Long-Acting Cabotegravir/Rilpivirine Concentrations in Combination With Intravenous Rifampin: A Case Report.

As antiretroviral therapy advancements focus on long-acting medications, there is a need to assess the potential impact of drug-drug interactions. We present a real-world case of long-acting cabotegravir/rilpivirine co-administered with intravenous rifampin. The combination resulted in both cabotegravir and rilpivirine concentrations falling below 4 times the protein-adjusted IC90.

Acceptability, Feasibility, and Appropriateness of Implementation of Long-acting Injectable Antiretrovirals: A National Survey of Ryan White Clinics in the United States.

Background: The approval of long-acting injectable cabotegravir/rilpivirine (LAI CAB/RPV) heightened the urgency of ensuring effective implementation. Our study assesses readiness and barriers to implement LAI CAB/RPV across Ryan White-funded clinics in the United States. Methods: We conducted a cross-sectional survey between December 2020 and January 2021 using validated 4-item measures: acceptability of intervention measure (AIM), intervention appropriateness measure (IAM), and feasibility of intervention measure (FIM). Associations between measures and clinic characteristics were evaluated via Spearman rank correlations. A 5-point Likert scale ranked potential barriers of implementation responses. Open-ended questions were analyzed through a thematic approach. Results: Of 270 clinics, 44 (16%) completed the survey: 38% federally qualified health centers, 36% academic, 20% community-based organizations, 14% hospital outpatient, and 9% nonprofit. Means (SD; range) were as follows: AIM, 17.6 (2.4; 12-20); IAM, 17.6 (2.4; 13-20); and FIM, 16.8 (2.9; 7-20). Twenty percent were not at all ready to implement LAI CAB/RPV, and 52% were slightly or somewhat ready. There was a significant association between AIM and the proportion of Medicaid patients (AIM, rho = 0.312, P = .050). Community-based organizations scored the highest readiness measures (mean [SD]: AIM, 19.50 [1.41]; IAM, 19.25 [1.49]; FIM, 19.13 [1.36]) as compared with other clinics. Implementation barriers were cost and patients' nonadherence to visits. Conclusions: There is variability of readiness yet high levels of perceived acceptability and appropriateness of implementing LAI CAB/RPV among Ryan White clinics, necessitating tailored interventions for successful implementation. A special focus on addressing the barriers of adherence and the cost of implementation is needed.

Patient perspectives of antiretroviral pharmacy services: A cross-sectional cohort study.

BACKGROUND: Adherence to antiretroviral therapy (ART) remains the main predictor of sustained HIV virologic suppression for people with HIV (PWH). Mail-order pharmacy services are often offered to patients as an alternative option to traditional pharmacy services. Some payers mandate ART to be dispensed from specific mail-order pharmacies regardless of patient choice complicating ART adherence for patients affected by social disparities. Yet, little is known about patient perspectives regarding mail-order mandates. METHODS: Eligible patients of the HIV program at University of Nebraska Medical Center with experience receiving ART from both a local and mail-order pharmacy were invited to complete a 20-question survey with three core sections: experiences/perspectives on local and mail-order pharmacy settings; pharmacy attributes rankings; and pharmacy preference. Paired t-tests and Mann-Whitney tests were used to compare the agreement scores of pharmacy attributes. RESULTS: Sixty patients (N = 146; 41.1%) responded to the survey. Mean age was 52 years. Most were male (93%) and White (83%). The majority of participants were on ART for HIV treatment (90%) and 60% were using mail-order pharmacies for their prescription services. Significant scoring differences (p<0.05) were observed for all pharmacy attributes favoring local pharmacies. Refilling ease was the most important attribute noted. More respondents (68%) preferred local pharmacies versus mail-order pharmacies. Payer associated mail-order pharmacy mandates were experienced by 78% with half believing the mandates impacted their medical care negatively. CONCLUSIONS: In this cohort study, respondents preferred local pharmacies compared to mail-order pharmacy for ART prescription services and noted ease of refilling as the most important pharmacy attribute. Two-thirds of respondents believed mail-order pharmacy mandates negatively affected their health. Insurance payers should consider the removal of mail-order pharmacy mandates to allow patient choice of pharmacy, which may help remove barriers to ART adherence and improve long-term health outcomes.

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 >1000 copies/mL) PWH/SUD initiated B/F/TAF once daily for 48 weeks (W). The primary endpoint was proportion of participants with HIV RNA <50 copies/mL at W24. Secondary endpoints were proportion of participants with HIV-1 RNA <50 copies/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 <50 copies/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).

Antiretroviral Refill Histories as a Predictor of Future Human Immunodeficiency Virus Viremia.

BACKGROUND: The use of adherence measures as markers for virologic failure (VF) has been studied. Yet, there is currently no single adherence metric recommended for VF. Antiretroviral prescription refill histories, for people living with human immunodeficiency virus (HIV), are readily accessible and can be easily quantified to an estimated adherence level. METHODS: Participants from a Midwestern US HIV clinic were retrospectively evaluated from 2018 to 2020. Refill histories (RH) and last HIV RNA for each participant were abstracted for each study year. RH were quantified as a percentage of days covered (PDC) and VF was defined as HIV RNA >200 copies/mL. PDC values were matched with subsequent year HIV RNA (matched pair). Sample t test were used to compare mean PDC level by viral suppression status and generalized estimating equations models were used to determine the predictability of PDC level for VF. An optimal PDC threshold for VF was determined using receiver operating characteristic curve analysis and Youden index. RESULTS: A total of 1056 participants contributed to 1923 matched pairs (PDC/HIV RNA); mean age was 48.3 years, 24% women, and 30.6% Black. PDC levels differed significantly based on dichotomized HIV RNA (2018-2019: >200: 40% [95% confidence interval {CI}, 33%-46%] vs ≤200: 85% [95% CI, 84%-87%], P < .0001; 2019-2020: >200: 45% [95% CI, 38%-51%] vs ≤200: 87% [95% CI, 86%-89%], P < .0001). Based on the Youden index value of 0.66 (sensitivity 0.77, specificity 0.89), the optimal PDC threshold predictive of VF was 52%. CONCLUSIONS: Lower antiretroviral therapy (ART) adherence levels were predictive of future VF when PDC ≤52%.

Successful application of pharmacogenomic testing in the evaluation and management of a patient with human immunodeficiency virus and disseminated histoplasmosis.

OBJECTIVES: To demonstrate the successful use of pharmacogenomic testing to specifically tailor antifungal treatment to the phenotype of a patient with human immunodeficiency virus (HIV) and disseminated histoplasmosis who had clinical progression while on itraconazole and subsequently had insufficient therapeutic drug levels of voriconazole. CASE SUMMARY: We present the case of a patient with HIV and disseminated histoplasmosis with a persistently elevated serum Histoplasma capsulatum antigen and subtherapeutic levels of voriconazole. Pharmacogenomic testing revealed he was a CYP2C19 rapid metabolizer, thus explaining his persistent, subtherapeutic levels of voriconazole and prompting a change in therapy. PRACTICE IMPLICATIONS: Our case illustrates the importance of pharmacogenomic testing as a tool to evaluate subtherapeutic itraconazole or voriconazole levels, especially in patients with failed clinical or Histoplasmosis Ag response despite reporting full adherence to prescribed therapy.

Acute Weight Gain After Switch to Emtricitabine/Tenofovir Alafenamide for Human Immunodeficiency Virus Pre-Exposure Prophylaxis.

We report a case of acute weight gain after switching from emtricitabine/tenofovir disoproxil to emtricitabine/tenofovir alafenamide for human immunodeficiency virus pre-exposure prophylaxis.

Impact of Pharmacy Type on HIV Viral Suppression: A Retrospective Cross-Sectional Cohort Study.

BACKGROUND: People with HIV (PWH) use various pharmacy types beyond traditional local pharmacies. Some specialized pharmacies offer additive adherence services such as refill reminders, expedited delivery, and adherence packaging. METHODS: This single-center, retrospective cohort study evaluated the impact of pharmacy type on the gain or loss of HIV viral suppression (VS; HIV RNA ≤50 copies/mL). Patients (≥19 years) were categorized by VS and pharmacy type: HIV-specialized (additive adherence/delivery services) vs traditional (without adherence/delivery services). Fisher exact tests examined the effect of pharmacy type on differences in VS between years, and logistic regression models identified possible predictors of gaining or losing VS. RESULTS: During 2017-2018, no differences were observed for the gain or loss of VS across pharmacy types (VS gain vs continued viremia, P = .393; VS loss vs continued VS, P = .064). Predictors for the gain of VS included antiretroviral therapy adherence as percentage of days covered (PDC; adjusted odds ratio [aOR], 1.05; P < .001) and Federal Poverty Level 100%-138% (FPL; aOR, 0.17; P = .032). Predictors for the loss of VS included use of protease inhibitor (aOR, 2.85; P = .013), ≥1 other illicit substance including tobacco (aOR, 2.96; P = .024), PDC (aOR, 0.95; P < .001), FPL 139%-200% (aOR, 0.09; P = .031), and CD4 >200 cells/ccm (aOR, 0.19; P = .013). CONCLUSIONS: The gain or loss of VS among PWH in this retrospective cohort was not impacted by pharmacy transitions within the 2-year study period. However, PDC, FPL, illicit substance use, protease inhibitor use, and CD4 >200 cells/ccm were identified as factors associated with changes in VS.

HIV-1 Integrase Inhibitors: A Comparative Review of Efficacy and Safety.

The newest class of antiretrovirals for all persons living with HIV are the integrase strand transfer inhibitors (INSTIs). Since 2007, five INSTIs have been introduced: raltegravir, elvitegravir, dolutegravir, bictegravir, and cabotegravir. The INSTIs have favorable pharmacokinetic and pharmacodynamic properties, which contribute to both their effectiveness and their ease of use. With the exception of cabotegravir, each INSTI is US Food and Drug Administration approved for treatment-naïve individuals initiating antiretroviral therapy. All of the INSTIs, except raltegravir, are approved for antiretroviral treatment simplification for virologically suppressed patients without INSTI resistance. Data also support the use of dolutegravir and raltegravir in individuals with antiretroviral resistance as part of an optimized antiretroviral regimen. INSTIs are generally well tolerated by people living with HIV compared with older classes of antiretrovirals, but emerging data suggest that some INSTIs contribute to weight gain. Due to their efficacy, safety, and ease of use, HIV treatment guidelines recommend oral INSTIs as preferred components of antiretroviral therapy for individuals initiating therapy. The newest INSTI, cabotegravir, represents an alternative to oral administration of life-long antiretroviral therapy with the availability of a long-acting injectable formulation. This review summarizes the current use of INSTIs in adults living with HIV, highlighting the similarities and differences within the class related to pharmacodynamics, pharmacokinetics, safety, dosing, and administration that contribute to their role in modern antiretroviral therapy.

Sustained Virologic Suppression After 4 Weeks of Ledipasvir/Sofosbuvir in Human Immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) Co-Infection.

BACKGROUND Short-course hepatitis C (HCV) treatment with direct-acting antivirals (DAA) under 8 weeks in duration has resulted in variable efficacy rates in HCV mono-infection. Further, DAA courses under 8 weeks in duration have not been studied in HIV/HCV co-infection. We present a case report of 12-week sustained virologic suppression after treatment interruption of ledipasvir/sofosbuvir at 4 weeks in a patient with HIV/HCV co-infection. CASE REPORT A 28-year-old male patient diagnosed with well-controlled HIV infection and HCV co-infection (treatment-naïve, genotype 1a, unknown hepatic fibrosis) started a 12-week course of ledipasvir/sofosbuvir (LDV/SOF) for HCV treatment. The patient completed only 4 weeks of LDV/SOF before returning for follow-up 7 weeks after initiation. Ledipasvir/sofosbuvir treatment was discontinued. Sustained virologic suppression at 12 weeks was observed after completion of a short, 4-week course of LDV/SOF. CONCLUSIONS Compared to currently recommended treatment durations, clinical trials of short-course DAA treatments of less than 8 weeks have not demonstrated successful rates of SVR12. However, in cases of DAA interruption or incomplete treatment, clinicians may choose to assess for SVR12 prior to continuing or restarting the full treatment course.

Plasma and intracellular pharmacokinetics of tenofovir disoproxil fumarate and emtricitabine in transgender women receiving feminizing hormone therapy.

BACKGROUND: Transwomen have an increased risk of HIV acquisition compared with other adults. Drug-drug interactions between pre-exposure prophylaxis (PrEP) and gender-affirming therapy are cited as a reason for poor PrEP uptake among transwomen. We evaluated plasma tenofovir and emtricitabine pharmacokinetics and their active intracellular anabolites, tenofovir-diphosphate and emtricitabine-triphosphate, in transwomen receiving feminizing hormones. METHODS: We enrolled HIV-negative transwomen (≥19 years) not receiving PrEP. Participants took oral tenofovir disoproxil fumarate/emtricitabine 300/200 mg daily for 14 days. Plasma was collected at 0 h (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 12 h on day 14 post-tenofovir disoproxil fumarate/emtricitabine dose. The plasma AUC0-24 was calculated using the trapezoidal rule and compared with historical HIV-negative cisgender adults as geometric mean ratios (GMRs, 90% CI). Secondarily, tenofovir-diphosphate and emtricitabine-triphosphate from PBMCs collected at 0 h and 12 h were reported descriptively as geometric means (90% CI). Clinical trials registration: NCT03270969. RESULTS: Among 15 transwomen (mean age 32 years), geometric mean tenofovir and emtricitabine plasma AUC0-24 were lower compared with controls: tenofovir, 2.10 versus 2.76 mg·h/L, GMR 0.76 (0.65-0.90), P = 0.01; emtricitabine, 9.15 versus 10.64 mg·h/L, GMR 0.86 (0.75-0.98), P = 0.07. Tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in the literature: 167.1 (146.6-190.5) fmol/106 cells and 15.4 (13.8-17.3) pmol/106 cells, respectively. CONCLUSIONS: We observed lower plasma tenofovir and emtricitabine concentrations in transwomen compared with historical cisgender adults, yet intracellular tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in PBMCs. Understanding the differences of PrEP pharmacokinetics in plasma and tissue compartments and the resultant impact on efficacy remains important for transwomen.

Clinical Pharmacokinetics and Pharmacodynamics of Etravirine: An Updated Review.

Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of human immunodeficiency virus type 1 infection. It is a potent inhibitor of HIV reverse transcriptase and retains activity against wild-type and most NNRTI-resistant HIV. The pharmacokinetic profile of etravirine and clinical data support twice-daily dosing, although once-daily dosing has been investigated in treatment-naïve and treatment-experienced persons. Despite similar pharmacokinetic and pharmacodynamic results compared with twice-daily dosing, larger studies are needed to fully support once-daily etravirine dosing in treatment-naïve individuals. Etravirine is reserved for use in third- or fourth-line antiretroviral treatment regimens, as recommended, for example, in treatment guidelines by the US Department of Health and Human Services-Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Etravirine exhibits the potential for bi-directional drug-drug interactions with other antiretrovirals and concomitant medications through its interactions with cytochrome P450 (CYP) isozymes: CYP3A4, CYP2C9, and CYP2C19. This review summarizes the pharmacokinetic and pharmacodynamic parameters of etravirine, with particular attention to information on drug-drug interactions and use in special patient populations, including children/adolescents, women, persons with organ dysfunction, and during pregnancy.

Acceptability and feasibility of a pharmacist-led HIV pre-exposure prophylaxis (PrEP) program in the Midwestern United States.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) substantially reduces the risk of HIV acquisition, yet significant barriers exist to its prescription and use. Incorporating pharmacists in the PrEP care process may help increase access to PrEP services. METHODS: Our pharmacist-led PrEP program (P-PrEP) included pharmacists from a university-based HIV clinic, a community pharmacy, and two community-based clinics. Through a collaborative practice agreement, pharmacists conducted PrEP visits with potential candidates for PrEP, according to the recommended CDC guidelines, and authorized emtricitabine-tenofovir disoproxil fumarate prescriptions. Demographics and retention in care over 12 months were summarized and participant satisfaction and pharmacist acceptability with the P-PrEP program were assessed by Likert-scale questionnaires. RESULTS: Sixty patients enrolled in the P-PrEP program between January and June 2017 completing 139 visits. The mean age was 34 years (range 20-61 years) and 88% identified as men who have sex with men, 91.7% were men, 83.3% were white, 80% were commercially insured, and 89.8% had completed some college education or higher. Participant retention at 3, 6, 9, and 12 months was 73%, 58%, 43%, and 28%, respectively. To date, no participant has seroconverted. One hundred percent of the participants who completed the patient satisfaction questionnaire would recommend the P-PrEP program. Pharmacists reported feeling comfortable performing point-of-care testing and rarely reported feeling uncomfortable during PrEP visits (3 occasions - 2.2%) or experiencing workflow disruption (1 occasion - 0.7%). CONCLUSIONS: Implementation of a pharmacist-led PrEP program is feasible and associated with high rates of patient satisfaction and pharmacist acceptability.

Midwest pharmacists' familiarity, experience, and willingness to provide pre-exposure prophylaxis (PrEP) for HIV.

INTRODUCTION: Pharmacist provision of pre-exposure prophylaxis (PrEP) through collaborative practice agreements with physicians could expand access to people at risk for HIV. We characterized pharmacists' familiarity with and willingness to provide PrEP services in Nebraska and Iowa. METHODS: An invitation to complete an 18-question survey was emailed to 1,140 pharmacists in Nebraska and Iowa in June and July of 2016. Descriptive analyses and Pearson chi-square tests were used to determine to what extent demographics, familiarity and experience were associated with respondent willingness to provide PrEP. Wilcoxon rank-sum tests compared ages and years of experience between groups of respondents. RESULTS: One hundred forty pharmacists (12.3%) responded. Less than half were familiar with the use of PrEP (42%) or the CDC guidelines for its use (25%). Respondents who were older (p = .015) and in practice longer (p = .005) were less likely to be familiar with PrEP. Overall, 54% indicated they were fairly or very likely to provide PrEP services as part of a collaborative practice agreement and after additional training. While familiarity with PrEP use or guidelines did not affect respondents' willingness to provide PrEP, respondents were more likely to provide PrEP with prior experience counseling HIV-infected patients on antiretroviral therapy (OR 2.43; p = 0.023) or PrEP (OR 4.67; p = 0.013), and with prior HIV-related continuing education (OR 2.77; p = 0.032). CONCLUSIONS: Pharmacist respondents in Nebraska and Iowa had limited familiarity and experience with PrEP, but most indicated willingness to provide PrEP through collaborative practice agreements after additional training. Provision of PrEP-focused continuing education may lead to increased willingness to participate in PrEP programs.

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's 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's (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.