Neuropsychiatric adverse events in people with HIV initiating a new integrase strand transfer inhibitor-based regimen in Italy: findings from the NEURO-INSTI study
Abstract Background Although clinical trials reported a low and comparable rate of central nervous system (CNS)/neuropsychiatric (NP) disturbances among people with HIV (PWH) receiving integrase strand transfer inhibitors (INSTI) or other antiretroviral therapy (ART), higher rates of these disturban...
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2025-05-01
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| Online Access: | https://doi.org/10.1186/s12879-025-11090-3 |
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| author | Nicola Squillace Elena Delfina Ricci Giancarlo Orofino Gabriele Forcina Laura Albini Barbara Menzaghi Giuseppe Vittorio De Socio Stefania Piconi Paolo Maggi Giordano Madeddu Giovanni Francesco Pellicanò Eleonora Sarchi Benedetto Maurizio Celesia Filippo Lagi Elena Salomoni Antonio Di Biagio Paolo Bonfanti |
| author_facet | Nicola Squillace Elena Delfina Ricci Giancarlo Orofino Gabriele Forcina Laura Albini Barbara Menzaghi Giuseppe Vittorio De Socio Stefania Piconi Paolo Maggi Giordano Madeddu Giovanni Francesco Pellicanò Eleonora Sarchi Benedetto Maurizio Celesia Filippo Lagi Elena Salomoni Antonio Di Biagio Paolo Bonfanti |
| author_sort | Nicola Squillace |
| collection | DOAJ |
| description | Abstract Background Although clinical trials reported a low and comparable rate of central nervous system (CNS)/neuropsychiatric (NP) disturbances among people with HIV (PWH) receiving integrase strand transfer inhibitors (INSTI) or other antiretroviral therapy (ART), higher rates of these disturbances have been reported in clinical practice. Our aim was to compare the occurrence of CNS-NP disorders in the different INSTI drugs. Methods Using data from the SCOLTA project, a multicenter observational study following PWH who start antiretrovirals to identify adverse events (AEs) in real-life, we performed a retrospective analysis (NEURO-INSTI) to assess incidence rates (IRs) and 95% confidence intervals (95% CI) of CNS/NP AEs and related interruptions. Observation was truncated at the first occurrence of any CNS/NP AEs, even if not causing treatment discontinuation. IRs were calculated as number of first occurrences/100 person-years follow-up (PYFU). To identify risk factors for CNS/NP AEs occurrence, a Cox regression analysis for competing risks was used (hazard ratio, HR, and 95% CI), including variables associated with the outcome at a p level < 0.20 in the univariate analysis. Results We analyzed a sample of 2,922 PWH (mean age 47.2 years, 74.7% males) enrolled in raltegravir (RAL), dolutegravir (DTG), elvitegravir (EVG), and bictegravir (BIC) INSTI-cohorts since 2007. Over a median observation time of 28 months (interquartile range 14–45), 126 CNS/NP AEs and 72 related discontinuations occurred; IRs were 1.59/100 PYFU (95% CI, 1.34–1.90) and 0.91/100 PYFU (95% CI 0.72–1.15), respectively. In multivariate models, intravenous drug use history (IVDUh), current abacavir use, RAL use, and psychiatric illnesses were associated with a higher risk of CNS/NP AEs. IVDUh and current abacavir use were also associated with treatment discontinuation. Using an INSTI as a first-line therapy and starting with CD4 ≥ 350 cell/µL also increased the likelihood of discontinuation. Compared to DTG, BIC and EVG showed lower risks of CNS/NP AEs (adjusted HR 0.27, 95% CI 0.10–0.74, and 0.51, 95% CI 0.22–1.20, respectively), while RAL showed a higher risk (aHR 2.52, 95% CI 1.57–4.05). Conclusions Among PWH on INSTI treatment, IVDUh, concurrent psychiatric illness, abacavir and RAL use increased the risk of CNS/NP AEs occurrence. PWH on BIC were less likely to experience CNS/NP AEs and related treatment discontinuations. |
| format | Article |
| id | doaj-art-313513b4fa6848daa1c4f7f6de42818b |
| institution | DOAJ |
| issn | 1471-2334 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | BMC Infectious Diseases |
| spelling | doaj-art-313513b4fa6848daa1c4f7f6de42818b2025-08-20T03:16:40ZengBMCBMC Infectious Diseases1471-23342025-05-0125111010.1186/s12879-025-11090-3Neuropsychiatric adverse events in people with HIV initiating a new integrase strand transfer inhibitor-based regimen in Italy: findings from the NEURO-INSTI studyNicola Squillace0Elena Delfina Ricci1Giancarlo Orofino2Gabriele Forcina3Laura Albini4Barbara Menzaghi5Giuseppe Vittorio De Socio6Stefania Piconi7Paolo Maggi8Giordano Madeddu9Giovanni Francesco Pellicanò10Eleonora Sarchi11Benedetto Maurizio Celesia12Filippo Lagi13Elena Salomoni14Antonio Di Biagio15Paolo Bonfanti16Infectious Disease Unit, Fondazione IRCCS San Gerardo dei TintoriFondazione A.S.I.A. OnlusDivision I of Infectious and Tropical Diseases, ASL Città di TorinoGilead Sciences SrlGilead Sciences SrlUnit of Infectious Diseases, ASST della Valle Olona– Busto Arsizio (VA)Unit of Infectious Diseases, Santa Maria HospitalUnit of Infectious Diseases, A. Manzoni HospitalInfectious Diseases Unit, Università della Campania “Luigi Vanvitelli”, AORN Sant’Anna e San SebastianoUnit of Infectious Diseases, Department of Medicine, Surgery and Pharmacy, University of SassariUnit of Infectious Diseases, Department of Human Pathology of the Adult and the Developmental Age ‘G. Barresi’, University of MessinaInfectious Diseases Unit, S.Antonio e Biagio e Cesare Arrigo HospitalUnit of Infectious Diseases, Garibaldi HospitalAOU Infectious and Tropical Diseases, Careggi HospitalUnit of Infectious Diseases, SOC 1 USLCENTRO FIRENZE, Santa Maria Annunziata HospitalInfectious Diseases Unit, Department of Health’s Sciences, Ospedale Policlinico San Martino– IRCCS, University of GenoaInfectious Disease Unit, Fondazione IRCCS San Gerardo dei TintoriAbstract Background Although clinical trials reported a low and comparable rate of central nervous system (CNS)/neuropsychiatric (NP) disturbances among people with HIV (PWH) receiving integrase strand transfer inhibitors (INSTI) or other antiretroviral therapy (ART), higher rates of these disturbances have been reported in clinical practice. Our aim was to compare the occurrence of CNS-NP disorders in the different INSTI drugs. Methods Using data from the SCOLTA project, a multicenter observational study following PWH who start antiretrovirals to identify adverse events (AEs) in real-life, we performed a retrospective analysis (NEURO-INSTI) to assess incidence rates (IRs) and 95% confidence intervals (95% CI) of CNS/NP AEs and related interruptions. Observation was truncated at the first occurrence of any CNS/NP AEs, even if not causing treatment discontinuation. IRs were calculated as number of first occurrences/100 person-years follow-up (PYFU). To identify risk factors for CNS/NP AEs occurrence, a Cox regression analysis for competing risks was used (hazard ratio, HR, and 95% CI), including variables associated with the outcome at a p level < 0.20 in the univariate analysis. Results We analyzed a sample of 2,922 PWH (mean age 47.2 years, 74.7% males) enrolled in raltegravir (RAL), dolutegravir (DTG), elvitegravir (EVG), and bictegravir (BIC) INSTI-cohorts since 2007. Over a median observation time of 28 months (interquartile range 14–45), 126 CNS/NP AEs and 72 related discontinuations occurred; IRs were 1.59/100 PYFU (95% CI, 1.34–1.90) and 0.91/100 PYFU (95% CI 0.72–1.15), respectively. In multivariate models, intravenous drug use history (IVDUh), current abacavir use, RAL use, and psychiatric illnesses were associated with a higher risk of CNS/NP AEs. IVDUh and current abacavir use were also associated with treatment discontinuation. Using an INSTI as a first-line therapy and starting with CD4 ≥ 350 cell/µL also increased the likelihood of discontinuation. Compared to DTG, BIC and EVG showed lower risks of CNS/NP AEs (adjusted HR 0.27, 95% CI 0.10–0.74, and 0.51, 95% CI 0.22–1.20, respectively), while RAL showed a higher risk (aHR 2.52, 95% CI 1.57–4.05). Conclusions Among PWH on INSTI treatment, IVDUh, concurrent psychiatric illness, abacavir and RAL use increased the risk of CNS/NP AEs occurrence. PWH on BIC were less likely to experience CNS/NP AEs and related treatment discontinuations.https://doi.org/10.1186/s12879-025-11090-3CNS adverse eventsNeurologic disordersPsychiatric disordersHIVIntegrase strand transfer inhibitorsBictegravir |
| spellingShingle | Nicola Squillace Elena Delfina Ricci Giancarlo Orofino Gabriele Forcina Laura Albini Barbara Menzaghi Giuseppe Vittorio De Socio Stefania Piconi Paolo Maggi Giordano Madeddu Giovanni Francesco Pellicanò Eleonora Sarchi Benedetto Maurizio Celesia Filippo Lagi Elena Salomoni Antonio Di Biagio Paolo Bonfanti Neuropsychiatric adverse events in people with HIV initiating a new integrase strand transfer inhibitor-based regimen in Italy: findings from the NEURO-INSTI study BMC Infectious Diseases CNS adverse events Neurologic disorders Psychiatric disorders HIV Integrase strand transfer inhibitors Bictegravir |
| title | Neuropsychiatric adverse events in people with HIV initiating a new integrase strand transfer inhibitor-based regimen in Italy: findings from the NEURO-INSTI study |
| title_full | Neuropsychiatric adverse events in people with HIV initiating a new integrase strand transfer inhibitor-based regimen in Italy: findings from the NEURO-INSTI study |
| title_fullStr | Neuropsychiatric adverse events in people with HIV initiating a new integrase strand transfer inhibitor-based regimen in Italy: findings from the NEURO-INSTI study |
| title_full_unstemmed | Neuropsychiatric adverse events in people with HIV initiating a new integrase strand transfer inhibitor-based regimen in Italy: findings from the NEURO-INSTI study |
| title_short | Neuropsychiatric adverse events in people with HIV initiating a new integrase strand transfer inhibitor-based regimen in Italy: findings from the NEURO-INSTI study |
| title_sort | neuropsychiatric adverse events in people with hiv initiating a new integrase strand transfer inhibitor based regimen in italy findings from the neuro insti study |
| topic | CNS adverse events Neurologic disorders Psychiatric disorders HIV Integrase strand transfer inhibitors Bictegravir |
| url | https://doi.org/10.1186/s12879-025-11090-3 |
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