Molecular Evidence Of HIV-1 Transmission In A Criminal Case

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Molecular evidence of HIV-1 transmission in a criminal case
Michael L. Metzker*†, David P. Mindell‡, Xiao-Mei Liu*§, Roger G. Ptak¶ʈ, Richard A. Gibbs*, and David M. Hillis**
*Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; ‡Department of Ecology and Evolutionary Biology and
Museum of Zoology, University of Michigan, Ann Arbor, MI 48109-1079; ¶School of Dentistry, Biologic and Materials Sciences, University of Michigan,
Ann Arbor, MI 48109; and **Section of Integrative Biology and Center for Computational Biology and Bioinformatics, University of Texas,
Austin, TX 78712
Edited by Walter M. Fitch, University of California, Irvine, CA, and approved September 4, 2002 (received for review May 2, 2002)

A gastroenterologist was convicted of attempted second-degree murder by injecting his former girlfriend with blood or bloodproducts obtained from an HIV type 1 (HIV-1)-infected patient under his care. Phylogenetic analyses of HIV-1 sequences were admitted and used as evidence in this case, representing the first use of phylogenetic analyses in a criminal court case in the United States. Phylogenetic analyses of HIV-1 reverse transcriptase and env DNA sequences isolated from the victim, the patient, and a local population sample of
HIV-1-positive individuals showed the victim’s HIV-1 sequences to be most closely related to and nested within a lineage comprised of the patient’s HIV-1 sequences. This finding of paraphyly for the patient’s sequences was consistent with the direction of transmission from the patient to the victim. Analysis of the victim’s viral reverse transcriptase sequences revealed genotypes consistent with known mutations that confer resistance to AZT, similar to those genotypes found in the patient. A priori establishment of the patient and victim as a suspected transmission pair provided a clear hypothesis for phylogenetic testing. All phylogenetic models and both genes examined strongly supported the close relationship between the HIV-1 sequences of the patient and the victim. Resampling of blood from the suspected transmission pair and independent sequencing by different laboratories provided precaution against laboratory error.


n recent years, DNA testing has been widely used in the judicial system, mainly in violent crimes to link a perpetrator to the scene of the crime. Human DNA is generally stable, allowing the techniques of DNA fingerprinting to be used in analyzing multiple polymorphic markers for the purpose of excluding suspected individuals. Assessing phylogeny for HIV type 1 (HIV-1) strains, however, is more complex than human DNA testing because of the dynamic nature and rapid rates of HIV-1 change (1–4). However, this high rate of change among HIV sequences permits an application of phylogenetic methods, and several case studies have been described that investigated the relatedness of HIV-1 strains for the purpose of examining suspected viral transmission events. Probably the most well-known and scrutinized study is the ‘‘Florida dentist’’ case, which concluded that six patients became infected with HIV-1 while receiving care from an HIV-1-positive dentist (5–9). Other studies that have supported suspected transmissions of HIV-1 between individuals are the ‘‘Swedish rape case’’ (10) and the
‘‘French orthopedic surgeon’’ case (11). In addition, one published study rejected a hypothesis of transmission between a Baltimore surgeon and one of his patients (12).
Because of the rapid rate of evolution of HIV-1, phylogenetic analysis of HIV-1 DNA sequences is a powerful tool for the identification of closely related viral strains that may be used to infer the transmission between individuals. In the case of the State of
Louisiana vs. Richard J. Schmidt, the prosecution argued successfully that the methods of genomic DNA isolation, PCR, DNA sequencing, and phylogenetic analysis of HIV-1 DNA sequences to