HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors

TLDR

Combination antiretroviral therapy has reduced HIV morbidity, yet high rates of HIV‑associated neurocognitive disorders persist. This study aimed to assess whether CART altered the prevalence, clinical profile, and predictors of HAND by comparing large HIV‑positive and HIV‑negative cohorts before and after CART implementation. Researchers applied identical neurocognitive screening and impairment classification methods to 857 participants from 1988–1995 and 937 participants from 2000–2007. Results showed that impairment rates increased with disease stage in both eras, were higher in asymptomatic individuals during the CART era, were consistently predicted by nadir CD4, differed in symptom patterns (motor, speed, fluency pre‑CART versus memory, executive function post‑CART), and that mild NCI remains common, suggesting early ART initiation may reduce HAND.

Abstract

Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV−) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV − participants from the pre-CART era (1988–1995; N = 857) and CART era (2000–2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation.