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

Borghetti, Alberto; Baldin, Gianmaria; Lombardi, Francesca; Ciccullo, Arturo; Capetti, Amedeo; Rusconi, Stefano; Sterrantino, Gaetana; Latini, Alessandra; Cossu, MV; Gagliardini, Roberta; Luca, Andrea De; Giambenedetto, Simona Di

doi:10.1111/hiv.12611

Cited by 38 publications

(38 citation statements)

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“…Our cohort were older, with an average age of 60.5 years compared to 32.5 years (GEMINI 1 and 2) , 48.6 years (EUROSIDA HIV) and 51 years (Borghetti et al . ). Our cohort were medically complex with additional diagnoses of diabetes, hyperlipidaemia, and declining renal function, similar to the EUROSIDA HIV and Borghetti et al .…”

Section: Discussionmentioning

confidence: 97%

“…A multicentre study in Italy by Borghetti et al . looked at 206 patients stable on combination ART (cART) with a median age of 51 years who were switched to 3TC and DTG primarily for simplification (31%) or toxicity (54.4%). This is the largest cohort to date and the study similarly reported no virological failures, an absence of toxicity and improvements in CD4 count, CD4:CD8 ratio, lipid profile and eGFR.…”

Section: Discussionmentioning

confidence: 99%

“…Dual therapy as maintenance is an approach that is being evaluated as a means of reducing potential side effects and increasing tolerability by reducing the number of agents, as well as reducing drug–drug interactions. Data have been reported on the use of dolutegravir (DTG) combined with rilpivirine (RPV) and lamivudine (3TC) .…”

Section: Introductionmentioning

confidence: 99%

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Dual therapy with renally adjusted lamivudine and dolutegravir: a switch strategy to manage comorbidity and toxicity in older, suppressed patients?

et al. 2019

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Objectives The aim of the study was to evaluate the efficacy of dual therapy with lamivudine (3TC), with dose adjustment for renal function, and dolutegravir (DTG) in a subgroup of patients fully suppressed on treatment who were switched because of concerns about comorbidity and toxicity on their current triple drug regimen. Methods A retrospective evaluation of clinical and pathological parameters from an electronic patient record from a single centre was carried out. Results There were no virological failures in 52 patients with a median age of 60.5 years. The median duration of follow‐on dual therapy was 2.29 years (28 months; range 1.10–3.34 years). In 25 of 52 (48%) cases, the dose of 3TC was adjusted taking into account reduced renal function, and none of these patients experienced virological failure. Four additional patients discontinued early, because of side effects of the switch, with no failure. Conclusions This retrospective review suggests that 3TC and DTG may be effective in controlling viral load in older patients with comorbidities. This regimen appears to be a useful option in the context of comorbidities (including renal impairment) and polypharmacy in older patients. However, this review has been conducted in one centre and in a small population of patients. Therefore, further multicentre trials involving larger populations of patients are needed.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Dual therapy with renally adjusted lamivudine and dolutegravir: a switch strategy to manage comorbidity and toxicity in older, suppressed patients?

et al. 2019

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“…Several studies have shown the noninferior efficacy of lamivudine-based two-drug regimens compared to standard three-drug antiretroviral therapy (ART) [1] for the treatment of chronic HIV infection, both in na€ ıve [2] and in treatment-experienced patients [3,4]. In the setting of virological suppression, boosted protease inhibitors (bPIs) Correspondence: Dr Arturo Ciccullo, Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168 Rome, Italy.…”

Section: Introductionmentioning

confidence: 99%

“…In the setting of virological suppression, boosted protease inhibitors (bPIs) Correspondence: Dr Arturo Ciccullo, Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168 Rome, Italy. Tel: +39 0630155366; fax: +39 063054519; e-mail: arturo.ci-ccullo@gmail.com *Early results from this study were presented at the 17th National Congress of the Italian Society of Infectious and Tropical Diseases (SIMIT), Turin, Italy, 2-5 December 2018. plus lamivudine have the strongest evidence [3] but dolutegravir has also gained popularity as a result of evidence from observational studies [4].…”

Section: Introductionmentioning

confidence: 99%

Lamivudine‐based maintenance antiretroviral therapies in patients living with HIV‐1 with suppressed HIV RNA: derivation of a predictive score for virological failure

et al. 2019

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Objectives Two‐drug antiretroviral regimens based on lamivudine (3TC) plus either a protease inhibitor (PI) or dolutegravir (DTG) are becoming increasingly popular in switch strategies. Our goal was to derive a predictive score for virological failure (VF). Methods We retrospectively analysed data for a cohort of 587 virologically suppressed (HIV RNA < 37 HIV‐1 RNA copies/mL), adult (≥ 18 years old) patients starting lamivudine plus either a boosted PI or dolutegravir. Predictors of VF (defined as a single HIV RNA measurement ≥ 1000 copies/mL or two consecutive HIV RNA measurements ≥ 50 copies/mL) were identified using a multivariate Cox regression model. A ‘weighted’ score was assigned to each variable associated with VF; the discriminative power of the score obtained was expressed as the area under the receiver‐operator characteristic curve (ROC‐AUC). Results During a median 2 years of follow‐up time, 35 VFs occurred; predictors of VF were baseline residual HIV RNA between 20 and 36 copies/mL, African ethnicity, ≥ 10 therapeutic lines, the presence of at least one resistance‐associated mutation (RAM) for resistance to current drugs (excluding M184V), a non‐B viral subtype and a baseline CD4 count < 200 cells/μL. A score of 2 was assigned to non‐B viral subtype, 3 to residual viraemia ≥ 20 copies/mL, ≥ 10 previous therapeutic lines and African ethnicity, 4 to baseline CD4 count < 200 cells/μL, and 7 to the presence of at least one RAM (excluding M184V). The ROC‐AUC was 0.67 (95% confidence interval 0.57–0.77). Conclusions The presence of at least one RAM, higher residual viraemia and African ethnicity were among the major predictors of VF in our cohort. Studies with larger sample sizes are warranted to improve the predictive value of the derived score.

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

Mondi

Cozzi‐Lepri

Tavelli³

et al. 2019

J Intern AIDS Soc

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IntroductionConcerns about dolutegravir (DTG) tolerability in the real‐life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG‐based regimens from a large cohort of HIV‐infected individuals.MethodsWe performed a multicentre, observational study including all antiretroviral therapy (ART)‐naïve and virologically suppressed treatment‐experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG‐based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation.ResultsAbout 1679 individuals (932 ART‐naïve, 747 TE) were included. The one‐ and two‐year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART‐naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART‐naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART‐naïve (2.1%) and TE (1.7%) patients. In ART‐naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG‐based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC‐based triple‐therapies, aHR = 3.56, p = 0.012 for tenofovir‐based) and for toxicity (aHR = 5.26, p = 0.030 for ABC‐based, aHR = 6.60, p = 0.024 for tenofovir‐based). The one‐ and two‐year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group.ConclusionsIn this large cohort, DTG showed excellent efficacy and optimal tolerability both as first‐line and switching ART. The low risk of treatment‐limiting toxicities in ART‐naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice.

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

Abstract: Lamivudine plus dolutegravir was effective in maintaining viral suppression in our cohort and led to an improvement in metabolic and immunologic functions.

Cited by 38 publications

References 5 publications

Dual therapy with renally adjusted lamivudine and dolutegravir: a switch strategy to manage comorbidity and toxicity in older, suppressed patients?

Dual therapy with renally adjusted lamivudine and dolutegravir: a switch strategy to manage comorbidity and toxicity in older, suppressed patients?

Lamivudine‐based maintenance antiretroviral therapies in patients living with HIV‐1 with suppressed HIV RNA: derivation of a predictive score for virological failure

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

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