Tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC) is the backbone for both human immunodeficiency virus (HIV) treatment and pre-exposure prophylaxis (PrEP) worldwide. Tenofovir alafenamide (TAF) with FTC is increasingly used in HIV treatment and was recently approved for PrEP among men-who-have-sex-with-men. TDF and TAF are both metabolized into tenofovir (TFV). Antiretrovirals in plasma are taken up into hair over time, with hair levels providing a long-term measure of adherence. Here, we report a simple, robust, highly sensitive, and validated high-performance liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS)-based analytical method for analyzing TFV and FTC from individuals on either TDF/FTC or TAF/FTC in small hair samples. TFV/FTC are extracted from ~5 mg hair and separated on a column using a gradient elution. The lower quantification limits are 0.00200 (TFV) and 0.0200 (FTC) ng/mg hair; the assay is linear up to 0.400 (TFV) and 4.00 (FTC) ng/mg hair. The intra-day and inter-day coefficients of variance (CVs) are 5.39-12.6% and 6.40-13.5% for TFV and 0.571-2.45% and 2.45-5.16% for FTC. TFV concentrations from participants on TDF/FTC-based regimens with undetectable plasma HIV RNA were 0.0525 ± 0.0295 ng/mg, whereas those from individuals on TAF/FTC-based regimens were 0.0426 ± 0.0246 ng/mg. Despite the dose of TFV in TDF being 10 times that of TAF, hair concentrations of TFV were not significantly different for those on TDF versus TAF regimens. Pharmacological enhancers (ritonavir and cobicistat) did not boost TFV concentrations in hair. In summary, we developed and validated a sensitive analytical method to analyze TFV and FTC in hair and found that hair concentrations of TFV were essentially equivalent among those on TDF and TAF.

Objective

We examined whether human mobility was associated with antiretroviral treatment adherence, measured via antiretroviral hair concentrations.

Design

This is a cross-sectional analysis of adults on antiretroviral treatment in East Africa at baseline in an observational cohort study.

Methods

Participants reported recent mobility (overnight travel) and histories of migration (changes of residence), including reasons, frequency/duration, and locations. Hair antiretroviral concentrations were analyzed using validated methods. We estimated associations between mobility and antiretroviral concentrations via linear regression adjusted for age, sex, region, years on treatment.

Results

Among 383 participants, half were women and the median age was 40. Among men, 25% reported recent work-related mobility, 30% nonwork mobility, and 11% migrated in the past year (mostly across district boundaries); among women, 6 and 57% reported work-related and nonwork mobility, respectively, and 8% recently migrated (mostly within district). Those reporting work-related trips 2 nights or less had 72% higher hair antiretroviral levels (P = 0.02) than those who did not travel for work; in contrast, nonwork mobility (any duration, vs. none) was associated with 24% lower levels (P = 0.06). Intra-district migrations were associated with 59% lower antiretroviral levels than nonmigrants (P = 0.003) while inter-district migrations were not (27% higher, P = 0.40).

Conclusion

We found that localized/intra-district migration and nonwork travel-more common among women-were associated with lower adherence, potentially reflecting care interruptions or staying with family/friends unaware of the participants' status. In contrast, short work-related trips-more common among men-were associated with higher adherence, perhaps reflecting higher income. Adherence interventions may require tailoring by sex and forms of mobility.

Background

We examined change in antiretroviral treatment (ART) adherence after breastfeeding (BF) cessation using hair tenofovir (TFV) concentrations as an objective metric of medication consumption.

Methods

A subset of postpartum women in Zimbabwe randomized in IMPAACT PROMISE to take ART while BF and post-BF cessation had hair TFV measured longitudinally. Using linear mixed-effect models, we estimated differences in hair TFV levels after BF cessation, accounting for trends in levels over time regardless of BF status and change in slope after breastfeeding cessation. We also estimated the relative risk of viremia (>50 copies/mL) per doubling of hair TFV concentration.

Results

Among 55 women (median age 26, interquartile range 24-29 years), hair TFV levels (n = 305) were available for a median of 9 visits per woman between 3 and 29 months postpartum. Hair TFV levels ranged from undetected to 0.25 ng/mg (median 0.04 ng/mg). Controlling for trends since delivery [decline of 2.2% per month, 95% confidence interval (CI): -5.3 to 1.0], TFV levels averaged 24.4% higher (95% CI: -5.1 to 63.1) post-BF cessation than during BF, with no change in slope (0.0% per month, 95% CI: -3.8 to 3.9). Postpartum, 42% of women were ever viremic. Higher TFV levels were strongly protective; relative risk of viremia per doubling of TFV was 0.52 (95% CI: 0.43 to 0.63; P < 0.0001).

Conclusions

Leveraging an objective metric of ART use, we observed modestly declining adherence across the postpartum period, but no additional decline associated with breastfeeding cessation. High viremia frequency and varying postpartum TFV levels observed highlight the importance of enhanced adherence support with viral load monitoring among postpartum women.