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HIV Pipeline Drugs: IAS 2017 Update

August 15, 2017

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MK-8591 (EFdA)

MK-8591 -- a very interesting NRTI in early stages of development -- is notable for a very high potency, a long-half life and the potential for use both as HIV treatment and for HIV prevention.

Oral dosing might be weekly, and PrEP includes the potential for a small removable slow-release implant that would last a year.

Two interesting studies were presented at IAS 2017.

The first, in 30 HIV positive participants, reported mean viral load reductions seven days after a single dose that ranged from approximately -1.2 logs (for the tiny 0.5 mg, 1.0 mg and 2.0 mg groups) to approximately -1.6 logs (for the 10 mg and 30 mg group).12

Both plasma and intracellular drug levels were dose-related, with higher doses achieving levels approximately 1 log higher with the half-life in PBMCs ranging from 78 to 128 hours, allowing for a wide range of potential dosing schedules.

For reasons that are unclear, and against the study protocol, one participant did not begin full ART (risking drug resistance by continued monotherapy) although neither viral load nor resistance data were presented for the case.

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The second study was for PrEP in 16 macaques randomised to oral MK-8591 or placebo every week for 12 weeks, and were exposed to SIV rectally every week.13

All animals receiving the placebo became infected within 1 to 4 challenges compared to none of the MK-8591 animals, even after 12 challenges with continued follow-up for a further three months. MK-8591 resulted in a 41.5-fold lower risk of infection (95% CI: 7.3 to 237.9) compared to placebo (p< 0.0001).

Mean intracellular trough concentrations of MK-8591-TP at the time of challenge were similar to levels achieved using a once-weekly 10 mg oral dose of 10mg in HIV positive human studies.

Further details of both studies are included in a separate HTB report.14


Fostemsavir

Fostemsavir is an attachment inhibitor in phase 3 studies that as a new class of HIV drug might be especially important for people who have multidrug resistance to current ARVs.

Although no new efficacy or safety results were presented at IAS 2017 -- the ongoing phase 3 study doesn't finish until 2020 -- two small drug interactions studies were presented as posters.

The first reported increases in levels of methadone or buprenorphine, with a caution for monitoring for signs of sedation, but without a routine need to dose-adjust.15

The second poster reported that fostemsavir can be safely taken with a combined oral contraceptive containing norethindrone (1.5 mg) and reduced dose ethinyl estradiol (30 ug).16


Elsulfavirine

Finally, a poster was presented on a study in dogs for subcutaneous and intramuscullar injections of the new nanoformulations of investigational NNRTI elsulfavirine or its prodrug (VS-1500A) that is being developed for potential as treatment and prevention in some middle-income countries.17

Single injections of both SC and IM formulations of the prodrug maintained therapeutic drug levels for at least four weeks.


References

Unless stated otherwise, abstracts refer to the 9th IAS Conference on HIV Science, 23-26 July 2017, Paris.

  1. Collins S. HIV pipeline 2017: new drugs in development. HTB July 2017.
    http://i-base.info/pipeline-2017
  2. Molina JM et al. Efficacy and safety of switching from boosted-protease inhibitor plus emtricitabine/tenofovir disoproxil fumarate regimens to the single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in virologically-suppressed, HIV-1-infected adults through 24 weeks: EMERALD study. Oral abstract TUAB0101.
    http://programme.ias2017.org/Abstract/Abstract/4194
  3. Collins S. Darunavir/cobicistat/FTC/TAF: 24-week interim results from phase 3 switch study. HTB July/August 2017.
    http://i-base.info/htb/32165
  4. Gallant J et al. A phase 3 randomized controlled clinical trial of bictegravir in a fixed dose combination, B/F/TAF, vs ABC/DTG/3TC in treatment-naïve adults at week 48. IAS 2017, Paris. Late breaker oral abstract MOAB0105LB.
    http://programme.ias2017.org/Abstract/Abstract/5783
  5. Sax P et al. Phase 3 randomized, controlled clinical trial of bictegravir coformulated with FTC/TAF in a fixed-dose combination (B/F/TAF) vs dolutegravir (DTG) + F/TAF in treatment-naïve HIV-1 positive adults: week 48 results. IAS 2017, Paris. Late breaker poster abstract TUPDB0201LB.
    http://programme.ias2017.org/Abstract/Abstract/5793
  6. Collins S. Phase 3 results with bictegravir FDC: a new integrase inhibitor combined with FTC/TAF. HTB July/August 2017.
    http://i-base.info/htb/32149
  7. Squires KE et al. Fixed dose combination of doravirine/lamivudine/TDF is non-inferior to efavirenz/emtricitabine/TDF in treatment-naïve adults with HIV-1 infection: week 48 results of the Phase 3 DRIVE-AHEAD study. IAS 2017, Paris. Late breaker.
    http://programme.ias2017.org/Abstract/Abstract/5585
  8. Collins S. Doravirine/3TC/TDF compared to efavirenz/FTC/TDF as first-line ART. HTB July/August 2017.
    http://i-base.info/htb/32209
  9. Eron J et al. Safety and efficacy of long-acting CAB and RPV as two drug IM maintenance therapy: LATTE-2 week 96 results. IAS 2017, Paris. Late breaker oral abstract MOAX0205LB.
    http://programme.ias2017.org/Abstract/Abstract/5628
  10. Collins S. Continued viral suppression with long-acting cabotegravir/rilpivirine injections: 96-week LATTE-2 results. HTB July/August 2017.
    http://i-base.info/htb/32214
  11. Weinheimer S et al. Long-acting ibalizumab susceptibility in multi-drug resistant HIV patients. IAS 2017, Paris. Poster abstract MOPEB0352.
    http://programme.ias2017.org/Abstract/Abstract/4685
  12. Matthews RP. Single doses as low as 0.5 mg of the novel NRTTI MK-8591 suppress HIV for at least seven days. IAS 2017, Paris. Late breaker poster abstract TUPDB020.
    http://programme.ias2017.org/Abstract/Abstract/5525 (abstract and poster)
  13. Markowitz M et al. Weekly oral MK-8591 protects male rhesus macaques against repeated low dose intrarectal challenge with SHIVC109P3. IAS 2017, Paris. Late breaker oral abstract MOAX0203LB.
    http://programme.ias2017.org/Abstract/Abstract/5533
  14. Collins S. MK-8591: further compelling early results for both treatment and prevention. HTB July/August 2017.
    http://i-base.info/htb/32246
  15. Sevinsky H et al. The effect of fostemsavir on methadone and buprenorphine pharmacokinetics. IAS 2017, Paris. Poster abstract MOPEB0338.
    http://programme.ias2017.org/Abstract/Abstract/3300
  16. Magee M et al. The effect of fostemsavir on the pharmacokinetics of a combined oral contraceptive (OC) containing ethinyl estradiol (EE) and norethindrone (NE) in healthy female subjects. IAS 2017, Paris. Poster abstract MOPEB0339.
    http://programme.ias2017.org/Abstract/Abstract/3312
  17. Bichko V et al. Pre-clinical pharmacokinetics of elsulfavirine/VM1500A long acting injectable formulations. IAS 2017, Paris. Poster abstract WEPEA0190.
    http://programme.ias2017.org/Abstract/Abstract/1515

[Note from TheBodyPRO.com: This article was originally published by HIV i-Base on Aug. 10, 2017. We have cross-posted it with their permission.]

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This article was provided by HIV i-Base. It is a part of the publication The 9th International AIDS Society Conference on HIV Science. Visit HIV i-Base's website to find out more about their activities, publications and services.
 

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