Abstract
Background. Neurocognitive impairment remains a common complication of human immunodeficiency virus (HIV) despite effective antiretroviral therapy (ART). We previously reported improved neurocognitive functioning with ART initiation in 7 resource-limited countries for HIV+ participants from the AIDS Clinical Trials Group (ACTG) 5199 International Neurological Study (INS). Here, we apply normative data from the International Neurocognitive Normative Study (INNS) to INS to provide previously unknown rates of neurocognitive impairment. Methods. The A5199 INS assessed neurocognitive and neurological performance within a randomized clinical trial with 3 arms containing World Health Organization first-line recommended ART regimens (ACTG 5175; PEARLS). The ACTG 5271 INNS collected normative comparison data on 2400 high-risk HIV-negative participants from 10 voluntary counseling and testing sites aligned with INS. Normative comparison data were used to create impairment ratings for HIV+ participants in INS; associations were estimated using generalized estimating equations. Results. Among 860 HIV+ adults enrolled in ACTG 5199, 55% had no neurocognitive impairment at baseline. Mild neurocognitive impairment was found in 25%, moderate in 17%, and severe in 3% of participants. With the initiation of ART, the estimated odds of impairment were reduced 12% (95% confidence interval, 9%, 14%) for every 24 weeks (P < .0001) on ART. Mild impairment dropped slightly and then remained at about 18% out to week 168. Conclusions. Almost half of HIV+ participants had neurocognitive impairment at baseline before ART, based on local norms. With ART initiation, there were significant overall reductions in neurocognitive impairment over time, especially in those with moderate and severe impairments.
Original language | English (US) |
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Pages (from-to) | 1733-1738 |
Number of pages | 6 |
Journal | Clinical Infectious Diseases |
Volume | 68 |
Issue number | 10 |
DOIs | |
State | Published - May 1 2019 |
Funding
Potential conflicts of interest. J. S. (Clinical Trials Unit [CTU] grant UM1 AI069481-08). T. B. C., M.D. grant support from NIAID AIDS CTU # AI069450. reports grants from NIH, during the conduct of the study; personal fees from Gilead, personal fees from ViiV, personal fees from Theratechnologies, outside the submitted work. Deise Vieira M.D. and M. T. S., M.D. – PhD-IPEC-FIOCRUZ (Site 12101) Rio de Janeiro, Brazil, CTU Grant # AI69476 N. K., M.B.B.S., Ph.D. and Jabin Sharma-YRGCARE Medical Centre (Site 11701) CTU Grant # AI069432 Virginia M. Kayoyo, Franklin D. Kilembe, M.Ph. Mitch Matoga MBBS, M. C. H., M.D. University of North Carolina Project, Kamuzu Central Hospital, Lilongwe (Site 12001) CTU Grant # AI069518 Mauleen Waison and Rachel Mahachi-Parirenyatwa CRS (Site 30313) CTU Grant # BRS-ACURE-Q-08-00173-TOOI-OOO Cynthia Firnhaber, M.D. and Daphne S. Radebe, B.A. - Wits HIV Clinical Research Site (Helen Joseph Hosp) (Site 11101) CTU Grant# AI069463; BRS-ACURE-Q-07-00143 T006 Thira Sirisanthana, M.D. and Daralak Tavornprasit-Research Institute for Health Sciences-Chiang Mai University (Site 11501) CTU Grant # AI069399; AACTG.27.5199.06 Maria Siliprandi, M.D. and Renata Londero,M.D. -Hospital Nossa Senhora da Conceicao CRS (Site 12201) CTU Grant # 5 U01 AI069401 Anjali A. Joglekar, M.B.B.S. and S. T., M.D., M.B.B.S.-NARI Pune CRS (Site 11601) CTU Grant # 5U01AI069417-03 Jorge Sanchez, MD, MPH, and Juan Carlos Hurtado, M.D. - Asociación Civil Impacta Salud y Educación (Site 11301) CTU Grant # AI069438; BRS-ACURE-Q-08-00007-T-002 Manisha V. Ghate, M.B.B.S., D.C.H. and Madhura Nene, M.B.B.S. - NARI-NIV Clinic (Site 11603) CTU Grant # 5U01AI069417-03 Dr Raman Gnagakhedkar and Usha Katti, M.B.B.S.-Dr Kotnis Dispensary, NARI (Site 11602) CTU Grant # 5U01AI069417-03 Umesh Lalloo, M.D., F.R.C.P. and R. M., MB ChB –Durban, South Africa Adult HIV CRS (Site 11201) CTU Grant # 5U01AI069426-03 Ben Kalonga and Henry Chamba-Blantyre College of Medicine, Malawi-Johns Hopkins Project (Site 30301) CTU Grant # U01A1069518 Carlos Mosquera, M.D., and Rosa Infante, M.D.-INMENSA-Lince CRS Lima, Peru (Site 11302) CTU Grant # 5U01 AI069438-03; BRS-ACURE-Q-07-00141-T001-001 H. J. was funded in part by the Statistical and Data Management Center of the Adult AIDS Clinical Trials Group grant 1 U01 068634. K. M. reports grants from NIH, during the conduct of the study; grants from Merck, outside the submitted work. K. R. R. reports non-financial support from ViiV, personal fees from ViiV, outside the submitted work; K. S. reports grants from NIH, during the conduct of the study; A. L. R. reports grants from National Institute of Allergy and Infectious Diseases, during the conduct of the study; personal fees from MSD Peru, outside the submitted work; R. M. reports grants from NIH/NIAID, during the conduct of the study. N. K. reports a grant from the NIH. Acknowledgments. We gratefully acknowledge the participants in ACTG 5175, ACTG 5199, and ACTG 5271 and all ACTG personnel who made the study possible. We gratefully acknowledge the support of Dianne Rausch, Pim Brouwers, Jeymohan Joseph, and Kathy Kopnisky at National Institute of Mental Health (NIMH) for supporting this work. We also appreciate the code sent by Laura Smeaton. Financial support. The project described was supported by the NIAID (award U01AI068636) and by NIMH, National Institute of Dental and Craniofacial Research, and Statistical and Data Analysis Center (grant AI-068634). This work was also a part of ACTG DR005, which was partially supported by the University of North Carolina at Chapel Hill Center for AIDS Research (P30 AI50410) for work by K. M.
Keywords
- Antiretroviral
- HIV-associated neurocognitive disorders
- International settings
- Neurocognitive
- Neurology
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases