Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients

Abstract

BackgroundLittle is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients.MethodsIn this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA <50 copies/ml for 6 months or longer, negative for HBsAg and on a stable (>6 months) cART.ResultsNinety-four individuals were included. They were mostly men (77.7%) with a mean age of 53 years. They presented 159 co-morbidities including cardiovascular, bone, hepatic, kidney, and CNS diseases. Because of these pathologies, they took 207 non-ARV drugs (mean 2.2 per patient). Median duration of viral suppression was 77.5 months (IQR 61). All subjects were prospectively followed up to week 24 and all remained on dual therapy during the whole period. Neither virological failure, nor viral blip was detected.The median CD4 count rose from 658 cells/mcl (IQR 403) to 724 cells/mcl (IQR 401) (P = 0.006) without a significant (P = 0.44) change in the CD4/CD8 ratio. A significant (P < 0.0001) increment of median creatinine from 0.87 mg/dl (IQR 0.34) to 0.95 mg/dl (IQR 0.29) was observed in the first 2 months but thereafter leveled on these values (1.00 mg/dl; IQR 0.35) (P = 0.111 compared to 2 months). The lipid profile slightly improved. The daily cost of cART was significantly (P < 0.0001) reduced of 6.89 euros (SD 6.10).DiscussionSwitching to a dual cART regimen based on lamivudine + dolutegravir maintains virological efficacy up to week 24, and is associated to slight improvements of the immunologic and metabolic status. The strategy allows to freely using concomitant medications for associated pathologies. The dual therapy is less expensive in economic terms.ConclusionAlthough still limited evidence exists, a dolutegravir-based dual therapy in combination with lamivudine shows promising results to be confirmed in larger controlled trials.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2311-2) contains supplementary material, which is available to authorized users.

Virologic failure and HIV drug resistance on simplified, dolutegravir-based maintenance therapy: Systematic review and meta-analysis

“…Among the observational studies, the majority did not report detailed inclusion and exclusion criteria. Five observational studies reported virological outcomes at both time-points 12, 30– 33 . Amplification for drug resistance testing was successful for 19 of the 27 (70%) patients with VF.…”

Efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multicentre cohort of patients with suppressed HIV‐1 replication

“…However, dietary restrictions and drug interactions could represent a limit of the association of Rilpivirine + Dolutegravir. 3TC + DTG showed encouraging efficacy in previous switch studies , but these were limited by small sample sizes. In a randomized pilot study in virologically suppressed patients , 3TC + DTG was noninferior to standard three‐drug regimens, however, the study was limited by the small sample size and the strict inclusion criteria, and the 4% noninferiority margin indicated by the US Food and Drug Administration (FDA) for switch studies was not respected.…”

Effectiveness of dolutegravir‐based regimens as either first‐line or switch antiretroviral therapy: data from the Icona cohort

“…While simplification to DTG monotherapy has recently demonstrated suboptimal efficacy compared to triple ART , recent randomized trials have demonstrated the non‐inferiority to standard ART of the two‐drug regimens, DTG plus rilpivirine in virologically suppressed subjects and DTG plus lamivudine (3TC) in ART‐naïve patients . This latter combination has also showed promising results as a switching option in a non‐randomized trial and in observational studies , whereas a large randomized clinical trial exploring this strategy in now ongoing.…”