Abstract
There is a pressing need to effectively manage HIV Associated Neurocognitive Disorders (HAND) in sub-Saharan Africa (SSA) where the burden is among the highest in the world. Contemporary approaches based on the use of Highly Active Antiretroviral Therapy (HAART) alone are inadequate interventions for HAND, especially in SSA where there is limited availability of the required combinations of HAART for effective central nervous system penetration and where many currently prescribed agents, including efavirenz, have neurotoxicity as a major drawback. This article reviews data supporting the rationale for additive citalopram in antiretroviral therapy as a latent approach to abate HAND. It proposes the conduct of a HIV Associated Neurocognitive Disorders Subsidence through Citalopram addition in Anti-Retroviral therapy (HANDS-CARE) pilot feasibility trial (RCT) to assess whether the adjunctive use of citalopram, a widely prescribed serotonergic antidepressant, will lead to a meaningful improvement in neurocognitive functioning and quality of life in patients with HAND who are receiving HAART. A preliminarily feasible and efficacy-suggesting HANDS-CARE trial could generate statistical, clinical and operational data necessary to design and conduct a future definitive RCT. If successful, this intervention will be applicable to resource-limited settings as well as developed countries. Effective management of HAND will improve the quality of life of HIV patients, and reduce the cost of managing the disease.
Highlights
Countries in Sub-Saharan Africa (SSA) account for two-thirds of all People Living with Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (PLWHA) [1, 2]
HIV Associated Neurocognitive Disorders (HAND) are multifactorial complications resulting from the direct affectation of the central nervous system (CNS) by HIV [7]
The proposed proof of concept HANDS-CARE study could generate statistical, clinical and operational data necessary to design and conduct a future definitive RCT assessing whether the adjunctive use of citalopram, a widely prescribed serotonergic antidepressant, will lead to a meaningful improvement in neurocognitive functioning and quality of life in patients with HIV associated neurocognitive impairment while receiving
Summary
Countries in Sub-Saharan Africa (SSA) account for two-thirds of all People Living with Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (PLWHA) [1, 2]. In addition to the above listed hypotheses, the particular observation of independent reduction of brain RNA levels in PLWHA by citalopram, sertraline and trazodone [30] would suggest that it is difficult to ascribe the benefit of the antidepressants on CNS RNA suppression to the effect of the drugs in improving uptake or adherence to HAART. It would appear that the 2C19 iso-enzyme is mostly un-affected by a majority of available anti-retroviral agents For this reason, citalopram and escitalopram are regarded as the two SSRIs of first choice in patients with HIV/AIDS [48]. The proposed proof of concept HANDS-CARE study could generate statistical, clinical and operational data necessary to design and conduct a future definitive RCT assessing whether the adjunctive use of citalopram, a widely prescribed serotonergic antidepressant, will lead to a meaningful improvement in neurocognitive functioning and quality of life in patients with HIV associated neurocognitive impairment while receiving
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