Prevention of HIV-1 transmission with postexposure prophylaxis after inadvertent infected blood transfusion
Al-Hajjar, Sami H.a; Frayha, Husn H.a; Al-Hazmi, Mohammadb; Batawi, Reema; McIntosh, Kennethc,d; Sax, Paul E.d,e; Al-Thawadi, Sahara; Al-Jumaah, Sulaimana; Busch, Michael P.f,g; Hanhauser, Emilye; Kuritzkes, Daniel R.d,e; Li, Jonathan Z.d,e; Henrich, Timothy J.d,e
aKing Faisal Specialist Hospital & Research Center, Riyadh
bKing Fahad Central Hospital, Jazan, Saudi Arabia
cBoston Children's Hospital
dHarvard Medical School
eBrigham and Women's Hospital, Boston, Massachusetts
fBlood Systems Research Institute
gUniversity of California, San Francisco, California, USA.
Correspondence to Sami Al Hajjar, Pediatric Infectious Diseases, Department of Pediatrics, King Faisal Specialist Hospital & Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Tel: +966 1 4647271; fax: +9661 4427784; e-mail: firstname.lastname@example.org
Received 27 November, 2013
Revised 24 February, 2014
Accepted 24 February, 2014
Although postexposure prophylaxis (PEP) is commonly prescribed in the setting of occupational and nonoccupational HIV-1 exposures [1,2], there is limited evidence documenting efficacy in the setting of transfusion with infected blood. Furthermore, there is a paucity of data regarding blood-borne exposures that lead to passive transfer of antibodies against HIV [3,4]. We describe the efficacy of PEP in such a situation using highly sensitive assays for HIV-1 DNA and low-level residual viremia.
We report the case of a 12-year-old girl with sickle-cell disease admitted for management of a vaso-occlusive crisis who inadvertently received HIV-infected packed red blood cells (PRBCs). She required intermittent PRBC transfusions since the age of 2 years, with the last transfusion 5 years ago. Her white blood cell count was 10 100 per μl, and haemoglobin 9.6 g/dl. Haemoglobin electrophoresis revealed 57% haemoglobin S. During her admission, she was transfused with one PRBC unit that was collected 32 h prior to administration.
Despite the standard practice of prescreening blood products, the laboratory at the public hospital in the Kingdom of Saudi Arabia became aware that the PRBCs were contaminated with HIV-1 within hours of her transfusion as a result of human error involving mixing an un-screened bag with screened bags. The donor blood was discovered to be HIV-1 antibody positive and subsequently determined to have a viral load of 9740 copies/ml (subtype C); the donor was not receiving antiretroviral therapy (ART). The Ministry of Health conducted an in-depth investigation and halted blood transfusions at the responsible blood blank. Approximately 24 h after transfusion, the patient was started on tenofovir, emtricitabine, ritonavir-boosted darunavir (subsequently changed to lopinavir) and raltegravir. Blood tests were positive 24 h after transfusion for HIV antibodies by ELISA and confirmatory western blot, but negative for HIV-1 DNA and plasma HIV-1 RNA by PCR. The pattern of reactive bands on western blot was identical for samples obtained from the donor and patient (gp120, gp41, gp31, p24 and p17). Genotyping revealed that she was CCR5 wild-type.
The patient demonstrated no signs or symptoms of acute infection during 13 weeks of ART in a tertiary care centre. Testing of donor blood revealed no HIV-1 resistance to the antiretrovirals chosen. Longitudinal testing of the patient's plasma and peripheral blood mononuclear cells (PBMCs) was performed by both clinical laboratories and by sensitive research assays with thresholds of detection down to 0.1 HIV-1 DNA copies/106 PBMCs and 0.4 RNA copies/ml of plasma during and after ART. All tests were negative prior to and 8 months after ART interruption. She continued to have declining but detectable HIV-1 antibodies with positive confirmatory line immunoassay up to 5 months after transfusion, but confirmatory testing was negative by month 6. Viral load testing 8 months following exposure remained negative (Table 1).
We report the successful use of combination ART PEP following large-volume transfusion of HIV-infected blood from a viremic donor with passive transfer of antibodies to HIV-1. The observation that no HIV was detected in her blood after stopping ART and that antibody levels disappeared over time strongly suggests that PEP successfully prevented HIV acquisition. The overall transmission rate from HIV-1 antibody positive blood transfusions was 89% in one study with nontransmission attributed to lower viral load and prolonged blood-product storage . HIV-1 transmission from transfusion of PRBCs stored for less than 48 h is essentially 100% regardless of viral load . Furthermore, experiments of simian immunodeficiency virus primary infection in primate models suggest that infectivity of plasma virus from acute infection is higher than set-point virus, but the correlation between cell-associated HIV-1 DNA levels and transmissibility is poorly understood [6,7]. Our patient received effective prophylaxis despite transfusion with PRBCs stored for less than 36 h, but was from a donor with relatively low viral load.
Passive transfer of HIV-1 antibodies after occupational exposure has been documented but is rare [3,4]. For example, one individual became infected with resistant virus despite the use of zidovudine 2 h after a deep laceration with contaminated blood, whereas another individual was not infected after transfusion with a contaminated unit of PRBCs from a donor with a low viral load (2000 copies/ml); she was started on zidovudine, lamivudine and indinavir 19 days after exposure. These cases illustrate the sensitivity of current antibody testing platforms and cautions against presuming that individuals have preexisting HIV-1 infection, and not initiating or stopping PEP due to the presence of antibody reactivity immediately following contaminated blood exposure. Highly sensitive laboratory assays may also help guide the duration of PEP to guarantee the prevention of infection.
We would like to acknowledge Sheila Keating for help with antibody testing.
This work was supported by the Foundation for AIDS Research (amfAR) ARCHE grant, NIH grant UM1 AI068636, NIH/NIAID U19 AI096109 (DARE Collaboratory).
D.R.K receives consulting fees or honorariums from Gilead; P.E.S. receives consulting fees or honorariums from AbbView, Bristol-Meyers Squibb, Gilead, Glaxo-Smith-Kline, Janssen Pharmaceuticals and Merk, and receives grant support from Gilead, BMS and GSK.
Conflicts of interest
There are no conflicts of interest.
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