Antiretroviral Simplification with Darunavir/Ritonavir Monotherapy in Routine Clinical Practice: Safety, Effectiveness, and Impact on Lipid Profile

Abstract

BackgroundSimplification of antiretroviral treatment (ART) with darunavir/ritonavir (DRV/r) monotherapy has achieved sustained suppression of plasma viral load (pVL) in clinical trials; however, its effectiveness and safety profile has not been evaluated in routine clinical practice.Methodology/Principal FindingsWe performed a retrospective cohort analysis of HIV-1-infected patients who initiated DRV/r monotherapy once daily with a pVL <50 copies/mL under ART and at least 1 subsequent follow-up visit in our clinic. The primary study endpoints were the percentage of patients with virological failure (VF, defined as 2 consecutive pVL>50 copies/mL) at week 48, and time to VF. Other causes of treatment discontinuation and changes in lipid profile were evaluated up to week 48. Ninety-two patients were followed for a median (IQR) of 73 (57–92) weeks. The median baseline and nadir CD4+ T-cell counts were 604 (433–837) and 238 (150–376) cells/mm3, respectively. Patients had previously received a median of 5 (3–9) ART lines and maintained a pVL<50 copies/mL for a median of 76 (32–176) weeks before initiating DRV/r monotherapy. Nine (9.8%) patients developed VF at week 48; time to VF was 47.1 (IQR: 36.1–47.8) weeks among patients with VF. Other reasons for changing ART were gastrointestinal disturbances (n = 3), rash (n = 1), and impaired CD4 recovery (n = 2). Median low-density lipoprotein cholesterol levels increased from 116.1 mg/dL at baseline to 137.3 mg/dL at 48 weeks (p = 0.001).Conclusions/SignificanceTreatment simplification with DRV/r monotherapy seems safe and effective in routine clinical practice. Further research is needed to elucidate the effect of DRV/r monotherapy on cholesterol levels.

Virological efficacy of PI monotherapy for HIV-1 in clinical practice

“…19 When the indications for PI monotherapy were cited they were commonly treatment simplification or patient preference. 18,21–23 This is in line with European and Spanish guidelines, which since 2009 cite PI monotherapy as an alternative strategy in the management of selected patients. 24,25 French national guidelines have been more conservative, in 2010 deeming PI monotherapy to be inadequate, and in the 2013 iteration indicating that this strategy can be considered on a case-by-case basis.…”

“…Our cohort had a median baseline CD4 count of 455 cells/mm, 3 lower than the averages reported in the other clinical studies, which were between 541 and 608. 18,19,21–23 The median nadir CD4 count of 180 was within the range found in the clinical studies (medians were between 155 and 238). 18–21,23 We did not find an independent association between CD4 count and failure, as did four of the observational studies.…”

“…18,19,21–23 The median nadir CD4 count of 180 was within the range found in the clinical studies (medians were between 155 and 238). 18–21,23 We did not find an independent association between CD4 count and failure, as did four of the observational studies. 18,20,21,23 One study found an association between a nadir CD4 of <200 cells/mm 3 and virological failure.…”

“…18–21,23 We did not find an independent association between CD4 count and failure, as did four of the observational studies. 18,20,21,23 One study found an association between a nadir CD4 of <200 cells/mm 3 and virological failure. 19 Two of the trials, PROTEA 14 and MODAt, 15 found a low CD4 count was related to outcome, while MONET 7 did not find an independent association.…”

Antiretroviral reduction

“…Reductive ART may be particularly relevant in resource-limited settings, but there are scarce data and no supportive recommendations [16]. Interestingly, in a Spanish clinical setting where reductive strategies are being used, only nine of 92 patients (9.8%) had virologic rebound to above 50 copies/ml at 48 weeks after initiating darunavir/ ritonavir monotherapy [21,22]. Overall, the time is ripe for studies and expert opinion to harmonize approaches to ART reduction globally.…”