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Abstract

Background

The clinical impact of HIV genotypic resistance test (GRT) on peripheral blood mononuclear cells (PBMCs) in people with HIV (PWH) and low-level, detectable HIV-RNA, is still debated.

Methods

An observational, retrospective, monocentric study was conducted on treated PWH, undergoing GRT on PBMCs between 2012 and 2024 for detectable viral load (repeated HIV-RNA>50 cps/mL), and non-amplifiable gene sequences on RNA. Detection of major drug resistance mutations (DRMs) were obtained by Sanger sequencing using commercially available kits (ViroSeq HIV-1 Genotyping System, and Viroseq HIV-1 Integrase, Abbott) and interpreted based on Stanford University algorithm. Genotypic susceptibility score (GSS) for BL ART was calculated as the sum of activity of each drug in the regimen (1 indicated full viral susceptibility to the drug, whereas 0.75, 0.5, 0.25 and 0 indicated potential low-level, low-level, intermediate and high drug resistance, respectively). The agreement between GSS based on historical RNA and on PBMCs was evaluated with Pearson coefficient. Association of PBMCs-GSS with time to cART switch and with HIV-RNA>50 cps/mL at 12 months were evaluated by multivariable Cox regression and logistic regression, respectively.

Results

Sixty PWH were considered: 49 (81.7%) men, with 49 years of median age and 11 years of median HIV duration. Table 1 summarizes characteristics of study population. Historical GRT on RNA and PBMC showed that 7/36 (19.4%) and 6/58 (10.3%) PWH were on a regimen with <100% activity, respectively. Concordance of RNA and PBMC-GSS was found in 31/38 (81.6%) PWH, with a Pearson coefficient of 0.76 (P < 0.001). ART switch occurred in 48 PWH over 71.2 persons-years of follow-up. Detection of any DRM to current regimen on PBMCs (versus none: aHR 1.25, 95% 0.35–4.44; P = 0.732) did not predict time to switch, whereas at least one historical RNA-DRM to study drugs (versus none: 4.30, 95% CI 1.28–14.4; P = 0.018) significantly predicted treatment change, after adjusting for BL ART and BL HIV- RNA. DRMs to study regimen were not associated to detectable HIV-RNA at 12 months, neither according to historical GRT nor PBMCs-GRT.

Conclusions

GRT on PBMCs was not associated with treatment change nor virological suppression at 12 months.

Table 1.
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Baseline characteristics of study population

VariablesN = 60
Age, years, median (IQR)49 (39–55)
Sex at birth, male, n (%)49 (81.7)
Risk category for HIV acquisition, n (%)
- Heterosexual men and women14 (23.3)
- Men who have sex with men20 (33.3)
- Intravenous drug users9 (15.0)
- Other/unknown17 (28.4)
Caucasian ethnicity, n (%)49 (81.7)
Years living with HIV, median (IQR)11 (4–21)
Years since antiretroviral therapy start, median (IQR)8 (2–17)
Previous AIDS-defining event, n (%)22 (36.7)
Anti-HCV Antibodies, n (%)15 (25.0)
HBsAg positive serostatus, n (%)3 (5.0)
Zenith HIV-RNA (log10cps/mL), median (IQR)4.55 (3.62–5.01)
Nadir CD4+ count (cells/mL), median (IQR)198 (71–304)
Baseline HIV-RNA>50 cps/ml, n(%)36 (62.1)
Baseline CD4+ count (cells/mL), median (IQR)542 (277–869)
Baseline antiretroviral therapy:
2NRTIs+PIs19 (31.7)
2NRTIs+INIs11 (18.3)
2NRTI+NNRTIs8 (13.3)
4-drugtherapy4 (6.7)
PI+INI6 (10.0)
Other two-drug regimen7 (11.7)
Other5 (8.3)
Number of previous virological failures, median (IQR)2 (1–4)
Number of therapeutic lines, median (IQR)3 (2–6)
GSS based on cumulative historical GRT on RNA,
median (IQR)3 (2–3)
GSS based on GRT on PBMC, median (IQR)3 (2.5–3)
VariablesN = 60
Age, years, median (IQR)49 (39–55)
Sex at birth, male, n (%)49 (81.7)
Risk category for HIV acquisition, n (%)
- Heterosexual men and women14 (23.3)
- Men who have sex with men20 (33.3)
- Intravenous drug users9 (15.0)
- Other/unknown17 (28.4)
Caucasian ethnicity, n (%)49 (81.7)
Years living with HIV, median (IQR)11 (4–21)
Years since antiretroviral therapy start, median (IQR)8 (2–17)
Previous AIDS-defining event, n (%)22 (36.7)
Anti-HCV Antibodies, n (%)15 (25.0)
HBsAg positive serostatus, n (%)3 (5.0)
Zenith HIV-RNA (log10cps/mL), median (IQR)4.55 (3.62–5.01)
Nadir CD4+ count (cells/mL), median (IQR)198 (71–304)
Baseline HIV-RNA>50 cps/ml, n(%)36 (62.1)
Baseline CD4+ count (cells/mL), median (IQR)542 (277–869)
Baseline antiretroviral therapy:
2NRTIs+PIs19 (31.7)
2NRTIs+INIs11 (18.3)
2NRTI+NNRTIs8 (13.3)
4-drugtherapy4 (6.7)
PI+INI6 (10.0)
Other two-drug regimen7 (11.7)
Other5 (8.3)
Number of previous virological failures, median (IQR)2 (1–4)
Number of therapeutic lines, median (IQR)3 (2–6)
GSS based on cumulative historical GRT on RNA,
median (IQR)3 (2–3)
GSS based on GRT on PBMC, median (IQR)3 (2.5–3)
Table 1.
Open in new tab

Baseline characteristics of study population

VariablesN = 60
Age, years, median (IQR)49 (39–55)
Sex at birth, male, n (%)49 (81.7)
Risk category for HIV acquisition, n (%)
- Heterosexual men and women14 (23.3)
- Men who have sex with men20 (33.3)
- Intravenous drug users9 (15.0)
- Other/unknown17 (28.4)
Caucasian ethnicity, n (%)49 (81.7)
Years living with HIV, median (IQR)11 (4–21)
Years since antiretroviral therapy start, median (IQR)8 (2–17)
Previous AIDS-defining event, n (%)22 (36.7)
Anti-HCV Antibodies, n (%)15 (25.0)
HBsAg positive serostatus, n (%)3 (5.0)
Zenith HIV-RNA (log10cps/mL), median (IQR)4.55 (3.62–5.01)
Nadir CD4+ count (cells/mL), median (IQR)198 (71–304)
Baseline HIV-RNA>50 cps/ml, n(%)36 (62.1)
Baseline CD4+ count (cells/mL), median (IQR)542 (277–869)
Baseline antiretroviral therapy:
2NRTIs+PIs19 (31.7)
2NRTIs+INIs11 (18.3)
2NRTI+NNRTIs8 (13.3)
4-drugtherapy4 (6.7)
PI+INI6 (10.0)
Other two-drug regimen7 (11.7)
Other5 (8.3)
Number of previous virological failures, median (IQR)2 (1–4)
Number of therapeutic lines, median (IQR)3 (2–6)
GSS based on cumulative historical GRT on RNA,
median (IQR)3 (2–3)
GSS based on GRT on PBMC, median (IQR)3 (2.5–3)
VariablesN = 60
Age, years, median (IQR)49 (39–55)
Sex at birth, male, n (%)49 (81.7)
Risk category for HIV acquisition, n (%)
- Heterosexual men and women14 (23.3)
- Men who have sex with men20 (33.3)
- Intravenous drug users9 (15.0)
- Other/unknown17 (28.4)
Caucasian ethnicity, n (%)49 (81.7)
Years living with HIV, median (IQR)11 (4–21)
Years since antiretroviral therapy start, median (IQR)8 (2–17)
Previous AIDS-defining event, n (%)22 (36.7)
Anti-HCV Antibodies, n (%)15 (25.0)
HBsAg positive serostatus, n (%)3 (5.0)
Zenith HIV-RNA (log10cps/mL), median (IQR)4.55 (3.62–5.01)
Nadir CD4+ count (cells/mL), median (IQR)198 (71–304)
Baseline HIV-RNA>50 cps/ml, n(%)36 (62.1)
Baseline CD4+ count (cells/mL), median (IQR)542 (277–869)
Baseline antiretroviral therapy:
2NRTIs+PIs19 (31.7)
2NRTIs+INIs11 (18.3)
2NRTI+NNRTIs8 (13.3)
4-drugtherapy4 (6.7)
PI+INI6 (10.0)
Other two-drug regimen7 (11.7)
Other5 (8.3)
Number of previous virological failures, median (IQR)2 (1–4)
Number of therapeutic lines, median (IQR)3 (2–6)
GSS based on cumulative historical GRT on RNA,
median (IQR)3 (2–3)
GSS based on GRT on PBMC, median (IQR)3 (2.5–3)

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© The Author(s) 2025. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.
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