Moderately High Tenofovir Diphosphate in Dried Blood Spots Indicates Drug Resistance in Viremic Persons Living with HIV

Abstract

Background: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a strong predictor of viral suppression in persons living with HIV (PLWH). Its association with antiretroviral therapy (ART) resistance remains unknown. Methods: Blood was collected in PLWH receiving TDF-containing ART enrolled in a 48-week study. Tenofovir diphosphate/emtricitabine triphosphate (FTC-TP) were quantified from the same sample as HIV viral load (VL) in PLWH who developed resistance within ≤12 months. Results: The study enrolled 807 participants, of whom 10 had new resistance-conferring mutations. Among these, median (interquartile range) TFV-DP and HIV VL were 956 (407-1510) fmol/punch and 9840 (513-68,200) copies/mL, respectively. Five had quantifiable FTC-TP in DBS. Based on previously published data, a TFV-DP concentration of 956 fmol/punch would have an adjusted odds of virologic suppression of 32.8 versus TFV-DP <350 fmol/punch, making viremia of ∼10,000 copies/mL an unexpected outcome. Conclusion: Moderately high TFV-DP in DBS (700-1249 fmol/punch) in PLWH with high viremia suggest that antiretroviral drug resistance might be present.

Tenofovir diphosphate levels in dried blood spots are associated with virologic failure and resistance to first‐line therapy in South Africa: a case–control cohort study

“…Although the concentrations of TFV-DP in virologically suppressed PWH in our study were lower than previously observed in the United States [21], they are consistent with other studies in Africa [22,29,30]. Our findings are also consistent with a clinical cohort of PWH in the United States, where TFV-DP concentrations in study participants who developed new drug resistance-associated mutations were ∼40% lower than those observed in participants who were virologically suppressed [21,24]. These results are also similar to other studies that assessed ART adherence using qualitative [31,32] and other cumulative [15,33] pharmacologic measures.…”

“…However, its ability to identify treatment failure (i.e. VF) with drug resistance is poorly understood [24].…”

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

“…This group was also more diverse and contained both individuals who had maintained viral suppression and those who had not. This demonstrates that relying on viral load alone to assess adherence could be inadequate as it has been previously shown that mid-range adherence is more strongly associated with the development of ART resistance [25]. It has also been shown that TFV-DP in DBS, in combination with viral load, can be used to identify PWH with suspected ART resistance [22,25].…”

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

“… 15 , 17 More informative, however, would be high viremia in patients with high cumulative adherence, which is most likely due to antiretroviral resistance. 18 – 20 Thus, when facing this clinical presentation (i.e., high adherence and high viremia), providers could be more inclined to order HIV drug resistance testing rather than have repeated discussions about adherence (with the potential of further perpetuating the accumulation of drug resistance).…”