Genotypic analysis of the protease and reverse transcriptase of non-B HIV type 1 clinical isolates from naïve and treated subjects.
One hundred and ninety-two pol sequences of drug-naïve and drug-experienced subjects infected with non-B HIV-1 subtypes were analyzed to identify treatment-related amino acid changes which might be relevant for drug-resistance and possibly not included in the accepted mutation list for the B subtype. The correspondence analysis identified non-B-specific and subtype-specific polymorphisms which should not be mistaken for mutations. Multiple chi(2) were performed to detect the differences between naïve vs treated subjects and between different subtypes. To verify the contribution of each single mutation to the resistance levels as predicted by the Virtual Phenotype-LM, simple univariate linear regression was used with fold resistance as a dependent variable and individual mutations as predictors. Commonly accepted protease (PR) and reverse transcriptase (RT) positions along with mutants at RT positions 118 and 90 were significantly associated with treatment. Two unusual PR (K14R and I66F) and five RT positions (E28K, S68G, H221Y, L228R/H and P294A) were also associated with treatment (p<0.01). Only minimal variations were observed with respect to commonly accepted amino acid changes. All amino acid changes correlated with treatment influenced the resistance levels to each single drug. Our findings demonstrate that there are no substantial differences regarding known resistance-associated mutations and the newly emergent substitutions between non-B and B subtype strains.
Monno
Laura
L
Clinic of Infectious Diseases, University of Bari, Bari, Italy. l.monno@clininf.uniba.it
Scudeller
Luigia
L
Brindicci
Gaetano
G
Saracino
Annalisa
A
Punzi
Grazia
G
Chirianni
Antonio
A
Lagioia
Antonella
A
Ladisa
Nicoletta
N
Lo Caputo
Sergio
S
Angarano
Gioacchino
G
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics; D055815:Young Adult
D019380:Anti-HIV Agents; D012367:RNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease