Sequence clusters in human immunodeficiency virus type 1 reverse transcriptase are associated with subsequent virological response to antiretroviral therapy

Many amino acid (aa) sites in reverse transcriptase (RT) have been implicat ed in resistance to nucleoside (NRTI) and nonnucleoside antiretrovirals, In teractions between these in response to combination therapy remain poorly u nderstood. In a trial (ACTG 241) of zidovudine/didanosine (ddI) versus zido vudine/ddI/nevirapine in nucleoside-experienced patients, baseline sequence data from the RT coding region was analyzed from 55 individuals. Sequences were clustered by use of a parsimony method and the virological responses (ratio of baseline viral load to viral load after of therapy) for each clus ter were analyzed at week 8 and week 48. Both clusters and genotype at aa 2 15 were significantly associated with virological response at both time poi nts, whereas viral load showed a stronger association with sequence cluster s. Sequence clusters identified one group of patients who never developed h igh-level resistance to NRTIs despite prior nucleoside exposure and poor su ppression of viral replication.