Comparable long-term efficacy of Lopinavir/Ritonavir and similar drug-resistance profiles in different HIV-1 subtypes.
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.
Public Health School, Tel-Aviv University, Tel-Aviv, Israel.
Zehava
Z
Grossman
Sheba Medical Center, Ramat Gan, Israel.
Jonathan M
JM
Schapiro
Sheba Medical Center, Ramat Gan, Israel.
Itzchak
I
Levy
Kaplan Medical Center, Rehovot, Israel.
Daniel
D
Elbirt
Meir Medical Center, Kfar Saba, Israel.
Michal
M
Chowers
Soroka Medical Center, Beer Sheva, Israel.
Klaris
K
Riesenberg
Hadassah Medical Center, Jerusalem, Israel.
Karen
K
Olstein-Pops
Rambam Medical Center, Haifa, Israel.
Eduardo
E
Shahar
Hillel Yaffe Medical Center, Hadera, Israel.
Valery
V
Istomin
Kaplan Medical Center, Rehovot, Israel.
Ilan
I
Asher
Meir Medical Center, Kfar Saba, Israel.
Bat-Sheva
BS
Gottessman
Soroka Medical Center, Beer Sheva, Israel.
Yonat
Y
Shemer
Hadassah Medical Center, Jerusalem, Israel.
Hila
H
Elinav
Rambam Medical Center, Haifa, Israel.
Gamal
G
Hassoun
Kaplan Medical Center, Rehovot, Israel.
Shira
S
Rosenberg
Hadassah Medical Center, Jerusalem, Israel.
Diana
D
Averbuch
Kaplan Medical Center, Rehovot, Israel.
Keren
K
Machleb-Guri
Rambam Medical Center, Haifa, Israel.
Zipi
Z
Kra-Oz
Kaplan Medical Center, Rehovot, Israel.
Sara
S
Radian-Sade
National HIV Reference Lab, PHL, MOH, Ramat Gan, Israel.
Hagit
H
Rudich
National HIV Reference Lab, PHL, MOH, Ramat Gan, Israel.
Daniela
D
Ram
Hadassah Medical Center, Jerusalem, Israel.
Shlomo
S
Maayan
Kaplan Medical Center, Rehovot, Israel.
Nancy
N
Agmon-Levin
Kaplan Medical Center, Rehovot, Israel.
Zev
Z
Sthoeger
D000704:Analysis of Variance; D001483:Base Sequence; D004338:Drug Combinations; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007557:Israel; D061466:Lopinavir / Q000494:pharmacology*; D008969:Molecular Sequence Data; D012189:Retrospective Studies; D019438:Ritonavir / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D013045:Species Specificity
D004338:Drug Combinations; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D019438:Ritonavir