Table 1.

Epidemiological studies of p-tau and t-tau in HAND

Author, Year	Study	Subjects	Technique used	Tau detection range (pg/ml)	p-tau and/or t-tau result
Green et al. [35]	Cerebrospinal fluid tau concentrations in HIV infected patients with suspected neurological Disease	1) Mean age: 37 yr. with acute neurological episodes	ELISA (INNOTEST, Fujirebio Europe/Innogenetics, Ghent, Belgium)	t-tau: 75-316	1) CSF tau not elevated in 82% of patients, regardless of clinical diagnoses.
		2) N = 76 (24-HAD, 10 lymphoma, 20 cerebral infarctions, 22 miscellaneous conditions such as headache)			2) Elevated CSF tau was associated with poor outcome as 6 of 8 patients who died within 4 weeks of lumbar puncture.
		3) cART not accounted for
Brew et al. [37]	CSF amyloid beta42 and tau levels correlate with AIDS dementia complex	1) Mean age: 43 years	ELISA (INNOTEST, Fujirebio Europe/Innogenetics, Ghent, Belgium)	Upper limits not reported /lower limits: t-tau: 75, p-tau:16	1) HAND subjects had significantly increased t-tau and p-tau at residue 181 (p-Tau181) at concentrations similar to patients with AD
		2) N = 101 HIV positive subjects with or without ADC with 20 moderate to severe AD subjects as positive control			2) p-tau levels significantly increased in all of the ADC stages compared with the negative controls and the AD patients.
		3) cART not accounted for.
Anthony et al. [54]	Accelerated Tau deposition in the brains of individuals infected with human immunodeficiency virus-1 before and after the advent of highly active anti-retroviral therapy	1) Mean age: 40 for HIV- control group and HIV positive cases, 70 for HIV negative control group and 40 for HIV negative control group B	Immunohistocytochemistry (TSA was used in instances where avidin-biotin complex ABC was not sensitive enough, with DBA for visualization.)	NA: AT8 antibody used on paraffin sections	1) Higher levels of p-tau in HIV infectedsubjects vs. aged matched controls.
		2) N = 34			2) Greatest levels of p-tau were noted in cART-treated subjects.
		3) Nine cART treated subjects with excellent compliance for at least 18 months with pre-symptomatic HIV or AIDS and 20 pre-cART HIV subjects			3) Increased t- tau in hippocampal region of pre-cART HIV-infected groups compared to HIV-negative age-matched controls
Clifford et al. [39]	CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease	1) Mean age: normal cognition control group (50 years), HIV + normal cognition (43 years), HAND subjects (48 years), mild AD subjects (74 years)	ELISA, (INNOTEST, Fujirebio Europe/Innogenetics, Ghent, Belgium)	Not reported	HIV-positive subjects with HAND did not have CSF t-tau and p-tau181 characteristic of AD
		2) N = 188 (50 control, 68 AD subjects, 21 Neuro-normal HIV positive subjects and 49 HAND subjects.
		3) HIV patients were not treated with cART.
Patrick et al. [55]	Increased CDK5 expression in HIV encephalitis contributes to neurodegeneration via tau phosphorylation and is reversed with Roscovitine	1) Mean age: HIVE patients - 43.13 years, Non HIVE subjects (48.38 years )	Immunohistochemistry	N/A:AT8 and PHF-antibody detection on post-mortem brain	Elevated diffuse nonfibrriliar p-tau in HIVE group and HIV gp120 tg mice.
		2) N = 16: 8 HIVE subjects, 8 HIV positive without HIVE	(TSA was used in instances where avidin-biotin complex ABC was not sensitive enough, with DBA for visualization.)
		3) cART not accounted for
Steinbrink et. al. [56]	Cognitive impairment in HIV infection is associated with MRI and CSF pattern of neurodegeneration	1) Mean age: 45 ± 10 years	ELISA (INNOTEST, Fujirebio Europe/Innogenetics, Ghent, Belgium)	Not reported	1) Significant correlation between HAND and t-tau but not p-tau
		2) N = 94. All patients were HIV positive with varying levels of neuropsychological performance,			2) HAND severity correlated significantly with the t- tau level in CSF but not p-tau levels
		3) 68% cART treated
Smith et al. [57]	Brain viral burden, neuroinflammation and neurodegeneration in HAART-treated HIV positive injecting drug users	1) Mean age: 45.8 years for HIV+, 42.2 years for HIV-	Immunohistochemistry	NA: AT8 on post-mortem brain	1) IDU had more t- tau vs. non-DU
		2.) N = 20 :10 HIV + (6 IDU, 4 non-IDU),10 HIV (6 IDU, 4 non-IDU)	(TSA was used in instances where avidin-biotin complex ABC was not sensitive enough, with DBA for visualization.)		2) HIV + subjects had more t-tau than HIV -, but these differences did not achieve statistical significance.
		3) HIV + patients treated with cART for up to 7.9 years