Comparable Long-Term Efficacy of Lopinavir/Ritonavir and Similar Drug-Resistance Profiles in Different HIV-1 Subtypes

Zehava Grossman,Ilan Asher,Yonat Shemer,Diana Averbuch,Itzchak Levy,Keren Machleb-Guri,Zipi Kra-Oz,Zev Sthoeger,Sara Radian-Sade,Shira Rosenberg,Klaris Riesenberg,Bat-Sheva Gottessman,Karen Olstein-Pops,Shlomo Maayan,Michal Chowers,Gamal Hassoun,Eduardo Shahar,Daniela Ram,Daniel Elbirt,Valery Istomin,Hila Elinav,Jonathan Schapiro ,Nancy Agmon‐Levin ,H Rudich

doi:10.1371/journal.pone.0086239

Abstract

BackgroundAnalysis 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.MethodsClinical and demographic data were reported by physicians. Resistance was tested after treatment failure. Statistical analyses were conducted using SPSS.Results607 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).ConclusionsTreatment 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.

Highlights

Subtype B is the predominant human immunodeficiency virus type 1 (HIV-1) subtype in the resource rich countries, but most of those infected worldwide carry non-B virus [1,2]
No major mutations occur as polymorphisms in wild-type subtype-C HIV-1, several secondary mutations associated with drug failure are found at high frequency in viruses from drug-naive subtype-C patients (e.g., M36I and I93L) [11,12]
As subtype B patients were mainly men who have sex with Men (MSM), this group of patients was compared to subtype-C males

Summary

Introduction

Subtype B is the predominant HIV-1 subtype in the resource rich countries, but most of those infected worldwide carry non-B virus [1,2]. No major mutations occur as polymorphisms in wild-type subtype-C HIV-1, several secondary mutations associated with drug failure are found at high frequency in viruses from drug-naive subtype-C patients (e.g., M36I and I93L) [11,12]. These differences in baseline sequence between subtypes may result in the evolution of drug resistance along distinct mutational pathways, or in the incidence of different pathways [13,14,15,16,17,18]. 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

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Discussion

Conclusion