Prevalence of C-terminal gag cleavage site mutations in HIV from therapy-naïve patients

Summary 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-naive patients. Patients and methods HIV samples (collected before 1997: n = 94, after 1997: n = 1617) from drug-naive 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-naive HIV. Previously described therapy-associated CS mutations (431V/449F/449H/451T/452S/453A) were found in less than 0.5% of therapy-naive 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-naive 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-naive 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-naive patients might lower the genetic barrier of first-line therapies with protease inhibitors. Keywords: HIV; Cleavage sites; Mutations; Drug-naive