Claims for Patent: 6,635,646

Summary for Patent: 6,635,646

Title:	Pegylated interferon alfa-CCR5 antagonist combination HIV therapy
Abstract:	Methods for treating treatment-naive as well as treatment-experienced adult and pediatric patients having HIV-1 infections as well as patients co-infected with HIV-1 and HCV involving administering a therapeutically effective amount of pegylated interferon-alfa, e.g., pegylated interferon alfa-2b, in association with a therapeutically effective amount of a CCR5 antagonist or preferably further in association with a therapeutically effective amount of at least one of ribavirin, IL-2, IL-12, pentafuside alone or in combination with a therapeutically effective amount of an anti-HIV-1 drug therapy, e.g., HAART are disclosed.
Inventor(s):	Laughlin; Mark A. (Edison, NJ)
Assignee:	Schering Corporation (Kenilworth, NJ)
Application Number:	09/562,729
Patent Claims:	1. A method of treating patients having HIV-1 infections which comprises administering a therapeutically effective amount of pegylated interferon-alfa in association with a therapeutically effective amount of a CCR5 antagonist represented by the structural formula I or II or III or IV: ##STR65## or a pharmaceutically acceptable salt of I or II or III or IV, sufficient to lower HIV-1-RNA levels; wherein in the CCR5 antagonist compounds represented by structural formula I: ##STR66## X is --C(R.sup.13).sub.2 --, --C(R.sup.13)(R.sup.19)--, --C(O)--, --O--, --NH--, --N((C.sub.1 -C.sub.6)alkyl)--, ##STR67## R is R.sup.6 -phenyl, R.sup.6 -pyridyl, R.sup.6 -thiophenyl or R.sup.6 -naphthyl; R.sup.1 is hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.2 -C.sub.6 alkenyl; R.sup.2 is R.sup.7, R.sup.8, R.sup.9 -phenyl; R.sup.7, R.sup.8, R.sup.9 -substituted 6-membered heteroaryl; R.sup.7, R.sup.8, R.sup.9 -substituted 6-membered heteroaryl N-oxide; R.sup.10, R.sup.11 -substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl ##STR68## ##STR69## R.sup.3 is R.sup.6 -phenyl, R.sup.6 -heteroaryl or R.sup.6 -naphthyl; R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, fluoro-C.sub.1 -C.sub.6 alkyl, cyclopropylmethyl, --CH.sub.2 CH.sub.2 OH, --CH.sub.2 CH.sub.2 --O--(C.sub.1 -C.sub.6)akyl, --CH.sub.2 C(O)--O--(C.sub.1 -C.sub.6)alkyl, --CH.sub.2 C(O)NH.sub.2, --CH.sub.2 C(O)--NH(C.sub.1 -C.sub.6)alkyl or --CH.sub.2 C(O)--N((C.sub.1 -C.sub.6)alkyl).sub.2 ; R.sup.5 and R.sup.11 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6)-alkyl; R.sup.6 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, --CF.sub.3, CF.sub.3 O--, CH.sub.3 C(O)--, --CN, CH.sub.3 SO.sub.2 --, CF.sub.3 SO.sub.2 --, R.sup.14 -phenyl, R.sup.14 -benzyl, CH.sub.3 C(.dbd.NOCH.sub.3)--, CH.sub.3 C(.dbd.NOCH.sub.2 CH.sub.3)--, ##STR70## --NH.sub.2, --NHCOCF.sub.3, --NHCONH(C.sub.1 -C.sub.6 alkyl), --NHCO(C.sub.1 -C.sub.6 alkyl), --NHSO.sub.2 (C.sub.1 -C.sub.6 alkyl), 5-membered heteroaryl and ##STR71## wherein X.sup.b is --O--, --NH-- or --N(CH.sub.3)--; R.sup.7 and R.sup.8 are independently selected from the group consisting of (C.sub.1 -C.sub.6)alkyl, halogen, --NR.sup.20 R.sup.21, --OH, --CF.sub.3, --OCH.sub.3, --O-acyl, and --OCF.sub.3 ; R.sup.9 is R.sup.7, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2 F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.20, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.20)CONR.sup.21 R.sup.22, --NHCONH(chloro-(C.sub.1 -C.sub.6)alkyl), --NHCONH((C.sub.3 -C.sub.10)-cycloalkyl(C.sub.1 -C.sub.6)alkyl), --NHCO(C.sub.1 -C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2 N((C.sub.1 -C.sub.6)alkyl).sub.2, --NHSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --N(SO.sub.2 CF.sub.3).sub.2, --NHCO.sub.2 (C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.10 cycloalkyl, --SR.sup.23, --SOR.sup.23, --SO.sub.2 R.sup.23, --SO.sub.2 NH(C.sub.1 -C.sub.6 alkyl), --OSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --OSO.sub.2 CF.sub.3, hydroxy(C.sub.1 -C.sub.6)alkyl, --CON R.sup.20 R.sup.21, --CON(CH.sub.2 CH.sub.2 --O--CH.sub.3).sub.2, --OCONH(C.sub.1 -C.sub.6)alkyl, --CO.sub.2 R.sup.20, --Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2 ; R.sup.10 is (C.sub.1 -C.sub.6)alkyl, --NH.sub.2 or R.sup.12 -phenyl; R.sup.12 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6) alkyl, --CF.sub.3, --CO.sub.2 R.sub.20, --CN, (C.sub.1 -C.sub.6)alkoxy and halogen; R.sup.13, R.sup.14, R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6)alkyl; R.sup.17 and R.sup.18 are independently selected from the group consisting of hydrogen and C.sub.1 -C.sub.6 alkyl, or R.sup.17 and R.sup.18 together are a C.sub.2 -C.sub.5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R.sup.19 is R.sup.6 -phenyl, R.sup.6 -heteroaryl, R.sup.6 -naphthyl, C.sub.3 -C.sub.10 cycloalkyl, (C.sub.3 -C.sub.10)cycloalkyl(C.sub.1 -C.sub.6)alkyl or (C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl; R.sup.20, R.sup.21 and R.sup.22 are independently selected from the group consisting of H and C.sub.1 -C.sub.6 alkyl; and R.sup.23 is C.sub.1 -C.sub.6 alkyl or phenyl; and wherein in the CCR5 antagonist compounds represented by the structural formula II: ##STR72## or a pharmaceutically acceptable salt thereof, wherein (1) X.sup.a is --C(R.sup.13).sub.2 --, --C(R.sup.13)(R.sup.19)--, --C(O)--, --O--, --NH--, --N((C.sub.1 -C.sub.6)alkyl)--, ##STR73## R.sup.a is R.sup.6a -phenyl, R.sup.6a -pyridyl, R.sup.6a -thiophenyl or R.sup.6 -naphthyl; R.sup.1 is hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.2 -C.sub.6 alkenyl; R.sup.2 is R.sup.7, R.sup.8, R.sup.9 -phenyl; R.sup.7, R.sup.8, R.sup.9 -substituted 6-membered heteroaryl; R.sup.7, R.sup.8, R.sup.9 -substituted 6-membered heteroaryl N-oxide; R.sup.10, R.sup.11 -substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl ##STR74## or ##STR75## R.sup.3 is R.sup.10 -phenyl, pyridyl, pyrimidyl, pyrazinyl or thiazolyl; R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, fluoro-C.sub.1 -C.sub.6 alkyl, cyclopropylmethyl, --CH.sub.2 CH.sub.2 OH, --CH.sub.2 CH.sub.2 --O--(C.sub.1 -C.sub.6)alkyl, --CH.sub.2 C(O)--O--(C.sub.1 -C.sub.6)alkyl, --CH.sub.2 C(O)NH.sub.2, --CH.sub.2 C(O)--NH(C.sub.1 -C.sub.6)alkyl or --CH.sub.2 C(O)--N((C.sub.1 -C.sub.6)alkyl).sub.2 ; R.sup.5 and R.sup.11 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6)-alkyl; R.sup.6a is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, --CF.sub.3, CF.sub.3 O--, --CN, --CF.sub.3 SO.sub.2 --, R.sup.12 -phenyl, --NHCOCF.sub.3, 5-membered heteroaryl and ##STR76## wherein X.sup.b is --O--, --NH-- or --N(CH.sub.3)--; R.sup.6 is independently selected from the group consisting of R.sup.6a and CH.sub.3 SO.sub.2 --; R.sup.7 and R.sup.8 are independently selected from the group consisting of (C.sub.1 -C.sub.6)alkyl, halogen, --NR.sup.20 R.sup.21, --OH, --CF.sub.3, --OCH.sub.3, --O-acyl, and --OCF.sub.3 ; R.sup.9 is R.sup.7, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2 F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.20, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.20)CONR.sup.21 R.sup.22, --NHCONH(chloro-(C.sub.1 -C.sub.6)alkyl), --NHCONH((C.sub.3 -C.sub.10)-cycloalkyl(C.sub.1 -C.sub.6)alkyl), --NHCO(C.sub.1 -C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2 N((C.sub.1 -C.sub.6)alkyl).sub.2, --NHSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --N(SO.sub.2 CF.sub.3).sub.2, --NHCO.sub.2 (C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.10 cycloalkyl, --SR.sup.23, --SOR.sup.23, --SO.sub.2 R.sup.23, --SO.sub.2 NH(C.sub.1 -C.sub.6 alkyl), --OSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --OSO.sub.2 CF.sub.3, hydroxy(C.sub.1 -C.sub.6)alkyl, --CON R.sup.20 R.sup.21, --CON(CH.sub.2 CH.sub.2 --O--CH.sub.3).sub.2, --OCONH(C.sub.1 -C.sub.6)alkyl, --CO.sub.2 R.sup.20, --Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2 ; R.sup.10 is (C.sub.1 -C.sub.6)alkyl, --NH.sub.2 or R.sup.12 -phenyl; R.sup.12 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6) alkyl, --CF.sub.3, --CO.sub.2 R.sub.20, --CN, (C.sub.1 -C.sub.6)alkoxy and halogen; R.sup.13, R.sup.14, R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6)alkyl; R.sup.17 and R.sup.18 are independently selected from the group consisting of hydrogen and C.sub.1 -C.sub.6 alkyl, or R.sup.17 and R.sup.18 together are a C.sub.2 -C.sub.5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R.sup.19 is R.sup.6 -phenyl, R.sup.6 -heteroaryl, R.sup.6 -naphthyl, C.sub.3 -C.sub.10 cycloalkyl, (C.sub.3 -C.sub.10)cycloalkyl(C.sub.1 -C.sub.6)alkyl or (C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl; R.sup.20, R.sup.21 and R.sup.22 are independently selected from the group consisting of H and C.sub.1 -C.sub.6 alkyl; and R.sup.23 is C.sub.1 -C.sub.6 alkyl or phenyl; or (2): X.sup.a is --C(R.sup.13)(R.sup.19)--, --C(O)--, --O--, --NH--, --N((C.sub.1 -C.sub.6)alkyl)-, ##STR77## R.sup.a is R.sup.6b -phenyl, R.sup.6b -pyridyl or R.sup.6b -thiophenyl; R.sup.4a is fluoro-C.sub.1 -C.sub.6 alkyl, cyclopropylmethyl, --CH.sub.2 CH.sub.2 OH, --CH.sub.2 CH.sub.2 --O--(C.sub.1 -C.sub.6)alkyl, --CH.sub.2 C(O)--O--(C.sub.1 -C.sub.6)alkyl, --CH.sub.2 C(O)NH.sub.2, --CH.sub.2 C(O)--NH--(C.sub.1 -C.sub.6)alkyl or --CH.sub.2 C(O)--N((C.sub.1 -C.sub.6)alkyl).sub.2 ; R.sup.6b is CH.sub.3 SO.sub.2 --; and R.sup.1, R.sup.2, R.sup.3, R.sup.5, R.sup.14, R.sup.15, R.sup.16 and R.sup.19 are as defined in II(1); and wherein in the CCR5 antagonist compounds represented by the structural formula III: ##STR78## R is R.sup.8 -phenyl, R.sup.8 -pyridyl, R.sup.8 -thiophenyl or R.sup.8 -naphthyl; R.sup.1 is hydrogen or C.sub.1 -C.sub.6 alkyl; R.sup.2 is R.sup.9, R.sup.10, R.sup.11 -phenyl; R.sup.9, R.sup.10, R.sup.11 -substituted 6-membered heteroaryl; R.sup.9, R.sup.10, R.sup.11 -substituted 6-membered heteroaryl N-oxide; R.sup.12, R.sup.13 -substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl ##STR79## or ##STR80## R.sup.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, (C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.3 -C.sub.10 cycloalkyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -phenyl, R.sup.8 -phenyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -naphthyl, R.sup.8 -naphthyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -heteroaryl or R.sup.8 -heteroaryl(C.sub.1 -C.sub.6)alkyl; R.sup.4, R.sup.5, R.sup.7 and R.sup.13 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6)-alkyl; R.sup.6 is hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.2 -C.sub.6 alkenyl; R.sup.8 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, --CF.sub.3, CF.sub.3 O--, CH.sub.3 C(O)--, --CN, CH.sub.3 SO.sub.2 --, CF.sub.3 SO.sub.2 --, R.sup.14 -phenyl, R.sup.14 -benzyl, CH.sub.3 C(.dbd.NOCH.sub.3), CH.sub.3 C(.dbd.NOCH.sub.2 CH.sub.3), ##STR81## --NH.sub.2, --NHCOCF.sub.3, --NHCONH(C.sub.1 -C.sub.6 alkyl), --NHCO(C.sub.1 -C.sub.6 alkyl), --NHSO.sub.2 (C.sub.1 -C.sub.6 alkyl), 5-membered heteroaryl and ##STR82## wherein X.sup.b is --O--, --NH-- or --N(CH.sub.3)--; R.sup.9 and R.sup.10 are independently selected from the group consisting of (C.sub.1 -C.sub.6)alkyl, halogen, --NR.sup.17 R.sup.18, --OH, --CF.sub.3, --OCH.sub.3, --O-acyl, --OCF.sub.3 and --Si(CH.sub.3).sub.3 ; R.sup.11 is R.sup.9, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2 F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.17, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.17)CONR.sup.18 R.sup.19, --NHCONH(chloro-(C.sub.1 -C.sub.6)alkyl), --NHCONH((C.sub.3 -C.sub.1)cycloalkyl(C.sub.1 -C.sub.6)alkyl), --NHCO(C.sub.1 -C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2 N((C.sub.1 -C.sub.6)alkyl).sub.2, --NHSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --N(SO.sub.2 CF.sub.3).sub.2, --NHCO.sub.2 (C.sub.1 -C.sub.3)alkyl, C.sub.3 -C.sub.10 cycloalkyl, --SR.sup.20, --SOR.sup.20, --SO.sub.2 R.sup.20, --SO.sub.2 NH(C.sub.1 -C.sub.6 alkyl), --OSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --OSO.sub.2 CF.sub.3, hydroxy(C.sub.1 -C.sub.6)alkyl, --CON R.sup.17 R.sup.18, --CON(CH.sub.2 CH.sub.2 --O--CH.sub.3).sub.2, --OCONH(C.sub.1 -C.sub.6)alkyl, --CO.sub.2 R.sup.17, --Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2 ; R.sup.12 is (C.sub.1 -C.sub.6)alkyl, --NH.sub.2 or R.sup.14 -phenyl; R.sup.14 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6) alkyl, --CF.sub.3, --CO.sub.2 R.sub.17, --CN, (C.sub.1 -C.sub.6)alkoxy and halogen; R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and C.sub.1 -C.sub.6 alkyl, or R.sup.15 and R.sup.16 together are a C.sub.2 -C.sub.5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R.sup.17, R.sup.18 and R.sup.19 are independently selected from the group consisting of H and C.sub.1 -C.sub.6 alkyl; and R.sup.20 is C.sub.1 -C.sub.6 alkyl or phenyl; and wherein in the CCR5 antagopnist compounds represented by the structural formula IV: ##STR83## or a pharmaceutically acceptable salt thereof, wherein (1) R.sup.a is R.sup.8a -phenyl, R.sup.8b -pyridyl, R.sup.8b -thiophenyl or R.sup.8 -naphthyl; R.sup.1 is hydrogen or C.sub.1 -C.sub.6 alkyl; R.sup.2 is R.sup.9, R.sup.10, R.sup.11 -phenyl; R.sup.9, R.sup.10, R.sup.11 -substituted 6-membered heteroaryl; R.sup.9, R.sup.10, R.sup.11 -substituted 6-membered heteroaryl N-oxide; R.sup.12, R.sup.13 -substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl, ##STR84## or ##STR85## R.sup.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, (C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.3 -C.sub.10 cycloalkyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -phenyl, R.sup.8 -phenyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -naphthyl, R.sup.8 -naphthyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -heteroaryl or R.sup.8 -heteroaryl(C.sub.1 -C.sub.6)alkyl; R.sup.4, R.sup.5, R.sup.7 and R.sup.13 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6)-alkyl; R.sup.6 is hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.2 -C.sub.6 alkenyl; R.sup.8 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, --CF.sub.3, CF.sub.3 O--, CH.sub.3 C(O)--, --CN, CH.sub.3 SO.sub.2 --, CF.sub.3 SO.sub.2 --, R.sup.14 -phenyl, R.sup.14 -benzyl, CH.sub.3 C(.dbd.NOCH.sub.3), CH.sub.3 C(.dbd.NOCH.sub.2 CH.sub.3), ##STR86## --NH.sub.2, --NHCOCF.sub.3, --NHCONH(C.sub.1 -C.sub.6 alkyl), --NHCO(C.sub.1 -C.sub.6 alkyl), --NHSO.sub.2 (C.sub.1 -C.sub.6 alkyl), 5-membered heteroaryl and ##STR87## wherein X.sup.b is --O--, --NH-- or --N(CH.sub.3)--; R.sup.8a is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, --CF.sub.3, CF.sub.3 O--, --CN, CF.sub.3 SO.sub.2 --, R.sup.14 -phenyl, --NHCOCF.sub.3, 5-membered heteroaryl and ##STR88## wherein X.sup.b is as defined above; R.sup.8b is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, --CF.sub.3, CF.sub.3 O--, CH.sub.3 C(O)--, --CN, CF.sub.3 SO.sub.2 --, R.sup.14 -benzyl, CH.sub.3 C(.dbd.NOCH.sub.3), CH.sub.3 C(.dbd.NOCH.sub.2 CH.sub.3), ##STR89## --NHCOCF.sub.3, 5-membered heteroaryl and ##STR90## wherein X.sup.b is as defined above; R.sup.9 and R.sup.10 are independently selected from the group consisting of (C.sub.1 -C.sub.6)alkyl, halogen, --NR.sup.17 R.sup.18, --OH, --CF.sub.3, --OCH.sub.3, --O-acyl, --OCF.sub.3 and --Si(CH.sub.3).sub.3 ; R.sup.11 is R.sup.9, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2 F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.17, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.17)CONR.sup.18 R.sup.19, --NHCONH(chloro-(C.sub.1 -C.sub.6)alkyl), --NHCONH((C.sub.3 -C.sub.1) cycloalkyl(C.sub.1 -C.sub.6)alkyl), --NHCO(C.sub.1 -C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2 N((C.sub.1 -C.sub.6)alkyl).sub.2, --NHSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --N(SO.sub.2 CF.sub.3).sub.2, --NHCO.sub.2 (C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.10 cycloalkyl, --SR.sup.20, --SOR.sup.20, --SO.sub.2 R.sup.20, --SO.sub.2 NH(C.sub.1 -C.sub.6 alkyl), --OSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --OSO.sub.2 CF.sub.3, hydroxy(C.sub.1 -C.sub.6)alkyl, --CON R.sup.17 R.sup.18, --CON(CH.sub.2 CH.sub.2 --O--CH.sub.3).sub.2, --OCONH(C.sub.1 -C.sub.6)alkyl, --CO.sub.2 R.sup.17, --Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2 ; R.sup.12 is (C.sub.1 -C.sub.6)alkyl, --NH.sub.2 or R.sup.14 -phenyl; R.sup.14 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6) alkyl, --CF.sub.3, --CO.sub.2 R.sub.17, --CN, (C.sub.1 -C.sub.6)alkoxy and halogen; R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and C.sub.1 -C.sub.6 alkyl, or R.sup.15 and R.sup.16 together are a C.sub.2 -C.sub.5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R.sup.17, R.sup.18 and R.sup.19 are independently selected from the group consisting of H and C.sub.1 -C.sub.6 alkyl; and R.sup.20 is C.sub.1 -C.sub.6 alkyl or phenyl; or (2) R.sup.a is R.sup.8 -phenyl, R.sup.8 -pyridyl or R.sup.8 -thiophenyl; R.sup.2 is fluorenyl, diphenylmethyl, ##STR91## or ##STR92## and R.sup.1, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19 and R.sup.20 are defined in IV(1). 2. The method of claim 1, wherein the patients are treatment-naive patients. 3. The method of claim 1, wherein the patients are treatment-experienced patients. 4. The method of claim 1, wherein the pegylated interferon-alfa administered is pegylated interferon alfa-2a or pegylated interferon alfa-2b. 5. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.1 to about 9.0 micrograms per kilogram once a week. 6. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.5 to about 3.0 micrograms per kilogram once a week. 7. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.75 to about 1.5 micrograms per kilogram once a week. 8. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b. 9. The method of claim 1, wherein the pegylated interferon alfa administered is pegylated interferon alfa-2b, and wherein the pegylated interferon alfa-2b and CCR5 antagonist are administered with Highly Active Antiretroviral Therapy. 10. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2a and the amount of pegylated interferon alfa-2a administered is in the range of about 50 to about 500 micrograms once a week. 11. The method of claim 1, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2a and the amount of pegylated interferon alfa-2a administered is in the range of about 200 to about 250 micrograms once a week. 12. The method of claim 1, which further comprises administering a therapeutically effective amount of at least one of ribavirin, IL-2, IL-12, pentafuside alone or in combination with a therapeutically effective amount of Highly Active Antiretroviral Therapy. 13. A method of treating pediatric patients having HIV-1 infections which comprises administering a therapeutically effective amount of pegylated interferon-alfa in association with a therapeutically effective amount of Highly Active Antiretroviral Therapy and a therapeutically effective amount of a CCR5 antagonist represented by the structural formula I or II or III or IV: ##STR93## or a pharmaceutically acceptable salt of I or II or II or IV; sufficient to lower HIV-1RNA levels; wherein in the CCR5 antagonist compounds represented by structural formula I: ##STR94## X is --C(R.sup.13).sub.2 --, --C(R.sup.13)(R.sup.19)--, --C(O)--, --O--, --NH--, --N((C.sub.1 -C.sub.6)alkyl)-, ##STR95## R is R.sup.6 -phenyl, R.sup.6 -pyridyl, R.sup.6 -thiophenyl or R.sup.6 -naphthyl; R.sup.1 is hydrogen, (C.sub.1 -C.sub.6) alkyl or (C.sub.2 -C.sub.6) alkenyl; R.sup.2 is R.sup.7, R.sup.8, R.sup.9 -phenyl; R.sup.7, R.sup.8, R.sup.9 -substituted 6-membered heteroaryl; R.sup.7, R.sup.8, R.sup.9 -substituted 6-membered heteroaryl N-oxide; R.sup.10, R.sup.11 -substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl ##STR96## or ##STR97## R.sup.3 is R.sup.6 -phenyl, R.sup.6 -heteroaryl or R.sup.6 -naphthyl; R.sup.4 is hydrogen, (C.sub.1 -C.sub.6) alkyl, fluoro-(C.sub.1 -C.sub.6) alkyl, cyclopropylmethyl, --CH.sub.2 CH.sub.2 OH, --CH.sub.2 CH.sub.2 --O--(C.sub.1 -C.sub.6)alkyl, --CH.sub.2 C(O)--O--(C.sub.1 -C.sub.6)alkyl, --CH.sub.2 C(O)NH.sub.2, --CH.sub.2 C(O)--NH(C.sub.1 -C.sub.6)alkyl or --CH.sub.2 C(O)--N((C.sub.1 -C.sub.6)alkyl).sub.2 ; R.sup.5 and R.sup.11 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6)-alkyl; R.sup.6 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, (C.sub.1 -C.sub.6) alkyl, C.sub.1 -C.sub.6 alkoxy, --CF.sub.3, CF.sub.3 O--, CH.sub.3 C(O)--, --CN, CH.sub.3 SO.sub.2 --, CF.sub.3 SO.sub.2 --, R.sup.14 -phenyl, R.sup.14 -benzyl, CH.sub.3 C(.dbd.NOCH.sub.3)--, CH.sub.3 C(.dbd.NOCH.sub.2 CH.sub.3)--, ##STR98## --NH.sub.2, --NHCOCF.sub.3, --NHCONH(C.sub.1 -C.sub.6 alkyl), --NHCO(C.sub.1 -C.sub.6 alkyl), --NHSO.sub.2 (C.sub.1 -C.sub.6 alkyl), 5-membered heteroaryl and ##STR99## wherein X.sup.b is --O--, --NH-- or --N(CH.sub.3)--; R.sup.7 and R.sup.8 are independently selected from the group consisting of (C.sub.1 -C.sub.6)alkyl, halogen, --NR.sup.20 R.sup.21, --OH, --CF.sub.3, --OCH.sub.3, --O-acyl, and --OCF.sub.3 ; R.sup.9 is R.sup.7, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2 F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.20, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.20)CONR21R.sup.22, --NHCONH(chloro-(C.sub.1 -C.sub.6)alkyl), --NHCONH((C.sub.3 -C.sub.10)-cycloalkyl(C.sub.1 -C.sub.6)alkyl), --NHCO(C.sub.1 -C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2 N((C.sub.1 -C.sub.6)alkyl).sub.2, --NHSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --N(SO.sub.2 CF.sub.3).sub.2, --NHCO.sub.2 (C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.10 cycloalkyl, --SR.sup.23, --SOR.sup.23, --SO.sub.2 R.sup.23, --SO.sub.2 NH(C.sub.1 -C.sub.6 alkyl), --OSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --OSO.sub.2 CF.sub.3, hydroxy(C.sub.1 -C.sub.6)alkyl, --CON R.sup.20 R.sup.21, --CON(CH.sub.2 CH.sub.2 --O--CH.sub.3).sub.2, --OCONH(C.sub.1 -C.sub.6)alkyl, --CO.sub.2 R.sup.20, --Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2 ; R.sup.10 is (C.sub.1 -C.sub.6)alkyl, --NH.sub.2 or R.sup.12 -phenyl; R.sup.12 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6) alkyl, --CF.sub.3, --CO.sub.2 R.sub.20, --CN, (C.sub.1 -C.sub.6)alkoxy and halogen; R.sup.13, R.sup.14, R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6)alkyl; R.sup.17 and R.sup.18 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6) alkyl, or R.sup.17 and R.sup.18 together are a C.sub.2 -C.sub.5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R.sup.19 is R.sup.6 -phenyl, R.sup.6 -heteroaryl, R.sup.6 -naphthyl, C.sub.3 -C.sub.10 cycloalkyl, (C.sub.3 -C.sub.10)cycloalkyl(C.sub.1 -C.sub.6)alkyl or (C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl; R.sup.20, R.sup.21 and R.sup.22 are independently selected from the group consisting of H and C.sub.1 -C.sub.6 alkyl; and R.sup.23 is (C.sub.1 -C.sub.6) alkyl or phenyl; and wherein in the CCR5 antagonist compounds represented by the structural formula II: ##STR100## or a pharmaceutically acceptable salt thereof, wherein (1) X.sup.a is --C(R.sup.13).sub.2 --, --C(R.sup.13)(R.sup.19)--, --C(O)--, --O--, --NH--, --N((C.sub.1 -C.sub.6)alkyl)-, ##STR101## R.sup.a is R.sup.6a -phenyl, R.sup.6a -pyridyl, R.sup.6a -thiophenyl or R.sup.6 -naphthyl; R.sup.1 is hydrogen, (C.sub.1 -C.sub.6) alkyl or (C.sub.2 -C.sub.6)alkenyl; R.sup.2 is R.sup.7, R.sup.8, R.sup.9 -phenyl; R.sup.7, R.sup.8, R.sup.9 -substituted 6-membered heteroaryl; R.sup.7, R.sup.8, R.sup.9 -substituted 6-membered heteroaryl N-oxide; R.sup.10, R.sup.11 -substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl ##STR102## or ##STR103## R.sup.3 is R.sup.10 -phenyl, pyridyl, pyrimidyl, pyrazinyl or thiazolyl; R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, fluoro-C.sub.1 -C.sub.6 alkyl, cyclopropylmethyl, --CH.sub.2 CH.sub.2 OH, --CH.sub.2 CH.sub.2 --O--(C.sub.1 -C.sub.6)alkyl, --CH.sub.2 C(O)--O--(C.sub.1 -C.sub.6)alkyl, --CH.sub.2 C(O)NH.sub.2, --CH.sub.2 C(O)--NH(C.sub.1 -C.sub.6)alkyl or --CH.sub.2 C(O)--N((C.sub.1 -C.sub.6)alkyl).sub.2 ; R.sup.5 and R.sup.11 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6)-alkyl; R.sup.6a is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, --CF.sub.3, CF.sub.3 O--, --CN, --CF.sub.3 SO.sub.2 --, R.sup.12 -phenyl, --NHCOCF.sub.3, 5-membered heteroaryl and ##STR104## wherein X.sup.b is --O--, --NH-- or --N(CH.sub.3)--; R.sup.6 is independently selected from the group consisting of R.sup.6a and CH.sub.3 SO.sub.2 --; R.sup.7 and R.sup.8 are independently selected from the group consisting of (C.sub.1 -C.sub.6)alkyl, halogen, --NR.sup.20 R.sup.21, --OH, --CF.sub.3, --OCH.sub.3, --O-acyl, and --OCF.sub.3 ; R.sup.9 is R.sup.7, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2 F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.20, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.20)CONR.sup.21 R.sup.22, --NHCONH(chloro-(C.sub.1 -C.sub.6)alkyl), --NHCONH((C.sub.3 -C.sub.10)-cycloalkyl(C.sub.1 -C.sub.6)alkyl), --NHCO(C.sub.1 -C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2 N((C.sub.1 -C.sub.6)alkyl).sub.2, --NHSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --N(SO.sub.2 CF.sub.3).sub.2, --NHCO.sub.2 (C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.10 cycloalkyl, --SR.sup.23, --SOR.sup.23, --SO.sub.2 R.sup.23, --SO.sub.2 NH(C.sub.1 -C.sub.6 alkyl), --OSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --OSO.sub.2 CF.sub.3, hydroxy(C.sub.1 -C.sub.6)alkyl, --CON R.sup.20 R.sup.21, --CON(CH.sub.2 CH.sub.2 --O--CH.sub.3).sub.2, --OCONH(C.sub.1 -C.sub.6)alkyl, --CO.sub.2 R.sup.20, --Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2 ; R.sup.10 is (C.sub.1 -C.sub.6)alkyl, --NH.sub.2 or R.sup.12 -phenyl; R.sup.12 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6) alkyl, --CF.sub.3, --CO.sub.2 R.sub.20, --CN, (C.sub.1 -C.sub.6)alkoxy and halogen; R.sup.13, R.sup.14, R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6) alkyl; R.sup.17 and R.sup.18 are independently selected from the group consisting of hydrogen and C.sub.1 -C.sub.6 alkyl, or R.sup.17 and R.sup.18 together are a C.sub.2 -C.sub.5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R.sup.19 is R.sup.6 -phenyl, R.sup.6 -heteroaryl, R.sup.6 -naphthyl, C.sub.3 -C.sub.10 cycloalkyl, (C.sub.3 -C.sub.10)cycloalkyl(C.sub.1 -C.sub.6)alkyl or (C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl; R.sup.20, R.sup.21 and R.sup.22 are independently selected from the group consisting of H and (C.sub.1 -C.sub.6) alkyl; and R.sup.23 is (C.sub.1 -C.sub.6) alkyl or phenyl; or (2): X.sup.a is --C(R.sup.13)(R.sup.19)--, --C(O)--, --O--, --NH--, --N((C.sub.1 -C.sub.6)alkyl)-, ##STR105## R.sup.a is R.sup.6b -phenyl, R.sup.6b -pyridyl or R.sup.6b -thiophenyl; R.sup.4a is fluoro-C.sub.1 -C.sub.6 alkyl, cyclopropylmethyl, --CH.sub.2 CH.sub.2 OH, --CH.sub.2 CH.sub.2 --O--(C.sub.1 -C.sub.6)alkyl, --CH.sub.2 C(O)--O--(C.sub.1 -C.sub.6)alkyl, --CH.sub.2 C(O)NH.sub.2, --CH.sub.2 C(O)--NH--(C.sub.1 -C.sub.6)alkyl or --CH.sub.2 C(O)--N((C.sub.1 -C.sub.6)alkyl).sub.2 ; R.sup.6b is CH.sub.3 SO.sub.2 --; and R.sup.1, R.sup.2, R.sup.3, R.sup.5, R.sup.14, R.sup.15, R.sup.16 and R.sup.19 are as defined in II(1); and wherein in the CCR5 antagonist compounds represented by the structural formula III: ##STR106## R is R.sup.8 -phenyl, R.sup.8 -pyridyl, R.sup.8 -thiophenyl or R.sup.8 -naphthyl; R.sup.1 is hydrogen or (C.sub.1 -C.sub.6) alkyl; R.sup.2 is R.sup.9, R.sup.10, R.sup.11 -phenyl; R.sup.9, R.sup.10, R.sup.11 -substituted 6-membered heteroaryl; R.sup.9, R.sup.10, R.sup.11 -substituted 6-membered heteroaryl N-oxide; R.sup.12, R.sup.13 -substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl ##STR107## or ##STR108## R.sup.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, (C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.3 -C.sub.10 cycloalkyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -phenyl, R.sup.8 -phenyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -naphthyl, R.sup.8 -naphthyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -heteroaryl or R.sup.8 -heteroaryl(C.sub.1 -C.sub.6)alkyl; R.sup.4, R.sup.5, R.sup.7 and R.sup.13 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6)-alkyl; R.sup.6 is hydrogen, (C.sub.1 -C.sub.6) alkyl or (C.sub.2 -C.sub.6)alkenyl; R.sup.8 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, (C.sub.1 -C.sub.6) alkyl, C.sub.1 -C.sub.6 alkoxy, --CF.sub.3, CF.sub.3 O--, CH.sub.3 C(O)--, --CN, CH.sub.3 SO.sub.2 --, CF.sub.3 SO.sub.2 --, R.sup.14 -phenyl, R.sup.14 -benzyl, CH.sub.3 C(.dbd.NOCH.sub.3), CH.sub.3 C(.dbd.NOCH.sub.2 CH.sub.3), ##STR109## --NH.sub.2, --NHCOCF.sub.3, --NHCONH(C.sub.1 -C.sub.6 alkyl), --NHCO(C.sub.1 -C.sub.6 alkyl), --NHSO.sub.2 (C.sub.1 -C.sub.6 alkyl), 5-membered heteroaryl and ##STR110## wherein X.sup.b is --O--, --NH-- or --N(CH.sub.3)--; R.sup.9 and R.sup.10 are independently selected from the group consisting of (C.sub.1 -C.sub.6)alkyl, halogen, --NR.sup.17 R.sup.18, --OH, --CF.sub.3, --OCH.sub.3, --O-acyl, --OCF.sub.3 and --Si(CH.sub.3).sub.3 ; R.sup.11 is R.sup.9, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2 F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.17, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.17)CONR.sup.18 R.sup.19, --NHCONH(chloro-(C.sub.1 -C.sub.6)alkyl), --NHCONH((C.sub.3 -C.sub.1)cycloalkyl(C.sub.1 -C.sub.6)alkyl), --NHCO(C.sub.1 -C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2 N((C.sub.1 -C.sub.6)alkyl).sub.2, --NHSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --N(SO.sub.2 CF.sub.3).sub.2, --NHCO.sub.2 (C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.10 cycloalkyl, --SR.sup.20, --SOR.sup.20, --SO.sub.2 R.sup.20, --SO.sub.2 NH(C.sub.1 -C.sub.6 alkyl), --OSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --OSO.sub.2 CF.sub.3, hydroxy(C.sub.1 -C.sub.6)alkyl, --CON R.sup.17 R.sup.18, --CON(CH.sub.2 CH.sub.2 --O--CH.sub.3).sub.2, --OCONH(C.sub.1 -C.sub.6)alkyl, --CO.sub.2 R.sup.17, --Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2 ; R.sup.12 is (C.sub.1 -C.sub.6)alkyl, --NH.sub.2 or R.sup.14 -phenyl; R.sup.14 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6) alkyl, --CF.sub.3, --CO.sub.2 R.sub.17, --CN, (C.sub.1 -C.sub.6)alkoxy and halogen; R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6) alkyl, or R.sup.15 and R.sup.16 together are a C.sub.2 -C.sub.5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R.sup.17, R.sup.18 and R.sup.19 are independently selected from the group consisting of H and (C.sub.1 -C.sub.6) alkyl; and R.sup.20 is (C.sub.1 -C.sub.6) alkyl or phenyl; and wherein in the CCR5 antagonist compounds represented by the structural formula IV: ##STR111## or a pharmaceutically acceptable salt thereof, wherein (1) R.sup.a is R.sup.8a -phenyl, R.sup.8b -pyridyl, R.sup.8b -thiophenyl or R.sup.8 -naphthyl; R.sup.1 is hydrogen or (C.sub.1 -C.sub.6) alkyl; R.sup.2 is R.sup.9, R.sup.10, R.sup.11 -phenyl; R.sup.9, R.sup.10, R.sup.11 -substituted 6-membered heteroaryl; R.sup.9, R.sup.10, R.sup.11 -substituted 6-membered heteroaryl N-oxide; R.sup.12, R.sup.13 -substituted 5-membered heteroaryl; naphthyl; fluorenyl; diphenylmethyl, ##STR112## or ##STR113## R.sup.3 is hydrogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy(C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.3 -C.sub.10 cycloalkyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -phenyl, R.sup.8 -phenyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -naphthyl, R.sup.8 -naphthyl(C.sub.1 -C.sub.6)alkyl, R.sup.8 -heteroaryl or R.sup.8 -heteroaryl(C.sub.1 -C.sub.6)alkyl; R.sup.4, R.sup.5, R.sup.7 and R.sup.13 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6) alkyl; R.sup.6 is hydrogen, (C.sub.1 -C.sub.6) alkyl or (C.sub.2 -C.sub.6)alkenyl; R.sup.8 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, (C.sub.1 -C.sub.6) alkyl, C.sub.1 -C.sub.6 alkoxy, --CF.sub.3, CF.sub.3 O--, CH.sub.3 C(O)--, --CN, CH.sub.3 SO.sub.2 --, CF.sub.3 SO.sub.2 --, R.sup.14 -phenyl, R.sup.14 -benzyl, CH.sub.3 C(.dbd.NOCH.sub.3), CH.sub.3 C(.dbd.NOCH.sub.2 CH.sub.3), ##STR114## --NH.sub.2, --NHCOCF.sub.3, --NHCONH(C.sub.1 -C.sub.6 alkyl), --NHCO(C.sub.1 -C.sub.6 alkyl), --NHSO.sub.2 (C.sub.1 -C.sub.6 alkyl), 5-membered heteroaryl and ##STR115## wherein X.sup.b is --O--, --NH-- or --N(CH.sub.3)--; R.sup.8a is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, --CF.sub.3, CF.sub.3 O--, --CN, CF.sub.3 SO.sub.2 --, R.sup.14 -phenyl, --NHCOCF.sub.3, 5-membered heteroaryl and ##STR116## wherein X.sup.b is as defined above; R.sup.8b is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, --CF.sub.3, CF.sub.3 O--, CH.sub.3 C(O)--, --CN, CF.sub.3 SO.sub.2 --, R.sup.14 -benzyl, CH.sub.3 C(.dbd.NOCH.sub.3), CH.sub.3 C(.dbd.NOCH.sub.2 CH.sub.3), ##STR117## --NHCOCF.sub.3, 5-membered heteroaryl and ##STR118## wherein X.sup.b is as defined above; R.sup.9 and R.sup.10 are independently selected from the group consisting of (C.sub.1 -C.sub.6)alkyl, halogen, --NR.sup.17 R.sup.18, --OH, --CF.sub.3, --OCH.sub.3, --O-acyl, --OCF.sub.3 and --Si(CH.sub.3).sub.3 ; R.sup.11 is R.sup.9, hydrogen, phenyl, --NO.sub.2, --CN, --CH.sub.2 F, --CHF.sub.2, --CHO, --CH.dbd.NOR.sup.17, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, --N(R.sup.17)CONR.sup.18 R.sup.19, --NHCONH(chloro-(C.sub.1 -C.sub.6)alkyl), --NHCONH((C.sub.3 -C.sub.1) cycloalkyl(C.sub.1 -C.sub.6)alkyl), --NHCO(C.sub.1 -C.sub.6)alkyl, --NHCOCF.sub.3, --NHSO.sub.2 N((C.sub.1 -C.sub.6)alkyl).sub.2, --NHSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --N(SO.sub.2 CF.sub.3).sub.2, --NHCO.sub.2 (C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.10 cycloalkyl, --SR.sup.20, --SOR.sup.20, --SO.sub.2 R.sup.20, --SO.sub.2 NH(C.sub.1 -C.sub.6 alkyl), --OSO.sub.2 (C.sub.1 -C.sub.6)alkyl, --OSO.sub.2 CF.sub.3, hydroxy(C.sub.1 -C.sub.6)alkyl, --CON R.sup.17 R.sup.18, --CON(CH.sub.2 CH.sub.2 --O--CH.sub.3).sub.2, --OCONH(C.sub.1 -C.sub.6)alkyl, --CO.sub.2 R.sup.17, --Si(CH.sub.3).sub.3 or --B(OC(CH.sub.3).sub.2).sub.2 ; R.sup.12 is (C.sub.1 -C.sub.6)alkyl, --NH.sub.2 or R.sup.14 -phenyl; R.sup.14 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6) alkyl, --CF.sub.3, --CO.sub.2 R.sub.17, --CN, (C.sub.1 -C.sub.6)alkoxy and halogen; R.sup.15 and R.sup.16 are independently selected from the group consisting of hydrogen and (C.sub.1 -C.sub.6) alkyl, or R.sup.15 and R.sup.16 together are a C.sub.2 -C.sub.5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R.sup.17, R.sup.18 and R.sup.19 are independently selected from the group consisting of H and (C.sub.1 -C.sub.6) alkyl; and R.sup.20 is (C.sub.1 -C.sub.6) alkyl or phenyl; or (2) R.sup.a is R.sup.8 -phenyl, R.sup.8 -pyridyl or R.sup.8 -thiophenyl; R.sup.2 is fluorenyl, diphenylmethyl, ##STR119## or ##STR120## and R.sup.1, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19 and R.sup.20 are as defined in IV(1). 14. The method of claim 13, wherein the pediatric patients are treatment-naive patients. 15. The method of claim 13, wherein the pediatric patients are treatment-experienced patients. 16. The method of claim 13, wherein the pegylated interferon-alfa administered is pegylated interferon alfa-2a or pegylated interferon alfa-2b. 17. The method of claim 13, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.1 to about 9.0 micrograms per kilogram once a week. 18. The method of claim 13, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.5 to about 4.5 micrograms per kilogram once a week. 19. The method of claim 13, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 2.25 to about 2.6 micrograms per kilogram once a week. 20. The method of claim 13, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2a and the amount of pegylated interferon alfa-2a administered is in the range of about 50 to about 500 micrograms once a week. 21. The method of claim 13, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2a and the amount of pegylated interferon alfa-2a administered is in the range of about 300 to about 375 micrograms once a week. 22. The method of claim 13, wherein the pediatric patient is co-infected with HCV. 23. The method of claim 13, wherein ribavirin is administered to the pediatric patient in association the pegylated interferon-alfa and the amount of ribavirin is in a range of about 8 to about 15 mg per kilogram per day, in divided doses. 24. The method of claim 13, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.1 to about 9.0 micrograms per kilogram twice a week. 25. The method of claim 13, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 0.25 to about 2.25 micrograms per kilogram twice a week. 26. The method of claim 13, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2b and wherein the amount of pegylated interferon alfa-2b administered is in the range of about 1.1 to about 21.3 micrograms per kilogram twice a week. 27. The method of claim 13, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2a and the amount of pegylated interferon alfa-2a administered is in the range of about 50 to about 500 micrograms twice a week. 28. The method of claim 13, wherein the pegylated interferon-alfa administered is a pegylated interferon alfa-2a and the amount of pegylated interferon alfa-2a administered is in the range of about 150 to about 190 micrograms twice a week. 29. The method of claim 1, wherein the HIV-1 patient is co-infected with HCV and about 600 to about 1200 mg/day of ribavirin to said co-infected patient. 30. The method of claim 13, wherein said HIV-1 patient is co-infected with HCV and about 600 to about 1200 mgh/day of ribavirin to said co-infected patient.

Details for Patent 6,635,646

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2019-05-01
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2019-05-01
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2019-05-01
Hoffmann-la Roche Inc.	PEGASYS COPEGUS COMBINATION PACK	peginterferon alfa-2a and ribavirin		125083	06/04/2004		2019-05-01
Schering Corporation A Subsidiary Of Merck & Co., Inc.	PEGINTRON/ REBETOL COMBO PACK	peginterferon alfa-2b and ribavirin		125196	06/13/2008		2019-05-01