Background:
Lower tenofovir (TFV) & metabolite concentrations have been observed in plasma and dried blood spots (DBS) among women during pregnancy compared to non-pregnant periods. Hair TFV levels, which measure long-term adherence, may be less affected by physiologic changes during pregnancy that can influence blood-based measures. To date, PrEP levels have not been compared in hair and DBS during pregnancy and postpartum.
Methods:
The PrEP Implementation for Mothers in Antenatal Care Study evaluated PrEP delivery strategies for pregnant women who were followed 9-months postpartum. Hair and DBS samples were collected at visits from a subset of women who reported using PrEP in the last 30 days. PrEP drug levels were measured using liquid chromatography/tandem mass spectrometry. The correlations between TFV levels in hair and tenofovir-diphosphate (TFV-DP) levels in DBS were calculated using the Spearman coefficient. Median hair TFV levels were calculated based on benchmarks for PrEP dosing in DBS among pregnant/postpartum women in the IMPAACT 2009 study and hair benchmarks in non-pregnant women.
Results:
Overall, 34 hair-DBS paired samples were evaluated; 12 (35%) from pregnancy visits at a median of 32 weeks gestation and 22 (65%) from postpartum visits at a median of 3.5 months since birth. Median time since PrEP initiation was 18 weeks (IQR 7-33) at sample collection. TFV levels in hair were strongly correlated with TFV-DP levels in DBS (r=0.77, p< 0.001), with stronger correlation postpartum (r=0.82, p< 0.001) compared to pregnancy (r=0.57, p=0.05). Based on DBS benchmarks, 44% of DBS samples had TFV-DP levels indicative of ≥2 doses/week; 41% of hair samples had TFV levels indicative of ≥2 doses/week based on benchmarks from non-pregnant women. Median hair TFV levels for women who took < 2 and ≥2 doses/week were 0 ng/mg (IQR 0-0.006, n=19) and 0.035 ng/mg (0.021-0.039, n=15), respectively, based on DBS benchmarks; results were similar by pregnancy status (0.029 ng/mg pregnancy vs. 0.035 ng/mg postpartum, p=0.37, Table 1).
Conclusions:
Our findings suggest that hair PrEP measures are strongly correlated with DBS and may not need adjustment for PK differences over the perinatal period when used as adherence metrics. These data suggest an advantage of using hair measures for PrEP adherence during pregnancy and postpartum over blood-based measures which are more influenced by physiologic changes during the perinatal period.
Table 1. Tenofovir hair levels among women enrolled in the PrEP Implementation for Mothers in Antenatal Care Study (NCT03070600) during pregnancy and postpartum, by dosing benchmarks established in dried blood spots (DBS) and hair.