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Therapy for Cellulitis.

In Reply Dr Goldman and colleagues highlight aspects of the phylogenetic analyses used to investigate HIV transmission events in the PARTNER study.1 Previous studies have taken advantage of the now-discontinued Roche 454 deepsequencing platform to obtain sequence reads of sufficient length to allow reliable phylogenetic analyses of minority viral species. We have been conducting work to optimize the Illumina deep-sequencing platform to perform an analysis of minority species in couples in our study. The reconstruction of HIV haplotypes presents notorious technical and interpretative challenges when applied to the short sequence reads currently obtained by Illumina. We are also using conventional limiting dilution techniques to obtain single and near full-length genomes using established methods.2 These further analyses will be submitted for publication once completed. Also, Goldman and colleagues propose that some env pairwise genetic distances in samples from the PARTNER study were similar to those of samples found to be linked in another study.3 The proposed comparison of genetic distances is complicated by the fact that the sequences in the PARTNER study were considerably longer (2000 base pairs) than those reported in the other study (approximately 516 base pairs). Nonetheless, as shown in eTable 2 in the article Supplement, the median pairwise distance of env control sequences was at least 5 times lower than the median pairwise distance of the partners’ env sequences. When considering sequences falling within the upper limit of the previously reported range,3 the env phylogeny did not support linkage. Detailed analyses of the env sequences were made available to selected expert reviewers from JAMA and deemed robust. All phylogenies will be submitted for publication once study is completed. Goldman and colleagues are correct that phylogenetic analyses of putative transmission events should include control sequences drawn from epidemiologically relevant settings and take into account time since seroconversion.4 These factors were taken into account in the PARTNER study. The study design was such that patients were sampled never later than 6 to 8 months from seroconversion. Constraints dictated by the terms of the ethical approvals and need to protect patients’ confidentiality mean that the phylogenetic investigations must not reveal the geographic origin of the specimens undergoing analysis. Although we recognize the importance of disclosing to public scrutiny our detailed analyses, the confidential data we hold in this respect are entirely consistent with the reported conclusions of the PARTNER study. We are confident that clinicians are able to interpret the data and counsel patients appropriately, taking into account individual circumstances and tolerance of any risk, however small.