TY - JOUR
T1 - Association of tenofovir diphosphate and lamivudine triphosphate concentrations with HIV and hepatitis B virus viral suppression
AU - Lartey, Margaret
AU - Ganu, Vincent J.
AU - Tachi, Kenneth
AU - Yang, Hongmei
AU - Anderson, Peter L.
AU - Langaee, Taimour
AU - Ojewale, Oluwayemisi
AU - Boamah, Isaac
AU - Obo-Akwa, Adjoa
AU - Antwi, Kenneth
AU - Bushman, Lane R.
AU - Ellison, Lucas
AU - Kwara, Awewura
N1 - Publisher Copyright:
© 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - Objective:Concentrations of tenofovir diphosphate (TFV-DP) and lamivudine triphosphate (3TC-TP) in cells are correlates of medication adherence and antiviral activity. However, studies have yet to characterize the simultaneous relationship between TFV-DP and 3TC-TP concentrations with HIV and hepatitis B virus (HBV) suppression.Methods:Individuals with HIV/HBV coinfection on tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART) were enrolled. Peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) samples were collected and steady-state TFV-DP and 3TC-TP concentrations quantified using validated methods. The relationship between patient factors, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS with HBV and HIV viral suppression were examined.Results:Of 138 participants on TDF-containing ART for a median duration (range) of 6 (0.75-15) years, the median age was 43 years and 64% were women. Overall, 128 (92.8%) and 129 (93.5%) had suppressed HIV and HBV viral loads, respectively. Of the 128 participants with suppressed HIV, 122 (95.3%) had suppressed HBV. Self-reported ART adherence, recent change to dolutegravir-based ART, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS were associated with HIV RNA suppression, while HBe antigen positivity, HIV suppression, and TFV-DP concentrations in DBS were associated with HBV DNA suppression (including six persons with HBV nonsuppression and HIV suppression).Conclusion:Long-term TDF/3TC-conatining ART was highly efficacious in individuals with HIV/HBV coinfection. Higher TFV-DP concentrations were predictive of suppression for both viruses. Persistent HBV viremia on TDF/3TC-containg ART requires additional research, but may represent poor adherence and the need for adherence interventions or novel antivirals.
AB - Objective:Concentrations of tenofovir diphosphate (TFV-DP) and lamivudine triphosphate (3TC-TP) in cells are correlates of medication adherence and antiviral activity. However, studies have yet to characterize the simultaneous relationship between TFV-DP and 3TC-TP concentrations with HIV and hepatitis B virus (HBV) suppression.Methods:Individuals with HIV/HBV coinfection on tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART) were enrolled. Peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) samples were collected and steady-state TFV-DP and 3TC-TP concentrations quantified using validated methods. The relationship between patient factors, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS with HBV and HIV viral suppression were examined.Results:Of 138 participants on TDF-containing ART for a median duration (range) of 6 (0.75-15) years, the median age was 43 years and 64% were women. Overall, 128 (92.8%) and 129 (93.5%) had suppressed HIV and HBV viral loads, respectively. Of the 128 participants with suppressed HIV, 122 (95.3%) had suppressed HBV. Self-reported ART adherence, recent change to dolutegravir-based ART, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS were associated with HIV RNA suppression, while HBe antigen positivity, HIV suppression, and TFV-DP concentrations in DBS were associated with HBV DNA suppression (including six persons with HBV nonsuppression and HIV suppression).Conclusion:Long-term TDF/3TC-conatining ART was highly efficacious in individuals with HIV/HBV coinfection. Higher TFV-DP concentrations were predictive of suppression for both viruses. Persistent HBV viremia on TDF/3TC-containg ART requires additional research, but may represent poor adherence and the need for adherence interventions or novel antivirals.
KW - adherence
KW - HIV/hepatitis B virus coinfection
KW - lamivudine triphosphate
KW - tenofovir diphosphate
KW - viral suppression
UR - http://www.scopus.com/inward/record.url?scp=85184141423&partnerID=8YFLogxK
U2 - 10.1097/QAD.0000000000003764
DO - 10.1097/QAD.0000000000003764
M3 - Article
C2 - 37861682
AN - SCOPUS:85184141423
SN - 0269-9370
VL - 38
SP - 351
EP - 362
JO - AIDS
JF - AIDS
IS - 3
ER -