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Dolutegravir-Based Antiretroviral Regimens for HIV Liver Transplant Patients in Real-Life Settings.

ABSTRACT: BACKGROUND AND OBJECTIVES:Liver transplantation is now considered a safe procedure in patients with HIV because of the advent of potent antiretroviral therapies (ART). OBJECTIVE:We aimed to describe the use of dolutegravir-based maintenance ART in patients with HIV and liver transplant regularly followed in our hospital. METHODS:We searched the database of our Department of Infectious Diseases for liver transplant recipients receiving calcineurin inhibitor-based maintenance immunosuppression concomitantly treated with dolutegravir for at least 1 month. RESULTS:Ten HIV-positive liver transplant recipients were identified. At 4.6?±?3.5 years post-transplant, all the patients were switched to dolutegravir-based therapies for treatment simplification. However, at 1 year after the switch, five of the ten patients returned to their previous ART regimens because of increased serum transaminases (n?=?1), reversible increased serum creatinine (n?=?4), repeated episodes of nausea/vomiting (n?=?1) and variable out-of-range concentrations of tacrolimus or cyclosporine (n?=?2). However, it should be recognized that these events cannot be unequivocally ascribed to dolutegravir and, in the case of increased serum creatinine, are predictable. CONCLUSIONS:The management of HIV-positive liver transplant recipients in clinical practice is a complex task, where possibility of simplifying antiretroviral regimens must be balanced with the need to guarantee optimal immunosuppression and the finest treatment tolerability. A multidisciplinary approach involving physicians and clinical pharmacologists/pharmacists could help achieve this goal.

SUBMITTER: Cattaneo D

PROVIDER: S-EPMC7221036 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Dolutegravir-Based Antiretroviral Regimens for HIV Liver Transplant Patients in Real-Life Settings.

Cattaneo Dario D Sollima Salvatore S Meraviglia Paola P Milazzo Laura L Minisci Davide D Fusi Marta M Filice Carlo C Gervasoni Cristina C

Drugs in R&D 20200601 2

<h4>Background and objectives</h4>Liver transplantation is now considered a safe procedure in patients with HIV because of the advent of potent antiretroviral therapies (ART).<h4>Objective</h4>We aimed to describe the use of dolutegravir-based maintenance ART in patients with HIV and liver transplant regularly followed in our hospital.<h4>Methods</h4>We searched the database of our Department of Infectious Diseases for liver transplant recipients receiving calcineurin inhibitor-based maintenance ...[more]

PMID: 32189238

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Project description:BackgroundNumerous randomized clinical trials (RCTs) were conducted to evaluate dolutegravir based triple antiretroviral therapy (ART) compared to other triple antiretroviral regimens in naïve patients, and a summary of the available evidence is required to shed more light on safety and effectiveness issues.MethodsSystematic review and meta-analysis of RCTs comparing dolutegravir-containing ART to non-dolutegravir containing ART in HIV-infected naive patients. Primary outcomes: % of patients with viral load<50 copies/mL at 48 weeks, stratified according to baseline viral load levels (< or >100.000 copies/mL); overall rate of discontinuation and/or switching for any cause (virologic failure, clinical failure, adverse events). Measure of treatment effect: Risk Difference (RD) with 95% confidence intervals (CIs). The GRADE system was used to assess the certainty of the body of evidence.ResultsWe included 7 RCTs (13 reports, 6407patients) comparing dolutegravir containing to non-dolutegravir containing ART, both in combination with 2 NRTIs. Controls were raltegravir or bictegravir (3 RCTs), boosted atazanavir or darunavir (2 RCTs) or efavirenz (2 RCTs). Rates of patients with VL <50 copies/ml were higher in dolutegravir recipients compared to controls at 48 weeks (RD, 0.05; 95% CIs, 0.03/0.08, p = 0.0002) and 96 weeks (RD, 0.06; 95% CIs, 0.03/0.10, p<0.0001); the average benefit of using dolutegravir was particularly evident at 48 weeks in the subgroup of patients with high baseline viral load (RD, 0.10; 95% CIs, 0.05/0.15; p< 0.0001; GRADE assessment: "high certainty of evidence"). Overall rate of discontinuation were lower in dolutegravir compared to controls (RD,-0.03, 95% CIs -0.05/-0.01; p = 0.007). No significant differences were observed in rates of discontinuation due to adverse events (RD, -0.02; 95% CIs, -0.05/0.00), virologic failure (RD, -0.01; 95% CIs, -0.02/0.01), and most common adverse events (GRADE assessment: from "very-low" to "moderate certainty of evidence").ConclusionStarting treatment in naive patients with dolutegravir containing ART has an increased likelihood of achieving viral suppression in the comparison with non-dolutegravir containing ART. The average benefit is particularly evident in those with high baseline viral load.

Project description:BackgroundThe integrase inhibitor dolutegravir could have a major role in future antiretroviral therapy (ART) regimens in sub-Saharan Africa because of its high potency and barrier to resistance, good tolerability, and low cost, but there is uncertainty over appropriate policies for use relating to the potential for drug resistance spread and a possible increased risk of neural tube defects in infants if used in women at the time of conception. We used an existing individual-based model of HIV transmission, progression, and the effect of ART with the aim of informing policy makers on approaches to the use of dolutegravir that are likely to lead to the highest population health gains.MethodsWe used an existing individual-based model of HIV transmission and progression in adults, which takes into account the effects of drug resistance and differential drug potency in determining viral suppression and clinical outcomes to compare predicted outcomes of alternative ART regimen policies. We calculated disability adjusted life-years (DALYs) for each policy, assuming that a woman having a child with a neural tube defect incurs an extra DALY per year for the remainder of the time horizon and accounting for mother-to-child transmission. We used a 20 year time horizon, a 3% discount rate, and a cost-effectiveness threshold of US$500 per DALY averted.FindingsThe greatest number of DALYs is predicted to be averted with use of a policy in which tenofovir, lamivudine, and dolutegravir is used in all people on ART, including switching to tenofovir, lamivudine, and dolutegravir in those currently on ART, regardless of current viral load suppression and intention to have (more) children. This result was consistent in several sensitivity analyses. We predict that this policy would be cost-saving.InterpretationUsing a standard DALY framework to compare health outcomes from a public health perspective, the benefits of transition to tenofovir, lamivudine, and dolutegravir for all substantially outweighed the risks.FundingBill & Melinda Gates Foundation.

Dataset Information

Dolutegravir-Based Antiretroviral Regimens for HIV Liver Transplant Patients in Real-Life Settings.

Publications

Dolutegravir-Based Antiretroviral Regimens for HIV Liver Transplant Patients in Real-Life Settings.

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