Human immunodeficiency virus therapies utilizing N332-glycan-dependent antibodies and a reservoir activator

A method for inhibiting viral replication, reducing proviral DNA, or reducing viral load comprising administering to a subject infected with human immunodeficiency virus type 1 (HIV-1) a first regimen comprising one or more doses of an N332 glycan-dependent antibody and a reservoir activator until a proviral DNA level in a tissue of the subject is below about 1,000 DNA copies/106 cells, and, at least two months after completion of the first regimen, administering a second regimen comprising one or more doses of the N332 glycan-dependent antibody with or without a reservoir activator, wherein said N332 glycan-dependent antibody is selected from the group consisting of:

• (a) an antibody comprising:
• (i) a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 3, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• or
• (ii) a heavy chain variable domain having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:
• 7, and a light chain variable domain having at least 97% sequence identity to the sequence of SEQ ID NO:
• 8;
• (b) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 9, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 10, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 11, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 12, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 13, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 14;
• (c) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 17, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 18, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 19, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 20, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 21, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 22;
• (d) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 137, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 138, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 139, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 140, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 142, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 143;
• (e) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 25, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 26, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 27, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 28, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 29, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 30;
• (f) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 33, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 34, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 35, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 36, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 37, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 38;
• (g) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 41, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 42, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 43, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 44, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 45, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 46;
• (h) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 49, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 50, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 51, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 52, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 53, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 54;
• (i) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 57, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 58, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 59, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 60, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 61, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 62;
• (j) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 145, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 146, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 147, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 148, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 149, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 150;
• (k) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 153, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 154, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 155, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 156, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 157, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 158;
• (l) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 73, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 74, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 75, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 76, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 77, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 78;
• (m) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 81, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 82, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 83, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 84, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 85, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 86;
• (n) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 97, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 98, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 99, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 100, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 101, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 102;
• (o) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 169, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 170, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 171, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 172, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 173, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 174;
• (p) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 177, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 178, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 179, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 180, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 181, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 182;
• and
• (q) an antibody comprising
• a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 315, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 316, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 317, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 318, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 319, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 320.