title: Genotypic analysis of the protease and reverse transcriptase of non-B HIV type 1 clinical isolates from naïve and treated subjects.
abstract: 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.
authors: Clinic of Infectious Diseases, University of Bari, Bari, Italy. l.monno@clininf.uniba.it
authors: Laura
authors: L
authors: Monno
authors: Luigia
authors: L
authors: Scudeller
authors: Gaetano
authors: G
authors: Brindicci
authors: Annalisa
authors: A
authors: Saracino
authors: Grazia
authors: G
authors: Punzi
authors: Antonio
authors: A
authors: Chirianni
authors: Antonella
authors: A
authors: Lagioia
authors: Nicoletta
authors: N
authors: Ladisa
authors: Sergio
authors: S
authors: Lo Caputo
authors: Gioacchino
authors: G
authors: Angarano
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease