This article describes the potential of GS-6207, a small molecule that disrupts the functions of HIV capsid protein, as a long-acting agent to treat or prevent infection with HIV.
Clinical targeting of HIV capsid protein with a long-acting small molecule Read More »
The synthesis of the potent anti-HIV investigational treatment islatravir is described. The key step in this synthesis is a highly enantioselective catalytic asymmetric alkynylation of a ketone. This reaction is a rare example of the asymmetric addition of an alkyne nucleophile to a ketone through ligand-accelerated catalysis that was performed on a greater than 100
The emergence of new active pharmaceutical ingredient (API) polymorphs in pharmaceutical development presents significant risks. Even with thorough polymorph screening, new pathways toward alternate crystal phases can present themselves over the course of formulation development; thus, further improvements in phase screening methods are needed. Herein, a case study is presented of a thermodynamically stable crystalline
This study assess the terminal phase pharmacokinetics and safety of long-acting injectable cabotegravir in participants included in the HPTN 077 trial.
This is a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir-abacavir-lamivudine.
Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection. Read More »
This is a phase 3, open-label, multicenter, noninferiority trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter
Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression. Read More »
Single doses of islatravir as low as 0·5 mg significantly suppressed HIV-1 RNA by more than 1·0 log at day 7 in treatment-naive adults with HIV-1 infection and were generally well tolerated, supporting the further development of islatravir as a flexible-dose treatment for individuals with HIV-1 infection.
Long-acting injectable PrEP acceptability was high, especially at non-U.S. sites. Preferences for a LAI PrEP product compared to other methods was higher among males, many who were MSM, in the U.S., and higher among females in non-U.S. compared to U.S. sites, where both the need for new HIV prevention methods is greatest and contraceptive injectable
A stereoselective nine-step synthesis of the potent HIV nucleoside reverse transcriptase translocation inhibitor (NRTTI) islatravir (EfdA, MK-8591) from 2-deoxyribose is described. Key findings include a diastereodivergent addition of an acetylide nucleophile to an enolizable ketone, a chemoselective ozonolysis of a terminal olefin and a biocatalytic glycosylation cascade that uses a unique strategy of byproduct precipitation
Nine-Step Stereoselective Synthesis of Islatravir from Deoxyribose Read More »
The HIV Prevention Trials Network Study 077 evaluated changes in weight and fasting metabolic parameters in HIV-uninfected individuals randomized to cabotegravir or a placebo.
