Women receiving efavirenz-based antiretroviral therapy plus a contraceptive implant had significantly lower levonorgestrel pharmacokinetics than women not receiving antiretroviral therapy. An unexpected high pregnancy rate (3/20, 15%) occurred in the efavirenz group, highlighting the clinical significance of this interaction.

Background Human immunodeficiency virus (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 2 community-based clinics. Through a collaborative practice agreement, pharmacists conducted PrEP visits with potential candidates for PrEP, according to the recommended Centers for Disease Control and Prevention 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.

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Dolutegravir (DTG), elvitegravir (EVG) and raltegravir (RAL), are members of latest class of antiretrovirals (ARV) available to treat human immunodeficiency virus (HIV) infection, the integrase strand transfer inhibitors (INSTI). INSTIs are potent inhibitors of the HIV integrase enzyme with IC90/95 values in the low nanogram per milliliter range and they retain antiviral activity against strains of HIV with acquired resistance to other classes of ARVs. Each of the INSTIs have unique pharmacokinetic / pharmacodynamic properties, influencing their role in clinical use in specific subsets of patients. RAL and DTG have minimal drug-drug interaction profiles, as their metabolism has minimal cytochrome P450 (CYP) involvement. Conversely, EVG metabolism occurs primarily via CYP3A4 and requires pharmacokinetic boosting to achieve systemic exposures amenable to once daily dosing. EVG and DTG have the added benefit of the availability of fixed dose combination tablets, allowing for convenient and simplified ARV regimens. RAL is the only INSTI to be listed as a preferred agent on the current United States perinatal guidelines. All three of the INSTI agents are recommended regimens for treatment-naïve individuals on the United States Adult and Adolescent HIV treatment guidelines. This review summarizes and compares the pharmacokinetics and pharmacodynamics of the INSTI agents, and describes specific pharmacokinetic considerations for special patient conditions: hepatic impairment, renal dysfunction, pregnancy and co-infections.

Objective: We conducted a study of minocycline to assess its safety, tolerability, and efficacy for the treatment of HIV-associated cognitive impairment.Methods: HIV-1-infected individuals with progressive neurocognitive decline were enrolled in a double-blind, placebo-controlled study of minocycline. Participants were randomized to receive minocycline 100 mg or matching placebo orally every 12 hours. The primary efficacy measure was change in a neuropsychological test composite z score (NPZ-8) from baseline to week 24. Measures of safety included the frequency of adverse events and changes over time in laboratory tests. After 50% of participants completed the double-blind phase, an interim analysis of futility for the primary outcome measure was performed, and our Data and Safety Monitoring Board recommended early study termination.Results: A total of 107 HIV-1-infected individuals with cognitive impairment were enrolled. The minocycline group did not show improvement in the primary outcome measure (NPZ-8) (mean 24-week change ϭ 0.12) compared to placebo (mean 24-week change ϭ 0.17) (95% confidence interval ϭ [Ϫ0.26, 0.39], p ϭ 0.70). There were few severe adverse events or laboratory abnormalities in either treatment group.

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Intraindividually, plasma TFV concentrations significantly decreased while cell associated TFV-DP concentrations significantly increased after switching from a TDF to a TAF-containing antiretroviral therapy regimen.

The consequences of inactive empiric antimicrobial therapy are not well-described and may cause prolonged hospitalization or infection-related mortality. In vitro susceptibility results for 884 patients hospitalized at an academic medical center with gram-negative bloodstream infections (GNBI) from 2001 to 2003 were matched to antimicrobial orders within 24 h of culture. Clinical characteristics, organism, inpatient mortality, and length of stay after culture for patients with GNBI were compared between patients receiving active versus inactive empiric antimicrobial therapy. A total of 14.1% of patients with GNBI received inactive empiric therapy, defined as no antimicrobial therapy within 24 h of the culture active against the identified organism based on in vitro microbiology reports. Patients who received inactive therapy were more likely to be younger, to be infected with Pseudomonas aeruginosa, to have a nosocomial infection, and to receive antimicrobial monotherapy but less likely to be bacteremic with Escherichia coli or to have sepsis (P < 0.05). There were no significant differences in mortality between patients receiving active versus inactive empiric therapy (16.1% versus 13.6%, respectively) or in length of stay after positive culture (11.5 days versus 12.6 days, respectively). Only 45 patients had greater than 2 days of exposure to inactive therapy; however, 8/30 patients (26.7%) who never received active antimicrobial therapy died while in the hospital. Inactive empiric therapy was more common in healthier patients. Inactive antimicrobial therapy in the first 24 h did not significantly impact average outcomes for GNBI among hospitalized patients but may have caused harm to specific individuals.