Two treatment strategies for management of Neurosymptomatic cerebrospinal fluid HIV escape in Pune, India

Abstract

Symptomatic cerebrospinal fluid (CSF) viral escape (sCVE) is reported in people with HIV, who are on ritonavir-boosted protease inhibitor (PI/r) containing antiretroviral therapy (ART). Management of sCVE includes performing genotypic HIV-1 resistance testing (GRT) on CSF and plasma HIV and changing ART accordingly. Neither GRT nor newer drugs (Dolutegravir and Darunavir/ritonavir) are routinely available in India. As a result, management of sCVE includes 2 modalities: a) ART intensification by adding drugs that reach therapeutic concentrations in CSF, like Zidovudine, to existing ART or b) Changing to a regimen containing newer boosted PI/r and integrase strand transfer inhibitor (INSTI) as per GRT or expert opinion. In this retrospective study, we report the outcomes of above 2 modalities in treatment of sCVE in Pune, India. Fifty-seven episodes of sCVE in 54 people with HIV taking PI/r-containing ART were identified. Clinical, demographic, laboratory and ART data were recorded. Forty-seven cases had follow-up data available after ART change including measurement of plasma and CSF viral load (VL). Of the 47 cases, 23 received zidovudine intensification (Group A, median VL: plasma- 290, CSF- 5200 copies/mL) and 24 received PI/INSTI intensification (Group B, median VL: plasma- 265, CSF-4750 copies/mL). CSF GRT was performed in 16 participants: 8 had triple class resistance. After ART change, complete resolution of neurologic symptoms occurred in most participants (Group A: 18, Group B: 17). In Group A, follow-up plasma and CSF VL were available for 21 participants, most of whom achieved virologic suppression (VL < 20 copies/mL) in plasma (17) and CSF (15). Four participants were shifted to the PI/INSTI intensification group due to virologic failure (plasma or CSF VL > 200 copies/mL). In Group B, follow-up plasma and CSF VL were available for 23 participants, most of whom also achieved virologic suppression in plasma (21) and CSF (18). Four deaths were noted, 2 of which were in individuals who interrupted ART. This is a unique sCVE cohort that was managed with 1 of 2 approaches based on treatment history and the availability of GRT. At least 75% of participants responded to either approach with virologic suppression and improvement in symptoms.

Clinical Reasoning: Rapidly Progressive Dementia in a Man With HIV Infection and Undetectable Plasma Viral Load

“…Our patient improved transiently after steroids, although steroids are not a standard treatment of CSF discordance. 7,15 Although our patient did not have neuropathologic confirmation of CD8 + encephalitis (diagnostic gold standard) because of resource limitations, his MRI showed T2 white matter hyperintensities as are reported in CD8 + encephalitis. 9 Steroids often improve CD8 encephalitis, so it is possible that our patient had an overlap of CSF discordance and CD8 encephalitis that improved with both steroids and optimization of his ART regimen.…”

Reversal of CSF HIV-1 Escape during Treatment of HIV-Associated Cryptococcal Meningitis in Botswana

“…CSF viral escape did not develop even after months of ART suggesting that ART initiation at the early course of infection may help prevent the development of CSF viral escape [ 21 ]. Symptomatic CSF viral escape has also been reported in individuals on ART; one study showed that a switch to ARVs with a better CNS penetration effectiveness suppresses the HIV-1 VL and resolves the neurologic symptoms [ 44 ]. Lastly, we could not evaluate the impact of ART on compartmentalisation because almost half of the individuals on ART were recently initiated.…”

Biotypes of HIV-associated neurocognitive disorders based on viral and immune pathogenesis

“…1) with deep brain nuclei involvement and enhancement in some patients [22,25]. Patients with symptomatic viral escape benefit from changes to ART regimens that provide better CNS penetration or to compensate for viral mutations [22,25,38]. Although similar clinical manifestations can occur in patients with secondary viral escape, these patients may benefit from therapies targeting the co-infection or steroids that help to control inflammation [39].…”