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Long-Term Efavirenz Linked to Worse Neurocognitive Function in US CHARTER Group
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Here is the bullet summary from Scott Letendre, study author:
First, we looked at the entire group and EFV was worse
Then, we then looked at only the subgroup with undetectable plasma viral loads and EFV was worse. We did this because this subgroup is the most clinically relevant. We didn't look at the other subgroup because people taking failing therapy are of course typically switch to effective therapy.
Then, during the multivariable analyses, we observed the interaction between treatment group and HCV. We stratified the group by HCV serostatus to understand the nature of the interaction and found the relationships summarized in the poster figure (which you described very nicely in the summary).
So, based on the analysis, EFV was worse (1) overall (2) in the subgroup with undetectable plasma viral loads and (3) in the subgroup without HCV co-infection. LPV/r was worse in the subgroup with HCV co-infection.
20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta
Mark Mascolini
Long-term treatment with an efavirenz-based regimen correlated with worse neurocognitive function than did treatment with lopinavir/ritonavir, according to results of a retrospective case-control comparison within the US CHARTER cohort [1]. Worse performance with efavirenz held true in people without hepatitis C virus (HCV) coinfection or with a plasma viral load below 50 copies. In contrast, HCV-positive cohort members had worse neurocognitive performance if taking lopinavir/ritonavir.
Scott Letendre (University of California, San Diego) and CHARTER colleagues cautioned that "the complexity of these data is substantial and differences would best be evaluated in a randomized clinical trial."
HIV-associated neurocognitive disorders (HAND) remain prevalent in people responding well to current antiretroviral regimens. Antiretroviral neurotoxicity may be one factor accounting for persistence of these disorders. Because efavirenz has well-documented neurologic side effects, the CHARTER team planned this retrospective case-control analysis of people currently taking efavirenz or lopinavir/ritonavir with at least two other antiretrovirals for at least 12 weeks.
No study participants had severe neuropsychiatric morbidities, and all underwent comprehensive assessment of seven neurocognitive domains. Average age was similar in the 272 people taking efavirenz (43.9) and the 173 taking lopinavir (45.1). The efavirenz and lopinavir groups did not differ much in years of education (12.8 and 12.6), gender (81% and 79% men), or ethnicity (40% and 36% white). Duration of treatment was similar in the efavirenz and lopinavir groups (27.6 and 25.1 months).
The efavirenz cohort had a lower proportion of people coinfected with HCV (23% versus 32%, P = 0.046), a lower proportion with AIDS (64% versus 82%, P < 0.001), a shorter duration of HIV infection (109.8 versus 144 months, P < 0.001), a higher current CD4 count (472 versus 381, P = 0.01), a higher nadir CD4 count (166 versus 88, P < 0.001), a lower current plasma viral load (1.7 versus 1.8 log, P < 0.001), and a higher proportion with a cerebrospinal fluid load at or below 1.7 log (92% versus 74%, P < 0.001). The central nervous system penetration effectiveness score was significantly lower (worse) with efavirenz regimens that lopinavir regimens (7 versus 8, P < 0.001).
To compare neurocognitive test results, the CHARTER team divided study participants into those with and without HCV. In 328 people without HCV infection, a higher proportion of efavirenz takers had impairment in every domain assessed, and the difference was significant for executive functioning (P = 0.05), speed of information processing (P = 0.04), and a combined global functioning score (about 50% versus 40% impaired, P = 0.02). Verbal functioning was marginally worse in the efavirenz group (P = 0.08).
Among the 117 HCV-positive cohort members, the proportion with neurocognitive impairment was consistently higher with lopinavir/ritonavir and significantly higher for learning (P = 0.04), memory (P = 0.01), and the combined global functioning score (about 80% versus 40% impaired, P = 0.04). Motor functioning was marginally worse with lopinavir than efavirenz (P = 0.06).
In 269 people with a plasma viral load below 50 copies, efavirenz users had worse executive functioning (P = 0.03) and worse speed of information processing (P = 0.02) than lopinavir users.
The researchers noted that factors possibly affecting susceptibility to HIV-associated neurocognitive disorders differed substantially between the efavirenz and lopinavir groups. Some of those differences, they speculated, could reflect clinicians' tendency to prescribe lopinavir/ritonavir for people with more advanced HIV infection or as second-line therapy.
"Despite these differences," the CHARTER team concluded, "efavirenz users had worse neurocognitive functioning"--if they did not have HCV infection or if they did have an undetectable plasma viral load.
Reference
1. Letendre S, Vaida F, Croteau D, et al. Long-term efavirenz use is associated with worse neurocognitive functioning. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 407.
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