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BackgroundLittle is known about HIV-1 integrase inhibitor resistance in the CNS.ObjectivesThis study aimed to evaluate integrase inhibitor resistance in CSF, as a marker of the CNS, and compare it with the resistance in plasma.MethodsHIV integrase was sequenced both in plasma and CSF for 59 HIV-1 patients. The clinical and biological data were collected from clinical routine care.ResultsAmong the 59 HIV-1 patients, 32 (54.2%) were under antiretroviral (ARV) treatment. The median (IQR) HIV-1 RNA in the plasma of viraemic patients was 5.32 (3.85–5.80) and 3.59 (2.16–4.50) log10 copies/mL versus 4.79 (3.56–5.25) and 3.80 (2.68–4.33) log10 copies/mL in the CSF of ARV-naive and ARV-treated patients, respectively. The patients were mainly infected with non-B subtypes (72.2%) with the most prevalent recombinant form being CRF02_AG (42.4%). The HIV-1 integrase sequences from CSF presented resistance mutations for 9/27 (33.3%) and 8/32 (25.0%) for ARV-naive (L74I, n = 3; L74I/M, n = 1; T97A, n = 1; E157Q, n = 4) and ARV-treated (L74I, n = 6; L74M, n = 1; T97A, n = 1; N155H, n = 1) patients, respectively. Integrase inhibitor resistance mutations in CSF were similar to those in plasma, except for 1/59 patients.ConclusionsThis work shows similar integrase inhibitor resistance profiles in the CNS and plasma in a population of HIV-1 viraemic patients.

Objectives APOBEC3 editing activity contributes to sequences variation and viral diversification. We aimed to characterize virological and clinical factors associated with G-to-A mutations and stop codons in the HIV-1 reservoir, markers of APOBEC3 footprints, in order to better understand HIV-1 diversity among virologically suppressed HIV-1-infected patients. Methods Immuno-virological and clinical factors were compared between 92 patients harbouring G-to-A mutations and stop codons (APOBEC+) in the reverse transcriptase gene and 92 patients without G-to-A mutations (APOBEC–) and stop codons in their DNA genotypes. Results Patients were predominantly men (74.5%) and were mostly infected by B-subtype (69.0%), with 44.1% and 55.9% in APOBEC+ and APOBEC– groups, respectively. At time of HIV DNA genotypes, the total cell-associated HIV-1 DNA load was 2.34 log10 copies/106 cells (IQR 1.85–2.67) and 33.2% of them had a detectable ultrasensitive plasma viral load. Hypermutated sequences were identified in 28.2% of the APOBEC+ group. The median total cell-associated HIV-1 DNA level was significantly lower in APOBEC+ than APOBEC– group: 2.13 log10 copies/106 cells (IQR 1.60–2.60) versus 2.52 log10 copies/106 cells (IQR 2.19–2.71) (P Conclusions These results show an independent association between the presence of G-to-A mutations and stop codons with HIV-1 subtype non-B and low proviral DNA that could be explained by the APOBEC3 footprints and restriction of DNA synthesis and integration. However, further investigations are needed to study the contribution of Vif amino acid variability among HIV-1 subtypes.