Modulators of toll-like receptors for the treatment of HIV
Provided are methods, uses, pharmaceutical regimens, pharmaceutical compositions, and kits comprising modulators of TLR7, including those of Formula II: and pharmaceutically acceptable salts thereof, useful in treating HIV infections.
1. A method of treating an HIV infection in a human in need thereof, the method comprising
(a) administering to the human a pharmaceutically effective amount of a combination antiretroviral therapy regimen sufficient to lower the level of HIV detected in the human's blood or plasma to less than 50 copies of HIV-1 RNA per mL, thereby providing a virologically suppressed human;
(b) administering to the viroloically suppressed human a pharmaceutically effective amount of a TLR7 modulating compound having the formula
or a pharmaceutically acceptable salt thereof; and
(c) administering to the virologically suppressed human a pharmaceutically effective amount of broadly neutralizing HIV antibody PGT121,
thereby treating the HIV infection.
2. The method of claim 1 , wherein the TLR7 modulating compound is a compound of the formula:
or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the TLR7 modulating compound is a compound of the formula:
or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the combination antiretroviral therapy regimen comprises one or more agents selected from the group consisting of raltegravir, elvitegravir, soltegravir, GSK 1265744, dolutegravir, didanosine, tenofovir disoproxil fumarate, tenofovir alafenamide, emtricitabine, lamivudine, stavudine, zidovudine, abacavir, elvucitabine, CMX-157, festinavir, nevirapine, efavirenz, etravirine, rilpivirine, fosdevirine, MK-1439, lersivirine, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, saquinavir, tipranavir, fosamprenavir, maraviroc, enfuvirtide, BMS-663068, bevirimat, cobicistat, and ritonavir; or a pharmaceutically acceptable salt thereof.
5. The method of claim 1 , wherein the measurable viral load in the viroloically suppressed human is less than 20 copies of HIV-1 RNA per mL.
6. The method of claim 1 , further comprising the step of administering to the viroloically suppressed human a pharmaceutically effective amount of a latency-reversing agent.
7. A method of treating an HIV infection in a human in need thereof, the method comprising
(a) administering to the human a pharmaceutically effective amount of a combination antiretroviral therapy regimen sufficient to lower the level of HIV detected in the human's blood or plasma to less than 50 copies of HIV-1 RNA per mL, thereby providing a viroloically suppressed human;
(b) administering to the virologically suppressed human a pharmaceutically effective amount of
a TLR7 modulating compound having the formula
or a pharmaceutically acceptable salt thereof;
(c) administering to the virologically suppressed human a pharmaceutically effective amount of broadly neutralizing HIV antibody PGT 121; and
(d) administering to the virologically suppressed human a pharmaceutically effective amount of an HIV vaccine,
thereby treating the HIV infection.
8. The method of claim 7 , wherein the HIV vaccine is developed from Adenoviridae, Poxviridae, Herpesviridae, Adeno-associated viruses, rubella poliovirus, Venezuelan equine encephalitis virus, lentivirus or Sendai vectors.
9. The method of claim 7 , wherein the HIV vaccine comprises an Ad26 vector or a Modified Vaccinia Ankara (MVA) vector.