Comparison of the efficacy, safety and predictive value of HIV genotyping using distinct ritonavir-boosted protease inhibitors.
The pharmacokinetic profile of protease inhibitors (PI) is improved significantly by adding low doses of ritonavir (rit). The use of rit-boosted PI allows the reduction of pill burden, improves dosing schedules and enhances drug exposure, all factors that have been associated with a greater benefit of antiretroviral therapy. All patients receiving rit 100 mg bid together with saquinavir (SQV) soft gel 1000 mg bid, indinavir (IDV) 800 mg bid or lopinavir (LPV) 400 mg bid, as part of a salvage regimen, were retrospectively analyzed in a reference institution. Only subjects who had failed all three antiretroviral drug families in the past were included. A total of 299 patients were included in the study (121 on SQV, 62 on IDV and 116 on LPV). Mean plasma HIV-RNA and CD4 lymphocyte counts at baseline were less favourable in the LPV group (4.4 logs, 275 cells/microl) with respect to SQV (4.3 logs, 355 cells/microl) and IDV (3.7 logs, 409 cells/microl) groups (P < 0.05). The proportion of subjects experiencing virological success (attainment of either < 500 HIV-RNA copies/ml or > 1 log reduction) in an intent-to-treat analysis at 24 weeks was 61% with LPV, 49% with SQV and 48% with IDV. The CD4 count increased 48% with SQV, 45% with IDV and 37% with LPV. The proportion of subjects discontinuing therapy due to adverse events was higher using IDV (27%) than using either SQV (11%) or LPV (6%) (P < 0.05). The presence of < 5 or > 5 PI resistance mutations at baseline discriminated significantly better who would respond to therapy in all instances: 90 vs. 48% with LPV, 95 vs. 21% with SQV and 90 vs. 23% with IDV. The efficacy of rit-boosted PI combinations is greatly influenced by the extent of baseline PI resistance. Differences, not only in potency, but mainly in tolerance may favour the selection of one dual PI combination over others.
Barreiro
Pablo
P
Service of Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain.
Camino
Nuria
N
de Mendoza
Carmen
C
Valer
Luisa
L
Núñez
Marina
M
Martín-Carbonero
Luz
L
González-Lahoz
Juan
J
Soriano
Vincent
V
D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy; D016896:Treatment Outcome
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019438:Ritonavir