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

Sacktor N, Saylor D, Nakigozi G, Nakasujja N, Robertson K, Grabowski MK, Kisakye A, Batte J, Mayanja R, Anok A, Gray RH, Wawer MJ


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.


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


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.


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.


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.