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Predictive Value of Tenofovir Diphosphate in Dried Blood Spots for Future Viremia in Persons Living With HIV.

ABSTRACT: BACKGROUND:Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is associated with viral suppression in persons living with HIV (PLWH) taking tenofovir disoproxil fumarate (TDF). However, its value as a predictor of future viremia remained unknown. METHODS:Blood for plasma viral load (VL) and TFV-DP in DBS were collected (up to 3 visits within 48 weeks) in PLWH on TDF. TFV-DP cut points were selected using logistic prediction models maximizing the area under the receiver operation characteristic curve, and estimated adjusted odds ratio (aOR) of future viremia (?20 copies/mL) were compared to the highest TFV-DP category. RESULTS:Among all 451 participants in the analysis, aOR of future viremia for participants with TFV-DP <800 and 800 to <1650 fmol/punch were 4.7 (95% CI, 2.6-8.7; P < .0001) and 2.1 (95% CI, 1.3-3.3; P = .002) versus ?1650 fmol/punch, respectively. These remained significant for participants who were virologically suppressed at the time of the study visit (4.2; 95% CI, 1.5-12.0; P = .007 and 2.2; 95% CI, 1.2-4.0; P = .01). CONCLUSIONS:TFV-DP in DBS predicts future viremia in PLWH on TDF, even in those who are virologically suppressed. This highlights the utility of this biomarker to inform about adherence beyond VL. Clinical Trials Registration. NCT02012621.

SUBMITTER: Morrow M

PROVIDER: S-EPMC6639595 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Predictive Value of Tenofovir Diphosphate in Dried Blood Spots for Future Viremia in Persons Living With HIV.

Morrow Mary M MaWhinney Samantha S Coyle Ryan P RP Coleman Stacey S SS Gardner Edward M EM Zheng Jia-Hua JH Ellison Lucas L Bushman Lane R LR Kiser Jennifer J JJ Anderson Peter L PL Castillo-Mancilla Jose R JR

The Journal of infectious diseases 20190701 4

<h4>Background</h4>Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is associated with viral suppression in persons living with HIV (PLWH) taking tenofovir disoproxil fumarate (TDF). However, its value as a predictor of future viremia remained unknown.<h4>Methods</h4>Blood for plasma viral load (VL) and TFV-DP in DBS were collected (up to 3 visits within 48 weeks) in PLWH on TDF. TFV-DP cut points were selected using logistic prediction models maximizing the area under the receiver oper ...[more]

PMID: 30942881

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Project description:BackgroundTenofovir diphosphate (TFV-DP) concentration in dried blood spots is a marker of long-term adherence. We investigated the relationship between TFV-DP concentrations and virological outcomes in participants initiating tenofovir-lamivudine-dolutegravir (TLD) as first-line or second-line antiretroviral therapy.SettingThree primary care clinics in Khayelitsha, Cape Town, South Africa.MethodsWe conducted a post hoc analysis of 2 randomized controlled trials of participants initiating TLD. TFV-DP concentrations and viral loads were measured at 12, 24, and 48 weeks. Multivariable logistic regression was performed to assess the association with virological suppression (<50 copies/mL) per natural logarithm increase in TFV-DP concentration. Generalized estimating equations with logit link were used to assess associations with virological rebound. The Akaike Information Criterion and Quasi-likelihood Information Criteria were used to compare models built on continuous TFV-DP data to 4 previously defined concentration categories.ResultsWe included 294 participants in the analysis, 188 (64%) of whom initiated TLD as second-line therapy. Adjusted odds ratios (95% CIs) of virological suppression were 2.12 (1.23, 3.75), 3.11 (1.84, 5.65), and 4.69 (2.81, 8.68) per natural logarithm increase in TFV-DP concentration at weeks 12, 24, and 48, respectively. In participants with virological suppression at week 12, the adjusted odds ratio for remaining virologically suppressed was 3.63 (95% CI: 2.21 to 5.69) per natural logarithm increase in TFV-DP concentration. Models using continuous TFV-DP data had lower Akaike Information Criterion and Quasi-likelihood Information Criteria values than those using categorical data for predicting virological outcomes.ConclusionTFV-DP concentrations in dried blood spots exhibit a dose-response relationship with viral load. Analyzing TFV-DP concentrations as continuous variables rather than conventional categorization may be appropriate.

Dataset Information

Predictive Value of Tenofovir Diphosphate in Dried Blood Spots for Future Viremia in Persons Living With HIV.

Publications

Predictive Value of Tenofovir Diphosphate in Dried Blood Spots for Future Viremia in Persons Living With HIV.

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