Dolutegravir

About: Dolutegravir is a research topic. Over the lifetime, 1259 publications have been published within this topic receiving 23838 citations. The topic is also known as: GSK 1349572 & GSK-1349572.

Dolutegravir plus Abacavir–Lamivudine for the Treatment of HIV-1 Infection

Abstract: BACKGROUND Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir–lamivudine, may provide a simplified regimen. METHODS We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir–lamivudine once daily (DTG–ABC–3TC group) or combination therapy with efavirenz–tenofovir disoproxil fumarate (DF)–emtricitabine once daily (EFV–TDF–FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance. RESULTS A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG–ABC–3TC group than in the EFV–TDF–FTC group (88% vs. 81%, P = 0.003), thus meeting the criterion for superiority. The DTG– ABC–3TC group had a shorter median time to viral suppression than did the EFV– TDF–FTC group (28 vs. 84 days, P<0.001), as well as greater increases in CD4+ T-cell count (267 vs. 208 per cubic millimeter, P<0.001). The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG–ABC–3TC group than in the EFV–TDF–FTC group (2% vs. 10%); rash and neuropsychiatric events (including abnormal dreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV–TDF–FTC group, whereas insomnia was reported more frequently in the DTG–ABC–3TC group. No participants in the DTG– ABC–3TC group had detectable antiviral resistance; one tenofovir DF–associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV–TDF–FTC group. CONCLUSIONS Dolutegravir plus abacavir–lamivudine had a better safety profile and was more effective through 48 weeks than the regimen with efavirenz–tenofovir DF–emtricitabine. (Funded by ViiV Healthcare; SINGLE ClinicalTrials.gov number, NCT01263015.)

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society–USA Panel

Abstract: Importance New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. Objective To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. Evidence Review A panel of experts in HIV research and patient care convened by the International Antiviral Society–USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. Findings Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. Conclusions and Relevance Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.

Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model

Abstract: The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd