Long-term outcome of lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients | BMC Infectious Diseases

Patients are increasingly looking for simpler, more manageable and less harmful antiretroviral treatments. From a physician’s perspective, the main consideration about whether to switch from a triple combination therapy to an equally effective dual regimen or not is the supposed possibility of reducing long-term side effects, making a pro-active switch. From the patients’ point of view, the success of 2DR in real-practice is driven also by the ease and the handling of these drugs, in particular if used as single-tablet regimens, with the least impact on their daily life [15, 18].

The DTG/3TC regimen is indicated in the switching strategy based on randomized clinical trials (RCTs), such as the recently updated TANGO trial, which supports the effective virologic suppression at 144 weeks of DTG/3TC combination, not-inferior tenofovir-alafenamide-based ART [19]In patients with no previous virologic failure, NRTI resistance or HBV-co-infection is possible. This indication was reinforced by the SALSA study. [20].

Real-life studies have collected a lot of data about DTG/3TC. These data include evaluations of patient populations who, for different reasons would not have been eligible for a trial, but would most benefit from the switch in terms if there were fewer drug-drug interactions or toxicities, easier tolerability, and better adherence.

Patel et.al. conducted a meta analysis. confirmed the effectiveness and safety of DTG/3TC in clinical practice, combining the data reported in several real-world studies and, therefore, supporting outcome from RCTs; in particular, virologic suppression ranged from 97 to 100% and 92–100% at 48-weeks and 96-weeks of DTG/3TC in the real-life studies considered and available so far [21]. Although virologic failure was rare in these cohort analyses, they don’t last beyond 144 weeks. This allows for potentially valid questions about long-term outcomes.

Our study provides data for a 5-year follow-up and a total drug exposure of approximately 1000 patients/years. In our prospective cohort study, DTG/3TC discontinuation was more due to drug unrelated events or worsening pre-existing conditions.

These results support our hypothesis that DTG in dual formulations has a well-known, high genetic barrier to resistance and a high rate of adherence. This limits the risk of virologic failing and the development of resistance inducing mutants. This is the first case where a new NRTI mutant (M41M/L), was discovered at failure of DTG/3TC. [18]However, this is a role that is not clear in the occurrence or failure of failure. Only recently was the emergence of R263K mutations in the Integrase region detected by genotypic deep sequence in a patient with DTG/3TC. [22].

Our study has limitations. First, bias in clinically uncontrolled, clinically unselected cohorts is always possible due to unmeasured confounding such as drug adherence levels and not reporting adverse events. We decided to only report adverse events leading to drug discontinuation, or to clinically relevant decisions (e.g. Change in therapy Another caveat was the fact that we did not allow patients to be followed-up. This could have caused a bias in increasing the rate of treatment failure. Our study findings could not be applied to health care systems without HIV case management programs or free ART.

However, these long-term findings over 5 years confirm the durable efficacy, high barrier-to-treatment-emergent resistance and good tolerability DTG/3TC. Our results continue support the recommendation of switching to this 2DR for virologically suppressed and ART-experienced patients with HIV.