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Estimated potency of six different boosted protease inhibitors regimens in antiretroviral-experienced HIV patients
- Impact of baseline protease resistance mutations
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Response to 6 RTV-Boosted PIs in Salvage Therapy
Reported by Jules Levin
"Estimated Potency of Six Different Boosted PI Regimens in ART-Experienced HIV Patients: Impact of baseline protease resistance mutations"
Authors: G. Ramirez-Olivencia1, E. Ribera2, A. Pena3, C. de Mendoza1,
C. Garrido1, F. Garcia3, V. Falco2, J. Gonzalez-Lahoz1,
V. Soriano1, and on behalf of the Spanish Resistance
Network-RIS
This study was the subject of a poster presentation (abstract 73) at the recent European HIV Drug Resistance Workshop in Lisbon. The study was a retrospective analysis of 400+ patients at 3 clinics in Spain who received salvage therapy with ritonavir-boosted PI regimens. This report is a revision of the previous report sent out by NATAP during the workshop. Although the initial report said the findings of this poster were at odds with the results of the RESIST Study closer scrutiny of this poster does not warrant this conclusion. The RESIST Study found tipranavir/r superior to other boosted PI regimens in the RESIST study patients, who were patients with extensive ART & PI experience and ART resistance. FDA approval for tipranavir was based upon the RESIST 1 & 2 Studies.
Here is the full text of the poster.
Background
Regimens based on ritonavir-bbosted protease inhibitors (PI/r) are among the most potent anti-HIV combinations. Multiple mutations at the protease gene are generally required to compromise their antiviral activity. This high genetic barrier for resistance using PI/r has been further characterized using genotypic scores. However, information about the intrinsic potency of each different PI/r is scrarce and mainly derived from clinical trials, such as RESIST and POWER.
The aim of this study was to compare the estimated potency of six different boosted protease inhibitors regimens in ART-experienced HIV patients.
Materials & Methods
All HIV+ patients failing ARV therapy who initiated a salvage regimen including PI/r at 3 large Spanish HIV clinics were retrospectively analyzed. Previous exposure to ARVs as well as viral load & CD4 count at the time of starting the salvage regimen and on followup were recorded. For the purpose of this analysis, viral success was defined as >1 log decline or <50 c/ml at week 12. Moreover, only patients on treatment were analyzed. PI mutations recorded at the latest IAS-USA list (Sept 2006) were considered.
Regimens used were saquinavir (SQV)/r (1000/100 mg bid), indinavir (IDV)/r (800/100 mg bid), lopinavir)/r (400/100 mg bid), amprenavir (APV)/r (600/100 mg bid), fosamprenavir (fosAPV) (700/100 mg bid), atazanavir (ATV)/r (300/100 mg qd) and tipranavir (TPV)/r (500/200 mg bid).
Results
A total of 422 patients who started a salvage regimen based on PI/r and kept on therapy until week 24 were identified. Patients on TPV-based salvage therapy had higher median number of primary PI resistance mutations (3), number of prior PIs (5) and length of prior PI exposure to PIs than the others (p<0.001). Also, the concomitant use of T20 was almost restrict to TPV. Overall, there were no significant differences in viral success when comparing distinct PI/r regimens as salvage therapy after adjusting for viral load, CD4 counts, number of primary protease mutations, prior exposure to PIs, T20 use, and prescription of new ARVs in the salvage regimen. The number of PI mutations (OR=1.44; IC95% 1.20-1.72 for each additional mutation; p<0.001) and number of prior PIs (OR=1.63; IC95% 1.31-2.04; p<0.001) were significantly associated with viral failure. Use of T20 was significantly associated with viral success (OT=10.68; IC95% 3.11-36.66, p<0.001). (NOTE from Jules Levin: since the concomitant use of T20 was apparently almost restricted to TPV can you adjust for the use of T20 in a multivariate analysis? Adjusting for a higher number of PI mutations, number of prior PIs, and length of prior exposure to PIs should work in favor of TPV. The authorŐs conclusions appear to be overstated. A table in the poster says median number of prior PIs were 2 for patients taking SQV/r regimens, 3 for IDV/r regimens, 2 for ATV/r regimens, 1 for LPV/r regimens, 3 for APV/r regimens, and 4.5 for TPV/r regimens; length of prior PI exposure was 34 months for patients taking SQV/r, 57 for IDV/r regimens, 27 for ATV/r, 28 for LPV/r, 28 for APV/r, and 72 for TPV/r; for the number of primary PI mutations patients receiving TPV-based regimens had more.
Conclusions
In this study, the estimated potency of distinct RTV-boosted PI seems to be similar in ARV-exp patients tolerating the medication for up to 24 weeks. However, TPV-based regimen was the most frequent salvage therapy in patients with virological success anf higher number of PI mutations. The concomitant use of T20 was the major factor influencing the virologic success rate to PI/r regimens.
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