Background
Tenofovir (TFV)-diphosphate (TFV-DP) concentrations in dried blood spots (DBS) demonstrate strong associations with adherence, virologic suppression (VS) and future viremia in persons with HIV (PWH) but data are limited to the older TFV prodrug or PWH with VS on TFV alafenamide (TAF). We examined TFV-DP in DBS and its association with VS at baseline among PWH on TAF enrolled in ACTG A5359/LATITUDE, which is a unique clinical trial population with psychosocial challenges to ART adherence.
Methods
LATITUDE is an ongoing phase III, prospective, randomized, open-label study comparing long-acting CAB/RPV to oral ART in PWH with a history of adherence challenges (NCT03635788). This analysis focused on baseline results from PWH on TAF-containing regimens prior to entry. Health and behavioral instruments were used to assess psychosocial factors. TFV-DP in DBS (2x7mm punches) were quantified via LC-MS/MS (LLOQ 31.3 fmol/punches). For participants with quantifiable TFV-DP, logistic regression was used to model the probability (95% CI) of VS (<200 copies/mL) by ln(TFV-DP) and boosted PI use, as TFV-DP concentrations are increased by ~2.5 fold with boosters. Probabilities at select values from very low to very high adherence based on historical TFV-DP data were estimated. Exact confidence intervals were used for TFV-DP below limit of quantification (BLQ).
Results
Baseline data were available in 193 participants (71% male at birth; 4% transgender; 64% Black, 28% white, 20% Hispanic/Latino; median age 39 [IQR 31, 52] years). ART prior to entry contained either an INSTI or NNRTI (72%) or boosted PI (28%); 37% were VS and median CD4 count was 287 (IQR 126, 540) cells/mm3. Participants reported moderate to severe depression (22%), anxiety (27%), hazardous drinking (33%), drug dependence (4%) and prior/current IV drug use (10%). For TFV-DP concentrations of BLQ, 250 (very low), 450 (low), 950 (moderate), 1800 (high) and 3600 (very high) fmol/punches, the probability of VS in INSTI/NNRTI participants was 0 (0, 0.12), 0.33 (0.22, 0.46); 0.44 (0.34, 0.55), 0.60 (0.50, 0.70), 0.72 (0.61, 0.81) and 0.82 (0.70, 0.90) (Figure). The odds of VS were 5.7 (2.4, 13.2) times higher for regimens containing INSTIs/NNRTIs vs boosted PIs (p<0.001).
Conclusions
VS occurred from very low to very high adherence on TAF-containing regimens, with increased probabilities of VS as TFV-DP concentrations increased. Differential adherence-forgiveness is suggested between INSTI/NNRTI- and PI-containing ART among PWH.