Some antiretrovirals penetrate the blood-brain barrier considerably better than others, and “high-penetration” regimens, as defined by a standard central nervous system (CNS) penetration-effectiveness (CPE) score, are linked to lower cerebrospinal fluid viral loads. However, whether such regimens carry clinical benefits — specifically, a reduction in risk for HIV dementia and other HIV-associated neurologic disease — remains unclear.
To explore this issue, investigators pooled results from nine prospective cohort studies in Europe and the U.S. involving >60,000 antiretroviral-naive, HIV-infected adults without clinical AIDS who began treatment after January 1, 1998. Sixty-two percent of them started a regimen considered to have low CNS penetration (most commonly efavirenz/tenofovir/FTC; CPE=7), 29% started a medium-penetration regimen (most commonly efavirenz/AZT/3TC; CPE=9), and 9% started a high-penetration regimen (most commonly nevirapine/AZT/3TC; CPE=10).
During follow-up (median duration, 37 months), diagnoses of HIV dementia were quite rare (235 cases in total). However, individuals in the high-CPE group were about 70% more likely to be diagnosed with HIV dementia than those in the low-CPE group. In contrast, common opportunistic CNS infections such as toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy occurred with similar frequency across all CPE groups. The analysis controlled for CD4 and viral load values, and additional analyses using refinements of the CPE scoring system and excluding dementia diagnosed within the first year of treatment did not alter the results.