When will this occur?
Malbim: This explains that the first curse will occur in the days of David; he deposed Evyasar from Bnei Itamar, and appointed Tzadok.
Who is the trustworthy Kohen?
Rashi (from Tana d'Vei Eliyahu Rabah 11): It is Tzadok. 1 Radak - that is when the curse will take effect. This was when David was fleeing Avshalom; he deposed Evyasar and appointed Tzadok - "va'Ya'al Evyasar; va'Yomer ha'Melech l'Tzadok Hashev Es Aron
Malbim: "Bnei Tzadok Asher Shamru Es Mishmeres Makdishi bi'S'os Bnei Yisrael me'Alai" (Yechezkel 44:15).
Radak: Until then, there were Kohanim Gedolim from Itamar, i.e. Achiyah ben Achituv, Achimelech in Nov, and Evyasar (Yuma 73b). (There were Kohanim named Achituv and Achimelech both from Elazar and from Itamar - 14:3, Divrei ha'Yamim 1 5:30-34, 1:24:2). (PF)
What is the meaning of "Ka'asher bi'Lvavi uv'Nafshi"?
Radak: He will do like My desire; so says Targum Yonasan. 1
Malbim: His deeds and is not only like the command externally, rather, [also] according to the Divine intent, to increase Kevod Hashem and to receive his Kedushah. This is the soul of the Mitzvos.
Targum Yonasan translates "bi'Lvavi" as 'My word.'
What is "Bayis Ne'eman"?
Radak: It is a lasting [house]. This is like "b'Makom Ne'eman" (Yeshayah 22:23). The seed of Tzadok were Kohanim Gedolim. Divrei ha'Yamim (1:5:30) traces their lineage to Pinchas.
Why does it say "v'His'halech Lifnei Mashichi"?
Radak: The Kohen Gadol would come in front of the king to instruct him the good way. The king came in front of the Kohen Gadol only when he needed to ask from the Urim v'Tumim (Bamidbar 27:21) "v'Lifnei Elazar ha'Kohen Ya'amod v'Sha'al Lo b'Mishpat ha'Urim" (Yuma 73b). However, when the king wanted to speak to the Kohen Gadol, the Kohen Gadol would come to him. "V'Yashav u'Mashal Al Kis'o v'Hayah Chohen Al Kis'o va'Atzas Shalom Tihyeh Bein Sheneihem" (Zecharyah 6:13) - i.e. the king will be on his throne, and the Kohen will be Al Kis'o, i.e. in front of his throne. This is like "veha'Omdim Alav", "Nitzavim Alav" (Shoftim 3:19, Bereishis 18:2), i.e. in front of him. It seems that Yonason translated like I said.