Abstract
Background
The potential toxicity of long-term anti-retroviral therapy (ART) requires ongoing investigation of novel strategies for treatment of HIV-infected patients. Monotherapy with the integrase inhibitor (INSTI) dolutegravir (DTG) may offer a favourable safety profile. Additionally, DTG has a high barrier of resistance, crucial for successful maintenance of virological control. However, published data is sparse.
Methods
Retrospective, single-centre cohort study. We enrolled patients on suppressive ART who were switched to DTG monotherapy in routine clinical practice and fulfilled the following inclusion criteria: HIV RNA level <50 copies/ml for ≥6 months at time of switch (one blip <200 copies/ml with re-suppression accepted), no known INSTI resistance or prior INSTI failure, no replicative HBV infection and no history of AIDS.
Results
We identified 31 patients with 24-weeks of follow-up data. Previous ART included a non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an INSTI in 32%, 6% and 61% of patients, respectively. At week 24, HIV RNA remained <50 copies/ml in all but two patients (94%). One patient chose to discontinue DTG monotherapy and another developed confirmed virological failure (HIV RNA 538 copies/ml) with new INSTI mutations (Q148H/G140S). Immune status and renal and metabolic function showed no statistically significant changes, apart from a significant decrease in gamma-glutamyl transferase.
Conclusions
De-escalating to DTG monotherapy in selected patients might be a safe and feasible option. However, in one case evolution of INSTI resistance was observed. Further studies should assess particular risk factors for DTG mono-therapy failure. In the meanwhile, caution is warranted.