HIV forensics: pitfalls and acceptable standards in the use of phylogenetic analysis as evidence in criminal investigations of HIV transmission^*

Abstract

Phylogenetic analysis -the study of the genetic relatedness between HIV strains -has recently been used in criminal prosecutions as evidence of responsibility for HIV transmission. In these trials, the expert opinion of virologists has been of critical importance. PitfallsPhylogenetic analysis of HIV gene sequences is complex and its findings do not achieve the levels of certainty obtained with the forensic analysis of human DNA. Although two individuals may carry HIV strains that are closely related, these will not necessarily be unique to the two parties and could extend to other persons within the same transmission network. Acceptable standardsFor forensic purposes, phylogenetic analysis should be conducted under strictly controlled conditions by laboratories with relevant expertise applying rigorous methods. It is vitally important to include the right controls, which should be epidemiologically and temporally relevant to the parties under investigation. Use of inappropriate controls can exaggerate any relatedness between the virus strains of the complainant and defendant as being strikingly unique. It will be often difficult to obtain the relevant controls. If convenient but less appropriate controls are used, interpretation of the findings should be tempered accordingly. ConclusionsPhylogenetic analysis cannot prove that HIV transmission occurred directly between two individuals. However, it can exonerate individuals by demonstrating that the defendant carries a virus strain unrelated to that of the complainant. Expert witnesses should acknowledge the limitations of the inferences that might be made and choose the correct language in both written and verbal testimony.

Phylogenetically resolving epidemiologic linkage

“…Note also that with proper rooting many MM phylogenies render PM/consistent, which has information about direction of transmission that MM does not. In fact, the MM phylogeny has the least information about who infected whom because it cannot indicate direction or exclude intermediary links or common sources (7,25,26). With proper rooting, the MM phylogeny is typically suggestive of a common source but may also be the result of an intermediary unsampled link, especially when HIV diversification is slow in a host (Fig.…”

“…In response, it has been claimed that direction of transmission could not be established with most data and the existence of intermediary or common transmission links could never be excluded (7,(25)(26)(27). Thus, phylogenetic reconstruction seemed to only be able to reveal whether two persons were "epidemiologically linked" in some way (28).…”

Dilemma of concepts and strategies for the prevention of spread of HIV in relation to human behavior, law and human rights

“…The situation is even more difficult when IDUs are involved. Correlation causality becomes improbable due to the combination of the time delay, the phylogenetic burden of proof of the variability of the HIV genomic sequences in infectors as well as in those infected in certain circumstances, and the diversity in behavior when it comes to sexual activities (Bernard et al, 2007). Moreover, in certain cases even a deliberate intention along with extreme promiscuity (more than 100 partners a year) is not verifiable at the juridical level (Dennin et al, 2009). 3.…”

The Power and Pitfalls of HIV Phylogenetics in Public Health

“…Laboratory protocols for forensics require strict attention to: chain of custody; work flow; lab design; elimination of operator bias; the absence of specimen mix-up; and ultrastringent contamination control. 8 An obvious concern to health care providers, who order individual HIV drug resistance tests, is the potential use of these data to elucidate putative transmission chains. 9 One could envision scenarios wherein drug resistance genotyping data derived from a specific patient, who has been counseled with respect to transmission risks, might be phylogenetically linked to a cluster of new HIV infections.…”