Utility of HIV-1 DNA genotype in determining antiretroviral resistance in patients with low or undetectable HIV RNA viral loads

• Published in: Journal of antimicrobial chemotherapy Vol. 73; no. 11; pp. 3129 - 3136
• Main Authors: Boukli, Narjis, Boyd, Anders, Collot, Marianne, Meynard, Jean-Luc, Girard, Pierre-Marie, Morand-Joubert, Laurence
• Format: Journal Article
• Language: English
• Published: England Oxford University Press (OUP) 01.11.2018
• Subjects: Human health and pathology; Infectious diseases; Life Sciences; Microbiology and Parasitology; Santé publique et épidémiologie; Virology
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dky316

To investigate the extent to which drug resistance can be evaluated from proviral HIV-1 DNA genotype compared with RNA genotype at different timepoints. In HIV-1-infected patients routinely seen at a university hospital, who needed to change their current ART, antiretroviral drug resistance was determined from DNA genotype and was compared with past RNA genotype (group 1) or same-day RNA genotype (group 2). A 'resistance sum' was defined as the sum of agents to which resistance was present and was calculated across NRTI, NNRTI and PI. We defined 'loss of information' as when a lower resistance sum was observed in DNA than in RNA samples. Of the 74 and 26 patients included in groups 1 and 2, respectively, most had a long median duration of known HIV-1 infection (17.4 and 14.2 years) and ART (15.3 years and 13.5 years). For group 1, the median (range) resistance sums between DNA/RNA were 0 (0-6)/1 (0-6) for NRTIs, 0 (0-4)/0 (0-4) for NNRTIs and 0 (0-7)/0 (0-8) for PIs, which were comparable with group 2. Loss of information in DNA was substantial for group 1 (37.8%) and less so for group 2 (11.1%). In multivariable analysis, only longer ART duration was significantly associated with loss of information. Results were similar in patients harbouring resistance to one or more agents. In a real-life setting, genotyping DNA from PBMC has some degree of concordance compared with RNA. Loss of information in DNA would appear to coincide with longer periods of ART.