scholarly journals Urine Tenofovir Concentrations Correlate With Plasma and Relate to Tenofovir Disoproxil Fumarate Adherence: A Randomized, Directly Observed Pharmacokinetic Trial (TARGET Study)

2019 ◽  
Vol 70 (10) ◽  
pp. 2143-2151 ◽  
Author(s):  
Paul K Drain ◽  
Rachel W Kubiak ◽  
Oraphan Siriprakaisil ◽  
Virat Klinbuayaem ◽  
Justice Quame-Amaglo ◽  
...  
Keyword(s):  
Steady State ◽  
Tenofovir Disoproxil Fumarate ◽  
Point Of Care ◽  
Objective Measure ◽  
Plasma Samples ◽  
Directly Observed Therapy ◽  
Spot Urine ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Urine Concentrations

Abstract Background Direct measurement of tenofovir (TFV) in urine could be an objective measure to monitor adherence to preexposure prophylaxis (PrEP) or TFV-based antiretroviral therapy (ART). Methods We conducted a 3-arm randomized, pharmacokinetic study of tenofovir disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg among adults living with human immunodeficiency virus. Participants were randomized to receive controlled TDF/FTC dosing as (1) “perfect” adherence (daily); (2) “moderate” adherence (4 doses/week); or (3) “low” adherence (2 doses/week). We obtained trough spot urine and plasma samples during a 6-week directly observed therapy period and a 4-week washout period. TFV concentrations were compared between adherence arms using 1-way analysis of variance. Results Among 28 participants, the median age was 33 years and 16 (57%) were male. Correlation between TFV plasma and urine concentrations was strong (ρ = 0.78; P < .0001). Median (interquartile range) steady-state trough TFV concentrations (ng/mL) for perfect, moderate, and low TDF adherence were 41 (26–52), 16 (14–19), and 4 (3–5) in plasma; and 6480 (3940–14 300), 3405 (2210–5020), and 448 (228–675) in urine. Trough TFV concentrations at steady state were significantly different between the 3 adherence arms for plasma (P < .0001) and urine (P = .0002). Following drug cessation, TFV concentrations persisted longer in urine than plasma samples. Washout urine TFV concentrations and time to undetectable concentrations did not differ between the 3 randomized adherence groups. Conclusions Urine TFV concentrations can inform interpretation of novel point-of-care urine-based TFV assays to assess recent TDF adherence. Clinical Trials Registration NCT0301260.

scholarly journals Pharmacokinetic Evaluation of Oral Levofloxacin in Human Immunodeficiency Virus-Infected Subjects Receiving Concomitant Antiretroviral Therapy

2001 ◽  
Vol 45 (7) ◽  
pp. 2160-2162 ◽  
Author(s):  
P. Villani ◽  
P. Viale ◽  
L. Signorini ◽  
B. Cadeo ◽  
F. Marchetti ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Antiretroviral Therapy ◽  
Plasma Levels ◽  
Plasma Samples ◽  
Dosing Interval ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
Before And After ◽  
Pharmacokinetic Evaluation

ABSTRACT The purpose of this study was to evaluate the pharmacokinetics (PK) profile of oral levofloxacin in human immunodeficiency virus-positive patients in steady-state treatment with nelfinavir (NFV) or with efavirenz (EFV) and to determine the effects of levofloxacin on the PK parameters of these two antiretroviral agents. For levofloxacin, plasma samples were obtained at steady state during a 24-h dosing interval. Plasma NFV and EFV concentrations were evaluated before and after 4 days of levofloxacin treatment. Levofloxacin PK do not seem affected by NFV and EFV. There was no significant difference between NFV and EFV plasma levels obtained with and without levofloxacin.

scholarly journals Sex Hormone Therapy and Tenofovir Diphosphate Concentration in Dried Blood Spots: Primary Results of the Interactions Between Antiretrovirals And Transgender Hormones Study

2020 ◽  
Author(s):  
Robert M Grant ◽  
Marion Pellegrini ◽  
Patricia A Defechereux ◽  
Peter L Anderson ◽  
Michelle Yu ◽  
...  
Keyword(s):  
Hormone Therapy ◽  
Dried Blood Spots ◽  
Sex Hormone ◽  
Mean Difference ◽  
Directly Observed Therapy ◽  
Blood Spots ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Before And After ◽  
Serum Hormone

Abstract Background Sex hormone and preexposure prophylaxis (PrEP) drug interactions among transgender women (TGW), transgender men (TGM), and cisgender men (CGM) are not fully understood. Methods TGM and TGW on at least 6 months of stable sex hormone therapy containing testosterone or estradiol (respectively) were enrolled in a 4-week study of directly observed dosing of daily oral coformulated emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). TFV-DP in dried blood spots and sex hormones in serum were measured at weekly intervals. TFV-DP was compared with 2- and 4-week samples from Directly Observed Therapy Dried Blood Spots (DOT-DBS) Study (NCT02022657). Results From May 2017 to June 2018, 24 TGM and 24 TGW were enrolled. Testosterone (total and free) and estradiol concentrations were comparable before and after 4 weeks of PrEP use in TGM and TGW, respectively. Historical controls included 17 cisgender women (CGW) and 15 CGM. TFV-DP concentrations at week 4 were comparable between TGW and TGM (mean difference, −6%; 95% confidence interval [CI], −21% to 12%; P = .47), comparable between TGW and CGM (mean difference, −12%; 95% CI, −27% to 7%; P = .21) and were lower among TGM compared with CGW (mean difference, −23%; 95% CI, −36% to −7%; P = .007). All persons in all groups were projected to reach the TFV-DP threshold that has been associated with high protection from human immunodeficiency virus. Conclusions CGM, TGM, and TGW had comparable TFV-DP concentrations in dried blood spots after 4 weeks of directly observed daily FTC/TDF PrEP use. Serum hormone concentrations were not affected by FTC/TDF PrEP use. Clinical Trials Registration NCT04050371.

scholarly journals Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood Spots following Directly Observed Therapy

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Peter L. Anderson ◽  
Albert Y. Liu ◽  
Jose R. Castillo-Mancilla ◽  
Edward M. Gardner ◽  
Sharon M. Seifert ◽  
...  
Keyword(s):  
Steady State ◽  
San Francisco ◽  
Dried Blood Spots ◽  
Directly Observed Therapy ◽  
Blood Spots ◽  
Preexposure Prophylaxis ◽  
Dosing Regimens ◽  
Sex With Men ◽  
Tenofovir Diphosphate ◽  
Dose Proportional

ABSTRACT Studies of daily emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) for HIV preexposure prophylaxis (PrEP) in men who have sex with men (MSM) modeled intracellular tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) to assess adherence and corresponding PrEP outcomes. We conducted a prospective, randomized, crossover pharmacokinetic study of TFV-DP in DBS during 33%, 67%, or 100% of daily dosing under directly observed therapy (DOT). Participants were assigned to two 12-week dosing regimens, separated by a 12-week washout. Forty-eight adults (25 women) from Denver and San Francisco were included. TFV-DP exhibited a median half-life of 17 days, reaching steady state in 8 weeks. TFV-DP was dose proportional with mean (SD) steady-state concentrations of 530 (159), 997 (267), and 1,605 (405) fmol/punch for the 33%, 67%, and 100% arms, respectively. Prior work in MSM demonstrated clinically meaningful TFV-DP thresholds of 350, 700, and 1,250 fmol/punch, which were estimated 25th percentiles for 2, 4, and 7 doses/week. In the present study, corresponding TFV-DP was within 3% of the prior estimates, and subgroups by site, race, and sex were within 14% of prior estimates, although males had 17.6% (95% confidence intervals [CIs], 6.5, 27.4%) lower TFV-DP than females. The thresholds of 350, 700, and 1,250 fmol/punch were achieved by 75% of men taking ≥1.2, 3.2, and 6 doses/week and 75% of women taking ≥0.6, 2.0, and 5.3 doses/week, indicating that lower dosing reached these thresholds for both sexes. In conclusion, TFV-DP arising from DOT was similar to previous estimates and is useful for interpreting PrEP adherence and study outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT02022657.)

scholarly journals Is Emtricitabine-Tenofovir Disoproxil Fumarate Pre-exposure Prophylaxis for the Prevention of Human Immunodeficiency Virus Infection Safer Than Aspirin?

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Noah Kojima ◽  
Jeffrey D. Klausner
Keyword(s):  
Human Immunodeficiency Virus ◽  
Gastrointestinal Bleeding ◽  
Hiv Infection ◽  
Tenofovir Disoproxil Fumarate ◽  
African Women ◽  
Health Study ◽  
Heterosexual Couples ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Exposure Prophylaxis

Abstract Background.  The safety and effectiveness studies of emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) for human immunodeficiency virus (HIV) infection pre-exposure prophylaxis (PrEP) in men and women showed that daily use reduced the risk of HIV acquisition, but there still may concerns about safety. Methods.  A narrative review was done in September 2015 comparing the 5 major studies on PrEP for HIV infection—Preexposure Prophylaxis Initiative (N = 2499; 3324 person-years), Partners Preexposure Prophylaxis (N = 4747; 7830 person-years), TDF2 (N = 1219; 1563 person-years), Preexposure Prophylaxis Trial for HIV Prevention among African Women (N = 2056; 1407 person-years), and Vaginal and Oral Interventions to Control the Epidemic (N = 4969; 5509 person-years)—and the 2 major studies on aspirin safety—Physicians' Health Study (N = 22 071; over 110 000 person-years) and the Women's Health Study (N = 39 876; approximately 400 000 person-years). The numbers needed to harm (NNH) were calculated for FTC-TDF for HIV infection PrEP and aspirin. Results.  The NNH for FTC-TDF in men who have sex with men and transgender women was 114 for nausea and 96 for unintentional weight loss; in heterosexual couples, the NNH was 68 for moderate decreased absolute neutrophil count. For aspirin, the NNH was 909 for major gastrointestinal bleeding, 123 for any gastrointestinal bleeding, and 15 for any bleeding problems in men. In women, the NNH for easy bruising was 10. Conclusions.  We conclude that FTC-TDF for PrEP for HIV infection favorably compares with aspirin in terms of user safety. Although long-term studies are needed, providers should feel reassured about the safety of short- and medium-term PrEP for HIV infection with FTC-TDF.

scholarly journals Long-Acting Cabotegravir Protects Macaques Against Repeated Penile Simian-Human Immunodeficiency Virus Exposures

2020 ◽  
Vol 222 (3) ◽  
pp. 391-395
Author(s):  
Charles Dobard ◽  
Natalia Makarova ◽  
Kenji Nishiura ◽  
Chuong Dinh ◽  
Angela Holder ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Confidence Interval ◽  
Tenofovir Disoproxil Fumarate ◽  
Transmission Model ◽  
Heterosexual Men ◽  
High Efficacy ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Long Acting

Abstract We used a novel penile simian-human immunodeficiency virus (SHIV) transmission model to investigate whether long-acting cabotegravir (CAB LA) prevents penile SHIV acquisition in macaques. Twenty-two macaques were exposed to SHIV via the foreskin and urethra once weekly for 12 weeks. Of these, 6 received human-equivalent doses of CAB LA, 6 received oral emtricitabine/tenofovir disoproxil fumarate, and 10 were untreated. The efficacy of CAB LA was high (94.4%; 95% confidence interval, 58.2%–99.3%) and similar to that seen with oral emtricitabine/tenofovir disoproxil fumarate (94.0%; 55.1%–99.2%). The high efficacy of CAB LA in the penile transmission model supports extending the clinical advancement of CAB LA preexposure prophylaxis to heterosexual men.

scholarly journals Changes in Bone Mass After Discontinuation of Preexposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine in Young Men Who Have Sex With Men: Extension Phase Results of Adolescent Trials Network Protocols 110 and 113

2019 ◽  
Vol 70 (4) ◽  
pp. 687-691 ◽  
Author(s):  
Peter L Havens ◽  
Suzanne E Perumean-Chaney ◽  
Amit Patki ◽  
Stacey S Cofield ◽  
Craig M Wilson ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Human Immunodeficiency Virus ◽  
Tenofovir Disoproxil Fumarate ◽  
Network Protocols ◽  
Whole Body ◽  
Mineral Density ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Z Scores ◽  
Sex With Men

AbstractHuman immunodeficiency virus–seronegative men aged 15–22 years who lost bone mineral density (BMD) during tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) showed BMD recovery 48 weeks following PrEP discontinuation. Lumbar spine and whole body BMD z-scores remained below baseline 48 weeks off PrEP in participants aged 15–19 years.Clinical Trials Registration. NCT01772823 (ATN 110) and NCT01769456 (ATN 113).

scholarly journals Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide for Human Immunodeficiency Virus Preexposure Prophylaxis at a Boston Community Health Center

2021 ◽  
Vol 8 (8) ◽  
Author(s):  
Julia L Marcus ◽  
Kenneth Levine ◽  
Whitney C Sewell ◽  
Patricia Solleveld ◽  
Kenneth H Mayer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Human Immunodeficiency Virus ◽  
Cardiovascular Risk ◽  
Creatinine Clearance ◽  
Cardiovascular Risk Factors ◽  
Tenofovir Disoproxil Fumarate ◽  
Community Health Center ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Tenofovir Alafenamide

Abstract Background Efforts to end the human immunodeficiency virus (HIV) epidemic may be threatened if limited preexposure prophylaxis (PrEP) resources are funneled from tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) to tenofovir alafenamide with emtricitabine (TAF/FTC) without proportional clinical benefits. Methods The study population was patients at a Boston community health center who were assigned male sex at birth, aged ≥18 years, and prescribed TDF/FTC for PrEP in the 12 months before TAF/FTC approval (October 2019). We determined the frequency of switching to TAF/FTC in the 12 months after approval, including clinically indicated switching (ie, creatinine clearance <60 mL/minute or reduced bone density), potentially unnecessary switching (ie, no indications for switching and no cardiovascular risk factors), and potentially harmful switching (ie, no indications for switching and either obesity or dyslipidemia). Results Of 2892 TDF/FTC users, mean age was 38 years, 96.0% were cisgender men, and 78.9% were white. A total of 343 (11.9%) switched to TAF/FTC. Based on documented renal, bone, and cardiovascular risk factors, we identified 24 (7.0%) with clinically indicated switching, 271 (79.0%) with potentially unnecessary switching, and 48 (14.0%) with potentially harmful switching. When indications for switching additionally included hypertension, diabetes, and creatinine clearance 60–70 mL/minute, 27.1% of switching was clinically indicated. Conclusions Few who switched to TAF/FTC had documented indications for switching, although some appear to have been switched in anticipation of indications developing. As generic TDF/FTC is further discounted, provider education and patient decision aids are needed to facilitate selection of PrEP medications that is both clinically sound and cost-effective.

scholarly journals Lower Urine Tenofovir Concentrations among Individuals Taking Tenofovir Alafenamide versus Tenofovir Disoproxil Fumarate: Implications for Point-of-Care Testing

2021 ◽  
Author(s):  
Kelly A Johnson ◽  
Xin Niu ◽  
David V Glidden ◽  
Jose R Castillo-Mancilla ◽  
Jenna Yager ◽  
...  
Keyword(s):  
Tenofovir Disoproxil Fumarate ◽  
Point Of Care ◽  
Lateral Flow ◽  
Lateral Flow Immunoassay ◽  
Directly Observed Therapy ◽  
Point Of Care Testing ◽  
Separate Point ◽  
Tenofovir Alafenamide ◽  
Adherence Monitoring ◽  
Therapy Studies

Abstract From directly-observed-therapy studies, urine tenofovir (TFV) levels were 74% lower when taking tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate. Urine TFV remains quantifiable across a range of TAF adherence patterns, but a separate point-of-care lateral flow immunoassay with a lower TFV threshold will be needed to support TAF adherence monitoring.

scholarly journals Single-Dose and Steady-State Pharmacokinetics of Tenofovir Disoproxil Fumarate in Human Immunodeficiency Virus-Infected Children

2004 ◽  
Vol 48 (1) ◽  
pp. 124-129 ◽  
Author(s):  
Rohan Hazra ◽  
Frank M. Balis ◽  
Antonella N. Tullio ◽  
Ellen DeCarlo ◽  
Carol J. Worrell ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Single Dose ◽  
Steady State ◽  
Antiretroviral Therapy ◽  
Tenofovir Disoproxil Fumarate ◽  
Geometric Mean ◽  
Transcriptase Inhibitor ◽  
Time Curve ◽  
Immunodeficiency Virus ◽  
Tenofovir Df

ABSTRACT Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse transcriptase inhibitor approved for the treatment of human immunodeficiency virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of tenofovir were evaluated following administration of tenofovir DF in treatment-experienced HIV-infected children requiring a change in antiretroviral therapy. Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m2; the median administered dose was 208 mg/m2. Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve from 0 h to ∞ (AUC0-∞) was 2,150 ng · h/ml and the geometric mean maximum concentration (C max) was 266 ng/ml. Subsequently, other antiretrovirals were added to each patient's regimen based upon treatment history and baseline viral resistance results. Steady-state pharmacokinetics were evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the 24-h dosing interval was 2,920 ng · h/ml and was significantly higher than the AUC0-∞ after the first dose (P = 0.0004). The geometric mean C max at steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated. Steady-state tenofovir exposures in children receiving tenofovir DF-containing combination antiretroviral therapy approached values seen in HIV-infected adults (AUC, ∼3,000 ng · h/ml; C max, ∼300 ng/ml) treated with tenofovir DF at 300 mg.

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