Prevalence of Comorbidities and Polypharmacy in a Historically Minoritized Community and Their Impact on Virologic Suppression in Persons with HIV.

Improved life expectancy from advances in antiretroviral therapy (ART) has been followed by a rise in comorbidities and polypharmacy in this aging population. Historically, polypharmacy has been associated with suboptimal virologic outcomes in persons with HIV, although data in the current ART era and among historically marginalized populations in the United States are limited. We measured the prevalence of comorbidities and polypharmacy, evaluating their impact on virologic suppression. This retrospective IRB-approved cross-sectional study reviewed health records of adults with HIV on ART and receiving care (≥2 visits) in 2019 at a single center in a historically minoritized community. Virologic suppression (HIV RNA <200 copies/mL) based on polypharmacy (≥5 non-HIV medications) or multimorbidity (≥2 chronic conditions) was evaluated. Logistic regression analyses were performed to identify factors associated with virologic suppression, with age, race/ethnicity, and CD4 < 200 cells/mm3 as covariates. Of the 963 individuals that met the criteria, 67%, 47%, and 34% had ≥1 comorbidity, multimorbidity, and polypharmacy, respectively. The cohort demographics were: mean of 49 years (range, 18-81), 40% cisgender women, 46% Latinx individuals, 45% Black individuals, 8% White individuals. Virologic suppression rates were 95% among patients with polypharmacy compared with 86% in those with a lower pill burden (p = 0.0001). The odds of virologic success were higher for individuals with polypharmacy [adjusted odds ratio, aOR = 2.3 (95% confidence interval, CI: 1.2-4.4)] and Latinx identity [aOR = 2.4 (95% CI: 1.5-3.8)], but lower if a CD4 count <200 cells/mm3 [aOR = 0.07 (95% CI: 0.04-0.1)]. The comorbidity burden was higher than previously described, which are driving polypharmacy rates. In the current ART era, polypharmacy is not inherently associated with worse virologic outcomes.

When Coadministration Cannot Be Avoided: Real World Experience of Direct Acting Antivirals for the Treatment of Hepatitis C Virus Infection in Patients on First Generation Anticonvulsants.

BACKGROUND: Coadministration of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection and first generation anticonvulsants is currently not recommended due to a drug-drug interaction that could potentially lead to subtherapeutic DAA levels and subsequent treatment failure. Currently, there is limited data evaluating this interaction and timely treatment of HCV infection with DAAs is imperative to prevent liver-related morbidity and mortality. METHODS: A retrospective case series evaluating clinical cure of chronic HCV infection, defined as sustained virologic response (SVR) 12 weeks after completion of DAA therapy, in patients from three inner-city clinics who remained on first generation anticonvulsants during the treatment course. RESULTS: A total of five patients received standard dose DAAs for treatment of chronic HCV infection while being maintained on first generation anticonvulsants. The most common HCV genotype was 1a (80%), followed by 1b (20%). The majority of patients were treated with glecaprevir/pibrentasvir (80%) for eight weeks and one patient was treated with ledipasvir/sofosbuvir for 12 weeks. Anticonvulsant regimens consisted of carbamazepine, phenytoin, phenytoin plus phenobarbital, phenytoin plus levetiracetam, and phenobarbital plus lacosamide. All five patients achieved sustained virologic response (SVR) despite this drug-drug interaction. CONCLUSION: Although every effort to prevent concomitant use of DAAs and potent inducers should be made, clinical cure may still be achieved in patients whom cannot avoid this coadministration.

Evaluating Empiric Therapy for Acute Uncomplicated Cystitis in the Outpatient Setting: A Retrospective Cohort Study.

OBJECTIVES: To evaluate the empiric therapy prescribed for acute uncomplicated cystitis in the outpatient setting (emergency department and ambulatory care clinics) and to characterize uropathogens for discordance between the therapy prescribed and susceptibility. METHODS: A retrospective review was conducted at an inner-city emergency department and multiple clinics to evaluate the empiric therapy prescribed and the uropathogens isolated from culture for patients with acute uncomplicated cystitis. RESULTS: A total of 144 urine cultures were included. Among the patients, 53.4% were empirically prescribed cephalexin, 20.1% ciprofloxacin, 11% nitrofurantoin, and 8.3% trimethoprim/sulfamethoxazole. The most common uropathogen was Escherichia coli (72.4%), followed by Streptococcus agalactiae (7.6%) and Klebsiella pneumoniae (4.8%). Of the 107 E. coli isolates, 9 were extended spectrum beta-lactamase-producing. E. coli antimicrobial susceptibilities were as follows: ceFAZolin (97%), nitrofurantoin (96%), cefTRIAXone (91%), ciprofloxacin (87%), and trimethoprim-sulfamethoxazole (59%). The concordance rates with the Infectious Diseases Society of America treatment guidelines for acute uncomplicated cystitis and local resistance patterns were as follows: empiric therapy prescribed (70%), dosing of empiric therapy (77%), and duration of empiric therapy (22%). For empiric therapy prescribed and susceptibility mismatch, 5.6% of the isolates were not susceptible to therapy, 76.4% were susceptible to therapy, 14% did not have susceptibilities, and 4.2% did not receive therapy. CONCLUSIONS: Most of the cases of acute uncomplicated cystitis at the subject institution can be managed safely and effectively with nitrofurantoin or first-generation cephalosporins. Institutions should use national guidelines in conjunction with local resistance and prescribing patterns to improve antibiotic prescribing in the outpatient setting.

Drug interaction after ritonavir discontinuation: considerations for antiretroviral therapy changes in renal transplant recipients.

Organ transplantation among people living with human immunodeficiency virus (PLHIV) is increasing. Guidelines recommend any changes in antiretroviral therapy (ART) prior to transplantation, but there are limited data regarding ART changes post transplantation. We report a case where an ART switch from a protease inhibitor-based regimen to dolutegravir plus emtricitabine/tenofovir alafenamide in a renal transplant recipient led to subtherapeutic tacrolimus concentrations and an increased serum creatinine (SCr). A workup for graft rejection was performed (including kidney biopsy and cytomegalovirus and BK virus polymerase chain reaction) following the rise in SCr, which was higher than expected from dolutegravir initiation (via organ cation transporter 2 inhibition). This case highlights the potential challenges of switching ART regimens in PLHIV post transplantation.