People taking antiretroviral regimens that include the NRTIs lopinavir (Kaletra) or atazanavir (Reyataz) appear to have a higher likelihood of developing HIV-associated dementia compared to people taking an efavirenz-containing regimen, an analysis of data on 45,308 participants from Europe and the Americas that was published in Journal of Acquired Immune Deficiency Syndrome found. However, changes in prescribing trends and unmeasured cofounders might be responsible for these findings, study authors cautioned.
The data stem from the HIV-CAUSAL Collaboration among 15 cohort studies in Europe, North America and Brazil. Efavirenz, taken by the vast majority of participants, served as the base against which the other medications were compared. All participants started their first nucleoside reverse transcriptase inhibitor-based regimen in or after 2004; data included in this analysis spanned from 2004 to 2015.
The analysis explored reported incidence of four AIDS-defining neurological conditions, collectively referred to as neuroAIDS. Overall incidence of these four conditions -- cryptococcal meningitis, HIV dementia, progressive multifocal leukoencephalopathy, and toxoplasmosis -- was low, with 201 total cases of any neuroAIDS opportunistic infection and 113 cases of HIV dementia. Relative to people taking efavirenz, the hazard ratio for any neuroAIDS condition was statistically significantly higher for people taking lopinavir (1.61), but fell short of statistical significance for people taking atazanavir or darunavir (Prezista).
When it came to HIV dementia specifically, relative to efavirenz, the adjusted hazard ratio was statistically significantly higher for both atazanavir (1.72) and lopinavir (2.21) -- but the risk was also significantly lower among people who started treatment after 2008. This finding in particular led the authors to caution against inferring a causal relationship between these drugs and neuroAIDS. It is possible, they write, "that the increased risk found in our main analysis could be the result of changes in pre-scribing trends over time such as prescribing zidovudine as an NRTI backbone, prescribing [integrase inhibitor]-based regimens to individuals who could be at higher risk for neuroAIDS, or starting [HIV treatment] at higher CD4 levels."