Differential evolution of Human Immunodeficiency Virus type 1 Protease and Reverse Transcriptase genes between HAART-failing and naïve-treated individuals.
We described differential selective pressures along codon sites of the RT and PR genes of HIV-1 from HAART-failing and naïve-treated individuals, through the comparison of the ratio of non-synonymous mutations (d(N)) to synonymous mutations (d(S)) substitution per site. Resistance-associated mutations were found in 1/71 (1.4%) and 109/117 (93.1%) samples from naïve-treated and HAART-failing individuals, respectively, although most of positively selected codons represented polymorphisms in positions 123, 211, 245, 297 in RT and 37, 63 in PR of naïve-treated samples and positions 122, 123, 245, 272, 277, 286, 297 in RT and 10, 15, 20, 35, 37, 62, 63, 64, 71, 72, 77, 93 in PR of HAART-failing samples, except by ARV-resistance codons 74, 184, 215 in RT and 90 in PR exclusively found in HAART-failing group. The number and diversity of sites under selective pressure at populational level also increased in RT but not in PR of treated individuals. Our results demonstrated no evolution of drug-associated codons among untreated individuals, indicating unlikely transmission and adaptation of resistant HIV-1 strains in a free drug environment. Polymorphic sites observed exclusively in HAART-failing group, may contribute to HIV-1 escape and adaptation at individual and populational levels in a drug environment, although those mutually found in HIV-1 despite of previous exposure to ARV treatment, should not be considered accurate resistance markers.
Varella
Rafael B
RB
Department of Infectious Diseases UNIFESO, A2-097, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. rafael_varella@hotmail.com
Schrago
Carlos G
CG
Zalis
Mariano G
MG
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D005814:Genes, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D017211:Treatment Failure
D004279:DNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease