Failure of double protease inhibitor therapy as a salvage therapy for HIV-infected patients resistant to conventional triple therapy.
A therapeutic dilemma arises once HIV-infected patients develop a break-through of HIV-replication under potent antiretroviral therapy. Therefore, we studied whether patients (n = 12) who failed double nucleoside reverse transcriptase (NRTI) plus indinavir or ritonavir triple therapy can be rescued when therapy is switched to double protease inhibitor (PI) treatment (nelfinavir and hard gel saquinavir) and stavudine. With the rescue regimen HIV-RNA levels initially dropped from 148,571 +/- 45,258 copies/ml to 9,310 +/- 6, 965 copies/ml at week 4 (p = 0.0117). However, virus load subsequently increased to almost baseline levels (131,230 +/- 37,743 copies/ml) at week 12. Likewise, CD4-cell counts could only be stabilized initially (baseline 267 +/- 51; week 4 296 +/- 65 cells/microl), but gradually declined thereafter (216 +/- 34 cells/microl week 12). Before therapy was switched, the viral protease gene from 5 analyzed patients showed 3-5 amino acid substitutions. Moreover, 4 of these patients had one amino acid substitution associated with resistance to nelfinavir. Our data suggest that HIV-infected patients resistant to indinavir or ritonavir and double NRTI combination therapy respond to double PI nelfinavir/saquinavir and D4T rescue therapy only initially but have no sustained benefit.
Rockstroh
J K
JK
Department of Medicine, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. EurJMedRes@t-online.de
Altfeld
M
M
Kupfer
B
B
Kaiser
R
R
Fätkenheuer
G
G
Salzberger
B
B
Schneweis
K E
KE
Spengler
U
U
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D019888:Nelfinavir / Q000008:administration & dosage / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016879:Salvage Therapy; D019258:Saquinavir / Q000008:administration & dosage / Q000627:therapeutic use*; D018119:Stavudine / Q000008:administration & dosage / Q000627:therapeutic use; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D019888:Nelfinavir; D019258:Saquinavir