Beyond HIV viral load: application of pharmacologic measures to identify ART adherence mismatch

Kristofich, Michael; Anderson, Peter L.; Castillo‐Mancilla, José

doi:10.1177/20499361211010596

Cited by 7 publications

(10 citation statements)

References 18 publications

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“…The values of the DBS drug concentrations can also give HIV care providers more nuanced insight into their patients’ clinical management as they review more continuous, real-time patterns of adherence than is provided by viral load. Furthermore, when used in conjunction with viral load, high drug concentrations in DBS in the presence of viremia may help identify patients with ART drug resistance [12,22,25]. These findings create opportunities for future research in exploring the most impactful ways to use long-acting drug metabolite testing in conjunction with traditional viral load testing and how best to provide drug concentration-based feedback to participants and providers.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the large numbers of DBS and viral load pairs established a ‘suppressive range’ for this population. A result in the suppressive range would provide reassurance and positive feedback on a patient's adherence, whereas a result below the threshold may provide an opportunity for a clinic level intervention to improve adherence through education and support, prior to the patient experiencing virologic failure [12]. Last, DBS are easy to collect and transport in a clinic setting and, furthermore, there is a current study evaluating home collection of DBS to quantify TFV-DP [28].…”

Section: Discussionmentioning

confidence: 99%

“…For example, in South Africa, because of limited healthcare resources, PWH on ART only receive adherenceenhancing interventions after viral breakthrough has been identified; and viral loads are only drawn at 4 and 12 months post-ART initiation and annually thereafter [14]. Thus, intervening before viral breakthrough to maintain viral suppression would promote better health outcomes, and help reduce transmission [12].…”

Section: Introductionmentioning

confidence: 99%

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Tenofovir diphosphate in dried blood spots predicts future viremia in persons with HIV taking antiretroviral therapy in South Africa

Jennings

Robbins²,

Nguyen

et al. 2022

Aids

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Objectives:Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is used as a biomarker of antiretroviral therapy (ART) adherence. Recent treatment studies have shown that TFV-DP predicts future viremia in persons with HIV (PWH) but there are few data from high-burden settings. We investigated whether TFV-DP in DBS predicts future viral breakthrough in South African PWH.Design:Prospective observational cohort.Methods:We enrolled 250 adults receiving tenofovir-containing regimens, currently virally suppressed (<50 copies/ml) but at risk of future viral breakthrough, from four primary health clinics in Cape Town. Paired viral load and DBS for TFV-DP were collected monthly for 12 months. Viral breakthrough was the first confirmed viral load greater than 400 copies/ml. Logistic regression estimated the odds ratio (OR) and 95% confidence intervals for future viral breakthrough at the next visit.Results:Participants provided 2944 paired DBS and viral load samples. Median (IQR) age was 34 (27–42) years; median duration on ART at study entry was 11 (4–12) months;78% were women. Twenty-one (8%) participants developed viral breakthrough. Participants with TFV-DP 400 fmol/punch or less had an adjusted OR of 16.1 (95% CI: 3.9–67.4; P < 0.001) for developing viral breakthrough 1 month later compared with participants with TFV-DP greater 800 fmol/punch.Conclusion:TFV-DP in DBS strongly predicted future viral breakthrough in a clinical cohort of South African PWH. A biomarker able to identify PWH at risk for future viral breakthrough has the potential to improve health outcomes through timely intervention. Future studies exploring the clinical use of TFV-DP in DBS in conjunction with viral load in ART monitoring are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tenofovir diphosphate in dried blood spots predicts future viremia in persons with HIV taking antiretroviral therapy in South Africa

Jennings

Robbins²,

Nguyen

et al. 2022

Aids

Self Cite

View full text Add to dashboard Cite

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“…Collectively, these features support the conduct of controlled clinical trials where the use of objective pharmacologic measures of adherence to complement the information provided by routine viral load monitoring is evaluated. Such studies could prove particularly useful in PWH who are not fully virologically suppressed (ie, HIV VL 20–1000 copies/mL), in whom resistance testing is not always feasible [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Low-Level Viremia Is Associated With Cumulative Adherence to Antiretroviral Therapy in Persons With HIV

Castillo‐Mancilla

Morrow

Coyle

et al. 2021

Open Forum Infectious Diseases

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The drivers of low-level viremia (LLV) between 20-200 copies/mL remain unclear. In 1,042 person-visits from 497 persons with HIV on TDF-containing ART, the association between LLV and cumulative antiretroviral adherence (quantified using tenofovir diphosphate (TFV-DP) in dried blood spots) was assessed. Lower TFV-DP levels were associated with higher odds of LLV. As TFV-DP (fmol/punch) categories decreased from >1,650 to 800-1,650; 800-1,650 to <800; and >1,650 to <800, the adjusted odds ratios for LLV versus HIV VL <20 copies/mL were: 2.0 [1.2, 3.1]; 2.4 [1.1, 5.0]; and 4.6 [2.2, 9.9], respectively. This suggests that adherence could impact LLV.

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“…Additionally, low concentrations of TFV-DP in DBS has been shown to be predictive of future viremia (.20 copies/mL)-even in people with HIV who are virologically suppressed at the time of the visit, providing the opportunity to identify pregnant and PP women at higher risk of viremia during the peripartum period. 57,58 Intermediate TFV-DP concentrations are also associated with increased drug resistance mutations. 59 To maximize the durability of firstline ART regimens, including dolutegravir-based regimens, which are often combined with TDF in LMIC, monitoring of TFV-DP concentrations may serve as an early warning indicator for the development of drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Tenofovir Diphosphate in Dried Blood Spots in Pregnant and Postpartum Women With HIV in Kenya: A Novel Approach to Measuring Peripartum Adherence

Abuogi

Castillo‐Mancilla

Hampanda

et al. 2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background:Adherence to antiretroviral therapy (ART) among pregnant and postpartum women with HIV (PWLWH) is critical to promote maternal health and prevent HIV transmission. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is an objective assessment of cumulative ART adherence that has not been fully assessed in PWLWH.Setting:Southwestern Kenya.Methods:PWLWH receiving tenofovir disoproxil fumarate-based ART from 24 health facilities provided DBS samples at 3 time points [pregnancy/early postpartum (PP), 6 months PP, and 9–12 months PP]. Thresholds for daily adherence were defined as TFV-DP in DBS ≥650 fmol/punch in pregnancy and ≥950 PP. Descriptive analysis is presented. Cluster adjusted χ2 and t-tests were used to test for association with clinical and demographic factors.Results:A total of 419 DBS samples were collected from 150 PWLWH. Median TFV-DP in DBS was lowest, 552 fmol/punch [interquartile range (IQR), 395–759] in pregnancy and declined over time [914 (IQR, 644–1176) fmol/punch; early PP; 838 (IQR, 613–1063) fmol/punch 6 months PP; and 785 (IQR, 510–1009) fmol/punch 9–12 months; P < 0.001]. Only 42% of samples in pregnancy and 38.5% of samples in PP met thresholds for daily adherence. Clinical or demographic factors were not associated with suboptimal adherence levels.Conclusion:Cumulative ART exposure in PWLWH, quantified by TFV-DP in DBS, demonstrated a stepwise decrease (ie, adherence) PP. Most women demonstrated less than daily adherence throughout the peripartum period. Use of TFV-DP in DBS as a measure of cumulative ART adherence could help optimize health outcomes in PWLWH and their infants.

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Beyond HIV viral load: application of pharmacologic measures to identify ART adherence mismatch

Cited by 7 publications

References 18 publications

Tenofovir diphosphate in dried blood spots predicts future viremia in persons with HIV taking antiretroviral therapy in South Africa

Tenofovir diphosphate in dried blood spots predicts future viremia in persons with HIV taking antiretroviral therapy in South Africa

Low-Level Viremia Is Associated With Cumulative Adherence to Antiretroviral Therapy in Persons With HIV

Tenofovir Diphosphate in Dried Blood Spots in Pregnant and Postpartum Women With HIV in Kenya: A Novel Approach to Measuring Peripartum Adherence

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