We examined whether genotyping based on cellular HIV-1 DNA during controlled viraemia identifies resistance mutations detected in plasma HIV-1 RNA during treatment with previous antiretroviral regimens. All 169 patients enrolled in the Agence Nationale de Recherche sur le SIDA Ipilimumab datasheet (ANRS) 138-intEgrase inhibitor MK_0518 to Avoid Subcutaneous Injections of EnfuviRtide (EASIER) trial had already received three antiretroviral drug
classes [nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI)] and had plasma HIV-1 RNA < 400 copies/ml at baseline. The results of previous resistance genotyping of plasma HIV-1 RNA in individual patients were compared www.selleckchem.com/PI3K.html with those of resistance genotyping of whole-blood
HIV-1 DNA at randomization. A median of 4 plasma RNA genotypes were available for the 169 patients. The median numbers of resistance mutations in HIV-1 RNA and DNA were, respectively, 5 and 4 for NRTIs, 2 and 1 for NNRTIs, and 10 and 8 for PIs. The difference was significant for all three drug classes (P = 0.001). Resistance to at least one antiretroviral drug was detected exclusively in HIV-1 RNA or in DNA in 63% and 13% of patients for NRTI, 47% and 1% of patients for NNRTI, and 50% and 7% of patients for PI, respectively. This study shows that, among highly treatment-experienced patients on effective highly Silibinin active antiretroviral therapy, resistance genotyping of HIV-1 DNA detects fewer resistance mutations than previous analyses of HIV-1 RNA. These results have implications for patient management and for the design of switch studies. Antiretroviral therapy currently provides sustained control of HIV replication in about 85% of patients, and most
regimen changes are driven by the desire to improve long-term tolerability and quality of life. It is crucial to take into account the resistance background during previous periods of uncontrolled viraemia in order to limit the risk of treatment failure and the accumulation of resistance mutations [1]. In patients with good virological control, the ideal resistance test would capture the full sequence of resistance events, if any, which have occurred in the past, despite undetectable plasma HIV-1 RNA at the time of testing. Clinicians currently use the patient’s treatment history and the results of plasma-based genotypic resistance tests during previous virological failures to predict switch drug efficacy. This approach is time-consuming and often incomplete, as it entails retrieving the relevant information, sometimes over a period of decades.