Evaluation of HIV-1 reservoir levels as possible markers for virological failure during boosted darunavir monotherapy
S Rutsaert, W De Spiegelaere… - Journal of …, 2019 - academic.oup.com
S Rutsaert, W De Spiegelaere, L De Clercq, L Vandekerckhove
Journal of Antimicrobial Chemotherapy, 2019•academic.oup.comBackground The gold standard for HIV-1 treatment is to administer triple antiretroviral
therapy, but a shift to simplified regimens is being explored. Boosted darunavir monotherapy
can be considered for patients who are for specific reasons not good candidates for dual or
triple therapy. Still, a number of patients fail virologically or need to switch treatment.
Objectives To identify predictive markers for those patients that are more likely to sustain
virological control under monotherapy, virological and immunological markers were …
therapy, but a shift to simplified regimens is being explored. Boosted darunavir monotherapy
can be considered for patients who are for specific reasons not good candidates for dual or
triple therapy. Still, a number of patients fail virologically or need to switch treatment.
Objectives To identify predictive markers for those patients that are more likely to sustain
virological control under monotherapy, virological and immunological markers were …
Background
The gold standard for HIV-1 treatment is to administer triple antiretroviral therapy, but a shift to simplified regimens is being explored. Boosted darunavir monotherapy can be considered for patients who are for specific reasons not good candidates for dual or triple therapy. Still, a number of patients fail virologically or need to switch treatment.
Objectives
To identify predictive markers for those patients that are more likely to sustain virological control under monotherapy, virological and immunological markers were explored in HIV-1-positive patients that experienced virological failure on ritonavir-boosted darunavir monotherapy in the PROTEA trial.
Methods
As a retrospective nested study of the PROTEA study (NCT01448707), we analysed 77 HIV-1-infected patients who were on darunavir/ritonavir 800/100 mg monotherapy up to 96 weeks. Patients were appointed to three distinct cohorts based on viral loads (VLs): (i) undetectable VL after 96 weeks; (ii) very-low-level viraemia (5–39 copies/mL); and (iii) failing treatment. Total HIV-1 DNA, integrated HIV-1 DNA and 2-long terminal repeat circular HIV-1 DNA (2LTR circles) were measured in PBMCs at baseline, week 48 and week 96.
Results
Total HIV-1 DNA and integrated HIV-1 DNA at baseline differed significantly between patients who experienced virological failure on monotherapy (P < 0.01 and P < 0.001). Although a higher level of HIV-1 DNA was measured in failures, this marker by itself does not provide enough predictive value to prospectively predict virological failure in patients on monotherapy.
Conclusions
HIV-1 reservoir markers correlate with therapy failure in ritonavir-boosted darunavir monotherapy. However, their role as a predictive marker combined with other markers in a routine clinical setting should be further explored.
Oxford University Press