ABSTRACT
Background: Although switching antiretroviral therapy (ART) in people with human immunodeficiency virus experiencing insomnia due to dolutegravir-related neurotoxicity is well founded upon evidence, there is a lack of proof in regard to the outcome of stopping dolutegravir-based ART in people without insomnia but reporting poor sleep quality. Methods: This is a randomized, multicenter, open-label study to evaluate the reversibility of patient-reported sleep disturbances in patients on dolutegravir/lamivudine/abacavir without insomnia after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants were randomized to switch ART at baseline or at week 4 and then completed 8 weeks of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Our primary objective was to compare changes in sleep quality between arms at week 4. Secondary objectives were to compare changes in mood and neuropsychiatric symptoms (NS) at week 4 and 4 and 8 weeks after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants completed a survey, including the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression scale (HADS), and specific questions to explore NS, at each visit to assess those objectives. Results: We included 72 participants. The results show that study arms were similar at baseline; however, at week 4, PSQI scores remained unchanged with dolutegravir/lamivudine/abacavir, whereas patients improved significantly after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Similar differences between arms were also observed in HADS and NS changes. At weeks 4 and 8 after all participants switched to darunavir/cobicistat/emtricitabine/tenofovir alafenamide, we have observed significant improvements in PSQI and HAD scores and in NS. Conclusions: In patients reporting subclinical sleep disturbances without insomnia, switching from dolutegravir/lamivudine/abacavir to darunavir/cobicistat/emtricitabine/tenofovir alafenamide was associated with better sleep quality and improvements in mood and NS.
ABSTRACT
INTRODUCTION: Penetration of protease inhibitors (PI) in the central nervous system (CNS) is limited. Therefore, there are concerns about the capacity of PI monotherapy (MT) to control HIV in CNS and preserve brain integrity. METHODS: Exploratory case-control study designed to compare neuronal integrity and brain inflammation in HIV-suppressed patients (>2 years) with and without neurocognitive impairment (NI), treated with MT or triple therapy (TT), 3-Tesla cerebral magnetic resonance image (MRI) and spectroscopy (MRS) were used to evaluate neuronal integrity (volume of cerebral structures and MRS levels of N-acetyl-aspartate (NAA)) and brain inflammation (MRS levels of myo-inositol (MI) and choline (CHO)). MRS biomarkers were measured in 4 voxels located in basal ganglia, frontal (2) and parietal lobes. A comprehensive battery of tests (14 tests - 7 domains) was used to diagnose neurocognitive impairment (1). RESULTS: We included 18 neurocognitively impaired patients (MT: 10, TT: 8) and 21 without NI (MT: 9; TT: 12, Table 1). Subset of patients with NI: cerebral volumes and MRS biomarkers were mostly similar between MT and TT with exception of the right cingulate nucleolus volume (MT: 8854±1851 vs TT: 10482±1107 mm(3); p<0.04), CHO levels in basal ganglia (MT: 0.44±0.05 vs TT: 0.37±0.03 MMOL/L; p<0.01) and the NAA levels in parietal lobe (MT: 1.49±0.12 vs 1.70±0.13 MMOL/L; p<0.01). Subset of patients without NI: cerebral volumes and MRS biomarkers were mostly similar between MT and TT with exception of MI levels in frontal lobe (MT: 1.20±0.36 vs 0.81±0.25 MMOL/L; p=0.01). CONCLUSIONS: We did not find significant differences in cerebral volumes or MRS biomarkers in most areas of the brain. However, we found higher levels of inflammation and neuronal damage in some brain areas of patients who received MT. This observation has to be taken into caution while we could not adjust our results by potential confounders. Further investigation is needed to confirm these preliminary results.
ABSTRACT
INTRODUCTION: The prevalence of risky alcohol consumption, associated factors and its impact on the brain is not well established in clinically stable HIV patients. MATERIALS AND METHODS: Within the PIVOT neurocognitive sub-study, effectively suppressed HIV-infected adults on either standard cART or ritonavir-boosted PI monotherapy completed the Alcohol Use Disorders Identification Test (AUDIT) designed to detect risky alcohol consumption. They also completed a brief neuropsychological assessment (NPZ 5) composed by five measures. For this cross-sectional analysis, we calculated rates of hazardous (AUDIT=8-15) or harmful (AUDIT=16-19) consumption and likely dependence (AUDIT>20). We explored the association between risky alcohol intakes (AUDIT>8) and clinical/demographical variables, conducting logistic regressions when significant association was found (p<.05). Also, the association between cognitive performance and alcohol consumption was calculated and adjusted by potential confounders. RESULTS: Of the 146 included participants, the majority were male (86.3%), white (81.5%) and educated (mean years on formal education=15, SD=3.9). Average age was 47.6 years (SD=8.7), and 36.3% had risky consumption (29.5% hazardous, 6.2% harmful, 0.7% likely dependence). White ethnicity and male sex were positively associated with risky consumption (Table 1). After adjustments, white ethnicity remained significantly associated with risky consumption (1.64 [95% CI 0.34-2.95]; p=0.013). Better cognitive performance was associated with risky alcohol consumption in the univariate analysis (p<.001). After adjustment by ethnicity, sex and years of education, cognitive performance and risky alcohol consumption maintained significant association (0.45 [95% CI 0.19-0.70] p=0.001). CONCLUSIONS: Despite the substantially high prevalence of risky alcohol consumption, it was not associated with worse adherence, immunological or quality of life measures in this cohort of effectively suppressed patients but prevalence of likely alcohol dependency was extremely low. White patients were more vulnerable to risky consumption. Moreover, positive association between cognitive performance and risky alcohol consumption remained after adjustment. In our study, the association we found between cognitive function and alcohol consumption does not reflect the effect of alcohol dependency on cognition.
