Antiretroviral Therapy and Central Nervous System HIV Type 1 Infection

Abstract

Central nervous system (CNS) human immunodeficiency virus type 1 (HIV-1) infection begins during primary viremia and continues throughout the course of untreated systemic infection. Although frequently accompanied by local inflammatory reactions detectable in cerebrospinal fluid (CSF), CNS HIV-1 infection usually is not clinically apparent. In a minority of patients, CNS HIV-1 infection evolves into encephalitis during the late stages of systemic infection, which compromises brain function and presents clinically as acquired immunodeficiency syndrome dementia complex (ADC). Combination antiretroviral therapy (ART) has had a major impact on all aspects of CNS HIV-1 infection and disease. In those with asymptomatic infection, ART usually effectively suppresses HIV-1 in CSF and markedly reduces the incidence of symptomatic ADC. In those presenting with ADC, ART characteristically prevents neurological progression and leads to variable, and at times substantial, recovery. Similarly, treatment has reduced CNS opportunistic infections. With better control of these severe disorders, attention has turned to the possible consequences of chronic silent infection and the issue of whether indolent, low-grade brain injury might require earlier treatment intervention.

Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy

“…Unexpectedly, in the patients with systemic treatment failure in Fig. 1(C) (plasma VL>50 copies/mL), while many of the CSF VLs were detected, the difference between CSF and plasma increased to nearly 2 logs, i.e., CSF was proportionally more suppressed than plasma in these patients with drug resistance and reduced adherence [14]. Figure 1(D) shows findings in patients with neurosymptomatic escape that will be discussed later that contrast markedly with these more common relationships in treated patients.…”

“…Figure 1 illustrates the relationship of CSF to plasma HIV in four clinical settings, and Fig. 1(A) uses previously published data from untreated patients [14] to illustrate this relationship. As with systemic infection, CNS virus populations also evolve within the individual infected host and may change importantly as systemic disease progresses [15,16,13].…”

“…1 The data in panels A-C are from a cohort study previously published (ref. [14]). The plasma and CSF HIV RNA levels were from the initial study visit when subjects were classified on the basis of treatment status (A off treatment, either naïve or off ART) and for those on treatment of plasma VLs below 50 copies/mL (B success) or above that level (C failure).…”

Computerized testing augments pencil-and-paper tasks in measuring HIV-associated mild cognitive impairment*

“…It occurs in 30-50% of patients, depending on both the cohort under study and how the impairment is identified [1][2][3][4][5][6][7][8]. The current diagnostic approach is descriptive: HIV-associated neurocognitive disorder (HAND) is termed 'asymptomatic neurocognitive impairment' when found on testing in the absence of symptoms, and 'mild neurocognitive disorder' when both signs and symptoms are present, but are not severe enough to constitute frank dementia [9].…”

HIV-1-assoziierte neurokognitive Störung

“…HIV-Patienten mit einem initial schlechten Immunstatus (niedrige CD4-Zellzahlen), der sich unter cART verbesserte, waren einige Jahre nach cART-Beginn kognitiv noch gering schlechter als HIV-Negative, mit teilweise allerdings weiterer kognitiver Besserung im Verlauf [69]. Während somit schwere Ausprägun-gen von HAND, wie sie vor der cART-Ära üblich waren, bei antiretroviral behandelten Patienten nun selten sind [84], werden in der klinischen Praxis leichtere kognitive Störungen beobachtet, die zudem in früheren Infektionsstadien auftreten [49,50,92].…”