Neurocognitive impairment in patients randomized to second-line lopinavir/ritonavir-based antiretroviral therapy vs. lopinavir/ritonavir monotherapy

J Neurovirol. 2012 Dec;18(6):479-87. doi: 10.1007/s13365-012-0127-9. Epub 2012 Sep 20.

Abstract

We compared rates of neurocognitive impairment (NCI) among 93 Thai adults failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy (cART) before and after switching to lopinavir/ritonavir monotherapy (mLPV/r) vs. tenofovir/lamivudine/LPV/r (TDF/3TC/LPV/r). Participants completed the Color Trails 1 and 2, Digit Symbol, and Grooved Pegboard at weeks 0, 24, and 48. We calculated z-scores using normative data from 451 healthy HIV-negative Thais. We defined NCI as performance of <-1 SD on ≥2 tests. The Thai depression inventory was used to capture depressive symptoms. Lumbar puncture was optional at week 0 and 48. At baseline, median (IQR) age was 36.9 (32.8-40.5) years, and 46 % had primary school education or lower. The median CD4 count was 196 (107-292) cells/mm(3), and plasma HIV RNA was 4.1 (3.6-4.5) log(10) copies/ml. Almost all (97 %) had circulating recombinant CRF01_AE. At baseline, 20 (47 %) of the mLPV/r vs. 22 (44 %) of TDF/3TC/LPV/r arms met NCI criteria (p = 0.89). The frequency of NCI at week 48 was 30 vs. 32 % (p = 0.85) with 6 vs. 7 % (p = 0.85) developing NCI in the mLPV/r vs. TDF/3TC/LPV/r arms, respectively. Having NCI at baseline and lower education each predicted NCI at week 48. Depression scores at week 48 did not differ between arms (p = 0.47). Cerebrospinal fluid HIV RNA of <50 copies/ml at 48 weeks was observed in five out of seven in mLPV/r vs. three out of four in TDF/3TC/LPV/r arm. The rates of NCI and depression did not differ among cases failing NNRTI-based cART who received mLPV/r compared to LPV/r triple therapy.

Trial registration: ClinicalTrials.gov NCT00627055.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adenine / therapeutic use
  • Adult
  • CD4 Lymphocyte Count
  • Cognition Disorders / etiology
  • Cognition Disorders / psychology*
  • Cognition Disorders / virology
  • Depression / etiology
  • Depression / psychology*
  • Depression / virology
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / psychology
  • HIV Infections / virology
  • HIV Protease Inhibitors / pharmacology
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Lamivudine / pharmacology
  • Lamivudine / therapeutic use
  • Lopinavir / pharmacology
  • Lopinavir / therapeutic use
  • Male
  • Organophosphonates / pharmacology
  • Organophosphonates / therapeutic use
  • RNA, Viral / blood
  • RNA, Viral / cerebrospinal fluid
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Ritonavir / pharmacology
  • Ritonavir / therapeutic use
  • Tenofovir
  • Viral Load / drug effects

Substances

  • HIV Protease Inhibitors
  • Organophosphonates
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Lopinavir
  • Lamivudine
  • Tenofovir
  • Adenine
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00627055