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Effect of HIV Subtype and Antiretroviral Therapy on HIV-Associated Neurocognitive Disorder Stage in Rakai, Uganda

Sacktor, Ned, MDa; Saylor, Deanna, MD, MHSa; Nakigozi, Gertrude, MBChBb; Nakasujja, Noeline, MBChB, MPHc; Robertson, Kevin, PhDd; Grabowski, M. Kate, PhDe; Kisakye, Alice, MBChBb; Batte, James, MBChBb; Mayanja, Richard, BSb; Anok, Aggrey, BSb; Gray, Ronald H., MD, MSce; Wawer, Maria J., MD, MSHe

JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1, 2019 - Volume 81 - Issue 2 - p 216–223
doi: 10.1097/QAI.0000000000001992
Clinical Science

Background: Combination antiretroviral therapy (ART) improves HIV-associated neurocognitive disorder (HAND) stage in the United States where subtype B predominates, but the effect of ART and subtype on HAND stage in individuals in Uganda with subtypes D and A is largely unknown.

Setting: A community-based cohort of participants residing in Rakai, Uganda.

Methods: Three hundred ninety-nine initially ART-naive HIV-seropositive (HIV+) individuals were followed up over 2 years. Neurological and neuropsychological tests and functional assessments were used to determine HAND stage. Frequency and predictors of HAND and HIV-associated dementia (HAD) were assessed at baseline and at follow-up after ART initiation in 312 HIV+ individuals. HIV subtype was determined from gag and env sequences.

Results: At 2-year follow-up, HAD frequency among HIV+ individuals on ART (n = 312) decreased from 13% to 5% (P < 0.001), but the overall frequency of HAND remained unchanged (56%–51%). Subtype D was associated with higher rates of impaired cognition (global deficit score ≥ 0.5) compared with HIV+ individuals with subtype A (55% vs. 24%) (P = 0.008). Factors associated with HAD at baseline were older age, depression, and plasma HIV viral load >100,000 copies/mL. At follow-up, age and depression remained significantly associated with HAD.

Conclusions: HIV+ individuals on ART in rural Uganda had a significant decrease in the frequency of HAD, but HAND persists after 2 years on ART. The current guideline of immediate ART initiation after HIV diagnosis is likely to greatly reduce HAD in sub-Saharan Africa. Further studies of the effect of HIV subtype and neurocognitive performance are warranted.

aDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD;

bRakai Health Sciences Program, Kalisizo, Uganda;

cDepartment of Psychiatry, Makerere University, Kampala, Uganda;

dDepartment of Neurology, University of North Carolina-Chapel Hill, Chapel Hill, NC; and

eDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Correspondence to: Ned Sacktor, MD, Neurology, Johns Hopkins Bayview Medical Center, 301 Building, Suite 2100, 4940 Eastern Avenue, Baltimore, MD 21224 (e-mail:

Supported by the National Institutes of Health (NIH) (RO1 MH099733; P30 MH075673; R25 MH080661-08; R25 NS065729-0552; P30 AI094189-01A1) and the Johns Hopkins Center for Global Health.

Presented at the 2018 Conference on Retroviruses and Opportunistic Infections; March 5, 2008; Boston, MA.

The authors report no conflicts of interest.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

Received July 06, 2018

Accepted November 11, 2018

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