Interaction of Depot Medroxyprogesterone Acetate and Tenofovir Disoproxil Fumarate/Emtricitabine on Peripheral Blood Mononuclear Cells and Cervical Tissue Susceptibility to HIV Infection and Pharmacokinetics.

BACKGROUND: Depot medroxyprogesterone acetate (DMPA) is a widely used contraceptive method. HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is highly effective in reducing HIV acquisition in women. We sought to determine the impact of DMPA on F/TDF pharmacokinetics and pharmacodynamics. METHODS: Twelve healthy premenopausal cisgender women were enrolled and each completed 4 sequential conditions: (1) baseline, (2) steady-state F/TDF alone, (3) steady-state F/TDF + DMPA, and (4) DMPA alone. Assessments included clinical, pharmacokinetic, viral infectivity (ex vivo challenge of peripheral blood mononuclear cells by X4- and R5-tropic green fluorescent protein pseudoviruses and cervical tissue by HIV BaL ), endocrine, immune cell phenotyping, and renal function. RESULTS: Compared with baseline, F/TDF (± DMPA) significantly decreased both %R5- and X4-infected CD4 T cells and F/TDF + DMPA decreased cervical explant p24 (all P < 0.05). The %R5- and X4-infected CD4 T cells were higher during DMPA alone than during F/TDF periods and lower than baseline (not statistically significant). Cervical explant p24 fell between baseline and F/TDF values (not statistically significant). There were neither statistically significant differences in F/TDF pharmacokinetics, including total or renal clearance of either antiviral drug, nor changes in glomerular filtration rate with the addition of DMPA. There were few immune cell phenotypic differences across conditions. CONCLUSIONS: F/TDF decreased HIV infection in both challenge assays, whereas DMPA alone did not enhance HIV infection in either challenge assay. DMPA did not alter F/TDF pharmacokinetics or renal function.

Breakdown in the expedited partner therapy treatment cascade: from reproductive healthcare provider to the pharmacist.

BACKGROUND: The rising incidence rates of sexually transmitted infections in the United States highlight the need for concurrent treatment of patients and their sexual partners. Expedited partner therapy allows healthcare providers to offer antibiotic prescriptions or medications to an index patient for distribution to their sexual partner(s) without evaluating the partner. We hypothesized that there was a gap between expedited partner therapy policy at the state level and its downstream implementation by community pharmacists. OBJECTIVE: The objectives of our study were to evaluate pharmacists' expedited partner therapy knowledge and practices in 41 expedited partner therapy-permissible US states, to determine whether there were differences in practice based on the length of time expedited partner therapy was permissible in the state and chlamydia incidence rates, and to measure the cost of expedited partner therapy treatment. STUDY DESIGN: A randomized cohort of pharmacists (n=335) was invited to complete a telephone interview from November 2017 through January 2018. Descriptive statistics were calculated and stratified by early, mid, and late expedited partner therapy-adopter status based on the year of the state's expedited partner therapy enactment and the state's chlamydia incidence rate. Fisher's exact test and 1-way analyses of variance were used to compare measures across strata. RESULTS: We had 143 pharmacists (42.7%) agree to complete the survey. Among our respondents, 40.6% (n=58/143) indicated that they were aware of expedited partner therapy; 14.7% (n=21/143) reported that they had ever received an expedited partner therapy prescription, and 97% (n=139/143) reported that they would dispense an expedited partner therapy prescription if they received 1 in the future. These findings were stable across the 6 strata defined by early, mid, or late expedited partner therapy-adopter and high or low incidence rates of chlamydia status. Mean cost of azithromycin 1000 mg and cefixime 400 mg for treatment of chlamydia and gonorrhea was $22.17 (95% confidence interval, 20.29-24.05) and $30.46 (95% confidence interval, 28.65-32.26), respectively. CONCLUSION: Fewer than one-half of the pharmacists were aware of expedited partner therapy. A small minority of pharmacists reported ever having received an expedited partner therapy prescription, regardless of the length of time expedited partner therapy had been legal in their states and the incidence of chlamydia. However, almost all pharmacists reported that they would dispense an expedited partner therapy prescription if they received 1. Additionally, costs were high for expedited partner therapy for self-pay patients. These data suggest that there are opportunities to increase expedited partner therapy utilization by healthcare providers, patients, and pharmacists.

Pharmacy-level barriers to implementing expedited partner therapy in Baltimore, Maryland.

BACKGROUND: Addressing record high rates of Chlamydia trachomatis incidence in the United States requires the utilization of effective strategies, such as expedited partner therapy, to reduce reinfection and further transmission. Expedited partner therapy, which can be given as a prescription or medication, is a strategy to treat the sexual partners of index patients diagnosed with a sexually transmitted infection without prior medical evaluation of the partners. OBJECTIVE: There are multiple steps in the prescription-expedited partner therapy cascade, and we sought to identify pharmacy-level barriers to implementing prescription-expedited partner therapy for Chlamydia trachomatis treatment. STUDY DESIGN: We used spatial analysis and ArcGIS, a geographic information system, to map and assess geospatial access to pharmacies within Baltimore, MD, neighborhoods with the highest rates of Chlamydia trachomatis (1180.25-4255.31 per 100,000 persons). Expedited partner therapy knowledge and practices were collected via a telephone survey of pharmacists employed at retail pharmacies located in these same neighborhoods. Cost of antibiotic medication in US dollars was collected. RESULTS: Census tracts with the highest Chlamydia trachomatis incidence rates had lower median pharmacy density than other census tracts (26.9 per 100,000 vs 31.4 per 100,000, P < .001). We identified 25 pharmacy deserts. Areas defined as pharmacy deserts had larger proportions of black and Hispanic or Latino populations compared with non-Hispanic whites (93.1% vs 6.3%, P < .001) and trended toward higher median Chlamydia trachomatis incidence rates (1170.0 per 100,000 vs 1094.5 per 100,000, P = .110) than non-pharmacy desert areas. Of the 52 pharmacies identified, 96% (50 of 52) responded to our survey. Less than a fifth of pharmacists (18%, 9 of 50) were aware of expedited partner therapy for Chlamydia trachomatis. Most pharmacists (59%, 27 of 46) confirmed they would fill an expedited partner therapy prescription. The cost of a single dose of azithromycin (1 g) ranged from 5.00 to 39.99 US dollars (median, 30 US dollars). CONCLUSION: Limited geographic access to pharmacies, lack of pharmacist awareness of expedited partner therapy, and wide variation in expedited partner therapy medication cost are potential barriers to implementing prescription-expedited partner therapy. Although most Baltimore pharmacists were unaware of expedited partner therapy, they were generally receptive to learning about and filling expedited partner therapy prescriptions. This finding suggests the need for wide dissemination of educational material targeted to pharmacists. In areas with limited geographic access to pharmacies, expedited partner therapy strategies that do not depend on partners physically accessing a pharmacy merit consideration.

Comparison of Biochemical Recurrence-Free Survival after Radical Prostatectomy Triggered by Grade Reclassification during Active Surveillance and in Men Newly Diagnosed with Similar Grade Disease.

PURPOSE: We compared biochemical recurrence between men on active surveillance who underwent radical prostatectomy triggered by grade reclassification and men diagnosed with similar grade disease treated with immediate radical prostatectomy. MATERIALS AND METHODS: We retrospectively analyzed the records of men who underwent surgery from 1995 to 2015 at our institution. We identified 4 groups, including 94 and 56 men on active surveillance who underwent radical prostatectomy following reclassification to Gleason 7 (3 + 4) or greater (grade groups 2 or greater) and Gleason 7 (3 + 4) (grade group 2), and 3,504 and 1,979 in the immediate prostatectomy group diagnosed with grade group 2 or greater and 2, respectively. Biochemical recurrence was assessed by Kaplan-Meir analysis and a multivariable Cox model. RESULTS: Men on active surveillance had a lower incidence of biochemical recurrence than men in the immediate radical prostatectomy groups for biopsy grade groups 2 or greater and 2 (each p <0.05). One, 5 and 10-year biochemical recurrence-free survival for men in the active surveillance group vs the immediate radical prostatectomy group was 97.9% vs 85.5%, 76.6% vs 65.1% and 69.0% vs 54.2% in biopsy grade groups 2 or greater (p = 0.009) and 96.4% vs 91.2%, 89.6% vs 74.0% and 89.6% vs 63.9%, respectively, in biopsy grade group 2 (p = 0.071). For biopsy grade groups 2 or greater there was no significant difference in the risk of biochemical recurrence between the groups after adjusting for age, biopsy extent of cancer and prostate specific antigen density. CONCLUSIONS: Patients on active surveillance reclassified to grade groups 2 or greater are at no greater risk for treatment failure than men newly diagnosed with similar grades.