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  21st Conference on Retroviruses and
Opportunistic Infections
Boston, MA March 3 - 6, 2014
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Impact of Plasma HIV RNA on Neurocognitive Decline
--and Difference With PIs vs NNRTIs
  CROI 2014, March 3-6, 2014, Boston
Mark Mascolini
Compared with HIV-negative people, a significantly higher proportion of HIV-positive people with an always-detectable HIV load in plasma had declining neurocognitive performance through 2.5 years of follow-up [1]. But people with an always-undetectable or sometimes-undetectable plasma load did not decline faster in neurocognition than HIV-negative people. Among participants with an always-undetectable plasma load, those taking a nonnucleoside (NNRTI) regimen had faster neurocognitive decline than those taking a protease inhibitor (PI) regimen.
Despite abundant research on neurocognitive performance in antiretroviral-treated people, the level of viral suppression in plasma needed to prevent neurocognitive loss remains undefined. Nor has research delivered a definitive answer on whether PI and NNRTI regimens differ in neuroprotective ability. To address these questions, researchers compared neurocognitive performance in HIV-positive CHARTER cohort members and HIV-negative controls from the HIV Neurobehavioral Research Program (HNRP).
Everyone had at least 2 years of follow-up and neurocognitive assessment every 6 months according to Frascati criteria. The researchers determined neurocognitive decline with regression-based norms for neurocognitive performance change that corrected for factors that may influence test-retest differences in people with normal performance [2]. They divided HIV-positive people into three groups: (1) always suppressed (plasma load below 50 copies throughout follow-up), (2) sometimes suppressed (plasma load sometimes above and sometimes below 50 copies), and (3) always detectable (plasma load above 50 copies throughout follow-up).
The 346 HIV-positive people averaged 43.8 years in age, compared with 36.1 in HIV-negative controls (P < 0.01). The HIV group included a higher proportion of men (81% versus 67%, P < 0.01), a lower proportion of whites (45% versus 66%, P < 0.01), and a higher average number of neurocognitive evaluations (6.7 versus 5.2, P = 0.07). Both groups averaged 12.9 years in education.
The HIV group consisted of 103 always suppressed people, 112 sometimes suppressed, and 131 always detectable. The always-suppressed group had an average older age than the sometimes-suppressed and always-detectable (46.4 versus 44.3 versus 41.4, P < 0.01), a higher proportion of whites (55.3% versus 37.5% versus 42.8%, P = 0.03), a higher proportion positive for HCV antibody (33% versus 25% versus 19%, P = 0.05), and a longer median time since HIV diagnosis (12.4 versus 12 versus 8.1 years, P < 0.01). Education averaged about 13 years in all three groups.
Median current CD4 counts were 489 in the always-suppressed group, 410 in the sometimes-suppressed group, and 447 in the always-detectable group (P = 0.01). Respective nadir CD4 counts were 137, 108, and 315 (P < 0.01). Baseline testing rated neurocognitive performance normal in 51.5% of the always-suppressed group, 51.8% of the sometimes-suppressed group, and 63.4% of the always-detectable group.
Through a median 2.5 years of follow-up and after statistical adjustment for age, gender, ethnicity, and number of neurocognitive evaluations, 15% of HIV-negative controls had neurocognitive decline, compared with 18.5% in the always-suppressed group with HIV, 22.3% in the sometimes-suppressed group, and 26% in the always-detectable group. Only the difference between the always-detectable group and the HIV-negative group reached statistical significance (P < 0.05).
Limiting the analysis to 43 always-suppressed people taking a PI regimen (plus 2 nucleosides) and 37 taking an NNRTI (plus 2 nucleosides), the researchers determined that 7.0% taking a PI regimen had a neurocognitive decline, compared with 24.3% taking an NNRTI regimen (P = 0.03). Age, gender, ethnicity, years of education, HCV status, and AIDS status did not differ between the two groups. But the PI group had a significantly longer duration of known HIV infection (median 13.8 versus 8.7 years, P = 0.02), a significantly lower CD4 nadir (median 93 versus 180, P = 0.04), and a modestly but significantly lower central nervous system penetration effectiveness score (median 7 versus 8, P = 0.04). The PI and NNRTI groups did not differ in nucleoside pairs being taken or years taking antiretroviral therapy. Statistical analysis adjusting for these differences determined that people taking an NNRTI regimen had more than a tripled chance of neurocognitive decline (relative risk 3.41, 95% confidence interval 1.02 to 11.93).
1. Perez-Valero I, Heaton R, Franklin D, et al. HIV-replication control rates needed to prevent neurocognitive performance decline. CROI 2014. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2014. Boston. Abstract 478.
2. Cysique LA, Franklin D Jr, Abramson I, et al; CHARTER Group; HNRC Group. Normative data and validation of a regression based summary score for assessing meaningful neuropsychological change. J Clin Exp Neuropsychol. 2011;33:505-522.