Management of a human immunodeficiency virus case with discordant antiviral drug resistance profiles in cerebrospinal fluid compared with plasma: a case report

Abstract

Background: Human immunodeficiency virus-1-associated neurocognitive disorder is a known complication in individuals treated with antiretroviral therapy. Cerebrospinal fluid escape, which is defined as discordant higher cerebrospinal fluid viremia than plasma, may occur in antiretroviral therapy-experienced individuals. Different cerebrospinal fluid versus plasma mutation patterns have been observed in individuals with cerebrospinal fluid escape.

Case presentation: A 46-year-old adult African male with human immunodeficiency virus-1 infection and acquired immunodeficiency syndrome based on cerebral toxoplasmosis and a chronic hepatitis B virus infection developed cerebrospinal fluid escape. A different human immunodeficiency virus-1 genotypic drug resistance profile was observed in plasma compared with cerebrospinal fluid. Brain biopsy and cerebral magnetic resonance imaging indicated the development of human immunodeficiency virus encephalopathy. A discordant protease inhibitor mutation/wild-type T74PT in plasma but not in cerebrospinal fluid indicated poor central nervous system penetration due to the selective pressure of drug therapy. An intensified antiretroviral therapy regimen including dolutegravir with good central nervous system penetration improved conditions.

Conclusions: This case shows the importance of measuring human immunodeficiency virus drug resistance in cerebrospinal fluid, which might differ from resistance detected in plasma samples and target effective antiretroviral therapy treatment accordingly.

Keywords: AIDS; Cerebrospinal fluid; HIV; HIV-associated neurocognitive disorder; Protease inhibitor drug resistance.

Fig. 1

Resistance mutation development, antiretroviral therapy, human immunodeficiency virus-1 RNA viral load, and cluster of differentiation 4 cell count over time. a human immunodeficiency virus resistance mutation patterns are shown (red background), susceptible (green background), cerebrospinal fluid findings (yellow background), and time in months from the initial presentation (T = 0). b Plasma and cerebrospinal human immunodeficiency virus-1 RNA viral load and cluster of differentiation 4 cell count are shown over time. Antiretroviral therapy was commenced with a three-drug combination therapy including two nucleoside(tide) reverse-transcriptase inhibitors (lamivudine, zidovudine), and the non-nucleoside reverse transcriptase EFV 60 months after initial presentation. The non-nucleoside reverse transcriptase was discontinued and a protease inhibitor was added (month 75). Therapy was intensified to a four-drug regimen (month 169) with the inclusion of the INI raltegravir, and later substituted by the more potent dolutegravir (month 227). The different nucleoside(tide) reverse-transcriptase inhibitors used for treatment included lamivudine, zidovudine, tenofovir, abacavir, and emtricitabine). Protease inhibitors used were nelfinavir, lopinavir/ritonavir, atazanavir, and darunavir