Infrequent transmission of HIV-1 drug-resistant variants.
Transmission of drug-resistant variants is influenced by several factors, including the prevalence of drug resistance in the population of HIV-1-infected patients, HIV-1 RNA levels and transmission by recently infected patients. In order to evaluate the impact of these factors on the transmission of drug-resistant variants, we have defined the population of potential transmitters and compared their resistance profiles to those of newly infected patients. Sequencing of pol gene was performed in 220 recently infected patients and in 373 chronically infected patients with HIV-1 RNA >1000 copies/ml. Minimal and maximal drug-resistance profiles of potential transmitters were estimated by weighting resistance profiles of chronically infected patients with estimates of the Swiss HIV-1-infected population, the prevalence of exposure to antiviral drugs and the proportion of infections attributed to primary HIV infections. The drug-resistance prevalence in recently infected patients was 10.5% (one class drug resistance: 9.1%; two classes: 1.4%; three classes: 0%). Phylogenetic analysis revealed significant clustering for 30% of recent infections. The drug-resistance prevalence in chronically infected patients was 72.4% (one class: 29%; two classes: 27.6%; three classes: 15.8%). After adjustment, the risk of transmission relative to wild-type was reduced both for one class drug resistance (minimal and maximal estimates: odds ratio: 0.39, P<0.001; and odds ratio: 0.55, P=0.011, respectively), and for two to three class drug resistance (odds ratios: 0.05 and 0.07, respectively, P<0.001). Neither sexual behaviour nor HIV-1 RNA levels explained the low transmission of drug-resistant variants. These data suggest that drug-resistant variants and in particular multidrug-resistant variants have a substantially reduced transmission capacity.
Yerly
Sabine
S
Laboratory of Virology and AIDS Center, Geneva University Hospital, Geneva, Switzerland.
Jost
Stéphanie
S
Telenti
Amalio
A
Flepp
Markus
M
Kaiser
Laurent
L
Chave
Jean-Philippe
JP
Vernazza
Pietro
P
Battegay
Manuel
M
Furrer
Hansjakob
H
Chanzy
Bruno
B
Burgisser
Philippe
P
Rickenbach
Martin
M
Gebhardt
Martin
M
Bernard
Marie-Charlotte
MC
Perneger
Thomas
T
Hirschel
Bernard
B
Perrin
Luc
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D018562:Disease Transmission, Infectious; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015751:Genes, pol; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010802:Phylogeny; D015995:Prevalence; D012367:RNA, Viral / Q000032:analysis; D012307:Risk Factors; D013557:Switzerland / Q000453:epidemiology
D044966:Anti-Retroviral Agents; D012367:RNA, Viral