OBJECTIVES: HIV protease - as well as gag cleavage site (CS) - mutations occur in HIV with PI resistance but little is known about the prevalence of CS mutations in drug-naïve patients. PATIENTS AND METHODS: HIV samples (collected before 1997: n=94, after 1997: n=1617) from drug-naïve patients were analysed in the C-terminal gag and pol gene. Additionally, sequences from HIV Stanford database were included according to the collection date of the blood sample (before 1997: n=200, after 1997: n=375). RESULTS: Only CS mutations 431V and 452S were correlated with primary PI resistance in drug-naïve HIV. Previously described therapy-associated CS mutations (431V/449F/449H/451T/452S/453A) were found in less than 0.5% of therapy-naïve HIV without primary drug resistance and were totally absent in HIV isolates collected before 1997. The detection of 431V in the absence of PR mutations was significantly correlated with the presence of 429K. The treatment-associated CS mutations (436R/437V/453L) were generally found in more than 1% of drug-naïve HIV with differences between HIV subtypes. Natural polymorphisms were frequently found and also differed between HIV subtype B and non-B subtypes. CONCLUSIONS: The majority of therapy-associated CS mutations were rarely detected in drug-naïve HIV, but can be found in the absence of protease mutations. Moreover, the prevalence of these CS mutations seemed to have increased in recent years. The presence of treatment-associated CS mutations in drug-naïve patients might lower the genetic barrier of first-line therapies with protease inhibitors.
OBJECTIVES: HIV protease - as well as gag cleavage site (CS) - mutations occur in HIV with PI resistance but little is known about the prevalence of CS mutations in drug-naïve patients. PATIENTS AND METHODS: HIV samples (collected before 1997: n=94, after 1997: n=1617) from drug-naïve patients were analysed in the C-terminal gag and pol gene. Additionally, sequences from HIV Stanford database were included according to the collection date of the blood sample (before 1997: n=200, after 1997: n=375). RESULTS: Only CS mutations 431V and 452S were correlated with primary PI resistance in drug-naïve HIV. Previously described therapy-associated CS mutations (431V/449F/449H/451T/452S/453A) were found in less than 0.5% of therapy-naïve HIV without primary drug resistance and were totally absent in HIV isolates collected before 1997. The detection of 431V in the absence of PR mutations was significantly correlated with the presence of 429K. The treatment-associated CS mutations (436R/437V/453L) were generally found in more than 1% of drug-naïve HIV with differences between HIV subtypes. Natural polymorphisms were frequently found and also differed between HIV subtype B and non-B subtypes. CONCLUSIONS: The majority of therapy-associated CS mutations were rarely detected in drug-naïve HIV, but can be found in the absence of protease mutations. Moreover, the prevalence of these CS mutations seemed to have increased in recent years. The presence of treatment-associated CS mutations in drug-naïve patients might lower the genetic barrier of first-line therapies with protease inhibitors.
Authors: Lucile Larrouy; C Chazallon; R Landman; C Capitant; G Peytavin; G Collin; C Charpentier; A Storto; G Pialoux; C Katlama; P M Girard; P Yeni; J P Aboulker; F Brun-Vezinet; D Descamps Journal: Antimicrob Agents Chemother Date: 2010-05-03 Impact factor: 5.191
Authors: Zainab K Sanusi; Thavendran Govender; Glenn E M Maguire; Sibusiso B Maseko; Johnson Lin; Hendrik G Kruger; Bahareh Honarparvar Journal: J Comput Aided Mol Des Date: 2018-02-03 Impact factor: 3.686
Authors: Noortje M van Maarseveen; Dan Andersson; Martin Lepšík; Axel Fun; Pauline J Schipper; Dorien de Jong; Charles A B Boucher; Monique Nijhuis Journal: Retrovirology Date: 2012-04-01 Impact factor: 4.602
Authors: E Anadol; R Kaiser; J Verheyen; E Schülter; J Emmelkamp; C Schwarze-Zander; B Kupfer; J C Wasmuth; J K Rockstroh Journal: Eur J Med Res Date: 2010-05-18 Impact factor: 2.175