Biktarvy for treating HIV-1 infection

The U.S. Food and Drug Administration (FDA) has approved Biktarvy (bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg, BIC/FTC/TAF), a once-daily single tablet regimen (STR) for the treatment of HIV-1 infection.

Biktarvy combines the novel, unboosted integrase strand transfer inhibitor (INSTI) bictegravir, with the demonstrated safety and efficacy profile of the Descovy (FTC/TAF) dual nucleoside reverse transcriptase inhibitor (NRTI) backbone, and is the smallest INSTI-based triple-therapy STR available.

Biktarvy is indicated as a complete regimen for the treatment of HIV-1 infection in adults who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 c/mL) on a stable antiretroviral regimen for at least three months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy. No dosage adjustment of Biktarvy is required in patients with estimated creatinine clearance greater than or equal to 30 mL per minute.

Biktarvy does not require testing for HLA-B*5701, has no food intake requirements, and has no baseline viral load or CD4 count restrictions. According to Biktarvy’s Prescribing Information, prior to or when initiating treatment with Biktarvy, healthcare providers should test for hepatitis B virus (HBV) infection and renal function, and monitor renal function as clinically appropriate during therapy.

In clinical trials through 48 weeks, no patients taking the regimen of bictegravir plus FTC/TAF developed treatment-emergent resistance, results that were observed both in people new to therapy and those who were virologically suppressed and chose to switch regimens. The most common adverse reactions in patients taking Biktarvy were diarrhea, nausea and headache.

Biktarvy does not cure HIV infection or AIDS. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of Biktarvy.

Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Biktarvy. If appropriate, anti-hepatitis B therapy may be warranted. Coadministration: Do not use Biktarvy with dofetilide or rifampin. Most common adverse reactions (incidence ≥5%; all grades) in clinical studies were diarrhea (6%), nausea (5%), and headache (5%).
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Gene editing kills HIV-1 infection in animals

A permanent cure for HIV infection remains difficult because the virus can hide in their reservoirs.

 Scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) and the University of Pittsburgh show that they can remove HIV DNA from the genomes of living animals to prevent further infection.

They  demonstrate that HIV-1 replication can be removed completely and the virus eliminated from infected cells in animals with a powerful gene editing technology known as CRISPR/Cas9.

Previously, scientists used transgenic rat and mouse models with HIV-1 DNA incorporated into the genome of every tissue of the animals' bodies. They demonstrated that their strategy could delete the targeted fragments of HIV-1 from the genome in most tissues in the experimental animals.

In the new study, the team genetically inactivated HIV-1 in transgenic mice, reducing the RNA expression of viral genes by roughly 60 to 95 percent, confirming their earlier findings. They then tested their system in mice acutely infected with EcoHIV, the mouse equivalent of human HIV-1.

"During acute infection, HIV actively replicates. With EcoHIV mice, scientists were able to investigate the ability of the CRISPR/Cas9 strategy to block viral replication and potentially prevent systemic infection." The excision efficiency of their strategy reached 96 percent in EcoHIV mice, providing the first evidence for HIV-1 eradication by prophylactic treatment with a CRISPR/Cas9 system.

In the third animal model, latent HIV-1 infection was recapitulated in humanized mice engrafted with human immune cells, including T cells, followed by HIV-1 infection.

 "These animals carry latent HIV in the genomes of human T cells, where the virus can escape detection," Dr. Hu explained. Following a single treatment with CRISPR/Cas9, viral fragments were successfully excised from latently infected human cells embedded in mouse tissues and organs.

In all three animal models, the researchers utilized a recombinant adeno-associated viral (rAAV) vector delivery system based on a subtype known as AAV-DJ/8. "The AAV-DJ/8 subtype combines multiple serotypes, giving us a broader range of cell targets for the delivery of our CRISPR/Cas9 system,"