Persistence of Transmitted HIV-1 Drug Resistance Mutations Associated with Fitness Costs and Viral Genetic Backgrounds

Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. transmitted drug resistance mutations (tdrm) can persist in the absence of drugs for considerable time. it is generally believed that differential tdrm-persistence is caused,at least partially,by variations in tdrm-fitness-costs. however,in vivo epidemiological evidence for the impact of fitness costs on tdrm-persistence is rare.here,we studied the persistence of tdrm in hiv-1 using longitudinally-sampled nucleotide sequences from the swiss-hiv-cohort-study (shcs). all treatment-naïve individuals with tdrm at baseline were included. persistence of tdrm was quantified via reversion rates (rr) determined with interval-censored survival models. fitness costs of tdrm were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities) and were included in the survival models as explanatory variables.in 857 sequential samples from 168 treatment-naïve patients,17 tdrm were analyzed. rr varied substantially and ranged from 174.0/100-person-years;ci=[51.4,588.8] (for 184v) to 2.7/100-person-years;[0.7,10.9] (for 215d). rr increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs). when subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background,we found that both components were significantly associated with reversion-rates.our results show that the substantial variations of tdrm persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation. © 2015 yang et al.