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Improved Central Nervous System Symptoms in People with HIV without Objective Neuropsychiatric Complaints Switching from Efavirenz to Rilpivirine Containing cART.

ABSTRACT: Objective: Occult central nervous system (CNS) symptoms not recognized by people living with HIV (PLWH) receiving efavirenz or their clinicians could occur and impact people's quality of life. The aim of this study was to determine whether CNS parameters improve in PLWH when switching from efavirenz to rilpivirine. Methods: PLWH receiving tenofovir disoproxil fumarate, emtricitabine, efavirenz (Atripla™) with undetectable HIV RNA, and no CNS symptoms were switched cART to tenofovir disoproxil fumarate, emtricitabine, rilpivirine (Eviplera™). CNS parameters including sleep, anxiety, and depressive symptoms were evaluated using patient-reported outcome measures at baseline, 4, 12, and 24 weeks after switching therapy. A median CNS score was derived from the sum of CNS toxicities of all the grades collected in the study questionnaires. Cognitive function was assessed using a computerized test battery. Results: Of 41 participants, median age was 47 years, Interquartile range (IQR) 31, 92% were male and 80% were of white ethnicity. A significant reduction in total CNS score (10 to 7) was observed at 4 weeks (p = 0.028), but not thereafter. Significant improvements in sleep and anxiety were observed 4, 12 and 24 weeks after switching therapy (p < 0.05). No significant change in global cognitive scores was observed. Conclusions: Switching from efavirenz to rilpivirine based regimens in virologically suppressed PLWH without perceived CNS symptoms was well tolerated and slightly improved overall CNS symptoms.

SUBMITTER: Vera JH

PROVIDER: S-EPMC6721293 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Improved Central Nervous System Symptoms in People with HIV without Objective Neuropsychiatric Complaints Switching from Efavirenz to Rilpivirine Containing cART.

Vera Jaime H JH Bracchi Margherita M Alagaratnam Jasmini J Lwanga Julianne J Fox Julie J Winston Alan A Boffito Marta M Nelson Mark M

Brain sciences 20190809 8

<b>Objective:</b> Occult central nervous system (CNS) symptoms not recognized by people living with HIV (PLWH) receiving efavirenz or their clinicians could occur and impact people's quality of life. The aim of this study was to determine whether CNS parameters improve in PLWH when switching from efavirenz to rilpivirine. <b>Methods:</b> PLWH receiving tenofovir disoproxil fumarate, emtricitabine, efavirenz (Atripla™) with undetectable HIV RNA, and no CNS symptoms were switched cART to tenofovir ...[more]

PMID: 31405046

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Project description:PurposeEfavirenz-based combination antiretroviral therapy (cART) is associated with neuropsychiatric adverse events. We investigated the time to onset, duration, clinical implications, impact of pharmacogenetic variations, and anti-tuberculosis co-treatment on efavirenz-associated neuropsychiatric manifestations.MethodsProspective cohort study of cART naïve HIV patients with or without tuberculosis (HIV-TB) co-infection treated with efavirenz-based cART. Rifampicin-based anti-tuberculosis therapy was initiated 4 weeks prior to efavirenz-based cART in HIV-TB patients. Data on demographic, clinical, laboratory, and a 29-item questionnaire on neuropsychiatric manifestations were collected for 16 weeks after cART initiation. Genotyping for CYP2B6, CYP3A5, SLCO1B1, and ABCB1 and quantification of efavirenz plasma concentration were done on the 4th and 16th week.ResultsData from 458 patients (243 HIV-only and 215 HIV-TB) were analyzed. Overall incidence of neuropsychiatric manifestations was 57.6% being higher in HIV-only (66.7%) compared to HIV-TB patients (47.4%) (p?<?0.01). HIV-only patients were more symptomatic, with proportionately higher grades of manifestations compared to HIV-TB patients. Median time to manifestations was 1 week after cART initiation in HIV-only and 6 weeks after anti-TB (i.e., 2 weeks after cART initiation) in HIV-TB patients. HIV-only patients had significantly higher efavirenz plasma concentrations at 4 weeks after cART compared to HIV-TB patients. No association of sex or genotype was seen in relation to neuropsychiatric manifestations. Risk for neuropsychiatric manifestations was three times more in HIV-only patients compared to HIV-TB (p?<?0.01).ConclusionsIncidence of neuropsychiatric manifestations during early initiation of efavirenz-based cART is high in Tanzanian HIV patients. Risk of neuropsychiatric manifestations is lower in HIV patients co-treated with rifampicin containing anti-TB compared to those treated with efavirenz-based cART only.

Project description:IntroductionEfavirenz (EFV) is commonly used for first-line antiretroviral therapy in children and adolescents with HIV, but is associated with neuropsychiatric and metabolic side effects. Rilpivirine (RPV) is better tolerated, and switching from EFV to RPV in virologically suppressed adults has been safe and efficacious, but data in adolescents are limited. Our primary objective was to describe the 48-week immunologic and virologic outcomes in virologically suppressed adolescents switching from EFV- to RPV-based antiretroviral therapy. Secondary objectives included assessment of neuropsychiatric adverse events, quality of life (QOL) and metabolic profiles while on RPV.MethodsWe conducted an open-label, single-arm, multi-centre study in Thailand in virologically suppressed adolescents aged 12-18 years receiving EFV plus two nucleoside/tide reverse transcriptase inhibitors (NRTIs/NtRTI) for ≥3 months. Participants were switched to an RPV (25 mg) tablet once daily, with the same NRTIs. HIV RNA viral load, CD4 cell count, fasting total cholesterol (TC), triglyceride, glucose, neuropsychiatric adverse events, depression and QOL were assessed over 48 weeks. Data were collected between February 2016 and September 2018.ResultsOne hundred and two (52% male) adolescents were enrolled. Median age at entry was 15.5 years (IQR 14.4-17.0), median CD4 count was 664 cells/mm3 (29.9%); 58% were receiving tenofovir-DF and emtricitabine. At weeks 24 and 48, 96 (94.1%) and 94 (92.2%) participants were virologically suppressed, respectively, with no significant change in CD4 cell counts from baseline. Six (5.9%) participants experienced virologic failure, two of whom had RPV-associated mutations (K101E and Y181C) and a lamivudine-associated mutation (M184V/I). There were significant decreases in TC, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) at weeks 24 and 48 and a significant increase in LDL/HDL ratio at week 48 compared to baseline. No substantial changes in EFV-related symptoms, depression score or health-related QOL were observed over time; however, there was significant improvement in performance-based assessments of executive function at week 24.ConclusionsA high proportion of adolescents (>92%) remained virologically suppressed up to 48 weeks after switching from EFV to RPV along with no significant change in CD4 cell counts. RPV was well tolerated and associated with improvements in metabolic profiles and executive function.

Project description:IntroductionLittle information is available on the efficacy and safety of the dual combination of ripivirine plus dolutegravir. This work aims at beginning to fill this gap.MethodsAll HIV-1 infected subjects treated with ripivirine plus dolutegravir between October 2014 and September 2015 in eight Italian centres were included in an observational cohort. Data were collected at baseline and at weeks 4, 12, 24 and 48.ResultsOne hundred and thirty-two subjects were followed for a median of 24 months, mean 33 months. One subject discontinued the study drug at week 24 for headache, one for drug interaction and one died after week 24 of illicit drug abuse. The mean age was 51.8, females 31.7% and non-caucasians 10%. Fifty-seven (43.2%) had at least one failure in their treatment history. Reasons for switching were simplification (53.0%), toxicity (34.8%), drug interactions (n = 7), persistent low-level viremia (n = 4), non-adherence (n = 3) and viral failure (n = 2). Sixty patients (45.5%) had reverse transcriptase (RT) mutations and 69 (44,7%) had protease (PR) mutations. Sixteen had baseline viral replication, 27 had < 50 HIV-1 RNA copies/mL and in 89 (67.4%) no virus was detected (NVD, 0 copies/mL). At w4, 114 (86.4%) had NVD, 15 had 1 to 49 HIV-1 RNA copies/mL and 3 had 50 to 57 copies/mL. At week 24 one subject had viral rebound without mutations due to missed drug refill, 19 had 1 to 49 copies/mL, and 112 had NVD. All 132 subjects were tested at weeks 4 and 24. Of the 50 subjects who had a 48-week follow-up, one had a treatment interruption, four had 1 to 49 copies/mL and 45 had NVD. Among the entire population, one subject had low-level, one intermediate and 4 high-level resistance to rilpivirine: none failed by week 48. Mean serum creatinine increased by +0.1 mg/dL. During the follow-up one patient reported headache and insomnia.ConclusionsRipivirine plus dolutegravir proved safe and effective in this cohort of non-naïve HIV-1 infected subjects.

Dataset Information

Improved Central Nervous System Symptoms in People with HIV without Objective Neuropsychiatric Complaints Switching from Efavirenz to Rilpivirine Containing cART.

Publications

Improved Central Nervous System Symptoms in People with HIV without Objective Neuropsychiatric Complaints Switching from Efavirenz to Rilpivirine Containing cART.

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