antibody, and HIV p24 antigen and cultures for HIV were negative. Use of the optimized RNA method to retest plasma obtained before treatment yielded an HIV RNA load of 3 copies/mL. Plasma samples obtained 1 and 4 weeks after initiation of therapy yielded values below the limit of detection.

The recipient had the CCR5/CCR5 genotype. In HIV RNA from the donor, only two secondary protease inhibitor mutations were detected (L63P and A71T); no primary mutations were found. Likewise, no mutations linked to reverse transcriptase inhibitor resistance were detected. Transfusion of HIV-infected blood did not lead to HIV infection in a transfusion recipient who underwent prompt postexposure antiretroviral prophylaxis. The recipient was followed for 6 months after treatment cessation and persistently tested negative for HIV infection according to various measures; she was therefore declared uninfected. The positive HIV RNA signal detected in plasma obtained from the recipient before therapy began should be interpreted with caution; the quantity equals the detection limit and later samples all tested negative. Infection was most likely avoided through prolonged and vigorous postexposure prophylaxis, which was initiated 50 hours after transfusion.

The patient donated blood during the window period before HIV infection became detectable. He reported having been involved in a bloody altercation at a gay bar 2.5 weeks earlier. Although bloody head-butting represents an unusual mode of HIV transmission, it has been reported previously. Earlier studies of patients who received HIV-infected blood have found an infection rate of almost 100%. It is believed that every transfusion from an HIV-infected donor will lead to infection of the recipient provided that the blood has not been stored for more than 2 to 3 weeks. The few cases of nontransmission are probably the result of tracing errors: that is, the recipients did not receive the HIV-infected blood units. The blood bank at Rigshospitalet uses bar coding and electronic data processing to ensure that transfused blood can be traced with certainty. We reviewed all the documented steps in the procedure and ascertained that the recipient in our case report did in fact receive the red blood cells donated by the patient.

Because the recipient tested negative for HIV DNA and HIV RNA before treatment was initiated, we cannot determine whether the recipient's lack of infection was due to the eradication of the infection by the therapy or whether the donation of the HIV-infected blood would not have led to infection even without therapy. However, because the recipient had the CCR5 genotype, she was not refractory to HIV infection.

Postexposure prophylaxis with zidovudine has been shown to be effective in reducing vertical transmission and transmission after percutaneous exposure. Experience from a vertical transmission study and data from animal studies indicate that postexposure prophylaxis [with zidovudine and (R)-9-(2-phosponylmethoxypropyl)adenine, respectively] may be efficacious if it is initiated within 1 to 2 days after exposure. The optimal duration of postexposure prophylaxis remains to be determined.