Dataset Information

No Evidence That HIV-1 Subtype C Infection Compromises the Efficacy of Tenofovir-Containing Regimens: Cohort Study in the United Kingdom.

ABSTRACT: Concern has been expressed that tenofovir-containing regimens may have reduced effectiveness in the treatment of human immunodeficiency virus type 1 (HIV-1) subtype C infections because of a propensity for these viruses to develop a key tenofovir-associated resistance mutation. We evaluated whether subtype influenced rates of virological failure in a cohort of 8746 patients from the United Kingdom who received a standard tenofovir-containing first-line regimen and were followed for a median of 3.3 years. In unadjusted analyses, the rate of failure was approximately 2-fold higher among patients infected with subtype C virus as compared to those with subtype B virus (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.50-2.31; P < .001). However, the increased risk was greatly attenuated in analyses adjusting for demographic and clinical factors (adjusted HR, 1.14; 95% CI, .83-1.58; P = .41). There were no differences between subtypes C and subtypes non-B and non-C in either univariate or multivariate analysis. These observations imply there is no intrinsic effect of viral subtype on the efficacy of tenofovir-containing regimens.

SUBMITTER: White E

PROVIDER: S-EPMC5079361 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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No Evidence That HIV-1 Subtype C Infection Compromises the Efficacy of Tenofovir-Containing Regimens: Cohort Study in the United Kingdom.

White Ellen E Smit Erasmus E Churchill Duncan D Collins Simon S Booth Clare C Tostevin Anna A Sabin Caroline C Pillay Deenan D Dunn David T DT

The Journal of infectious diseases 20160524 9

Concern has been expressed that tenofovir-containing regimens may have reduced effectiveness in the treatment of human immunodeficiency virus type 1 (HIV-1) subtype C infections because of a propensity for these viruses to develop a key tenofovir-associated resistance mutation. We evaluated whether subtype influenced rates of virological failure in a cohort of 8746 patients from the United Kingdom who received a standard tenofovir-containing first-line regimen and were followed for a median of 3 ...[more]

PMID: 27732929

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Project description:Background: Hepatitis B virus (HBV) coinfection is common in HIV-positive patients. HIV infection modifies the natural course of HBV infection, leading to a faster progression of liver-related morbidity and mortality than is observed in HBV mono-infected patients. This systematic review and meta-analysis evaluates the current clinical evidence regarding the use of oral tenofovir disproxil fumarate (TDF)-based treatments in patients coinfected with HIV and HBV. Methods: We performed a comprehensive literature search in PubMed and Web of Science. Supplementary searches were conducted in Google Scholar and Clinicaltrials.gov. We conducted a random effects meta-analysis using the event rate (ER) to estimate the incidence of HBV seroconversion. A subgroup meta-analysis was performed to assess the moderate effects of demographic and disease-related variables on HBsAg loss. This review is registered in the PROSPERO database (CRD42018092379). Results: We included 11 studies in the review. The immunological effects of oral TDF-based Pre-exposure prophylaxis (PrEP) treatment in patients with HIV-HBV coinfection were 0.249 for HBeAg loss, 0.237 for HBeAg conversion, 0.073 for HBsAg loss, and 0.055 for HBsAg conversion. The factors associated with HBsAg loss were the baseline HBV viral load, participant's location, and a history of exposure to lamivudine/emtricitabine (3TC/FTC) (all p < 0.05). A trend toward a negative relationship between the baseline CD4+ T-cell count and HBsAg loss was observed (p = 0.078). Conclusion: This systematic review and meta-analysis demonstrated that TDF-containing regimens are effective at stimulating HBeAg loss (24.9%), HBeAg conversion (23.7%), HBsAg loss (7.3%), and HBsAg conversion (5.5%) in HIV-HBV coinfected patients. The moderator analysis showed that HBV viral load, the location of participants, and prior exposure to 3TC/FTC are factors associated with HBsAg loss. Asian ethnicity, prior exposure to 3TC, and a nondetectable baseline HBV viral load are associated with lower odds of HBsAg loss. Well-designed prospective cohort studies and randomized controlled trials (RCTs) with large sample sizes are required for the investigation of potential predictors and biological markers associated with strategies for achieving HBV remission in patients with HIV-HBV coinfection, which is a matter of considerable importance to clinicians and those responsible for health policies.

Project description:BACKGROUND: Tenofovir alafenamide (TAF) is a new formulation of tenofovir disoproxil fumarate (TDF) that was approved in 2015. While clinical trial evidence suggests that TAF has more favorable outcomes related to kidney injury and loss of bone mineral density, TAF also leads to higher lipid levels compared with TDF. OBJECTIVES: To (a) determine prescribing rates of TDF and TAF among new recipients from 2014 to 2018 in a large academic health system and (b) compare baseline patient characteristics of those newly prescribed TDF versus TAF before and after the approval of TAF in November 2015. METHODS: Electronic health record data were used to identify new recipients of TDF or TAF from 2014 to 2018 and describe their total monthly TDF and TAF prescriptions by indication. Patient characteristics were compared among new recipients of TDF before November 2015, new recipients of TDF after November 2015, and new recipients of TAF. RESULTS: Monthly TAF prescribing rates increased to match TDF prescribing rates by April 2018 (82 vs. 88 prescriptions per month). TAF recipients and new recipients of TDF before November 2015 had similar racial distributions; both of these groups were more likely to be Black compared with new recipients of TDF after November 2015 (55% and 53% vs. 37%; P < 0.0001). TAF recipients also tended to have more comorbidities, including chronic kidney disease (7% vs. 2% and 2%; P < 0.0001), hepatitis C virus (8% vs. 5% and 3%; P < 0.0001), diabetes (13% vs. 5% and 6%; P < 0.0001), hypertension (27% vs. 13% and 13%; P < 0.0001), coronary artery disease (5% vs. 3% and 2%; P < 0.0001), hyperlipidemia (21% vs. 6% and 7%; P < 0.0001), and congestive heart failure (3% vs. 1% and 1%; P < 0.0001), compared with both new recipients of TDF before and after November 2015. CONCLUSIONS: TAF prescribing rates grew substantially in the 2.5 years after FDA approval. TAF is being prescribed more often than TDF in patients with chronic kidney disease and in patients with cardiovascular disease, suggesting that prescribers may be prioritizing the kidney safety profile over the effect on lipids. DISCLOSURES: This work was supported by the Duke Clinical Research Institute Executive Director's Pathway for Supplemental Funding. The research team received additional support from the National Institute of Diabetes, Digestive, and Kidney Disease R01DK112258 and P01DK056492 (CW) and from the National Institute of Allergy and Infectious Diseases 5T32AI100851 (MHM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Hung reports past employment by Blue Cross Blue Shield Association and CVS Health and a grant from Pharmaceutical Research and Manufacturers of America (PhRMA), unrelated to this work. The other authors have nothing to disclose. This work was accepted as a poster presentation for the AMCP Nexus 2020 Virtual, October 19-23, 2020.

Project description:ObjectivesTenofovir 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).MethodsThis 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).ResultsWe 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).ConclusionsIn 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.

Dataset Information

No Evidence That HIV-1 Subtype C Infection Compromises the Efficacy of Tenofovir-Containing Regimens: Cohort Study in the United Kingdom.

Publications

No Evidence That HIV-1 Subtype C Infection Compromises the Efficacy of Tenofovir-Containing Regimens: Cohort Study in the United Kingdom.

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