Estimating the minimum antiretroviral adherence required for plasma HIV-1 RNA viral load suppression among people living with HIV who use unregulated drugs

Abstract

Objectives: Owing to advances in antiretroviral therapy (ART), we re-examined minimum ART adherence levels necessary to achieve sustained HIV-1 viral load (VL) suppression among people with HIV who use drugs (PHIV-PWUD). Design and methods: We used data from ACCESS, a community-recruited prospective cohort of PHIV-PWUD in Vancouver, Canada. We calculated adherence using the proportion of days of ART dispensed in the year before each VL measurement. We used generalized linear mixed-effects models to identify adherence- and ART regimen-related correlates of VL suppression (<200 copies/ml). We employed probit regression models and generated dose–response curves to estimate the minimum adherence level needed to produce VL suppression in 90% of measures, stratified by regimen and calendar-year. Results: Among 837 ART-exposed PHIV-PWUD recruited between 1996 and 2017, the overall estimated adherence level necessary to achieve 90% VL suppression was 93% (95% confidence interval [CI]: 90–96). This differed by regimen: 69% (95% CI: 45–92) for integrase inhibitor (INSTI)-, 96% (95% CI: 92–100) for boosted protease inhibitor (bPI)-, and 98% (95% CI: 91–100) for non-nucleoside reverse transcriptase inhibitor-based regimens. In multivariable analysis, INSTI-based regimens were positively associated with VL suppression (vs. bPIs), while un-boosted PIs and other regimens were negatively associated. We observed a decreasing temporal trend of estimated adherence necessary for 90% VL suppression, dropping to 64% (95% CI: 50–77) during 2016–2017. Conclusion: Although high levels of ART adherence were necessary to achieve consistent VL suppression, the minimum necessary adherence levels decreased over time. Overall, INSTI-based regimens performed the best, suggesting that they should be preferentially prescribed to PHIV-PWUD.

Real World Data on Forgiveness to Uncomplete Adherence to Bictegravir/ Emtricitabine/Tenofovir Alafenamide

“…Data derived from a cohort of PLWH using unregulated drugs 34 support our results indicating that a lower adherence threshold (69%; 95% CI 45-92) was needed to maintain HIV-RNA suppression in 90% of patients treated with integrase inhibitors compared to a level equal or superior to 95% to obtain the same results in PLWH treated with boosted PIs or NNRTIs. These results are slightly higher than those obtained by the Patient-centered HIV Care Model demonstration project that found an overall estimated adherence level necessary to achieve viral suppression in 90% of viral load tests of 82%, with high variation by regimen type, being sufficient for integrase inhibitor- based levels of 75%.…”

“…B/F/TAF was very robust in forgiving lower adherence rates. Further, PDC, with the dispensing correction we adopted, could potentially overestimate adherence rates, 34 as drug possession is not necessarily synonymous of effectively taking the drug, but cannot underestimate it (eg one cannot take a drug that does not have) though strengthening the meaning of our findings as the lower limits we observed could be even lower. Due to the nature of collected data, we cannot differentiate the real dynamics of bad adherence in terms of sporadic and repeated single days off versus prolonged drug holidays, as well as actual pill-taking behavior, including taking medication according to the prescriber's instructions or on the prescribed time schedule.…”

“…As a matter of fact a recent study conducted in British Columbia revealed that the PDC rate necessary to obtain a 90% success rate defined as a HIV-RNA level < 200 copies/ml was 64% (95% CI 50-77) in more recent years compared to an overall necessary rate of 93% (95% CI 90-96). 34 The Authors concluded that these results could be attributable to the increased use of more potent ART drugs such as INSTIs.…”

“…The fact that most enrolled subjects had a long history of HIV infection and antiretroviral therapy does not allow us to differentiate chronically treated PLWH from subjects with a recent start of ART. 33,34 The uncontrolled nature and retrospective design of our study may be seen as further limits. Finally, the decision to limit the enrollment period to the very recent years, reduced the potential amplitude of the casuistry, however, on the other hand eliminated the confounding bias of calendar year.…”

Cocaine regulates antiretroviral therapy CNS access through pregnane-x receptor-mediated drug transporter and metabolizing enzyme modulation at the blood brain barrier

“…Interestingly, other illicit substances also modulate CYP3A4 and other cytochrome P450’s [ 181 – 187 ]. Furthermore, substance use can impact plasma concentrations of ART and viral rebound, independent of adherence concerns [ 188 – 190 ]. Together, our findings demonstrate that additional attention is warranted in the clinical care of substance using populations with HIV, where measures of viral suppression and plasma ART concentrations are evaluated more regularly to evaluate treatment efficacy.…”