Abstract
BackgroundThere is conflicting information as to whether antiretroviral drugs with better central nervous system (CNS) penetration (neuroHAART) assist in improving neurocognitive function and suppressing cerebrospinal fluid (CSF) HIV RNA. The current review aims to better synthesise existing literature by using an innovative two-phase review approach (qualitative and quantitative) to overcome methodological differences between studies.MethodsSixteen studies, all observational, were identified using a standard citation search. They fulfilled the following inclusion criteria: conducted in the HAART era; sample size > 10; treatment effect involved more than one antiretroviral and none had a retrospective design. The qualitative phase of review of these studies consisted of (i) a blind assessment rating studies on features such as sample size, statistical methods and definitions of neuroHAART, and (ii) a non-blind assessment of the sensitivity of the neuropsychological methods to HIV-associated neurocognitive disorder (HAND). During quantitative evaluation we assessed the statistical power of studies, which achieved a high rating in the qualitative analysis. The objective of the power analysis was to determine the studies ability to assess their proposed research aims.ResultsAfter studies with at least three limitations were excluded in the qualitative phase, six studies remained. All six found a positive effect of neuroHAART on neurocognitive function or CSF HIV suppression. Of these six studies, only two had statistical power of at least 80%.ConclusionsStudies assessed as using more rigorous methods found that neuroHAART was effective in improving neurocognitive function and decreasing CSF viral load, but only two of those studies were adequately statistically powered. Because all of these studies were observational, they represent a less compelling evidence base than randomised control trials for assessing treatment effect. Therefore, large randomised trials are needed to determine the robustness of any neuroHAART effect. However, such trials must be longitudinal, include the full spectrum of HAND, ideally carefully control for co-morbidities, and be based on optimal neuropsychology methods.
Highlights
There is conflicting information as to whether antiretroviral drugs with better central nervous system (CNS) penetration assist in improving neurocognitive function and suppressing cerebrospinal fluid (CSF) HIV RNA
Without proactive assessment of HIV-associated neurocognitive disorders (HAND), the individuals with asymptomatic neurocognitive impairment (ANI) and Mild Neurocognitive Impairment (MND) [2], which represent the greatest proportion of HAND are likely not to be considered for a specific therapeutic strategy
This study found that in the preHAART era, individuals with HAD were preferentially treated with antiretrovirals with greater CNS penetration
Summary
There is conflicting information as to whether antiretroviral drugs with better central nervous system (CNS) penetration (neuroHAART) assist in improving neurocognitive function and suppressing cerebrospinal fluid (CSF) HIV RNA. The possibility that some antiretroviral drugs with more efficient Central Nervous System (CNS) penetration as part of Highly Active Antiretroviral Therapy (HAART) may be associated with better neurocognitive (NC) functioning and more efficient cerebrospinal fluid (CSF) HIV RNA suppression than other ARVs has important clinical and therapeutic implications [1]. This was still sub-optimal as it used preHAART drugs They found that in the HAART era, the treatment strategy as assessed retrospectively, did not favour neuroHAART for individuals with HAD, while ANI and MND were not considered at all
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