In certain cases, when RNA-based genotypic resistance testing is not possible, proviral DNA may be used to assess genotypic resistance. Several studies have presented data showing good concordance between proviral DNA resistance mutations and mutations detected in plasma RNA genotypes and/or related to previously administered antiretroviral drugs prior to virologic suppression.
Lübke et al investigated the concordance between viral plasma RNA and proviral DNA mutations in 48 treatment-naïve and 30 treatment-experienced patients.1 Among all drug resistance-associated mutations detected by either method, 75% were detected in both RNA and DNA, 23% were found exclusively in RNA, and 2% were found exclusively in proviral DNA.
Porter et al investigated the clinical utility of proviral DNA resistance analysis for virologically suppressed patients in the SPIRIT study to evaluate the safety and efficacy of switching to a rilpivirine/emtricitabine/tenofovir regimen.2 They found that 89% of occurrences of NRTI and NNRTI resistance-associated mutations reported by historical genotype were also detectable in proviral DNA.
Zaccarelli et al investigated proviral DNA resistance mutations in 149 virologically suppressed patients with 2 or more plasma RNA genotypes performed prior to virologic suppression.3 They found that 51% of patients had proviral DNA primary resistance mutations that were previously identified in plasma RNA. Primary resistance mutations that were mostly detected in proviral DNA were found to be related to previously administered antiretrovirals and/or to drugs with a low genetic barrier to resistance. Thus, proviral DNA resistance testing may be useful for detecting archived resistance mutations in the setting of low viral load when prior plasma RNA genotypes are not available.
Allavena et al performed proviral DNA resistance testing on 69 virologically suppressed patients with no history of virologic failure.4 They found that 88% of proviral protease mutations and 76% of proviral reverse transcriptase mutations were concordant with plasma RNA genotypes obtained prior to initiation of therapy.