HIV–1 resistance to dolutegravir: update and new insights
نویسندگان
چکیده
Integrase strand transfer inhibitors (INSTIs) are the latest class of potent anti-HIV drugs. Currently, three INSTIs have been approved by the US Food and Drug Administration: raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG). Resistance mutations to RAL and EVG emerge rapidly, and significant cross-resistance between these compounds has been documented. In addition, limited cross-resistance has been observed among DTG, a newer INSTI, and RAL and EVG even though clinical resistance to DTG, or mutations associated with DTG resistance in treatment-naïve patients, has not yet been observed. This review summarises progress in studies on understanding resistance to DTG, mechanisms of possible resistance to DTG, and reasons for the absence of DTG-associated resistance mutations when the drug has been used in first-line therapy.
منابع مشابه
Potential benefit of dolutegravir once daily: efficacy and safety
The viral integrase enzyme has recently emerged as a primary alternative target to block HIV-1 replication, and integrase inhibitors are considered a pivotal new class of antiretroviral drugs. Dolutegravir is an investigational next-generation integrase inhibitor showing some novel and intriguing characteristics, ie, it has a favorable pharmacokinetic profile with a prolonged intracellular half...
متن کاملOnce-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study.
BACKGROUND Dolutegravir (S/GSK1349572) is a once-daily HIV integrase inhibitor with potent antiviral activity and a favourable safety profile. We compared dolutegravir with HIV integrase inhibitor raltegravir, as initial treatment for adults with HIV-1. METHODS SPRING-2 is a 96 week, phase 3, randomised, double-blind, active-controlled, non-inferiority study that began on Oct 19, 2010, at 100...
متن کاملAddition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity.
BACKGROUND The results of several clinical trials suggest that the integrase inhibitor dolutegravir may be less prone than other drugs to the emergence of HIV drug resistance mutations in treatment-naive patients. We have shown that the R263K mutation commonly emerged during tissue culture selection studies with dolutegravir and conferred low levels of resistance to this drug while simultaneous...
متن کاملComparative replication capacity of raltegravir-resistant strains and antiviral activity of the new-generation integrase inhibitor dolutegravir in human primary macrophages and lymphocytes.
OBJECTIVES To evaluate the replication capacity and phenotypic susceptibility to dolutegravir and raltegravir of wild-type and raltegravir-resistant HIV-1 strains in several cellular systems. METHODS The antiviral activities of dolutegravir and raltegravir were evaluated in human primary monocyte-derived macrophages (MDMs), peripheral blood mononuclear cells (PBMCs) and C8166 T lymphocytic ce...
متن کاملDiscordant predictions of residual activity could impact dolutegravir prescription upon raltegravir failure.
BACKGROUND Dolutegravir is approved for the treatment of HIV-1 patients exposed to other integrase inhibitors, but the decision to use dolutegravir in this setting should be informed by drug resistance testing. OBJECTIVES This study determined the extent of disagreement in predicted residual dolutegravir activity after raltegravir use, and identified individual mutational patterns for which u...
متن کامل