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Comparable Long-Term Efficacy of Lopinavir/Ritonavir and Similar Drug-Resistance Profiles in Different HIV-1 Subtypes
Authors:Zehava Grossman  Jonathan M. Schapiro  Itzchak Levy  Daniel Elbirt  Michal Chowers  Klaris Riesenberg  Karen Olstein-Pops  Eduardo Shahar  Valery Istomin  Ilan Asher  Bat-Sheva Gottessman  Yonat Shemer  Hila Elinav  Gamal Hassoun  Shira Rosenberg  Diana Averbuch  Keren Machleb-Guri  Zipi Kra-Oz  Sara Radian-Sade  Hagit Rudich  Daniela Ram  Shlomo Maayan  Nancy Agmon-Levin  Zev Sthoeger
Affiliation:1. Public Health School, Tel-Aviv University, Tel-Aviv, Israel.; 2. Sheba Medical Center, Ramat Gan, Israel.; 3. Kaplan Medical Center, Rehovot, Israel.; 4. Meir Medical Center, Kfar Saba, Israel.; 5. Soroka Medical Center, Beer Sheva, Israel.; 6. Hadassah Medical Center, Jerusalem, Israel.; 7. Rambam Medical Center, Haifa, Israel.; 8. Hillel Yaffe Medical Center, Hadera, Israel.; 9. National HIV Reference Lab, PHL, MOH, Ramat Gan, Israel.; University of Pittsburgh, United States of America,
Abstract:

Background

Analysis of potentially different impact of Lopinavir/Ritonavir (LPV/r) on non-B subtypes is confounded by dissimilarities in the conditions existing in different countries. We retrospectively compared its impact on populations infected with subtypes B and C in Israel, where patients infected with different subtypes receive the same treatment.

Methods

Clinical and demographic data were reported by physicians. Resistance was tested after treatment failure. Statistical analyses were conducted using SPSS.

Results

607 LPV/r treated patients (365 male) were included. 139 had HIV subtype B, 391 C, and 77 other subtypes. At study end 429 (71%) were receiving LPV/r. No significant differences in PI treatment history and in median viral-load (VL) at treatment initiation and termination existed between subtypes. MSM discontinued LPV/r more often than others even when the virologic outcome was good (p = 0.001). VL was below detection level in 81% of patients for whom LPV/r was first PI and in 67% when it was second (P = 0.001). Median VL decrease from baseline was 1.9±0.1 logs and was not significantly associated with subtype. Median CD4 increase was: 162 and 92cells/µl, respectively, for patients receiving LPV/r as first and second PI (P = 0.001), and 175 and 98, respectively, for subtypes B and C (P<0.001). Only 52 (22%) of 237 patients genotyped while under LPV/r were fully resistant to the drug; 12(5%) were partially resistant. In48%, population sequencing did not reveal resistance to any drug notwithstanding the virologic failure. No difference was found in the rates of resistance development between B and C (p = 0.16).

Conclusions

Treatment with LPV/r appeared efficient and tolerable in both subtypes, B and C, but CD4 recovery was significantly better in virologically suppressed subtype-B patients. In both subtypes, LPV/r was more beneficial when given as first PI. Mostly, reasons other than resistance development caused discontinuation of treatment.
Keywords:
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