Twelve-year neurocognitive decline in HIV is associated with comorbidities, not age: a CHARTER study

Abstract

Modern antiretroviral therapy (ART) has increased longevity of people with HIV and shifted the age distribution of the HIV pandemic upward toward that of the general population. This positive development has also led to concerns about premature and/or accelerated neurocognitive and physical ageing due to the combined effects of chronic HIV, accumulating comorbidities, adverse effects or possible toxicities of ART and biological ageing. Here we present results of comprehensive assessments over 12 years of 402 people with HIV in the CNS HIV ART Effects Research (CHARTER) programme, who at follow-up were composed of younger (<60 years) and older (≥60 years) subgroups. Over the 12 years, ART use and viral suppression increased in both subgroups as did systemic and psychiatric comorbidities; participants in both subgroups also evidenced neurocognitive decline beyond what is expected in typical ageing. Contrary to expectations, all these adverse effects were comparable in the younger and older CHARTER subgroups, and unrelated to chronological age. Neurocognitive decline was unrelated to HIV disease or treatment characteristics but was significantly predicted by the presence of comorbid conditions, specifically diabetes, hypertension, chronic pulmonary disease, frailty, neuropathic pain, depression and lifetime history of cannabis use disorder. These results are not consistent with premature or accelerated neurocognitive ageing due to HIV itself but suggest important indirect effects of multiple, potentially treatable comorbidities that are more common among people with HIV than in the general population. Good medical management of HIV disease did not prevent these adverse outcomes, and increased attention to a range of comorbid conditions in people with HIV may be warranted in their care.

Keywords: HIV; brain; cognition; neurologic complications.

Figure 1

Change by decliner status. (A) Global T-score by decliner status at baseline and 12 years (values are mean and 95% confidence interval). (B) Global neurocognitive impairment by decliner status at baseline and 12 years (values are observed proportions).

Figure 2

GCS and decliner status by comorbidity indices at baseline and at 12 Years. (A) GCS by number of comorbidities at baseline. (B) GCS by number of comorbidities at 12 years. (C) Proportion of decliners by number of comorbidities at baseline. (D) Proportion of decliners by number of comorbidities at 12 years. Values in A and B are mean and 95% confidence intervals. In C and D, values are proportions.