Open AccessDifferences in human immunodeficiency virus-1C viral load and drug resistance mutation between plasma and cerebrospinal fluid in patients with human immunodeficiency virus-associated cryptococcal meningitis in Botswana
Author(s) -
Nametso Kelentse,
Sikhulile Moyo,
Mompati Mogwele,
Kwana Lechiile,
Natasha O. Moraka,
Dorcas Maruapula,
Kaelo K Seatla,
Lerato Esele,
Kesaobaka Molebatsi,
Tshepo Leeme,
David Lawrence,
Rosemary Musonda,
Ishmael Kasvosve,
Thomas S. Harrison,
Joseph N Jarvis,
Simani Gaseitsiwe
Publication year - 2020
Publication title -
medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 148
eISSN - 1536-5964
pISSN - 0025-7974
DOI - 10.1097/md.0000000000022606
Subject(s) - interquartile range , medicine , viral load , cerebrospinal fluid , virology , viral meningitis , lentivirus , drug resistance , immunology , virus , viral disease , biology , microbiology and biotechnology , bacterial meningitis
To determine effects of cryptococcal meningitis (CM) on human immunodeficiency virus (HIV)-1C cerebrospinal fluid (CSF) viral escape, CSF/plasma viral discordance, and drug resistance mutation (DRM) discordance between CSF and plasma compartments, we compared CSF and plasma viral load (VL) and DRMs in individuals with HIV-associated CM in Botswana. This cross-sectional study utilized 45 paired CSF/plasma samples from participants in a CM treatment trial (2014–2016). HIV-1 VL was determined and HIV-1 protease and reverse transcriptase genotyping performed. DRMs were determined using the Stanford HIV database. CSF viral escape was defined as HIV-1 ribonucleic acid ≥0.5 log 10 higher in CSF than plasma and VL discordance as CSF VL > plasma VL. HIV-1 VL was successfully measured in 39/45 pairs, with insufficient sample volume in 6; 34/39 (87.2%) participants had detectable HIV-1 in plasma and CSF, median 5.1 (interquartile range: 4.7–5.7) and 4.6 (interquartile range:3.7–4.9) log 10 copies/mL, respectively ( P ≤.001). CSF viral escape was present in 1/34 (2.9%) and VL discordance in 6/34 (17.6%). Discordance was not associated with CD4 count, antiretroviral status, fungal burden, CSF lymphocyte percentage nor mental status. Twenty-six of 45 (57.8%) CSF/plasma pairs were successfully sequenced. HIV-1 DRM discordance was found in 3/26 (11.5%); 1 had I84IT and another had M46MI in CSF only. The third had K101E in plasma and V106 M in CSF. Our findings suggest that HIV-1 escape and DRM discordance may occur at lower rates in participants with advanced HIV-disease and CM compared to those with HIV associated neurocognitive impairment.