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

Abstract

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.

Attention/Working Memory, Learning and Memory in Adult Cameroonians: Normative Data, Effects of HIV Infection and Viral Genotype

“…The proportion of cases in this study with impairment based on individual tests or domain T-scores (17-23%) is in line with our previous findings (Kanmogne et al, 2018;Kanmogne et al, 2010;Njamnshi et al, 2009;Njamnshi et al, 2008) and some previously reported prevalence of HAND in Nigeria (21.5%) (Yusuf et al, 2017) and South Africa (23%) (Joska, Fincham, Stein, Paul, & Seedat, 2010). However, these are much lower than HAND prevalence reported among HIV-infected adults in other studies in Nigeria, China, and India (26-28%) (Jumare et al, 2019;Royal et al, 2012); South Africa (36-53%) (Joska et al, 2011;Mogambery, Dawood, Wilson, & Moodley, 2017), Botswana (37-38%) (Lawler et al, 2011), Zambia (34-35%) (Kabuba et al, 2017), Uganda (38-64%) (Nakku, Kinyanda, & Hoskins, 2013;Sacktor et al, 2019;Yechoor et al, 2016), and the United States (36-45%) (Heaton et al, 2015). Test instruments used in these studies varied from simpler International HIV Dementia Scale to more complete NP batteries, and such differences could have played a role in the wide variations in HAND prevalence observed across studies.…”

Effects of HIV infection, antiretroviral therapy, and immune status on the speed of information processing and complex motor functions in adult Cameroonians

“…In addition to improving performance in tests of fine motor functions and speed of mental processing, ART use is also associated with improved performance in NP tests assessing concentration, memory and mental flexibility 5 ; and treatment failure is associated with poor performance on NP tests 9 . Despite these positive effects of ART on performance on some NP tests and the fact that ART use is associated with decreased prevalence of HAD, the overall prevalence of HAND in the current ART era remains high 5,12,13 .…”

“…Cross-sectional and longitudinal studies have shown that the odds of neurocognitive impairment increased in subjects with high plasma viral loads (VL) 10 and that such impairment is associated with poor health-related quality of life 11 . Although the prevalence of HIV-associated dementia (HAD), the most severe form of HAND, has markedly decreased in the current ART era 5 , 12 , 13 , milder forms of HAND [asymptomatic neurocognitive impairment and mild neurocognitive disorders] and overall neurocognitive impairment still occur in up to 50% of HIV-infected persons 13 – 17 .…”

“…HIV/AIDS epidemiology is characterized by a high clade diversity and differential geographic distribution based on viral subtypes 26 , 27 . There is evidence that the frequency of neurocognitive impairments among infected subjects varies based on HIV subtypes 13 , 28 – 31 but current understanding of HIV neuropathology and HAND mostly comes from studies of Western populations infected with HIV-1 clade-B 14 , 15 , 17 . Over two-thirds of the 38 million people living with HIV/AIDS (PLWH) are in Sub-Saharan Africa (SSA) and are mostly infected with different (non-B) HIV clades 32 .…”

HIV‐associated neurocognitive impairment in stable people living with HIV on ART in rural Tanzania

“…Demographically adjusted normative data were obtained from 400 HIV‐negative healthy Ugandan adults [43]. Neurocognitive data from every participant were adjusted for age and education, as described previously [44].…”