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Half With Undetectable Plasma Load
Have Neurocognitive Impairment in UK Group
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13th European AIDS Conference, October 12-15, 2011, Belgrade
Mark Mascolini
Half of all participants entering a large UK trial with an undetectable viral load in plasma had neurocognitive impairment [1]. Higher proportions of blacks than whites had neurocognitive impairment in this trial population. However, unlike people in the US CHARTER cohort [2], CD4 nadir (the lowest recorded CD4 count) did not predict neurocognitive impairment in the UK group.
Prevalence of neurocognitive impairment remains high in people HIV infection as survival improves thanks in part to combination antiretroviral therapy (cART) [2,3]. In the UK the proportion of people with a plasma load below 50 copies rose from below 70% in 2000 to above 80% in 2012 [4]. Over the same period the proportion of people with a CD4 count under 200 has dropped below 10%.
To determine prevalence and predictors of neurocognitive function in patients with an undetectable plasma load, researchers assessed people enrolling in the PIVOT trial, which is testing ongoing triple therapy versus protease inhibitor monotherapy after people achieve and maintain an undetectable load with triple therapy.
The investigators assessed function in five domains--attention, executive function, verbal learning, verbal memory, and fine motor skills. They transformed raw scores from each test to z scores by using normative data from the general population (matched by age for all tests and by education for attention and executive function tests). Then the PIVOT team figured a global neurocognitive score (QNPZ-5) and the percentage of people with test scores more than 1 standard deviation below population averages in QNPZ-5 and in at least two domains (the Frascati score).
About 16% of the general population are expected to have a single neurocognitive test result more than 1 standard deviation below the average. Because general-population scores rely mostly on data from people in the US and Canada, the PIVOT investigators further adjusted this comparison by using a (limited) dataset on neurocognitive performance in African Americans. In this way they hoped to provide a comparison that better reflected their racially diverse study group than the straight general-population scores. In this race-adjusted analysis, they figured that 20% of the general population would have a single neurocognitive test result more than 1 standard deviation below normal.
All study participants had a plasma viral load below 50 copies for at least 6 months on cART and completed all neurocognitive function tests when entering the trial. This group included 560 people, 382 (68%) Caucasian and 158 (28%) black. Men accounted for 93% of the Caucasian group but only 39% of the black group. Age averaged 44 years overall and did not differ between the two racial groups.
Both racial groups had an average 15 years of education and an undetectable viral load for an average 4 years. Current CD4 count averaged 571 in the Caucasian group and 511 in the black group. Respective nadir CD4 counts were 189 and 146. Efavirenz was the principal antiretroviral in both Caucasians (37%) and blacks (45%). About one third of patients in both groups reported moderate anxiety. About 4% of the study group had hepatitis C virus (HCV) antibody, including 5% of whites and 1% of blacks.
When calculated against general-population normative data, 51% of study participants had a low Frascati score (more than 1 standard deviation below average in at least two domains). The proportion of blacks with a low Frascati score was significantly higher than the proportion of whites (81% versus 38%, P < 0.001). Overall, 31% of study participants had a QNPZ-5 score more than 1 standard deviation below average, and again the proportion was significantly higher in blacks than whites (66% versus 17%, P < 0.001).
When calculated against race-adjusted general-population normative data, the higher proportion of black people with a QNPZ-5 score more than 1 standard deviation below the average remained significant (55% versus 45% with scores in the normal range, P = 0.001). In this analysis only 38% of whites had a low QNPZ-5 score versus 62% with a normal score. When calculated against race-adjusted normative data, the higher proportion of blacks with a Frascati score more than 1 standard deviation below the average in at least two domains was 69%, but that high proportion fell short of statistical significance when compared with proportion who had normal scores (P = 0.156). Compared with race-adjusted normative data, 62% of whites had a low Frascati score in at least two domains and 38% were within the normal range.
Multivariate analysis determined that being black independently raised the risk of a below-average QNPZ-5 score (beta -1.10, 95% confidence interval [CI] -1.28 to -0.92, P < 0.001). In whites, hepatitis C virus coinfection was associated with a low QNPZ-5 score (beta -0.33, 95% CI -0.65 to -0.01, P = 0.045). But no other variables--including nadir CD4 count--were associated with a low QNPZ-5 score. The PIVOT investigators suggested that the long time on cART in this group may explain the lack of association between nadir CD4 and neurocognitive impairment.
The investigators believe their findings underline the importance of having appropriate control data to understand neurocognitive test results in people with HIV. They noted that the "clinical relevance of high rates of abnormal results using categorical scoring systems (such as Frascati criteria) remain unclear."
References
1. Winston A, Arenas-Pinto A, Stoehr W, et al. Factors influencing neurocognitive function in a large cohort of HIV infected patients on effective antiretroviral therapy. 13th European AIDS Conference. October 12-15, 2011. Belgrade. Abstract PS2/4.
2. Ellis RJ, Badiee J, Vaida F, et al; CHARTER Group. CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS. 2011;25:1747-1751.
3. Dore GJ, McDonald A, Li Y, et al. Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS. 2003;17:1539-1545.
4. Bansi L, Sabin C, Delpech V, et al; UK Collaborative HIV Cohort (CHIC) Study and the Health Protection Agency. Trends over calendar time in antiretroviral treatment success and failure in HIV clinic populations. HIV Med. 2010;11:432-438.
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