Relationship Between Tenofovir Diphosphate Concentrations in Dried Blood Spots and Virological Outcomes After Initiating Tenofovir–Lamivudine–Dolutegravir as First-Line or Second-Line Antiretroviral Therapy

Abstract

Background: Tenofovir 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. Setting: Three primary care clinics in Khayelitsha, Cape Town, South Africa. Methods: We 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. Results: We 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. Conclusion: TFV-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.

Histomorphometric changes in testis following administration of tenofovir nanoparticles in an animal model

“…Notably, recent in-vivo and in-vitro studies have demonstrated advances and promising results have been noted when TDF-loaded nanoparticles were studied on various cell lines and rat organs for their potential application to manage HIV and associated complications [ 21 – 23 ]. Although, the current HIV treatment regimen in South Africa containing the preferred first-line ART combination of tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) has produced better treatment outcomes such as viral load suppression, enhanced immune response, and improved clinical indices [ 24 – 26 ]. Emerging studies have documented several adverse effects including virologic failure and cardio-metabolic disorders secondary to excessive weight gain following initiation and treatement with dolutegravir-based regimen [ 27 – 29 ].…”