Dataset Information

Neurocognitive impairment in patients treated with protease inhibitor monotherapy or triple drug antiretroviral therapy.

ABSTRACT:

Background

In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment.

Methods

In this observational, cross-sectional study we included patients with plasma virological suppression (? 1 year) without concomitant major neurocognitive confounders, currently receiving for ? 1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed.

Results

Of the 191 included patients--triple therapy: 96, 1-2 years of monotherapy: 40 and >2 years of monotherapy: 55--proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9-33.6); triple therapy, 31.6% (22.1-41.0); short-term monotherapy, 25.0% (11.3-38.7); long-term monotherapy: 21.4% (10.5-32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29-2.50) and for long-term monotherapy 0.40 (0.14-1.15).

Conclusions

Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.

SUBMITTER: Perez-Valero I

PROVIDER: S-EPMC3723908 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Neurocognitive impairment in patients treated with protease inhibitor monotherapy or triple drug antiretroviral therapy.

Pérez-Valero Ignacio I González-Baeza Alicia A Estébanez Miriam M Montes-Ramírez María L ML Bayón Carmen C Pulido Federico F Bernardino José I JI Zamora Francisco X FX Monge Susana S Gaya Francisco F Lagarde María M Rubio Rafael R Hernando Asunción A Arnalich Francisco F Arribas José R JR

PloS one 20130725 7

<h4>Background</h4>In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment.<h4>Methods</h4>In this observational, cross-sectional study we included patients with plasma virological suppression (≥ 1 year) without concomitant major neurocognitive confounders, currently receiving for ...[more]

PMID: 23936029

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Project description:BackgroundHIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children's neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes. We compared the neurocognitive function between children living with HIV receiving PI-based and non PI-based ART.MethodsWe recruited a consecutive sample of clinically stable Ugandan children living with HIV aged 5-12 years who received PI-based or non PI-based ART for ≥ 1 year (viral load < 1000 copies). Neurocognitive function was assessed using the Kaufman Assessment Battery for Children, the Test of Variables of Attention, and Bruininks-Oseretsky Test of Motor Proficiency. Age-adjusted neurocognitive z-scores for the two groups were compared using linear regression models in STATA version 13. The Hommel's method was used to adjust for multiple testing.ResultsWe enrolled 76 children living with HIV; 34 on PI ART and 42 on non-PI ART. Mean (±SD) age was greater in the non-PI vs. PI group (9.5 ± 1.9 vs. 8.5 ± 2.0) years (p = 0.03). Children in the non-PI group had lower socioeconomic scores (5.7 ± 3.3 vs. 7.4 ± 2.8, p = 0.02). There was no difference in neurocognitive function between the groups (adjusted p > 0.05) for KABC and TOVA. Children in the PI group had better total BOT scores than their counterparts (46.07 ± 1.40) vs. 40.51 (1.24), p = 0.03).ConclusionsWe detected no difference in neurocognitive function among children on PI and non PI-based ART therapy based on KABC and TOVA tests. Children on PI based ART had better motor function than their counterparts. We recommend a prospective study with a larger sample size.

Project description:BackgroundMajor protease mutations are rarely observed following failure with protease inhibitors (PI), and other viral determinants of failure to PI are poorly understood. We therefore characterized Gag-Protease phenotypic susceptibility in subtype A and D viruses circulating in East Africa following viral rebound on PIs.MethodsSamples from baseline and treatment failure in patients enrolled in the second line LPV/r trial SARA underwent phenotypic susceptibility testing. Data were expressed as fold-change in susceptibility relative to a LPV-susceptible reference strain.ResultsWe cloned 48 Gag-Protease containing sequences from seven individuals and performed drug resistance phenotyping from pre-PI and treatment failure timepoints in seven patients. For the six patients where major protease inhibitor resistance mutations did not emerge, mean fold-change EC50 to LPV was 4.07 fold (95% CI, 2.08-6.07) at the pre-PI timepoint. Following viral failure the mean fold-change in EC50 to LPV was 4.25 fold (95% CI, 1.39-7.11, p = 0.91). All viruses remained susceptible to DRV. In our assay system, the major PI resistance mutation I84V, which emerged in one individual, conferred a 10.5-fold reduction in LPV susceptibility. One of the six patients exhibited a significant reduction in susceptibility between pre-PI and failure timepoints (from 4.7 fold to 9.6 fold) in the absence of known major mutations in protease, but associated with changes in Gag: V7I, G49D, R69Q, A120D, Q127K, N375S and I462S. Phylogenetic analysis provided evidence of the emergence of genetically distinct viruses at the time of treatment failure, indicating ongoing viral evolution in Gag-protease under PI pressure.ConclusionsHere we observe in one patient the development of significantly reduced susceptibility conferred by changes in Gag which may have contributed to treatment failure on a protease inhibitor containing regimen. Further phenotype-genotype studies are required to elucidate genetic determinants of protease inhibitor failure in those who fail without traditional resistance mutations whilst PI use is being scaled up globally.

Dataset Information

Neurocognitive impairment in patients treated with protease inhibitor monotherapy or triple drug antiretroviral therapy.

Background

Methods

Results

Conclusions

Publications

Neurocognitive impairment in patients treated with protease inhibitor monotherapy or triple drug antiretroviral therapy.

Similar Datasets

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