Detection of the protease codon 35 amino acid insertion in sequences from treatment-naïve HIV-1 subtype C infected individuals in the Central Region of Portugal

Abstract

Results: A threonine insertion (E35E T) was detected in 2.69% (n = 7) of the sequences analyzed and all the sequences that possessed this insertion were identified as subtype C. All the seven inserted sequences clustered in the same lineage of the phylogenetic tree. Heterosexual and intravenous drug use were found to be the routes of infection. No major mutations in the PR coding region associated with resistance to PIs were detected. Conclusions: It was found the highest prevalence of PR codon 35 insertion among treatment-naïve HIV-1 infected individuals ever reported in the western countries. Epidemiological data and Phylogenetic analysis indicated the possibility of transmission of this insertion. The results suggested that these inserted strains have normal susceptibility to PIs containing regimens. This study demonstrated the spreading epidemic of PR codon 35 inserted strains from subtype C in the Central Region of Portugal, during the past eight years.

Highly Resistant HIV-1 Proteases and Strategies for Their Inhibition

“…The majority of these mutations associated with resistance are single amino acid substitutions, as illustrated in Table 1. Rarely, insertions have been observed in the protease gene and may play a role in PI resistance [13–15]. Multiple mutations accumulate, and high level resistance may require a combination of 10–20 mutations in the protease.…”

HIV-1 Protease: Structural Perspectives on Drug Resistance

“…Also, protease drug resistance can emerge due to mutations in the Gag substrate alone, rather than in the enzyme [51]. In addition, recent reports indicate a role for amino acid insertions in the drug resistance of HIV protease [52–54]. …”

Zero prevalence of primary drug resistance-associated mutations to protease inhibitors in HIV-1 drug-naive patients in and around Aligarh, India

“…The high mutation rate of the HIV genome is associated with the low fidelity of the reverse transcriptase (RT) and the lack of proofreading function; eventually, the high selective pressure of the specific drugs lead to increases in genetic mutation, causing resistance to current ART therapy [5]. Due to the widespread use of antiretroviral drugs, it has been hypothesized that there will be an increase in the transmission rate of drug-resistant viruses, which will raise the prevalence of resistant variants.…”