Commonly prescribed antiretroviral therapy regimens and incidence of AIDS-defining neurological conditions. JAIDS
Caniglia et al. on behalf of the HIV-CAUSAL Collaboration aimed to investigate the potential effect of commonly prescribed combination antiretroviral therapy (cART) regimens among HIV-infected individuals from Europe and the Americas on the clinical diagnoses of the following 4 neuro AIDS conditions: HIV dementia and the opportunistic infections toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy.
The analysis was restricted to previously ART–naïve HIV-positive individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor (NRTI) backbone and either boosted atazanavir, boosted lopinavir, boosted darunavir, or efavirenz. Only a small number of individuals started cART with integrase strand transfer inhibitors (InSTIs) and were therefore excluded.
26’172 individuals initiated efavirenz, 5’858 initiated atazanavir, 8’479 initiated lopinavir, and 4’799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% confidence intervals) were
1.72 (1.00 to 2.96) for atazanavir,
2.21 (1.38 to 3.54) for lopinavir, and
1.41 (0.61 to 3.24) for darunavir.
The respective hazard ratios (95% confidence intervals) for the combined end point were
1.18 (0.74 to 1.88) for atazanavir,
1.61 (1.14 to 2.27) for lopinavir, and
1.36 (0.74 to 2.48) for darunavir.
The results varied in subsets defined by calendar year, nucleoside reverse transcriptase inhibitor backbone, and age.
In conclusion, the study-findings are consistent with an increased risk of HIV dementia after initiating cART regimens containing lopinavir or atazanavir and with an increased risk of neuro-AIDS opportunistic infections after initiating cART regimens containing lopinavir, compared with efavirenz. However, the findings need to be interpreted with caution because a large proportion of the cases were diagnosed within a few months of initiation, and the increased relative risk was substantially attenuated among individuals initiating cART in 2008 or later. It is therefore possible that the increased risk found in the main analysis could be the result of changes in prescribing trends over time, prescribing InSTI-based regimens to individuals who could be at higher risk for neuro-AIDS, or starting cART at higher CD4 levels.