Evaluation of HIV-1 reservoir levels as possible markers for virological failure during boosted darunavir monotherapy.

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.