A case of cerebrospinal fluid viral escape on a dual antiretroviral regimen: worth the risk?

TO THE EDITOR—Among human immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART), incomplete viral suppression in cerebrospinal fluid (CSF) may occur even with undetectable plasma viremia [1–4]. Treatment simplification with “less-drug regimens” may favor adherence and reduce toxicity, but raises concerns on lower central nervous system (CNS) drug penetration and subsequent CNS viral escape [5, 6], as in the case we report herein. A 47-year-old HIV-infected woman, receiving different ART regimens since 2002, in 2007 withdrew emtricitabine due to lower-limb neuropathy, and maintained plasma viral control with darunavir/ritonavir 600/100 mg twice daily and tenofovir (in February 2013: HIV RNA <40 copies/mL; CD4 lymphocyte count, 508 cells/μL). InMarch 2013, shewas hospitalized after complaining of lower-limb weakness and pain, headache, dizziness, and dysarthria. Brain magnetic resonance imaging (MRI) showed extensive signal abnormalities (Figure 1A); lumbar puncture revealed CSF total protein of 76 mg/dL with oligoclonal immunoglobulin G bands, normal glycorrhachia, and cell count. CSF cultures and examinations for opportunistic infections (Cryptococcus neoformans, Epstein-Barr virus, cytomegalovirus, human herpesvirus 8, JC virus) were negative, and the CSF HIV RNA load was 2715 copies/mL. Genotypic testing showed the presence of multiple protease inhibitor (PI)–associated mutations (V32I, I54V, V82A, I84V, L10I, L33F, K20R, M36I) conferring intermediate resistance to darunavir, and nucleoside/nucleotide reverse transcriptase inhibitor–associated mutations (M41L, T215Y, V90I), conferring intermediate resistance to tenofovir. Thus, antiretroviral treatment was changed with darunavir/ritonavir 600/ 100 mg twice daily plus raltegravir 400 mg twice daily plus etravirine 200 mg twice daily. Two months later, the patient reported significant symptom improvements: the CD4 count was 759 cells/μL; both plasma and CSF HIV RNAwere undetectable. One year later, brain MRI showed clear improvements in radiological signs (Figure 1B). To our knowledge for the first time, here we describe a case of CSF viral escape in an HIV-infected patient on suppressive ART with a dual regimen. Previous cases of CSF viral escape (with or without neurological symptoms) were reported in patients with incomplete plasma HIV RNA suppression, or treated with suboptimal ART [1, 2]. Compared to others, this case clearly illustrates the improvements of neurological symptoms and radiological signs (Figure 1A and 1B) after switching ART, guided by genotypic resistance testing on CSF. Recently, a higher CNS penetration effectiveness ranking score of ART has been associated with lower levels of CSFHIVRNA, as well as improvements in neurological and cognitive functions [7, 8]. Meanwhile, new therapeutic schemes have been proposed for patients on suppressive therapy to reduce toxicity and costs, such as switching to dual regimens or to boosted PI monotherapy [5,9].These approaches may, however, be limited by lower CNS drug penetration, potentially leading to CSF viral escape (already described with boosted PI monotherapy) [5, 6]. In this report, the results of HIV genotyping in CSF suggest a CNS virus compartmentalization, with subsequent selection of