OBJECTIVES Pharmacokinetic studies in animal models are important for assessing the prophylactic potential of antiretroviral drugs for HIV prevention. This study sought to identify clinically relevant doses of the marketed integrase inhibitors raltegravir, elvitegravir and dolutegravir in macaques and investigate drug penetration and antiviral activity in mucosal secretions. METHODS Macaques ...

INTRODUCTION Dolutegravir is a second generation integrase inhibitor with a proposed high genetic barrier to resistance. However, in clinical trials, decreased virological response was seen in a subset of patients with prior exposure to raltegravir and multiple integrase resistance mutations. METHODS We describe two cases of HIV subtype B-infected patients starting dolutegravir after previous...

Dolutegravir, cabotegravir, and bictegravir are three integrase inhibitors, which were used for HIV-1 in the clinic. In this paper, a continuous three-step synthetic strategy was developed to prepare dolutegravir, better yield, compared initial step-by-step procedure. Different solvents, temperature, times optimized. course of industrial production active pharmaceutical ingredient (API), protoc...

Human immunodeficiency virus (HIV) infection persists despite decades of active antiretroviral therapy (ART), effectively preventing viral eradication. Treatment decreases plasma viral RNA, but viral DNA persists, mostly integrated within the genome of nucleated blood cells. Viral DNA blood levels correlate with comorbidities and the rapidity of viral rebound following treatment interruption. T...

ObjectivesThe impact of very low-level viremia (VLLV) and (LLV) are rarely investigated among people living with HIV (PLWH) receiving dolutegravir- vs protease inhibitor (PI)-based antiretroviral therapy (ART).MethodsVirally suppressed PLWH long-term PI-containing ART were included in this study. The incidences developing VLLV (plasma RNA load (PVL) 20–49 copies/ml), LLV (PVL 50–999 virological...

HIV drug resistance has been one of the major obstacles to HIV eradication and has contributed to the need for the constant development of new antiretroviral drugs over the past 25 years. With the recent approval of dolutegravir for human therapy by the U.S. Food and Drug Administration, health practitioners may soon have access to three integrase strand transfer inhibitors to treat individuals...

We report two patients who had taken levothyroxine at the same dose for several years and who had stable thyroid stimulating hormone (TSH) levels, and who developed clinical and biological hyperthyroidism following switch from ritonavir-boosted protease inhibitors (PIs) to dolutegravir-based HAART. Levothyroxine is metabolized by deiodination and glucuronidation and the induction of glucuronida...

Novel integrase inhibitors are in advanced clinical development, and cross-resistance data are needed to consider the possibility to plan a sequential usage within this class of antiretroviral drugs. Ex vivo phenotypic assays were conducted on 11 wild-type and 27 fully replicating recombinant viruses obtained from 11 patients failing previous raltegravir-containing regimens. Dolutegravir mainta...

Bioanalysis is a chemical analysis used to determine the levels of xenobiotic substances and biotic in biological systems. In pharmaceutical world, bioanalysis plays role development new drugs, monitoring drug therapy, also bioequivalence. The bioanalytic research that will be discussed this journal about dolutegravir urine, saliva (saliva), blood plasma samples. technique can detect content sa...

Drug resistance prevents the successful treatment of HIV-positive individuals by decreasing viral sensitivity to a drug or a class of drugs. In addition to transmitted resistant viruses, treatment-naïve individuals can be confronted with the problem of drug resistance through de novo emergence of such variants. Resistant viruses have been reported for every antiretroviral drug tested so far, in...