Three decade neurological and neurocognitive follow-up of hiv-1 infected patients

Terttu J Heikinheimo1, Erja T Poutiainen2, Oili Salonen3, Irina Elovaara4, Matti Ristola5
Affiliates: 1Terttu Heikinheimo, Department of Neurology, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290, Helsinki, Finland. 2Erja Poutiainen, Rehabilitation Foundation, Helsinki, Finland 3 Oili Salonen, Department of Radiology, Helsinki University Central Hospital 4Irina Elovaara, Deparment of Neurology, Tampere University Hospital 5Matti Ristola, Department of Infectious Diseases at Aurora Hospital, Helsinki University Central Hospital

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Since the development of combined antiretroviral treatment (cART) in the mid-1990s, the HIV-associated dementia (HAD) has become rare. Little is known how a very long-term HIV infection affects neurological and neurocognitive functions. We invited our study-patients that have lived with HIV for more than 25 years to be re-investigated by the team of neurologist, neuropsychologist and neuroradiologist.

In this interventional follow-up study we re-invited our study population of HIV-infected patients that were examined in three time periods: during the years 1986-1990, in 1997, and in 2013. They participated clinical examinations, laboratory investigations, and magnet resonance imaging (MRI) of the brain. Expanded Disability Status Scale (EDSS) and Fatigue Severity Scale (FSS) were used as a part of neurological examination. Neuropsychological examination included several measures, including subtests Weschler Adult Intelligence Scale (WAIS), and Weschler Memory Scale – revised (WMS-R), list learning, fluency, Stroop, and Trail-Making-B test. Depression was evaluated using the Beck Depression Inventory (BDI). The three examination time periods were compared with relevant follow-up analyses.

Of the original 80 patients, 23 participated in the 1997 evaluation, and 17 in all three examinations. They were all male. Their median (range) age was 59 (46-75) years of age as of the latest examination. The time from the HIV diagnosis was 27 (23 to 30) years, the CD4+ lymphocyte count at the diagnosis was 630 (29 to 870) cells/mm3, and the CD4+ nadir was 170 (4 to 408) cells/mm3. The time on any antiretroviral therapy was19 (9 to 24) years, and on cART was 13 (5 to 17) years. There were no iv-drug abusers, or heavy alcohol drinkers.
All 17 patients were fully ambulatory. Nine (53 %) of them suffered from fatigue (FSS >37) and five (29 %) had significant polyneuropathy (EDSS >3.0). Three (18 %) of them had lacunar infarcts in the brain, some of which were already seen in 1997 MRI images. Since 1997, there was a subtle increase of brain atrophy in three (18 %) patients. BDI revealed mild depression in all time periods (mean 4.65, 5.53 and 5.00, respectively). The neuropsychological follow-up showed normal and typical age-related cognitive changes including alterations in mental flexibility and memory functions. No HAD describing features were detected.

In our sample polyneuropathy, fatigue and mild depression were common but more severe neurological features were absent. These long-term surviving HIV-seropositive patients were largely free of cognitive symptoms, while on best-available treatment.