Effectiveness and safety of dolutegravir two‐drug regimens in virologically suppressed people living with HIV: a systematic literature review and meta‐analysis of real‐world evidence

Abstract

Dolutegravir (DTG) is widely recommended within three-drug regimens. However, similar efficacy and tolerability have also been achieved with DTG within two-drug regimens in clinical trials. This study evaluated the real-world effectiveness and discontinuations in people living with HIV-1 (PLHIV) switching to DTG with lamivudine (3TC) or rilpivirine (RPV). MethodsThis was a one-arm meta-analysis utilizing data from a systematic literature review. Data from real-world evidence studies of DTG + RPV and DTG + 3TC were extracted, pooled and analysed. The primary outcome was the proportion of patients with viral failure (VF; ≥ 50 copies/mL in two consecutive measurements and/or ≥ 1000 copies/mL in a single measurement) at week 48 (W48) and week 96 (W96). Other outcomes included virological suppression (VS; < 50 copies/mL) and discontinuations (W48 and W96). Estimates were calculated for VF, VS as per snapshot (VSS) and on treatment analysis (VSOT), and discontinuations. ResultsPooled mean estimates of VF for DTG + 3TC and DTG + RPV were 0.8% [95% confidence interval (CI): 0.4-1.3] and 0.6% (95% CI: 0.0-1.6), respectively, at W48. VSS rate at W48 was 85.0% (95% CI: 82.3-87.5) for DTG + 3TC regimen and 92.4% (95% CI: 85.0-97.7) in the DTG + RPV regimen. The DTG + 3TC and DTG + RPV regimens led to discontinuations in 13.6% (95% CI: 11.1-16.2) and 7.2% (95% CI: 2.1-14.4) of patients, respectively, at W48. Similar results were observed at W96. ConclusionsTreatment with DTG + 3TC or DTG + RPV in clinical practice provides a low rate of VF and a high rate of VS when initiated in virologically suppressed PLHIV with diverse backgrounds.

Predictors of Viral Non-Suppression among Patients Living with HIV under Dolutegravir in Bunia, Democratic Republic of Congo: A Prospective Cohort Study

“…Even with the discovery of treatment, HIV infection remains a major public health problem in the world. Despite the proven efficacy of triple therapy with tenofovir, lamivudine, and dolutegravir (TDF + 3TC + DTG), predicting resistance and adverse events in patients on this regimen is a necessity to monitor virological failure (VF) [1,2], especially in resource-limited countries stricken by political and security instability. Antiretroviral therapy (ART) is aimed at achieving an undetectable viral load (VL) (<50 copies/mL) within 6 months of treatment initiation.…”

Two-Drug Regimens for HIV—Current Evidence, Research Gaps and Future Challenges

“…In this open label clinical trial, switching to DTG/3TC achieved a similar virological response to the control arm (93.2% vs. 93%, respectively) [26]. Furthermore, several real-life cohort studies have also found a great virological response in patients treated with DTG/3TC [35].…”

Qualitative study exploring the experiences and perceptions of dolutegravir/lamivudine dual antiretroviral therapy (the PEDAL study) in people living with HIV: protocol

“…A recent systematic review and meta-analysis explored real-world effectiveness and tolerability of DTG/3TC in virologically suppressed patients and documented long-term virological outcomes consistent with findings from randomised clinical trials. 10 Although there is clinical evidence of the safety, effectiveness and tolerability of dual-drug regimens, [11][12][13][14][15][16] there is limited insight into patient experiences and perceptions of dual-drug combinations, including the DTG/3TC regimen. A qualitative study conducted in the USA and in Spain explored patients' perspectives and experiences in 39 patients on dual-drug combinations and documented that participants viewed dual-drug regimens as a significant and positive advance, in terms of its effectiveness, with reduced toxicity and essentially no reported side effects.…”