Nonnucleoside reverse transcriptase inhibitor pharmacokinetics in a large unselected cohort of HIV-infected women.

BackgroundSmall intensive pharmacokinetic (PK) studies of medications in early-phase trials cannot identify the range of factors that influence drug exposure in heterogenous populations. We performed PK studies in large numbers of HIV-infected women on nonnucleoside reverse transcriptase inhibitors (NNRTIs) under conditions of actual use to assess patient characteristics that influence exposure and evaluated the relationship between exposure and response.MethodsTwo hundred twenty-five women on NNRTI-based antiretroviral regimens from the Women's Interagency HIV Study were enrolled into 12-hour or 24-hour PK studies. Extensive demographic, laboratory, and medication covariate data were collected before and during the visit to be used in multivariate models. Total NNRTI drug exposure was estimated by area under the concentration-time curves.ResultsHepatic inflammation and renal insufficiency were independently associated with increased nevirapine exposure in multivariate analysis: crack cocaine, high fat diets, and amenorrhea were associated with decreased levels (n = 106). Higher efavirenz exposure was seen with increased transaminase, albumin levels, and orange juice consumption; tenofovir use, increased weight, being African American, and amenorrhea were associated with decreased exposure (n = 119). With every 10-fold increase in nevirapine or efavirenz exposure, participants were 3.3 and 3.6 times likely to exhibit virologic suppression, respectively. Patients with higher drug exposure were also more likely to report side effects on therapy.ConclusionsOur study identifies and quantitates previously unrecognized factors modifying NNRTI exposure in the "real-world" setting. Comprehensive PK studies in representative populations are feasible and may ultimately lead to dose optimization strategies in patients at risk for failure or adverse events

Lower liver‐related death in African‐American women with human immunodeficiency virus/hepatitis C virus coinfection, compared to Caucasian and Hispanic women

UnlabelledAmong individuals with and without concurrent human immunodeficiency virus (HIV), racial/ethnic differences in the natural history of hepatitis C virus (HCV) have been described. African Americans have lower spontaneous HCV clearance than Caucasians, yet slower rates of liver fibrosis once chronically infected. It is not clear how these differences in the natural history of hepatitis C affect mortality, in either HIV-positive or -negative individuals. We conducted a cohort study of HIV/HCV coinfected women followed in the multicenter Women's Interagency HIV Study to determine the association of self-reported race/ethnicity with all-cause and liver-related mortality. Survival analyses were performed using Cox's proportional hazards models. The eligible cohort (n = 794) included 140 Caucasians, 159 Hispanics, and 495 African Americans. There were 438 deaths and 49 liver-related deaths during a median follow-up of 8.9 years and maximum follow-up of 16 years. African-American coinfected women had significantly lower liver-related mortality, compared to Caucasian (hazard ratio [HR], 0.41; 95% confidence interval [CI]: 0.19-0.88; P = 0.022) and Hispanic coinfected women (HR, 0.38; 95% CI: 0.19-0.76; P = 0.006). All-cause mortality was similar between racial/ethnic groups (HRs for all comparisons: 0.82-1.03; log-rank test: P = 0.8).ConclusionsAfrican-American coinfected women were much less likely to die from liver disease, as compared to Caucasians and Hispanics, independent of other causes of death. Future studies are needed to investigate the reasons for this marked racial/ethnic discrepancy in liver-related mortality

Association of Pharmacogenetic Markers With Atazanavir Exposure in HIV‐Infected Women

SORCS2 rs73208473 was recently associated with decreased atazanavir (ATV) concentration in the hair of women with seropositive HIV. Herein, we report on a pharmacogenetic study of women with seropositive HIV demonstrating a similar association between rs73208473 and dose-adjusted plasma ATV concentration in African Americans

Improved antiretroviral refill adherence in HIV-focused community pharmacies

OBJECTIVE: To determine differences in patient characteristics, antiretroviral therapy (ART) regimen characteristics, and regimen refill adherence for HIV-focused pharmacy (HIV-P) versus traditional pharmacy (TP) users. DESIGN: Retrospective cohort study SETTING: California Walgreens pharmacies, May 2007 – August 2009 PARTICIPANTS: HIV-positive (HIV+) patients with greater than 30 days of antiretroviral prescription claims. MAIN OUTCOME MEASURES: Modified medication possession ratio (mMPR) to calculate regimen refill adherence, and dichotomous measure of optimal adherence ≥ 95%. RESULTS: 4254 HIV-P and 11679 TP users were included. Compared to TP users, HIV-P users traveled farther to pharmacies (5.03 vs. 1.26 miles), filled more chronic disease medications (35% vs. 30%), and received more fixed-dose combination tablets (92% vs. 83%); all p < 0.01. Median mMPR was higher for HIV-P users (90% vs. 77%, p < 0.0001). After adjustment for age, gender, insurance, medication use, and distance from pharmacy, use of HIV-P (OR= 2.18, 95% CI 1.88–2.52) and use of fixed-dose combination antiretroviral tablets (OR=2.43, 95% CI 1.83–3.22) were factors most strongly associated with having ≥ 95% regimen refill adherence. CONCLUSION: For HIV+ patients struggling with antiretroviral adherence, clinicians could consider minimizing pill burden with combination tablets and referral to an HIV-focused pharmacy