Systematic review of renal and bone safety of the antiretroviral regimen efavirenz, emtricitabine, and tenofovir disoproxil fumarate in patients with HIV infection

<p><b>Background:</b> Tenofovir disoproxil fumarate (TDF) is a component of many combinations of antiretroviral treatment (ART) regimens. Although potent and generally well tolerated, TDF may cause renal and bone toxicity. The magnitude of off-target side effects is proposed to be related to tenofovir plasma concentrations, which are affected by food and drug–drug interactions with concomitant antiretrovirals.</p> <p><b>Objective:</b> To perform a systematic literature review and qualitatively report on renal and bone safety outcomes associated with efavirenz (EFV), emtricitabine (FTC), and TDF (EFV+FTC+TDF) ART.</p> <p><b>Methods:</b> Embase and PubMed databases were searched for randomized clinical trials and observational cohort studies reporting on HIV treatment with EFV+FTC+TDF. Relevant articles were hand-searched for renal (Grade 3–4 serum creatinine/estimated glomerular filtration rate elevations, renal adverse events [AEs], discontinuation due to renal AEs, and urinary biomarkers) and bone outcomes (bone mineral density [BMD] reductions, bone turnover markers, and fracture), and results compiled qualitatively.</p> <p><b>Results:</b> Of 337 retrieved articles, 29 reporting renal and 11 reporting bone outcomes met the review criteria. EFV+FTC+TDF was associated with a low frequency of renal AEs and treatment discontinuations due to renal AEs. Renal AEs were more frequent when TDF was taken with protease inhibitor (PI)- or cobicistat-containing ART. EFV+FTC+TDF was associated with reduced BMD and increased bone turnover markers, but BMD reductions were less than with PI-containing ART. No treatment-related bone fractures were identified.</p> <p><b>Conclusions:</b> EFV+FTC+TDF appeared to have a more favorable renal safety profile than TDF administered with a PI or cobicistat. BMD decreased with EFV+FTC+TDF, but no treatment-related fractures were identified.</p

Atazanavir and Cardiovascular Risk Among Human Immunodeficiency Virus-Infected Patients: A Systematic Review

<p>Article full text</p> <p>The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s40121-016-0132-z"><b>here</b></a>.</p> <p>Provide enhanced content for this article</p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p>Other enhanced features include, but are not limited to:</p> <ul> <li>Slide decks</li> <li>Videos and animations</li> <li>Audio abstracts</li> <li>Audio slides</li> </ul

Persistence, adherence, and all-cause healthcare costs in atazanavir- and darunavir-treated patients with human immunodeficiency virus in a real-world setting

<p><b>Objectives:</b></p> <p>Atazanavir (ATV) and darunavir (DRV) are protease inhibitors approved for HIV treatment in combination with ritonavir (/r). The objectives of this study were to compare persistence (time to treatment discontinuation/modification), adherence, and healthcare costs among patients with human immunodeficiency virus (HIV) initiating ATV/r or DRV/r.</p> <p><b>Methods:</b></p> <p>This retrospective cohort study used commercial and Medicaid administrative insurance claims data. Patients initiating ATV/r or DRV/r from 2006–2013 with continuous enrollment for ≥6 months before and ≥3 months after initiation were included. Patients were followed from initiation until discontinuation/modification (≥30 day gap in ATV or DRV or initiation of a new antiretroviral medication), during which time adherence (proportion of days covered [PDC], with PDC ≥80% or 95% considered adherent) and per-patient per-month (PPPM) total healthcare costs were measured. DRV/r patients were propensity score matched to ATV/r patients at a 1:1 ratio to achieve balance on potentially confounding demographic and clinical factors. Commercial and Medicaid samples were analyzed separately, as were antiretroviral (ART)-naïve and experienced patients.</p> <p><b>Results:</b></p> <p>The final samples comprised 2988 commercially-insured and 1158 Medicaid-insured patients. There were no significant differences in hazards of discontinuation/modification between the ATV/r or DRV/r cohorts. With respect to odds of being adherent, the only marginally significant result was comparing odds of achieving PDC ≥80% among ART-naïve Medicaid patients, which favored ATV/r. All other adherence comparisons were not significant. Although ATV/r cohorts tended to have lower PPPM costs, the majority of these differences were not statistically significant.</p> <p><b>Conclusions:</b></p> <p>Patients with HIV treated with either ATV/r or DRV/r had similar time to treatment discontinuation/modification, adherence, and monthly healthcare costs. Results were similar across the pre-specified sub-groups. These findings are useful not only as an insight into clinical practice, but also as a resource for healthcare providers and payers evaluating treatment options for HIV+ individuals.</p

Patient demographic and baseline characteristics in the renal analysis.

<p>Patient demographic and baseline characteristics in the renal analysis.</p

Incidence rates for fracture by STR.

<p>Incidence rates for fracture by STR.</p

Univariate IRRs (95% CI) for risk factors for fracture among patients prescribed single-tablet regimens.

<p>Bold typeface indicates that the CI does not cross unity. CI: confidence interval; IRR: incidence rate ratio. *Defined as at least 60 days of cumulative exposure within an 18-month period.</p

Real-World Assessment of Renal and Bone Safety among Patients with HIV Infection Exposed to Tenofovir Disoproxil Fumarate-Containing Single-Tablet Regimens

<div><p>Objectives</p><p>Tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens have been associated with an increased incidence of renal and bone adverse outcomes. Here, we estimated the real-world incidence of renal and bone adverse outcomes among patients with HIV infection receiving different TDF-containing single-tablet regimens (STRs).</p><p>Methods</p><p>This cohort study used US health insurance data spanning the years 2008–2014. We identified HIV-infected patients aged ≥18 years (all HIV patients) and those with ≥6 months of continuous enrollment prior to initiating efavirenz/emtricitabine/TDF (EFV/FTC/TDF), rilpivirine/FTC/TDF (RPV/FTC/TDF) or elvitegravir/cobicistat/FTC/TDF (EVG/COBI/FTC/TDF). Renal adverse outcomes were identified using renal International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Bone adverse outcomes were identified using ICD-9-CM diagnosis codes for fracture. Incidence rates (IRs) and associated 95% confidence intervals (CIs) were estimated assuming a Poisson distribution, and outcomes between STRs were compared using IR ratios (IRRs) and IR differences (IRDs).</p><p>Results</p><p>We identified 9876 and 10,383 eligible patients for the renal and fracture analyses, respectively. Observed IRs for renal adverse outcomes were 9.7, 10.5, 13.6, and 18.0 per 1000 person-years among those receiving EFV/FTC/TDF, RPV/FTC/TDF, or EVG/COBI/FTC/TDF, or all HIV patients, respectively. Corresponding values for IRs of fracture were 3.4, 3.6, 7.2, and 4.4 per 1000 person-years, respectively. Renal adverse outcomes with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRD −3.96; 95% CI: −7.31, −1.06). No IRR differences were identified for the renal analysis. Fractures with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRR 0.47; 95% CI: 0.27, 0.81 and IRD −3.85; 95% CI: −5.02, −2.78).</p><p>Conclusions</p><p>In this large real-world database, observed IRs for renal adverse outcomes with TDF-containing STRs were lower or similar to those for all HIV patients, with the lowest IRs observed among patients receiving EFV/FTC/TDF. Compared with all HIV patients, the observed IR for fracture was higher with EVG/COBI/FTC/TDF, comparable with RPV/FTC/TDF, and lower with EFV/FTC/TDF.</p></div

Systematic Literature Review and Meta-Analysis of Renal Function in Human Immunodeficiency Virus (HIV)-Infected Patients Treated with Atazanavir (ATV)-Based Regimens

<div><p>Some HIV antiretroviral therapies (ART) have been associated with renal toxicities, which become of increasing concern as HIV-infected patients age and develop comorbidities. The objective of this study was to evaluate the relative impact of atazanavir (ATV)-based regimens on the renal function of adult patients with HIV. We conducted a systematic literature review by searching PubMed, EMBASE, Cochrane library, and the CRD from 2000 until March 2013. Major HIV-related conferences occurring in the past two years were also searched. All randomized clinical trials and large cohort studies assessing renal function in treatment-naïve and/or treatment-experienced HIV patients on ATV-based regimens were included. Fixed-effect mixed-treatment network analyses were carried out on the most frequently reported renal outcomes. 23 studies met the inclusion criteria, and change in estimated glomerular filtration rate (eGFR) from baseline to 48 weeks was identified as the main outcome. Two networks including, respectively, six studies (using the Cockcroft-Gault method) and four studies (using MDRD and CKD-EPI) were analysed. With CG network, ATV/r + TDF/FTC was associated with lower impact on the decline of eGFR than ATV/cobicistat + TDF/FTC but with higher decrease in eGFR than ATV/r + ABC/3TC (difference in mean change from baseline in eGFR repectively +3.67 and –3.89). The use of ATV/cobicistat + TDF/FTC led to a similar decline in eGFR as EVG/cobicistat/TDF/FTC. With respect to third agents combined with TDF/FTC, ATV/r had a lower increase in eGFR in comparison to EFV, and no difference was shown when compared to SQV/r and DRV/r. The effect of ATV-based regimens on renal function at 48 weeks appears similar to other ART regimens and appears to be modest regardless of boosting agent or backbone, although TDF containing backbones consistently leads to greater decline in eGFR.</p></div

Patient demographic and baseline characteristics in the fracture analysis.

<p>Patient demographic and baseline characteristics in the fracture analysis.</p

Incidence rates for renal adverse outcomes by STR.

<p>Incidence rates for renal adverse outcomes by STR.</p