Session 27Oral Abstract Presentations Antiretroviral Drug Resistance Session Day and Time: Thursday 10 - 11:45 am Presentation Time: 11:00 Room: Ballroom C
145 Are Drug-resistance Variants Transmitted with Lower Efficiency than Wild-type? S Yerly*1, S Jost1, A Telenti2, M Flepp3, L Kaiser1, J P Chave4, P Vernazza5, M Battegay6, H Furrer7, C Michon8, P Burgisser2, M Rickenbach9, M Gebhardt10, B Hirschel1, L Perrin1 1Geneva Univ Hosp Switzerland; 2Lausanne Univ Hosp Switzerland; 3Zurich Univ Hosp, Switzerland; 4Lausanne La Source Hosp, Switzerland; 5St Gall Univ Hosp, Switzerland; 6Basel Univ Hosp, Switzerland; 7Bern Univ Hosp, Switzerland; 8Annecy Hosp, France; 9Swiss HIV Cohort Study, Lausanne, Switzerland; and 10Swiss Federal Office of Publ Hlth, Bern, Switzerland
Background: We assessed whether HIV-1 transmission is influenced by mutations associated with drug-resistance by comparing drug-resistance profiles between recently infected (RI) individuals and potential transmitters.
Methods: From 1999-2001, sequencing of pol gene was performed in 225 consecutive Swiss RI patients (pts) and in all chronically infected (CI) pts enrolled in the Geneva Swiss HIV Cohort Study with viremia > 1000 copies/ml (n = 373). Genotypic resistance was defined according to the consensus USA Panel (2000). The impact of RI pts on transmission was assessed through phylogenetic analysis (identification of RI sequences with bootstrap values > 90%). The drug-resistance profiles of potential transmitters was estimated by weighting the CI resistance profiles according to the minimal and maximal estimates of HIV-1 infected persons living in Switzerland (14,000-15,400), to the proportion of the drug-exposed Swiss CI population (51%-57%) and to the impact of RI on new infections.
Results: The prevalence of drug-resistance in RI pts was 10.5% (1 class drug-resistance, 9.1%; 2 classes, 1.4%; 3 classes, 0%). Phylogenetic analysis revealed significant clustering for 94 pts (29 clusters) suggesting that 30% of RI pts were infected by RI pts. After adjustment, the prevalence of drug-resistance in potential transmitters varied between 29.0%-35.2% (1 class drug-resistance, 13.1%-17.0%; 2 classes, 10.3%-11.9%; and 3 classes, 5.7%-6.3%). After exclusion of patients with isolated 184V/I mutation (known to be associated with a decreased replication capacity), the prevalence of one class drug-resistance in potential transmitters decreased to 10.1%-13.7%, a value close to the 9.1% value observed in RI patients. Viremia level did not explain transmission difference between 1 and 3 classes drug-resistance (4.00 vs. 4.40 log copies RNA/ml, respectively) suggesting that in vivo transmission capacity of drug-resistant HIV-1 was not directly related to viremia levels. There were no significant differences among CI pts with different resistance profiles regarding the percentage having had anal or vaginal sex, infrequent use of condoms, or having occasional partners.
Conclusions: A decreased transmission capacity of multi-drug resistant HIV-1 is a likely explanation for the reduced spreading of these variants in newly infected pts.
