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BackgroundPeople 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.MethodsViremic (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 ResultsForty-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 ConclusionsB/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).

OBJECTIVES: To determine if double-dose levonorgestrel emergency contraception (EC) in combination with efavirenz or rifampicin, two drugs known to decrease levonorgestrel exposure, resulted in similar pharmacokinetics compared to standard-dose levonorgestrel EC without drug-drug interactions. STUDY DESIGN: We conducted a phase 2, open-label, multicenter, partially randomized, four parallel group trial in pre-menopausal females ≥16 years old without an indication for EC and not on hormonal contraception. Participants on dolutegravir-based antiretroviral therapy (ART) received levonorgestrel 1.5mg (control group); those on rifampicin-containing tuberculosis therapy received levonorgestrel 3mg; those on efavirenz-based ART were randomized 1:2 to levonorgestrel 1.5mg or 3mg. Plasma was collected through 48h post-dose to assess levonorgestrel pharmacokinetics. Area under the concentration-time curve (AUC) over 8 hours was the primary outcome. Levonorgestrel pharmacokinetic parameters were compared between groups using geometric mean ratios (GMR) with 90% confidence intervals. RESULTS: The median (Q1, Q3) age for all participants (n=118) was 34 (27, 41) years and BMI was 23.2 (20, 26.3) kg/m(2). Participants receiving levonorgestrel 1.5mg plus efavirenz (n=17) had 50% lower AUC(0–8h) compared to the control group (n=32) [0.50 (0.40, 0.62)]. Participants receiving levonorgestrel 3mg had a similar AUC(0–8h) when receiving either efavirenz (n=35) [0.99 (0.81, 1.20)] or rifampicin (n=34) [1.16 (0.99, 1.36)] compared to control. Levonorgestrel 3mg resulted in similar or higher maximum concentration with either efavirenz [1.17 (0.96, 1.41)] or rifampicin [1.27 (1.09, 1.49)] compared to the control group. CONCLUSIONS: Doubling the dose of levonorgestrel EC successfully increased levonorgestrel exposure over the first 8 hours in participants receiving either efavirenz-based ART or rifampicin-containing tuberculosis therapy.

The Brief Rifapentine–Isoniazid Efficacy for TB Prevention/A5279 trial demonstrated a 1-month daily regimen of rifapentine and isoniazid was noninferior to 9 months of isoniazid alone for preventing TB in persons living with HIV (PLWH). Our objective was to evaluate rifapentine pharmacokinetics in trial participants receiving antiretroviral therapy (ART) and perform simulations to compare weight-based rifapentine dosing with a standard, fixed dose. Nonlinear mixed effect modeling was used to estimate rifapentine and 25-desacetyl rifapentine population pharmacokinetic characteristics. The pharmacokinetic model was validated using a nonparametric bootstrap and visual predictive checks. Monte Carlo simulations were performed to compare weight-based and fixed dose regimens. Rifapentine and 25-desacetyl rifapentine concentrations (347 of each; 185 participants) were each described with a one-compartment model with one-way conversion between rifapentine and 25-desacetyl rifapentine. The absorption rate was nearly doubled in fed versus fasting states. Rifapentine clearance was increased 31% in those receiving efavirenz (EFV)-based versus nevirapine-based ART. Metabolite clearance was allometrically scaled with fat-free mass. Simulations showed lower rifapentine exposures with weight-based compared with fixed dosing. With 10 mg/kg weight-based regimens, 26% and 62% of simulated exposures in

Background A 4-month regimen containing rifapentine and moxifloxacin has noninferior efficacy compared to the standard 6-month regimen for drug-sensitive tuberculosis. We evaluated the effect of regimens containing daily, high-dose rifapentine on efavirenz pharmacokinetics and viral suppression in patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB). Methods In the context of a Phase 3 randomized controlled trial, HIV-positive individuals already virally suppressed on efavirenz--containing antiretroviral therapy (ART) (EFV1), or newly initiating efavirenz (EFV2) received TB treatment containing rifapentine (1200 mg), isoniazid, pyrazinamide, and either ethambutol or moxifloxacin. Mid-interval efavirenz concentrations were measured (a) during ART and TB cotreatment (Weeks 4, 8, 12, and 17, different by EFV group) and (b) when ART was taken alone (pre- or post-TB treatment, Weeks 0 and 22). Apparent oral clearance (CL/F) was estimated and compared. Target mid-interval efavirenz concentrations were > 1 mg/L. Co-treatment was considered acceptable if > 80% of participants had mid-interval efavirenz concentrations meeting this target. Results EFV1 and EFV2 included 70 and 41 evaluable participants, respectively. The geometric mean ratio comparing efavirenz CL/F with vs without TB drugs was 0.79 (90% confidence interval [CI] .72–.85) in EFV1 and 0.84 [90% CI .69–.97] in EFV2. The percent of participants with mid-interval efavirenz concentrations > 1mg/L in EFV1 at Weeks 0, 4, 8, and 17 was 96%, 96%, 88%, and 89%, respectively. In EFV2, at approximately 4 and 8 weeks post efavirenz initiation, the value was 98%. Conclusions TB treatment containing high-dose daily rifapentine modestly decreased (rather than increased) efavirenz clearance and therapeutic targets were met supporting the use of efavirenz with these regimens, without dose adjustment. Clinical Trials Registration NCT 02410772.

Background Multiple tissue reservoirs are established soon after HIV infection, and some tissues may also be pharmacological sanctuaries. Parenteral administration of antiretroviral (ARV) drugs for treatment and prevention of HIV infection is an active area of drug development. The influence of route of administration on ARV tissue pharmacokinetics is not known. Objectives To investigate ARV pharmacokinetics in lymphatic and select non-lymphatic tissues (e.g. brain and testes) after intramuscular and subcutaneous administration compared with oral in BALB/c mice. Methods Tissue concentrations of cobicistat, efavirenz, elvitegravir, maraviroc, rilpivirine, tenofovir alafenamide and tenofovir disoproxil fumarate were determined. The tissue penetration ratio (TPR) was the primary measure for comparison; a change in TPR arises from factors affecting tissue distribution controlling for changes in systemic bioavailability. Results Intramuscular and subcutaneous delivery increased TPRs in the lymph node and spleen for 27 of 28 (96%) drug administration events. Decreased TPRs, however, were found in some tissues such as the brain and testes. Conclusions These results demonstrate a change in route of drug administration from oral to intramuscular or subcutaneous can change tissue uptake. This has implications for HIV pharmacotherapy. For example, HIV persists in lymphoid tissues despite long-term oral ARV therapy, and low ARV concentrations have been found in lymphoid tissues. The improved ARV lymphatic tissue bioavailability with intramuscular and subcutaneous administration allows future studies to investigate these routes of drug administration as a therapeutic manoeuvre to limit viral persistence and eliminate viral sanctuaries in the lymphatic tissues, which is a prerequisite for eradication of HIV.

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.

Occasional zoonotic viral attacks on immunologically naive populations result in massive death tolls that are capable of threatening human survival. Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent that causes coronavirus disease (COVID-19), has spread from its epicenter in Wuhan China to all parts of the globe. Real-time mapping of new infections across the globe has revealed that variable transmission patterns and pathogenicity are associated with differences in SARS-CoV-2 lineages, clades, and strains. Thus, we reviewed how changes in the SARS-CoV-2 genome and its structural architecture affect viral replication, immune evasion, and transmission within different human populations. We also looked at which immune dominant regions of SARS-CoV-2 and other coronaviruses are recognized by Major Histocompatibility Complex (MHC)/Human Leukocyte Antigens (HLA) genes and how this could impact on subsequent disease pathogenesis. Efforts were also placed on understanding immunological changes that occur when exposed individuals either remain asymptomatic or fail to control the virus and later develop systemic complications. Published autopsy studies that reveal alterations in the lung immune microenvironment, morphological, and pathological changes are also explored within the context of the review. Understanding the true correlates of protection and determining how constant virus evolution impacts on host-pathogen interactions could help identify which populations are at high risk and later inform future vaccine and therapeutic interventions.

OBJECTIVE: The effect of rifapentine plus isoniazid on efavirenz pharmacokinetics was characterized in AIDS Clinical Trials Group protocol A5279 (NCT01404312). The present analyses characterize pharmacogenetic interactions between these drugs, and with nevirapine. METHODS: A subset of HIV-positive individuals receiving efavirenz- or nevirapine-containing antiretroviral therapy in A5279 underwent pharmacokinetic evaluations at baseline, and again weeks 2 and 4 after initiating daily rifapentine plus isoniazid. Associations with polymorphisms relevant to efavirenz, nevirapine, isoniazid and rifapentine pharmacokinetics were assessed. RESULTS: Of 128 participants, 101 were evaluable for associations with rifapentine and its active 25-desacetyl metabolite, 87 with efavirenz, and 38 with nevirapine. In multivariable analyses, NAT2 slow acetylators had greater week 4 plasma concentrations of rifapentine (p = 2.6 × 10(−3)) and 25-desacetyl rifapentine (p = 7.0 × 10(−5)) among all participants, and in efavirenz and nevirapine subgroups. NAT2 slow acetylators also had greater plasma efavirenz and nevirapine concentration increases from baseline to week 4, and greater decreases from baseline in clearance. CYP2B6 poor metabolizers had greater efavirenz concentrations at all weeks, and greater nevirapine concentrations at baseline. None of 47 additional polymorphisms in 11 genes were significantly associated with pharmacokinetics. CONCLUSIONS: Among HIV-positive individuals receiving efavirenz or nevirapine, and who then initiated rifapentine plus isoniazid in A5279, NAT2 slow acetylators had greater rifapentine and 25-desacetyl rifapentine concentrations, and greater increases from baseline in plasma efavirenz and nevirapine concentrations. These associations are likely mediated by greater isoniazid exposure in NAT2 slow acetylators.

The secondary lymphoid tissues (LT), lymph nodes (LN) and gut-associated lymphoid tissue are the primary sites of HIV replication and where the latent pool of virus is maintained. We compared the pharmacokinetics of tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in LT of 13 HIV-infected persons receiving a TDF-containing antiretroviral regimen who subsequently switched to a TAF-containing regimen. Study participants were on stable antiretroviral therapy for ≥12 months with plasma HIV-RNA < 48 copies/mL for 6 months before enrollment and entry CD4 cell counts > 300 cells/μL. Intracellular concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) were quantified in PBMCs and in mononuclear cells obtained from LN, ileum and rectal tissues. With TAF, the TFV-DP concentrations in PBMCs and LN were 7.3-fold and 6.4-fold higher (ratios of geometric means of TAF to TDF), respectively, compared with TDF; ileal and rectal concentrations, however, were lower with geometric mean ratios of 0.14 and 0.18, respectively. A statistically significant relationship was observed between PBMC and LN concentrations of TFV-DP. During TDF-containing therapy, the expected effect of cobicistat to increase TFV plasma concentrations was observed, as were higher TFV-DP concentrations in PBMCs and mononuclear cells from LN, ileum and rectal tissues. The higher TFV-DP concentrations achieved with TAF in the LN provides the first human correlate of the observation in animals that TAF produced higher tenofovir LN concentrations. The ability to increase LN concentrations allows investigations of whether antiretroviral regimens with improved LN pharmacokinetics elicit a more complete virologic response in that compartment.

BACKGROUND: Tuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 noninferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had noninferior efficacy and was safe for the treatment of drug-susceptible pulmonary TB (DS-PTB) compared with the standard 6-month regimen. We explored results among the prespecified subgroup of people with human immunodeficiency virus (HIV) (PWH). METHODS: PWH and CD4+ counts ≥100 cells/μL were eligible if they were receiving or about to initiate efavirenz-based antiretroviral therapy (ART). Primary endpoints of TB disease-free survival 12 months after randomization (efficacy) and ≥ grade 3 adverse events (AEs) on treatment (safety) were compared, using a 6.6% noninferiority margin for efficacy. Randomization was stratified by site, pulmonary cavitation, and HIV status. PWH were enrolled in a staged fashion to support cautious evaluation of drug–drug interactions between rifapentine and efavirenz. RESULTS: A total of 2516 participants from 13 countries in sub-Saharan Africa, Asia, and the Americas were enrolled. Among 194 (8%) microbiologically eligible PWH, the median CD4+ count was 344 cells/μL (interquartile range: 223–455). The rifapentine-moxifloxacin regimen was noninferior to control (absolute difference in unfavorable outcomes −7.4%; 95% confidence interval [CI] −20.8% to 6.0%); the rifapentine regimen was not noninferior to control (+7.5% [95% CI, −7.3% to +22.4%]). Fewer AEs were reported in rifapentine-based regimens (15%) than the control regimen (21%). CONCLUSIONS: In people with HIV-associated DS-PTB with CD4+ counts ≥100 cells/μL on efavirenz-based ART, the 4-month daily rifapentine-moxifloxacin regimen was noninferior to the 6-month control regimen and was safe. CLINICAL TRIALS REGISTRATION: NCT02410772.

Introduction: Women account for 23% of new human immunodeficiency virus diagnoses in the United States, yet remain understudied. Adherence to antiretroviral therapy and consequent viral suppression are keys to preventing human immunodeficiency virus transmission, reducing risk of drug resistance, and improving health outcomes. Objectives: This review identified and synthesized peer-reviewed studies in the United States describing factors associated with viral suppression among cisgender women living with human immunodeficiency virus. Methods: We searched five databases: Cumulative Index to Nursing and Allied Health (CINAHL), PubMed, Embase, Scopus, and PsycINFO, and reported the findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Eligible studies included: (1) peer-reviewed English-language articles published since 2010; (2) includes only cisgender women; (3) participants were at least 18 years of age; (4) reported metrics on viral loads; and (5) conducted in the United States. Results: Fourteen studies in total were reviewed. Eight studies had adult women living with human immunodeficiency virus, four recruited only pregnant women, and two included only racial minority women. The most commonly reported factors negatively associated with viral suppression were substance use ( n = 4), followed by availability of health insurance, financial constraint, complexity of human immunodeficiency virus treatment regimen ( n = 3), and intimate partner violence ( n = 2). Other factors were depression, race, and age. In addition, all four studies that included only pregnant women reported early human immunodeficiency virus care engagement as a significant predictor of low viral loads pre- and post-partum. Conclusion: Substance use, financial constraint, lack of health insurance, human immunodeficiency virus treatment regimen type, intimate partner violence, and late human immunodeficiency virus care pre–post pregnancy were the most common factors negatively associated with viral suppression. There is a paucity of data on viral suppression factors related to transgender and rural populations. More human immunodeficiency virus research is needed to explore factors associated with human immunodeficiency virus treatment outcomes in transgender women and cisgender women in rural U.S. regions.

Angiotensin Converting Enzyme 2 (ACE-2), Transmembrane Serine Protease 2 (TMPRSS-2) and Neuropilin-1 cellular receptors support the entry of SARS-CoV-2 into susceptible human target cells and are characterized at the molecular level. Some evidence on the expression of entry receptors at mRNA and protein levels in brain cells is available, but co-expression of these receptors and confirmatory evidence on brain cells is lacking. SARS-CoV-2 infects some brain cell types, but infection susceptibility, multiple entry receptor density, and infection kinetics are rarely reported in specific brain cell types. Highly sensitive Taqman ddPCR, flow-cytometry and immunocytochemistry assays were used to quantitate the expression of ACE-2, TMPRSS-2 and Neuropilin-1 at mRNA and protein levels on human brain-extracted pericytes and astrocytes, which are an integral part of the Blood-Brain-Barrier (BBB). Astrocytes showed moderate ACE-2 (15.9 ± 1.3%, Mean ± SD, n = 2) and TMPRSS-2 (17.6%) positive cells, and in contrast show high Neuropilin-1 (56.4 ± 39.8%, n = 4) protein expression. Whereas pericytes showed variable ACE-2 (23.1 ± 20.7%, n = 2), Neuropilin-1 (30.3 ± 7.5%, n = 4) protein expression and higher TMPRSS-2 mRNA (667.2 ± 232.3, n = 3) expression. Co-expression of multiple entry receptors on astrocytes and pericytes allows entry of SARS-CoV-2 and progression of infection. Astrocytes showed roughly four-fold more virus in culture supernatants than pericytes. SARS-CoV-2 cellular entry receptor expression and “in vitro” viral kinetics in astrocytes and pericytes may improve our understanding of viral infection “in vivo”. In addition, this study may facilitate the development of novel strategies to counter the effects of SARS-CoV-2 and inhibit viral infection in brain tissues to prevent the spread and interference in neuronal functions.

RNA interference (RNAi) molecules have tremendous potential for cancer therapy but are limited by insufficient potency after intravenous (IV) administration. We previously found that polymer complexes (polyplexes) formed between 3′-cholesterol-modified siRNA (Chol-siRNA) or DsiRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase RNAi potency against stably expressed LUC mRNA in primary syngeneic murine breast tumors after daily IV dosing. Chol-DsiRNA polyplexes, however, maintain LUC mRNA suppression for ~48 h longer after the final dose than Chol-siRNA polyplexes, which suggests that they are the better candidate formulation. Here, we directly compared the activities of Chol-siRNA polyplexes and Chol-DsiRNA polyplexes in primary murine 4T1 breast tumors against STAT3, a therapeutically relevant target gene that is overexpressed in many solid tumors, including breast cancer. We found that Chol-siSTAT3 polyplexes suppressed STAT3 mRNA in 4T1 tumors with similar potency (half-maximal ED50 0.3 mg/kg) and kinetics (over 96 h) as Chol-DsiSTAT3 polyplexes, but with slightly lower activity against total Stat3 protein (29% vs. 42% suppression) and tumor growth (11.5% vs. 8.6% rate-based T/C ratio) after repeated IV administration of equimolar, tumor-saturating doses every other day. Thus, both Chol-siRNA polyplexes and Chol-DsiRNA polyplexes may be suitable clinical candidates for the RNAi therapy of breast cancer and other solid tumors.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) is the causative agent of Corona Virus Disease 2019 (COVID-19). Lower production of type I and III interferons and higher levels of inflammatory mediators upon SARS-CoV2 infection contribute to COVID-19 pathogenesis. Optimal interferon production and controlled inflammation are essential to limit COVID-19 pathogenesis. However, the aggravated inflammatory response observed in COVID-19 patients causes severe damage to the host and frequently advances to acute respiratory distress syndrome (ARDS). Toll-like receptor 7 and 8 (TLR7/8) signaling pathways play a central role in regulating induction of interferons (IFNs) and inflammatory mediators in dendritic cells. Controlled inflammation is possible through regulation of TLR mediated response without influencing interferon production to reduce COVID-19 pathogenesis. This review focuses on inflammatory mediators that contribute to pathogenic effects and the role of TLR pathways in the induction of interferon and inflammatory mediators and their contribution to COVID-19 pathogenesis. We conclude that potential TLR7/8 agonists inducing antiviral interferon response and controlling inflammation are important therapeutic options to effectively eliminate SARS-CoV2 induced pathogenesis. Ongoing and future studies may provide additional evidence on their safety and efficacy to treat COVID-19 pathogenesis., Graphical Abstract Hyper regulation of TLR7/8 pathways during SARS-CoV2 infection increases production of inflammatory mediators but display lower IFN production but potent agonists can induce IFNs and thereby limit SARS-CoV2 replication.ga1

INTRODUCTION: Antiretroviral therapy (ART) is recommended for all people who are living with HIV to suppress viral load and to stop the progression and transmission of HIV-1. Fixed-dose combinations of antiretrovirals largely reduce pill burden. AREAS COVERED: The authors first provide an overview of the use of non-nucleoside reverse transcriptase inhibitor (NNRTI) based therapy in HIV care. They then summarize the properties of each drug in the fixed-dose combination of tenofovir alafenamide /emtricitabine/rilpivirine/ (TAF/FTC/RPV). The efficacy and safety of each component and the combination as a whole are reviewed: FTC is non-inferior to lamivudine (3TC) at assessed dosages; TAF was non-inferior to tenofovir disoproxil fumarate (TDF); the viral efficacy of RPV is non-inferior with EFV at the assessed dosage; TAF/FTC/RPV is non-inferior in efficacy but shows less of a decline in bone mineral density and renal function compared to TDF/FTC/RPV. Finally, adverse effects and drug-drug interaction data with FTC/RPV/TAF are discussed. EXPERT OPINION: TAF/FTC/RPV can be used as an initial regimen for people living with HIV whose HIV RNA 200 cells/mm(3) when INSTI-based regimens are not a treatment option. Future antiretroviral therapy development may focus on dual therapy-based regimens containing RPV, particularly as long-acting formulations.

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.

An international HIV pharmacology specialty laboratory (PSL) was established at the University of Zimbabwe to increase bioanalytical and investigator capacities. Quantitation of plasma nevirapine in samples from the AIDS Clinical Trials Group protocol 5279 was compared between the University of Nebraska Medical Center PSL and the University of Zimbabwe PSL. Both PSLs employed internally developed methods utilising reverse-phase high-performance liquid chromatography with ultraviolet detection. Eighty-seven percent of the cross-validation results exhibited ± 20% difference.

The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight for the coronavirus disease 19 (COVID-19) pandemic. Most SARS-CoV-2 exposed individuals experience mild to moderate symptoms, including fever, cough, fatigue, and loss of smell and taste. However, many individuals develop pneumonia, acute respiratory distress syndrome, septic shock, and multiorgan dysfunction. In addition to these primarily respiratory symptoms, SARS-CoV-2 can also infiltrate the central nervous system, which may damage the blood-brain barrier and the neuron's synapses. Resultant inflammation and neurodegeneration in the brain stem can further prevent efferent signaling to cranial nerves, leading to the loss of anti-inflammatory signaling and normal respiratory and gastrointestinal functions. Additionally, SARS-CoV-2 can infect enterocytes resulting in gut damage followed by microbial dysbiosis and translocation of bacteria and their byproducts across the damaged epithelial barrier. As a result, this exacerbates pro-inflammatory responses both locally and systemically, resulting in impaired clinical outcomes. Recent evidence has highlighted the complex interactions that mutually modulate respiratory, neurological, and gastrointestinal function. In this review, we discuss the ways SARS-CoV-2 potentially disrupts the gut-brain-lung axis. We further highlight targeting specific responses to SARS-CoV-2 for the development of novel, urgently needed therapeutic interventions. Finally, we propose a prospective related to the individuals from Low- and Middle-Income countries. Here, the underlying propensity for heightened gut damage/microbial translocation is likely to result in worse clinical outcomes during this COVID-19 pandemic.

Background Protease inhibitor-based antiretroviral therapy may be used in resource-limited settings in persons with human immunodeficiency virus and tuberculosis (HIV-TB). Data on safety, pharmacokinetics/pharmacodynamics (PK/PD), and HIV-TB outcomes for lopinavir/ritonavir (LPV/r) used with rifampin (RIF) or rifabutin (RBT) are limited. Methods We randomized adults with HIV-TB from July 2013 to February 2016 to arm A, LPV/r 400 mg/100 mg twice daily + RBT 150 mg/day; arm B, LPV/r 800 mg/200 mg twice daily + RIF 600 mg/day; or arm C, LPV/r 400 mg/100 mg twice daily + raltegravir (RAL) 400 mg twice daily + RBT 150 mg/day. All received two nucleoside reverse transcriptase inhibitors and other TB drugs. PK visits occurred on day 12 ± 2. Within-arm HIV-TB outcomes were summarized using proportions and 95% CIs; PK were compared using Wilcoxon tests. Results Among 71 participants, 52% were women; 72% Black; 46% Hispanic; median age, 37 years; median CD4+ count, 130 cells/mm3; median HIV-1 RNA, 4.6 log10 copies/mL; 46% had confirmed TB. LPV concentrations were similar across arms. Pooled LPV AUC12 (157 203 hours × ng/mL) and Ctrough (9876 ng/mL) were similar to historical controls; RBT AUC24 (7374 hours × ng/mL) and Ctrough (208 ng/mL) were higher, although 3 participants in arm C had RBT Cmax Conclusions Double-dose LPV/r+RIF and LPV/r+RBT 150mg/day had acceptable safety, PK and TB outcomes; HIV suppression was suboptimal but unrelated to PK. Faster RBT clearance and low Cmax in 3 participants on RBT+RAL requires further study.

Rationale: Rifapentine has been investigated at various doses, frequencies, and dosing algorithms, but clarity on the optimal dosing approach is lacking. Objectives: To characterize rifapentine population pharmacokinetics, including autoinduction, and determine optimal dosing strategies for short-course rifapentine-based regimens for latent tuberculosis infection. Methods: Rifapentine pharmacokinetic studies were identified though a systematic review of literature. Individual plasma concentrations were pooled, and nonlinear mixed-effects modeling was performed. A subset of data was reserved for external validation. Simulations were performed under various dosing conditions, including current weight-based methods; and alternative methods driven by identified covariates. Measurements and Main Results: We identified nine clinical studies with a total of 863 participants with pharmacokinetic data (n = 4,301 plasma samples). Rifapentine population pharmacokinetics were described successfully with a one-compartment distribution model. Autoinduction of clearance was driven by rifapentine plasma concentrations. The maximum effect was a 72% increase in clearance and was reached after 21 days. Drug bioavailability decreased by 27% with HIV infection, decreased by 28% with fasting, and increased by 49% with a high-fat meal. Body weight was not a clinically relevant predictor of clearance. Pharmacokinetic simulations showed that current weight-based dosing leads to lower exposures in individuals with low weight, which can be overcome with flat dosing. In HIV-positive patients, 30% higher doses are required to match drug exposure in HIV-negative patients. Conclusions: Weight-based dosing of rifapentine should be removed from clinical guidelines, and higher doses for HIV-positive patients should be considered to provide equivalent efficacy.

Bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir are members of the latest class of antiretrovirals available to treat human immunodeficiency virus (HIV) infection, the integrase strand transfer inhibitors. Integrase strand transfer inhibitors 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 antiretrovirals. Each of the integrase strand transfer inhibitors have unique pharmacokinetic/pharmacodynamic properties, influencing their role in clinical use in specific subsets of patients. Cabotegravir, approved for use in Canada but not yet by the US Food and Drug Administration, is formulated in both oral and intramuscular formulations; the latter of which has shown efficacy as a long-acting extended-release formulation. Cabotegravir, raltegravir, and dolutegravir have minimal drug-drug interaction profiles, as their metabolism has minimal cytochrome P450 involvement. Conversely, elvitegravir metabolism occurs primarily via cytochrome P450 3A4 and requires pharmacokinetic boosting to achieve systemic exposures amenable to once-daily dosing. Bictegravir metabolism has similar contributions from both cytochrome P450 3A4 and uridine 5'-diphospho-glucuronosyltransferase 1A1. Bictegravir, dolutegravir, and raltegravir are recommended components of initial regimens for most people with HIV in the US adult and adolescent HIV treatment guidelines. This review summarizes and compares the pharmacokinetics and pharmacodynamics of the integrase strand transfer inhibitor agents, and describes specific pharmacokinetic considerations for persons with hepatic impairment, renal dysfunction, pregnancy, and co-infections.

Dyskinesia induced by long-term L-Dopa (LID) therapy in Parkinson disease is associated with altered striatal function whose molecular bases remain unclear. Here, a transcriptomic approach was applied for comprehensive analysis of distinctively regulated genes in striatal tissue, their specific pathways, and functional- and disease-associated networks in a rodent model of LID. This approach has identified transforming growth factor beta type 1 (TGFβ1) as a highly upregulated gene in dyskinetic animals. TGFβ1 pathway is a top aberrantly regulated pathway in the striatum following LID development based on differentially expressed genes (> 1.5 fold change and P < 0.05). The induction of TGFβ1 pathway specific genes, TGFβ1, INHBA, AMHR2 and PMEPA1 was also associated with regulation of NPTX2, PDP1, SCG2, SYNPR, TAC1, TH, TNNT1 genes. Transcriptional network and upstream regulator analyses have identified AKT-centered functional and ERK-centered disease networks revealing the association of TGFβ1, IL-1β and TNFα with LID development. Therefore, results support that TGFβ1 pathway is a major contributor to the pathogenic mechanisms of LID.

Setting Anti-tuberculosis formulations necessitate uninterrupted treatment to cure tuberculosis (TB), but are characterised by suboptimal adherence, which jeopardises therapeutic efficacy. Long-acting injectable (LAI) formulations or implants could address these associated issues. Objective niazid, rifapentine, bedaquiline and delamanid-in adults for treatment for latent tuberculous infection (LTBI). Design PBPK models were developed and qualified against available clinical data by integrating drug physicochemical properties and in vitro and population pharmacokinetic data into a mechanistic description of drug distribution. Combinations of optimal dose and release rates were simulated such that plasma concentrations were maintained over the epidemiological cut-off or minimum inhibitory concentration for the dosing interval. Results The PBPK model identified 1500 mg of delamanid and 250 mg of rifapentine as sufficient doses for monthly intramuscular administration, if a formulation or device can deliver the required release kinetics of 0.001-0.0025 h-1 and 0.0015-0.0025 h-1, respectively. Bedaquiline and isoniazid would require weekly to biweekly intramuscular dosing. Conclusion We identified the theoretical doses and release rates of LAI anti-tuberculosis formulations. Such a strategy could ease the problem of suboptimal adherence provided the associated technological complexities for LTBI treatment are addressed.

Quantification of antiretroviral (ARV) drug concentrations in peripheral blood mononuclear cells (PBMCs) and tissue isolated mononuclear cells (TIMCs) from lymph node (LNMC) and rectum (RMC) is an important measure of bio-distribution. Normalization of drug concentrations is critical to represent tissue drug concentrations and to analyze both intra-individual and inter-individual variability in drug distribution. However, a molecular method to normalize intracellular drug concentrations in PBMCs and TIMCs methanol extracts is currently unavailable. In this study, a novel droplet digital PCR (ddPCR) assay was designed to amplify RPP30 gene sequence conserved in human and non-human primates (NHP). Genomic DNA (gDNA) isolated from 70 percent methanol embedded PBMCs and TIMCs was used as ddPCR template to quantitate precise RPP30 copies to derive cell counts. The novel molecular method quantitated RPP30 copies in human and rhesus macaque gDNA templates with greater accuracy and precision than qPCR. RPP30 ddPCR derived cell counts are strongly correlated with automated cytometer based cell counts in PBMC (R = 0.90, p = 0.001 and n = 20); LNMC (R = 0.85 p = 0.0001 and n = 22) and RMC (R = 0.92, p = 0.0001 and n = 20) and achieved comparable normalized drug concentrations. Therefore, the RPP30 ddPCR assay is an important normalization method in drug bio-distribution and pharmacokinetic studies in humans and NHPs.

Long-acting/extended-release drug formulations have proved very successful in diverse areas of medicine, including contraception, psychiatry and, most recently, human immunodeficiency virus (HIV) disease. Though challenging, application of this technology to anti-tuberculosis treatment could have substantial impact. The duration of treatment required for all forms of tuberculosis (TB) put existing regimens at risk of failure because of early discontinuations and treatment loss to follow-up. Long-acting injections, for example, administered every month, could improve patient adherence and treatment outcomes. We review the state of the science for potential long-acting formulations of existing tuberculosis drugs, and propose a target product profile for new formulations to treat latent tuberculous infection (LTBI). The physicochemical properties of some anti-tuberculosis drugs make them unsuitable for long-acting formulation, but there are promising candidates that have been identified through modeling and simulation, as well as other novel agents and formulations in preclinical testing. An efficacious long-acting treatment for LTBI, particularly for those co-infected with HIV, and if coupled with a biomarker to target those at highest risk for disease progression, would be an important tool to accelerate progress towards TB elimination.

Current strategies to treat tuberculosis (TB) and co-morbidities involve multidrug combination therapies. Rifamycin antibiotics are a key component of TB therapy and a common source of drug–drug interactions (DDIs) due to induction of drug metabolizing enzymes (DMEs). Management of rifamycin DDIs are complex, particularly in patients with co-morbidities, and differences in DDI potential between rifamycin antibiotics are not well established. DME profiles induced in response to tuberculosis antibiotics (rifampin, rifabutin and rifapentine) were compared in primary human hepatocytes. We identified rifamycin induced DMEs, cytochrome P450 (CYP) 2C8/3A4/3A5, SULT2A, and UGT1A4/1A5 and predicted lower DDIs of rifapentine with 58 clinical drugs used to treat co-morbidities in TB patients. Transcriptional networks and upstream regulator analyses showed FOXA3, HNF4α, NR1I2, NR1I3, NR3C1 and RXRα as key transcriptional regulators of rifamycin induced DMEs. Our study findings are an important resource to design effective medication regimens to treat common co-conditions in TB patients.

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.

Dolutegravir (DTG), elvitegravir (EVG) and raltegravir (RAL) are members of the latest class of antiretrovirals (ARVs) that have become available to treat human immunodeficiency virus (HIV) infection: integrase strand transfer inhibitors (INSTIs). INSTIs are potent inhibitors of the HIV integrase enzyme, with protein binding–adjusted concentration inhibiting viral replication by 90/95 % [IC90/95] values in the low nanogram per millilitre range, and they retain antiviral activity against strains of HIV with acquired resistance to other classes of ARVs. Each of the INSTIs has unique pharmacokinetic/pharmacodynamic properties, influencing its 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 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 in the current US perinatal treatment guidelines. All three INSTIs are recommended regimens for treatment-naive individuals in the US adult and adolescent HIV treatment guidelines. This review summarizes and compares the pharmacokinetics and pharmacodynamics of the INSTIs, and describes specific pharmacokinetic considerations for special patient conditions: hepatic impairment, renal dysfunction, pregnancy and co-infections.

Introduction Phase 2 clinical trials of tuberculosis treatment have shown that once-daily regimens in which rifampin is replaced by high dose rifapentine have potent antimicrobial activity that may be sufficient to shorten overall treatment duration. Herein we describe the design of an ongoing phase 3 clinical trial testing the hypothesis that once-daily regimens containing high dose rifapentine in combination with other anti-tuberculosis drugs administered for four months can achieve cure rates not worse than the conventional six-month treatment regimen. Methods/Design S31/A5349 is a multicenter randomized controlled phase 3 non-inferiority trial that compares two four-month regimens with the standard six-month regimen for treating drug-susceptible pulmonary tuberculosis in HIV-negative and HIV-positive patients. Both of the four-month regimens contain high-dose rifapentine instead of rifampin, with ethambutol replaced by moxifloxacin in one regimen. All drugs are administered seven days per week, and under direct observation at least five days per week. The primary outcome is tuberculosis disease-free survival at twelve months after study treatment assignment. A total of 2500 participants will be randomized; this gives 90% power to show non-inferiority with a 6.6% margin of non-inferiority. Discussion This phase 3 trial formally tests the hypothesis that augmentation of rifamycin exposures can shorten tuberculosis treatment to four months. Trial design and standardized implementation optimize the likelihood of obtaining valid results. Results of this trial may have important implications for clinical management of tuberculosis at both individual and programmatic levels. Trial registration: NCT02410772 . Registered 8 April 2015, https://www.clinicaltrials.gov/ct2/show/NCT02410772?term=02410772&rank=1

Background Allogeneic hematopoietic cell transplantation (allo-HCT) in a CCR5∆32 homozygous donor resulted in HIV cure. Understanding how allo-HCT impacts the HIV reservoir will inform cure strategies. Methods A 12-year-old with perinatally acquired, CCR5-tropic HIV and acute lymphoblastic leukemia underwent myeloablative conditioning and umbilical cord blood (UCB) transplantation from a CCR5∆32 homozygous donor. Peripheral blood mononuclear cells (PBMCs) and the rectum were sampled pre- and post-transplant. The brain, lung, lymph node (LN), stomach, duodenum, ileum, and colon were sampled 73 days after transplantation (day +73), when the patient died from graft-vs-host disease. Droplet digital polymerase chain reaction (ddPCR) and in situ hybridization (ISH) were used detect the HIV reservoir in tissues. CCR5 and CD3 expression in the LN was assessed using immunohistochemistry (IHC). Results HIV DNA (vDNA) was detected in PBMCs by ddPCR pretransplant but not post-transplant. vDNA was detected by ISH in the rectum at days –8 and +22, and in the LN, colon, lung, and brain day +73. vDNA was also detected in the lung by ddPCR. IHC revealed CCR5+CD3+ cells in the LN postmortem. Conclusions HIV was detected in multiple tissues 73 days after CCR5∆32 homozygous UCB allo-HCT despite myeloablative conditioning and complete donor marrow engraftment. These results highlight the importance of analyzing tissue during HIV cure interventions and inform the choice of assay used to detect HIV in tissue reservoirs.

Levonorgestrel (LNG) is a synthetic progestin that is available in oral contraceptive tablets, a subdermal implant, and an intrauterine system for contraception. LNG pharmacokinetics are a pivotal determinant of contraceptive efficacy and essential in assessing drug-drug interactions influencing LNG exposure following different routes of LNG administration. A highly sensitive LC-MS/MS method was developed and validated to quantify levonorgestrel in human plasma. Liquid-liquid extraction was utilized with a sample volume of 500 μL to extract levonorgestrel from plasma. Chromatographic separation of LNG was achieved with a Fortis™ C18 (3 μm: 100mm × 2.1mm) reverse phase analytical column. The mobile phases consisted of de-ionized water plus 0.1% NH(4)OH (100:0.1%, v/v) (A), and methanol plus 0.1% NH(4)OH (100:0.1%, v/v) (B) delivered as a gradient at a flow rate of 400 μL/min. Detection of LNG and internal standard (D-(-)-norgestrel-d7) was achieved using positive polarity mode monitoring at 313.2-245.2 amu and 320.1-251.2 amu, respectively. The assay was linear over the calibration range of 49.6 to 1500 pg/mL. This method was used to quantify plasma LNG released by subdermal implant in support of a drug interaction study among women with HIV receiving efavirenz- or nevirapine-based antiretroviral therapy.

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 (80%, 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. Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT 01404312","term_id":"NCT01404312"}}NCT 01404312.

Background. The approved tenofovir disoproxil fumarate (TDF) dose of 300 mg every 48 hours for adults with moderate renal impairment is often confusing and inconvenient. Using a new TDF formulation, we compared the pharmacokinetics of the standard dose with a dose of 150 mg once daily in HIV-infected adults. Methods. This was an open-label pharmacokinetic study. Virologically suppressed HIV-infected adults with a creatinine clearance 30 to

OBJECTIVES The aim of the study was to compare the intraindividual plasma and intracellular peripheral blood mononuclear cell (PBMC) pharmacokinetics of tenofovir (TFV) and its intracellular metabolite, TFV-diphosphate (TFV-DP) in patients switched from a fixed-dose combination (FDC) tablet of TFV disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir (EVG)/cobicistat (COBI) to a FDC containing TFV alafenamide (TAF)/FTC/EVG/COBI. DESIGN A single-arm, prospective, nonrandomized, cross-over, pharmacokinetic study in patients receiving a TDF-containing regimen (TDF 300 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg) switched to a TAF-containing FDC regimen (TAF 10 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg). METHODS Single, sparse plasma and PBMC samples were collected during TDF therapy and 4-8 weeks post-switch to the TAF-containing regimen. Plasma TFV and cell associated TFV-DP concentrations were determined with validated liquid chromatography tandem mass spectrometry methods. PBMC cell enumeration was performed by quantification of RNaseP (RPP30) gene copy numbers using a highly sensitive droplet digital PCR assay. Plasma and PBMC pharmacokinetics were summarized as geometric mean and compared as a geometric mean ratio with a Wilcoxon signed-rank test. RESULTS In 30 participants with evaluable data, TFV plasma concentrations decreased 90% [TDF: 99.98 (2.24) ng/ml vs. TAF: 10.2 (1.6) ng/ml, P

A novel assay using high pressure liquid chromatography (HPLC) coupled to mass spectrometer (MS) detection was developed and validated for the rifamycin anti-tuberculosis antibiotics rifampicin (RIF), rifabutin (RBT), rifapentine (RPT) and their active desacetyl metabolites (dRIF, dRBT and dRPT, respectively) in human plasma. The assay uses 50 μL of human plasma with a quick and simple protein-precipitation extraction to achieve a dynamic range of 75–30000 ng/mL for RIF, RBT and RPT and 37.5 to 15000 ng/mL for dRIF, dRBT and dRPT respectively. The average %CV and %deviation were less than 20% at the lower limit of quantitation and less than 15% over the range of the curve. The method was fully validated according to FDA criteria for bioanalytical assays and has successfully been used to support three large international tuberculosis trials.

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. Electronic supplementary material The online version of this article (10.1186/s12879-018-3226-2) contains supplementary material, which is available to authorized users.