Abstract

We described short-term HIV tropism changes occurring in peripheral blood mononuclear cells and the correlations with HIV DNA value in HIV-HCV co-infected patients cured for HCV disease and with undetectable HIV viremia or residual viremia (RV). Plasma HIV RNA, cellular HIV DNA and tropism were evaluated pre-HCV treatment (baseline, BL) and at 12(T1) and 24(T2) weeks after HCV treatment start. V3 sequences were interpreted using Geno2pheno and classified as R5 only if all three sequences had an FPR ≥ 10% and as X4 when at least one replicate sequence had an FPR < 10%. Forty-nine patients (21 with X4 and 28 with R5 virus) were enrolled. Five X4 patients and 9 R5 subjects experienced at least one tropism change,11 with RV:1/5 patients with X4 infection at BL switched at T1 versus 8/9 in the R5 group (p = 0.022977) and the difference was confirmed in subjects with RV (p = 0.02);6/9 R5 patients switching at T1 confirmed the tropism change at T2. No significant differences in HIV DNA values between patients with RV starting with a R5 or X4 tropism and experienced tropism switch or not were found. Short-term tropism switch involved almost a third of patients, in all but three cases with HIV RV. Being R5 at BL is associated to a higher instability, expressed as number of tropism changes and confirmed switch at T2.

Highlights

  • As the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have common routes of transmission, their co-infection is estimated to affect 5–7 million people w­ orldwide[1]

  • The present study aimed to describe short-term HIV tropism changes in the peripheral archive and correlations with HIV DNA value in HIV-HCV co-infected patients cured for HCV disease according to HIV disease control

  • Patients with HIV-HCV co-infection successfully treated with direct-acting antivirals (DAA), aged more than 18 years and with subtype B HIV-1 infection were included in the study if they fulfilled the following criteria: (1) hepatitis B surface antigen negativity; (2) no previous treatment with CCR5 antagonists; (3) CD4+ cell count ≥ 200 cells/mm[3] and successful anti-retroviral therapy (ART) ongoing when anti-HCV therapy started; (4) HCV RNA undetectable at week 12 (or < 12 IU/ml at week 12, but undetectable at week 16 and undetectable at W24 of study time regardless of anti-HCV treatment programmed length; (5) no plasma HIV RNA value ≥ 100 IU/ml[16] in all tests performed during the study period

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Summary

Introduction

As the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have common routes of transmission, their co-infection is estimated to affect 5–7 million people w­ orldwide[1]. We previously described a higher percentage increase in cellular HIV DNA in co-infected subjects with HCV clearance and undetectable plasma HIV viremia with respect to those with HIV low-level viremia in a 12-week study ­period[4] as well as a decrease of soluble CD163 and of soluble CD14 in plasma independent from HIV RNA detection and of cellular HIV DNA value in a 24-week ­period[5], suggesting a complex figure of HIV archive in relation to HCV viremia perturbation. The present study aimed to describe short-term HIV tropism changes in the peripheral archive and correlations with HIV DNA value in HIV-HCV co-infected patients cured for HCV disease according to HIV disease control (undetectable HIV viremia versus residual viremia)

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