TY - JOUR
T1 - Integrase Strand Transfer Inhibitor Start or Switch Impacts Learning in Women with HIV
AU - O'Halloran, Jane A.
AU - Wang, Kunbo
AU - Spence, Amanda B.
AU - Williams, Dionna W.
AU - Dastgheyb, Raha
AU - Fitzgerald, Kathryn C.
AU - Kamkwalala, Asante R.
AU - Maki, Pauline M.
AU - Sharma, Anjali
AU - Gustafson, Deborah R.
AU - Milam, Joel
AU - Weber, Kathleen M.
AU - Adimora, Adaora A.
AU - Ofotokun, Igho
AU - Fischl, Margaret A.
AU - Konkle-Parker, Deborah
AU - Lahiri, Cecile D.
AU - Sheth, Anandi N.
AU - Xu, Yanxun
AU - Rubin, Leah H.
N1 - Funding Information:
Supported by the Johns Hopkins University NIMH Center for novel therapeutics for HIV-associated cognitive disorders (P30MH075773) 2018 pilot award to L.H.R., the Johns Hopkins University Center for AIDS Research NIH/NIAID fund (P30AI094189) 2019 faculty development award to Y.X., and NSF DMS1918854 to Y.X. and L.H.R. J.A.O. is a scholar on the Sustained Training in HIV and Aging (STAHR) program, which is supported by the STAHR Training Grant (R25 MH108389). D.W.W.'s effort was supported by K99DA044838. C.D.L. is also supported by NIH/NIAID K23AI124913. A.S. has received funding from Gilead Sciences, Inc. Data in this manuscript were collected by the Women's Interagency HIV Study, now the MACS/WIHS Combined Cohort Study (MWCCS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). MWCCS (Principal Investigators): Atlanta CRS (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01‐HL146241; Baltimore CRS (Todd Brown and Joseph Margolick), U01‐HL146201; Bronx CRS (Kathryn Anastos and Anjali Sharma), U01‐HL146204; Brooklyn CRS (Deborah Gustafson and Tracey Wilson), U01‐HL146202; Data Analysis and Coordination Center (Gypsyamber D'Souza, Stephen Gange and Elizabeth Golub), U01‐HL146193; Chicago‐Cook County CRS (Mardge Cohen and Audrey French), U01‐HL146245; Chicago‐Northwestern CRS (Steven Wolinsky), U01‐HL146240; Connie Wofsy Women's HIV Study, Northern California CRS (Bradley Aouizerat, Jennifer Price, and Phyllis Tien), U01‐HL146242; Los Angeles CRS (Roger Detels), U01‐HL146333; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01‐HL146205; Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones), U01‐HL146203; Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo), U01‐HL146208; UAB‐MS CRS (Mirjam‐Colette Kempf and Deborah Konkle‐Parker), U01‐HL146192; UNC CRS (Adaora Adimora), U01‐HL146194. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional cofunding from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Human Genome Research Institute (NHGRI), National Institute On Aging (NIA), National Institute Of Dental & Craniofacial Research (NIDCR), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Neurological Disorders And Stroke (NINDS), National Institute Of Mental Health (NIMH), National Institute On Drug Abuse (NIDA), National Institute Of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). MWCCS data collection is also supported by UL1‐TR000004 (UCSF CTSA), P30‐AI‐050409 (Atlanta CFAR), P30‐AI‐050410 (UNC CFAR), and P30‐AI‐027767 (UAB CFAR).
Publisher Copyright:
© 2020 Wolters Kluwer Health, Inc.
PY - 2021/4/15
Y1 - 2021/4/15
N2 - Background:Integrase strand transfer inhibitors (INSTIs) are first-line regimens for HIV treatment. We aimed to examine their impact on cognitive performance and depressive symptoms in women with HIV (WWH).Setting:Women's Interagency HIV Study, a multisite, prospective, cohort study.Methods:WWH who started or switched to INSTI-based antiretroviral therapy (ART) and completed neuropsychological testing and the Center for Epidemiological Studies-Depression (CES-D) scale before and after INSTI start/switch were included in the analyses. Primary outcomes were demographically corrected cognitive domain T-scores. Linear mixed-effects models adjusted for relevant covariates were used to examine effects of start/switch of any INSTI and individual INSTI drugs on cognition and CES-D scores.Results:Six hundred thirty-nine WWH, median age 49 (interquartile range 12) years, 66% Black non-Hispanic, had neuropsychological and CES-D scale data before and after INSTI start/switch. Although 14% started INSTI-based ART, the remainder switched to INSTI-based ART from another regimen. Overall, any INSTI use was associated with poorer learning post-INSTI. Specifically, use of dolutegravir and elvitegravir, but not raltegravir, was associated with poorer learning. In analyses restricted to INSTI switch, any INSTI use, and dolutegravir use, was associated with poorer learning. Among those switching from a PI-based regimen, INSTIs overall and dolutegravir remained associated with poorer learning; switching from a nonnucleoside reverse transcriptase inhibitor to dolutegravir was also associated with poorer learning. INSTI start/switch was not related to depressive symptom changes.Conclusions:INSTI use was associated with poorer learning among WWH. These changes were mainly observed in elvitegravir and dolutegravir users, indicating that the impact of INSTI on cognition in WWH may not be a class effect.
AB - Background:Integrase strand transfer inhibitors (INSTIs) are first-line regimens for HIV treatment. We aimed to examine their impact on cognitive performance and depressive symptoms in women with HIV (WWH).Setting:Women's Interagency HIV Study, a multisite, prospective, cohort study.Methods:WWH who started or switched to INSTI-based antiretroviral therapy (ART) and completed neuropsychological testing and the Center for Epidemiological Studies-Depression (CES-D) scale before and after INSTI start/switch were included in the analyses. Primary outcomes were demographically corrected cognitive domain T-scores. Linear mixed-effects models adjusted for relevant covariates were used to examine effects of start/switch of any INSTI and individual INSTI drugs on cognition and CES-D scores.Results:Six hundred thirty-nine WWH, median age 49 (interquartile range 12) years, 66% Black non-Hispanic, had neuropsychological and CES-D scale data before and after INSTI start/switch. Although 14% started INSTI-based ART, the remainder switched to INSTI-based ART from another regimen. Overall, any INSTI use was associated with poorer learning post-INSTI. Specifically, use of dolutegravir and elvitegravir, but not raltegravir, was associated with poorer learning. In analyses restricted to INSTI switch, any INSTI use, and dolutegravir use, was associated with poorer learning. Among those switching from a PI-based regimen, INSTIs overall and dolutegravir remained associated with poorer learning; switching from a nonnucleoside reverse transcriptase inhibitor to dolutegravir was also associated with poorer learning. INSTI start/switch was not related to depressive symptom changes.Conclusions:INSTI use was associated with poorer learning among WWH. These changes were mainly observed in elvitegravir and dolutegravir users, indicating that the impact of INSTI on cognition in WWH may not be a class effect.
KW - antiretroviral therapy
KW - cognition
KW - integrase strand transfer inhibitors
KW - learning
KW - women with HIV
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U2 - 10.1097/QAI.0000000000002608
DO - 10.1097/QAI.0000000000002608
M3 - Article
C2 - 33394812
AN - SCOPUS:85102658198
VL - 86
SP - 593
EP - 599
JO - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology
JF - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology
SN - 1525-4135
IS - 5
ER -