The additional M184I mutation was observed in the plasma RNA but not in the proviral DNA, and confers high-level resistance to 3TC. This patient was treated with d4T, abacavir (ABC) and LPV/r combination therapy for 1 year before being changed to a 3TC+TDF+LPV/r regimen because of poor compliance.
Patient 33 had the M46M/I mixed population in the PR gene at the therapy-naïve stage. The plasma viral load was undetectable under HAART in most cases, GSK-3 beta pathway but follow-up analysis of the proviral resistance mutations showed the presence of mutations detected at the therapy-naïve stage without additional mutations, except in the sequence from patient 36. Overall, comparison of resistance mutation patterns in GSK2118436 ic50 CD4 cells with plasma RNA data or follow-up data for CD4 cells revealed similar results for the RT and PR genes, with one or two discrepant mutations. The analysis of DNA resistance evolution in all treated patients showed that the proportion of new mutations was 22%
(n=6) (P<0.0001 for the difference from 0), and these included three new key mutations. However, the appearance of new mutations was not correlated with the time elapsed between sample collections. A logistic regression was performed and a P value of 0.34 [unitary odds ratio (OR) 1.03; global OR 3.24] was obtained. All the other covariates (patient characteristics and use of antiretroviral therapy) were found not to influence the incidence rate of new mutations. The comparison of pre-HAART RNA genotyping with post-treatment DNA sequencing gave calculated prevalences of detected Cyclin-dependent kinase 3 mutations of 59 and 78%, respectively. The proportion of detected mutations (19%) in the DNA was significantly higher than in the pre-HAART RNA by the χ2 test
(P<0.0001), with moderately good agreement between the two methods in terms of the number of detected mutations (kappa coefficient 0.56). A kappa coefficient of 0.50 indicated moderately good agreement in terms of predicted drug activity between the pretreatment RNA and pretreatment DNA mutation profiles, and a kappa coefficient of 0.40 indicated only fairly good agreement between the pretreatment RNA and post-treatment DNA mutation profiles, as a result of the accumulation of new mutations. Genotyping for HIV-1 drug resistance mutations is routinely performed on a plasma sample. At present, guidelines do not recommend HIV-1 drug resistance testing on cellular proviral DNA. The proviral compartment archives the various strains, either wild-type or drug-resistant, that arise during infection. The long-term persistence of archived drug-resistant DNA may jeopardize the efficacy of targeted drugs, and represents the ‘resistance potential’ profile of a patient [40]. This is important when switching antiretroviral agents or initiating treatment in patients without available historical data or conserved samples.