Effectiveness and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Patients With HIV-1 Infection and Ongoing Substance Use Disorder: The BASE Study

BACKGROUND: People with human immunodeficiency virus (HIV) and substance use disorder (PWH/SUD) are at higher risk of nonadherence to antiretroviral therapy. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) exhibits high rates of efficacy with a favorable adverse event profile. The BASE study (NCT03998176) is a phase 4, single-arm study evaluating the effectiveness and safety of B/F/TAF among PWH/SUD. METHODS: Viremic (HIV RNA \u3e1000 copies/mL) PWH/SUD initiated B/F/TAF once daily for 48 weeks (W). The primary endpoint was proportion of participants with HIV RNA/mL at W24. Secondary endpoints were proportion of participants with HIV-1 RNA/mL at W48, safety, B/F/TAF adherence (dried blood spot [DBS] concentrations of emtricitabine triphosphate and tenofovir diphosphate [TFV-DP]), substance use (NIDA-ASSIST), and quality of life (SF-12). RESULTS: Forty-three participants were enrolled; 95% reported methamphetamine use. Median age was 38 (range, 21-62) years; 21% were female, 81% White, 14% Black, and 16% Hispanic. Thirty-two (74%) and 21 (49%) participants had HIV RNA/mL (intention-to-treat) at W24 and W48, respectively. Seven participants (16%) experienced confirmed virologic failure through W48; 1 developed emergent drug resistance (M184V). Fifteen participants (35%) experienced grade ≥3 adverse events. Five participants (12%) reported suicidal ideation; none resulted in discontinuation. Median DBS concentrations were representative of 5-6 doses/week (TFV-DP, 1603 fmol/punches). NIDA-ASSIST scores declined from baseline to W48 with methamphetamine use decreasing most (-7.9 points; -29%), and SF-12 physical/mental scores increased 1.2 and 7.6 points, respectively. CONCLUSIONS: B/F/TAF among a high-risk population of PWH/SUD resulted in an initial 72% viral suppression rate at W24 before dropping to 49% at W48 as retention declined. One participant developed emergent drug resistance (M184V)

Impact of efavirenz pharmacokinetics and pharmacogenomics on neuropsychological performance in older HIV-infected patients

Pharmacokinetics (PK) and pharmacodynamics of efavirenz and its 8-hydroxy metabolite (8-OH-efavirenz) have not been robustly evaluated in older HIV-infected persons

A Pharmacist-Led Medication Switch Protocol in an Academic HIV Clinic: Patient Knowledge and Satisfaction

BACKGROUND: Tenofovir alafenamide (TAF) is associated with less renal and bone toxicity compared with tenofovir disoproxil (TDF). TAF\u27s recent FDA approval has spurred HIV providers to consider switching antiretroviral therapy (ART) regimens containing TDF to TAF to minimize long term risks. Patient views on the process of such medication switches have not been explored. METHODS: Patients taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) following the Food and Drug Administration\u27s (FDA) approval of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) received medication education from an HIV pharmacist prior to switching to the tenofovir alafenamide (TAF) formulation. Patients were asked to complete a cross-sectional survey assessing satisfaction with the switch process and knowledge about the new medication 4 to 8 weeks post-switch. RESULTS: Sixty five patients completed the switch and 57 (88%) completed a follow-up survey. Most (86%) reported understanding why the switch was made, while 91% correctly identified that TAF is associated with reduced renal toxicity, and 73% correctly identified that TAF is associated with reduced bone toxicity. No statistically significant difference was found in satisfaction with or understanding of why the medication switch was made when assessed by sex, age, race, or education, but there was a trend toward significance in the distribution of answers based on education level with those with a high school diploma, General Educational Development (GED) or less being more likely to be satisfied with the medication switch (p = 0.074). CONCLUSIONS: Education from an ambulatory clinic-based HIV pharmacist resulted in high rates of patient satisfaction and understanding of the switch from TDF to TAF-containing ART

Optimizing Antiretroviral Therapy with Modern Rifapentine Containing TB Treatment

In the past decade there has been a multitude of phase 3 clinical trials targeting treatment shortening for tuberculosis (TB). The synthetic rifamycin derivative rifapentine (RPT) has been at the forefront of many of the treatment shortening approaches. RPT possesses greater potency and a longer pharmacokinetic (PK) half-life (t1/2) as compared with the long used rifamycin, rifampin (RIF). For TB preventative treatment, a 3-month, once weekly regimen of RPT and isoniazid (INH; 3HP) was shown to be as effective as 9-months of daily INH therapy in the PREVENT TB trial. Similarly, a 4-week course of daily RPT and INH (1HP) was shown to non-inferior to the daily INH therapy in people living with HIV (PLWH) in the BRIEF-TB trial. These RPT-containing regimens represent a significant shortening approach to TB preventative treatment. Furthermore, recently a 4-month course of a RPT based regimen was shown to be non-inferior to the standard 6-month RIF based treatment for active drug susceptible TB. This four month regimen was the first treatment shortening for active TB in over 40 years. However, use of rifamycins, including RPT, are complicated by their propensity to cause detrimental drug-drug interactions. This is especially important in the treatment of HIV-TB where antiretroviral therapy (ART) is often the victim of these drug-drug interactions. The work conducted in this dissertation develops novel pharmacology data to ensure the safe and effective use of modern antiretrovirals (ARVs) with RPT based TB regimens

Current strategies to treat tuberculosis [version 1; referees: 2 approved]

Tuberculosis (TB) has been a leading cause of death for more than a century. While effective therapies exist, treatment is long and cumbersome. TB control is complicated by the overlapping problems created by global inadequacy of public health infrastructures, the interaction of the TB and human immunodeficiency virus (HIV) epidemics, and the emergence of drug-resistant TB. After a long period of neglect, there is now significant progress in the development of novel treatment regimens for TB. Focusing on treatment for active disease, we review pathways to TB regimen development and the new and repurposed anti-TB agents in clinical development

Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention

Background. Concomitant use of rifamycins to treat or prevent tuberculosis can result in subtherapeutic concentrations of antiretroviral drugs. We studied the interaction of efavirenz with daily rifapentine and isoniazid in human immunodeficiency virus (HIV)–infected individuals receiving a 4-week regimen to prevent tuberculosis. Methods. Participants receiving daily rifapentine and isoniazid with efavirenz had pharmacokinetic evaluations at baseline and weeks 2 and 4 of concomitant therapy. Efavirenz apparent oral clearance was estimated and the geometric mean ratio (GMR) of values before and during rifapentine and isoniazid was calculated. HIV type 1 (HIV-1) RNA was measured at baseline and week 8. Results. Eighty-seven participants were evaluable: 54% were female, and the median age was 35 years (interquartile range [IQR], 29–44 years). Numbers of participants with efavirenz concentrations ≥1 mg/L were 85 (98%) at week 0; 81 (93%) at week 2; 78 (90%) at week 4; and 75 (86%) at weeks 2 and 4. Median efavirenz apparent oral clearance was 9.3 L/hour (IQR, 6.42–13.22 L/hour) at baseline and 9.8 L/hour (IQR, 7.04–15.59 L/hour) during rifapentine/isoniazid treatment (GMR, 1.04 [90% confidence interval, .97–1.13]). Seventy-nine of 85 (93%) participants had undetectable HIV-1 RNA (/mL) at entry; 71 of 75 (95%) participants had undetectable HIV-1 RNA at week 8. Two participants with undetectable HIV-1 RNA at study entry were detectable (43 and 47 copies/mL) at week 8. Conclusions. The proportion of participants with midinterval efavirenz concentrations ≥1 mg/L did not cross below the prespecified threshold of \u3e80%, and virologic suppression was maintained. Four weeks of daily rifapentine plus isoniazid can be coadministered with efavirenz without clinically meaningful reductions in efavirenz mid-dosing concentrations or virologic suppression