Simplification of combination antiretroviral therapy (cART) and the brain-a real-life experience

Modern antiretroviral combination therapy (cART) has transformed HIV from a life-threatening infection into a chronic disease. However, the life-long treatment has side effects that frequently have a negative impact on patients' quality of life. Thus, there are some efforts to "simplify" therapy, i.e. apply regimens with three or fewer antiretroviral substances. However, neurologists are relatively sceptical towards this cART "simplification", because the capacity of simplified regimens to access the cerebrospinal fluid (CSF) might be too weak to effectively suppress viral load in this compartment. Thus, data of a big Neuro-AIDS cohort of 4992 HIV-positive patients consecutively recruited over three decades were retrospectively analysed in terms of neurocognitive performance of patients switched to simplified therapy regimens. To test whether simplified drug regimens result in new neuropsychological deficits or the worsening of pre-existing ones in HIV+ patients. Three groups of HIV+ patients were switched from triple therapy to three different two drug regimens (n = 177 to lamivudine/PI, n = 37 to INI/PI, and n = 303 to dual PI); three other groups of patients put from one to an alternative triple combination (n = 290 ABC/3TC/PI, n = 244 TDF/FTC/PI, and n = 158 TDF/FTC/NNRTI) for whatever reason served as controls. All patients were followed up over 4 years maximum. Every patient group improved immunologically and virologically after the switch. However, patients who switched to INI/PI combinations remained stable in neuropsychological tests, while a considerable percentage of patients who switched to other treatments demonstrated a decline. Remarkably, a high percentage of the patients switched to "simplified drug regimens" was not well-controlled virologically before the switch. HIV-positive patients with simplified therapy regimens show some benefit in terms of systemic infection surrogate markers (CD4 ± cell count and plasma viral load); however, neurocognitive deficits do not improve, but remain stable in most cases.