期刊
AIDS RESEARCH AND HUMAN RETROVIRUSES
卷 22, 期 12, 页码 1260-1266出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/aid.2006.22.1260
关键词
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资金
- NCRR NIH HHS [5-M01-RR00083-37, RR16482] Funding Source: Medline
- NIAID NIH HHS [P30 AI60354, AI055273, AI052745, AI058845-02S1] Funding Source: Medline
- NIGMS NIH HHS [R01 GM086887] Funding Source: Medline
- NIMH NIH HHS [P30 MH59037, P30 MH62246] Funding Source: Medline
Careful examination of viral dynamics during antiretroviral treatment can provide important insights into HIV pathogenesis. We examined viral evolution during and after enfuvirtide (T-20) treatment with an objective of defining the characteristics of viral evolution during advanced HIV immunodeficiency. Specifically, we examined the viral quasispecies from nine patients who experienced incomplete viral suppression on an enfuvirtide-based regimen, and who subsequently interrupted enfuvirtide while remaining on a stable optimized background regimen (enfuvirtide partial treatment interruption). On average, eight clones were sequenced from three time points: pre-enfuvirtide, post-enfuvirtide failure, and post-enfuvirtide interruption. We utilized a Bayesian hierarchical phylogenetic model to assess the evolutionary relatedness of the virus that emerged over time. In most subjects, interruption of enfuvirtide was associated with continued viral evolution as enfuvirtide mutations waned; in no subject did we find clear evidence supporting the reemergence of archived wild-type variants (Bayes factor = 30.2, p = 0.01). Evidence supporting ongoing viral evolution was particularly strong in subjects whose virus remained diverse or became more diverse during enfuvirtide therapy. In contrast to observations when all drugs are interrupted, loss of resistance during enfuvirtide interruption is most likely due to ongoing viral evolution (and back-mutation), rather than emergence of an archived virus.
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