HIV‐1 drug resistance testing at low viral load may help to differentiate between ongoing replication and release from reservoirs

Abstract

Purpose of the studyLow level viraemia in HIV‐infected patients treated with anti‐retroviral therapy (ART) is a phenomenon still not fully understood. If the observed viraemia is a result of ongoing replication or if virus is released from cellular reservoirs remains unclear. We analysed our database of genotypic resistance and interpretations to screen for an effect of viral load on frequency of detected drug resistance.Methods1939 viral load and protease and reverse transcriptase sequence pairs from the years 2009 to 2011 were analysed. Drug resistance interpretation was performed by the HIV‐GRADE resistance interpretation rule set. Pairs were split up into viral load categories of below 200 cop/ml, 200–400, 400–1000, 1000–10,000, 10,000–100,000 and more than 100,000 cop/ml. Resistance interpretation was stratified in the following categories: no resistance, resistance against one, two or three drug classes. The collected data were then analysed using chi‐squared test (R Core Team; 2012; R: A language and environment for statistical computing).Summary of results1390 sequences showed no relevant drug resistance, while 336 sequences showed resistance against one drug class (two classes: 145, three classes: 38). In 25 samples viral load was below 200 cop/ml (200–400: 29, 400–1000: 63, 1000–10,000: 275, 10,000–100,000: 526, above 100,000: 472). In both groups below 400 cop/ml no significant increase of resistant variants was observed compared to the mean distribution, while in the groups with 400–1000 cop/ml and 1000–10,000 cop/ml significant more resistant variants were found than expected (p < 0.001). This reverses above 100,000 cop/ml, where significantly (p < 0.001) more susceptible variants were observed.ConclusionsAs in most of the samples with a viral load below 400 cop/ml, no mutations leading to resistance could be found, we conclude that virus in these cases is released from cellular reservoirs. Viral loads between 400 cop/ml and 10,000 cop/ml under ART are a clear sign for ongoing replication, because in this group the highest rate of drug resistance was observed. Viral loads above 100,000 cop/ml seems here to be a sign of missing selective pressure due to incompliance of the patients and thus no drug resistance was observed.