Healthcare Professionals' Perspectives on Improving Dietary Supplement Documentation in the Electronic Medical Record: Current Challenges and Opportunities to Enhance Quality of Care and Patient Safety.

Background: Around half the US population uses dietary supplements (DS), and concomitant use with medications is common. Many DS include bioactive substances that can interact with medications; therefore, accurate tracking is critical for patient safety. Unfortunately, documentation of patients' DS use is often missing or incomplete in the electronic medical record (EMR), leaving patients susceptible to potential adverse events. Novel approaches to assist healthcare professionals (HCPs) in capturing patients' DS use are needed. Objective: To assess HCPs' perspectives on challenges and facilitators of DS documentation in the EMR and their opinions on a proposed mHealth application (app) to aid in DS capture. Methods: HCPs, recruited from professional networks, largely in North Carolina, using purposive sampling, took part in semi-structured interviews. We inquired about HCPs' experiences with DS documentation in the EMR and their opinions about our proposed mHealth app. Interviews were recorded, transcribed, and coded. Thematic analysis included deductive codes based on the interview guide, and inductive codes that emerged during transcript review. Results: HCPs (N = 30) included 60% females, mean age 46 ± 10; 70% White. Pharmacists (20%), nurses (17%), and physicians (17%) were the most represented professions. Years in practice ranged from 3-35 years. Most HCPs were concerned about DS safety and potential supplement-drug interactions, and cited several barriers to accurate EMR DS documentation including time constraints, database inconsistencies, and poor patient-HCP communication about DS. HCPs' views on our proposed mHealth app were generally positive. They expressed that our proposed mHealth app could streamline documentation processes and enhance patient-provider communication. HCPs expressed desire for a high-quality mHealth app that includes access to evidence-based DS information, integrates with the EMR, and does not increase time burdens. Conclusion: HCPs believe documentation of patients' DS use is important but not accurately captured in the EMR. Support was expressed for our proposed barcode-scanning DS mHealth app.

Vaginal microbiome, antiretroviral concentrations, and HIV genital shedding in the setting of hormonal contraception initiation in Malawi.

OBJECTIVE: The aim of this study was to understand how vaginal microbiota composition affects antiretroviral concentrations in the setting of hormonal contraception initiation. METHODS: Cervicovaginal fluid (CVF) concentrations of tenofovir, lamivudine, and efavirenz from 73 Malawian women with HIV were compared before and after initiation of depot-medroxyprogesterone acetate (DMPA) or levonorgestrel implant. We evaluated antiretroviral concentrations and vaginal microbiota composition/structure in the context of contraception initiation and predicted genital shedding using multivariable repeated measurements models fit by generalized estimating equations. RESULTS: Mean lamivudine CVF concentrations decreased 37% 1 month after contraception initiation. Subgroup analyses revealed a 41% decrease in women 1 month after initiating levonorgestrel implant, but no significant difference was observed in DMPA group alone. Tenofovir, lamivudine, and efavirenz CVF concentrations were positively correlated with anaerobic bacteria associated with nonoptimal vaginal microbiota. Risk of genital HIV shedding was not significantly associated with tenofovir or lamivudine CVF concentrations [tenofovir relative risk (RR): 0.098, P = 0.75; lamivudine RR: 0.142, P = 0.54]. Lack of association between genital HIV shedding and efavirenz CVF concentrations did not change when adjusting for vaginal microbiota composition and lamivudine/tenofovir CVF concentrations (RR: 1.33, P = 0.531). CONCLUSION: No effect of hormone initiation on genital shedding provides confidence that women with HIV on either DMPA or levonorgestrel implant contraception will not have compromised ART efficacy. The unexpected positive correlation between antiretroviral CVF concentrations and certain bacterial taxa relative abundance requires further work to understand the mechanism and clinical relevance.

Heart transplantation and human immunodeficiency virus-navigating drug-drug interactions: a case report.

BACKGROUND: Antiretroviral therapy (ART) has led to a decline in human immunodeficiency virus (HIV)-related mortality, but comorbidities, including organ dysfunction, are increasingly the focus of care. Heart transplant (HT) is a very effective therapeutic strategy for end-stage heart failure (HF); however, clinicians may be hesitant due to concerns of complex drug-drug interactions (DDIs) between ART and HT immunosuppressive regimens and the potential impact of ART on long-term HT outcomes. In this report, we describe long-term (76-month) follow-up of a patient with HIV-positive status who underwent orthotopic HT with special emphasis on complex drug interactions. CASE PRESENTATION: A 58-year-old man with HIV-1 developed ischemic cardiomyopathy, progressed to end-stage HF and underwent orthotopic HT. To avoid DDIs with planned immunosuppressive therapies, the ART regimen was modified to consist of lamivudine, tenofovir disoproxil fumarate, rilpivirine, and raltegravir. Following HT, the patient's immunosuppression consisted of tacrolimus and mycophenolate mofetil. He has had normal cardiac function and no opportunistic infections and was subsequently switched to tenofovir alafenamide, emtricitabine, and bictegravir in combination for convenience. Serial HIV-1 RNA blood levels were constantly below the limit of quantification, and his CD4 count remained above 200 cells/mm3 (30-35%). Several DDIs were identified and addressed; however, his long-term post-HT complications included one episode of asymptomatic acute cellular rejection, adenocarcinoma of the prostate, basal cell carcinoma, cardiac allograft vasculopathy, and peripheral neuropathy. CONCLUSION: The clinical outcome of this case supports the conclusion of previously published reports, summarized here within, demonstrating that HIV-1 positive status should not preclude HT in carefully selected individuals. Both addressing potential DDIs prior to HT and long-term monitoring for routine post-transplant complications and secondary and incidental malignancies are imperative.

Patient Perspectives on the Development of a Novel Mobile Health (mHealth) Application for Dietary Supplement Tracking and Reconciliation-A Qualitative Focus Group Study.

BACKGROUND: More than 170 million adults use dietary supplements (DS) in the United States, which can have both benefit and harm to patient health. DS use is often poorly documented in the medical record and can pose health risks if not properly communicated with providers. Reasons for poor DS documentation include low disclosure rates, time constraints of clinical encounters, and providers' failure to inquire about DS use. This study was conducted to assess patients' views on the facilitators and barriers to using a mobile health (mHealth) application (app) to collect and share DS information with their healthcare providers. METHODS: Utilizing a theory-based conceptual model, we conducted 7 patient focus groups (FGs) to assess opinions on DS safety, provider communication, comfort with technology use, and our proposed mHealth app. Participants were recruited from the general public and through patient advisory groups. Patient views will inform the creation of an mHealth app to improve DS patient-provider communication and tracking and reconciliation in the electronic medical record (EMR). RESULTS: Overall, participants believe their DS information is inaccurately represented in the EMR, leading to safety concerns and negatively impacting overall quality of care. Participants desired an app designed with (1) Health Insurance Portability and Accountability Act (HIPAA) compliance; (2) ease of use for a variety of technical efficacy levels; (3) access to reliable DS information, including a DS-drug interaction checker; and (4) integration with the EMR. CONCLUSION: An app to simplify and improve DS entry and reconciliation was of interest to patients, as long as it maintained health autonomy and privacy and possessed key valuable features.

Enhanced Perinatal Programs for People in Prisons: A Summary of Six States' Programs.

Purpose: The purpose of this study was to examine enhanced perinatal support programs for pregnant and postpartum people in six state prisons, describe the service components offered by each program, and discuss similarities and differences of services offered between programs. Methods: In-depth, semi-structured interviews were conducted with each program's site lead(s) in order to collect information regarding each program's historical context, conception, and key aspects of the implementation of service components offered at each site. Results: Program components fell into five broad categories: group-based education and support, one-on-one support, labor and birth support, lactation facilitation and support, and other support services. Results highlight similarities and differences within and across programs and common themes that govern program success. Conclusions: This study provides an initial understanding of the variation in enhanced perinatal programming in six state prisons and offers insights for other states interested in establishing these types of programs. These programs implemented individual components piecemeal to fit site-specific context and needs, instead of adopting the entirety of another program model. Programs' success was largely dependent upon collaboration between program facilitators and partnering prison sites.

Feedback for Learning in Pharmacy Education: A Scoping Review.

Feedback is an effective pedagogy aimed to create cognitive dissonance and reinforce learning as a key component of clinical training programs. Pharmacy learners receive constant feedback. However, there is limited understanding of how feedback is utilized in pharmacy education. This scoping review sought to summarize the breadth and depth of the use of feedback within pharmacy education and identify areas for future research. PubMed, Embase, Scopus, and Web of Science were searched for English articles since January 2000 to identify studies related to feedback in pharmacy education. Sixty-four articles were included for analysis, stratified by moderate and major theory talk, where moderate theory talk explicitly included feedback into study design and major theory talk included feedback into both study design and analysis. Feedback was provided in Bachelor (14%), Master (15.6%), Doctor of Pharmacy (67.2%) and post-graduate programs (4.7%) on a variety of curricular objectives including communication and patient work up in didactic, objective structured clinical examination (OSCE), and experiential settings, and career/interview preparation in the co-curriculum. Feedback comments were mostly written in didactic courses, and both written and verbal in OSCE, experiential, and co-curricular settings. The pharmacy education feedback literature lacks depth beyond student perceptions, especially with respect to assessing the effectiveness and quality of feedback for learning. While feedback has been utilized throughout pharmacy education across myriad outcomes, several areas for inquiry exist which can inform the design of faculty and preceptor development programs, ensuring provision of effective, quality feedback to pharmacy learners.

Growth and Neurodevelopment Outcomes in HIV-, Tenofovir-, and Efavirenz-Exposed Breastfed Infants in the PMTCT Option B+ Program in Malawi.

BACKGROUND: Pregnant and breastfeeding women in Option B+ in Malawi received antiretroviral drugs (ARVs) containing efavirenz (EFV) and tenofovir disoproxil fumarate (TDF). However, effects on growth, renal, bone metabolism, and neurodevelopment of long-term exposure to low doses of these drugs through breast milk in HIV-exposed infants are unclear. METHODS: Prospective cohorts of TDF-and-EFV-exposed and TDF-and-EFV-unexposed breastfed infants of HIV-infected and HIV-uninfected mothers in Option B+ were recruited in 2:1 ratio, respectively, followed from birth to 18 months. Infants with low birth weight, premature birth, and congenital abnormalities were excluded. Anthropometrics were assessed at birth, 6 weeks, 3, 6, 12, and 18 months. Neurodevelopment assessments used the Bayley Scales of Infant and Toddler Development III from 6 weeks. Creatinine, alkaline phosphatase, and phosphorus were assessed at 3, 6, and 12 months. RESULTS: Of 260 HIV-and-ARV-exposed and 125 HIV-and-ARV-unexposed infants enrolled at birth, 87% and 57%, 78% and 59%, 77% and 54%, 73% and 51%, and 65% and 43% completed 6-weeks, 3, 6, 12, and 18 months visits, respectively. There were no significant differences in the mean Z-scores for length-for-age, weight-for-age, weight-for-length, mid-upper arm circumference-for-age, and head circumference-for-age between groups except at 6-weeks for length-for-age. No bone fractures occurred. Neurodevelopment outcomes were similar between groups. Of creatinine, alkaline phosphatase, and serum phosphate measurements, 1.7%, 2.6%, and 3.3% reached any toxicity levels grades 1-4, respectively, with no differences between groups. CONCLUSION: Long-term exposure to EFV and TDF through breastfeeding in infants of HIV-infected mothers does not seem to result in significant growth, neurodevelopment, renal, or bone adverse outcomes. Data support safety of breastfeeding through 18 months within the Option B+ program.

Effect of efavirenz on levonorgestrel concentrations among Malawian levonorgestrel implant users for up to 30 months of concomitant use: a subanalysis of a randomized clinical trial.

OBJECTIVES: Our primary objective was to compare geometric mean levonorgestrel concentrations between levonorgestrel implant users who were or were not taking the antiretroviral efavirenz, for up to 30 months after implant initiation. Our secondary objective was to evaluate the pregnancy rate among levonorgestrel implant users on efavirenz. STUDY DESIGN: We performed a subanalysis of 42 Malawian women randomized to initiate the levonorgestrel implant as part of a parent randomized clinical trial. Our subset included 30 HIV-infected women taking efavirenz and 12 HIV-uninfected women not taking efavirenz. They underwent urine pregnancy testing every 3 months and serum levonorgestrel testing at day 3 and months 1, 3, 6, 12, 18, 24, 27 and 30 after implant initiation. Geometric mean levonorgestrel concentrations were calculated for efavirenz users and non-efavirenz users at each time point. RESULTS: The geometric mean levonorgestrel concentrations were lower for efavirenz users than non-efavirenz users at every time point; the geometric mean ratio for efavirenz users:non-efavirenz users ranged from 0.60 [90% confidence interval (CI) 0.46-0.79] at 1 month to 0.27 (90% CI 0.12-0.61) at 30 months after implant insertion. No pregnancies occurred over 60 woman-years of concomitant levonorgestrel implant and efavirenz use, although 11 women had levonorgestrel concentrations < 180 pg/mL (the previously suggested minimum threshold concentration for efficacy). CONCLUSIONS: Efavirenz users had lower levonorgestrel concentrations than non-efavirenz users, and one third of our concomitant efavirenz and levonorgestrel implant users had concentrations < 180 pg/mL. Continued evaluation of the contraceptive efficacy of the levonorgestrel implant may be needed for efavirenz users. IMPLICATIONS: Among 42 Malawian women using the levonorgestrel implant for contraception, women who were taking the antiretroviral efavirenz had lower serum levonorgestrel concentrations than women who were not taking efavirenz. However, none of the women who were taking efavirenz became pregnant over 60 women-years of follow-up.

Endogenous Hormones and Antiretroviral Exposure in Plasma, Cervicovaginal Fluid, and Upper-Layer Packed Cells of Malawian Women Living with HIV.

Overlap in metabolism pathways of endogenous female sex hormones and antiretroviral drugs may lead to altered exposure to these compounds. In a family planning clinic in Lilongwe, Malawi, blood, blood cell, and cervicovaginal fluid (CVF) samples from seventy-three HIV positive Malawian women taken in follicular and luteal menstrual phases were assessed for estradiol and progesterone by chemiluminescent immunoassay, and for antiretroviral concentration by liquid chromatography-mass spectrometry. In both follicular and luteal phases, estradiol concentrations were lower in women receiving efavirenz compared with women on non-efavirenz regimens or no antiretroviral therapy (p < .01). Serum estradiol was moderately and negatively correlated with efavirenz plasma (r = -0.36, p < .001) and CVF (r = -0.50, p < .001) concentrations. Serum estradiol was a significant predictor of efavirenz CVF concentrations even after adjusting for efavirenz plasma concentrations (p = .02). In upper-layer packed cells (ULPCs), tenofovir diphosphate (TFVdp) concentrations were similar between follicular and luteal phases and were not correlated with estradiol or progesterone concentrations. Tenofovir concentrations in CVF were not associated with menstrual cycle or serum hormone concentrations. In CVF and plasma, efavirenz concentrations were negatively correlated with serum estradiol concentrations, suggesting a modulatory effect of estradiol on efavirenz metabolism and/or transport processes, and/or an effect of efavirenz on the metabolism of estradiol. Differences in CVF persisted even after adjusting for plasma concentrations, suggesting a mechanism specific to the female genital compartment separate from absorption or hepatic metabolism. In contrast, TFVdp concentrations in ULPC were not influenced by endogenous estradiol or progesterone concentrations.

Rural Focus and Representation in State Maternal Mortality Review Committees: Review of Policy and Legislation.

OBJECTIVES: Between 1990 and 2013, maternal mortality nearly doubled in the United States and rural residents experienced decreasing access to obstetric care. To improve maternal health, many states have established maternal mortality and morbidity review committees (MMRCs). We assessed the extent of rural representation in state policy efforts related to MMRCs. METHODS: We reviewed publicly available information on MMRCs (websites, statutes, bills, media) in all 50 states and the District of Columbia, separately identifying highly rural states (with >30% of the population being rural residents). We assessed whether each state 1) had established an MMRC, 2) had passed legislation requiring an MMRC, 3) had considered, but not passed, legislation requiring an MMRC, 4) mentioned rural populations in MMRC legislation, 5) required representation on the MMRC from any particular groups, and 6) required rural representation on the MMRC. RESULTS: As of December 2018, MMRCs were established in 45 states and the District of Columbia, an increase from 23 in 2010. Legislation was in place in 27 states, up from 6 in 2010. Only three states specifically mentioned rurality in legislation (including one highly rural state), and only two states required rural representation among their MMRC members (neither of which were highly rural states). CONCLUSIONS: Recent growth in MMRCs has had a limited focus on rural residents, despite their worse health outcomes and more limited access to health care, including obstetric services. Lack of rural representation may hamper geographically tailored efforts to reverse rising rates of maternal morbidity and mortality nationally.

Brief Report: HIV Shedding in the Female Genital Tract of Women on ART and Progestin Contraception: Extended Follow-up Results of a Randomized Clinical Trial.

BACKGROUND: Progestin contraception has been linked to higher risk of female to male sexual HIV transmission. SETTING: A clinical trial among HIV-infected women in Lilongwe, Malawi, randomized to initiation of depomedroxyprogesterone acetate injectable or levonorgestrel implant, and followed for up to 33 months, with the outcome of HIV shedding in the genital tract. METHODS: We compared the frequency and magnitude of HIV genital shedding before and after initiation of contraception and between study arms among women receiving antiretroviral therapy (ART). Genital HIV RNA was measured in TearFlo Strips using the Abbott RealTime HIV-1 assay. RESULTS: Among 68 HIV-infected Malawian women on ART, randomization to depot medroxyprogesterone acetate compared with the levonorgestrel implant was not associated with genital shedding and neither progestin contraceptive was associated with increased HIV genital shedding, for up to 33 months after contraceptive initiation. Having detectable plasma HIV [adjusted risk ratio (RR) 10.5; 95% confidence interval (CI): 3.18 to 34.7] and detectable genital shedding before contraceptive initiation (adjusted RR 3.53; 95% CI: 1.31 to 9.47) were associated with a higher risk of detectable genital shedding after contraceptive initiation. Higher plasma efavirenz concentrations were associated with a lower risk of detectable genital shedding (adjusted RR 0.85; 95% CI: 0.73 to 0.99, per increase of 1000 ng/mL). CONCLUSION: Among HIV-infected women receiving ART, our results provide evidence that progestin contraception does not impact women's risk of transmission of HIV to partners. Our finding that detectable genital shedding before contraceptive initiation independently predicts shedding suggests that there may be other individual-level biological or behavioral factors that increase the risk for shedding.

Antiretroviral Drug Concentrations in Breastmilk, Maternal HIV Viral Load, and HIV Transmission to the Infant: Results From the BAN Study.

BACKGROUND: Concentration of antiretroviral (ARV) drug found in plasma, and amounts of drug excreted into breastmilk, may affect HIV viral load and potentially perinatal HIV transmission. METHODS: In this cohort study with 2-phase sampling, we included mothers randomized to postpartum maternal ARVs or daily infant nevirapine during 28 weeks of breastfeeding in the Breastfeeding, Antiretrovirals, and Nutrition study. Among these, we included all mothers who transmitted HIV to their infants between 2 and 28 weeks and 15% of mothers who did not (n = 27 and 227, respectively). Spearman correlation coefficients (r) were used to assess the correlation between maternal plasma and breastmilk ARV concentration. Associations between the median effective drug concentration (EC50) and detectable maternal viral load (plasma: >40 copies per milliliter, breastmilk: >56 copies per milliliter) were assessed using mixed-effects models. Cox models were used to estimate the association between maternal or infant plasma drug concentration and breastmilk HIV transmission from 2 to 28 weeks. RESULTS: All ARV compounds exhibited substantial correlations between maternal plasma and breastmilk concentrations (r: 0.85-0.98, P-value <0.0001). Having plasma drug concentration above the EC50 was associated with lower odds of having detectable HIV RNA [maternal plasma odds ratio (OR) 0.64, 95% confidence interval (CI): 0.45 to 0.91; breastmilk OR 0.22, 95% CI: 0.14 to 0.35] and a reduced rate of breastmilk HIV transmission (hazard ratio 0.40, 95% CI: 0.18 to 0.93). Having breastmilk drug concentration above the EC50 was also associated with lower odds of having detectable maternal HIV RNA (plasma OR 0.62, 95% CI: 0.45 to 0.85; breastmilk OR 0.42, 95% CI: 0.29 to 0.59). CONCLUSIONS: Ensuring adequate drug concentration is important for viral suppression and preventing breastmilk HIV transmission.

Vaginal progesterone to reduce preterm birth among HIV-infected pregnant women in Zambia: a feasibility study protocol.

BACKGROUND: Women infected with HIV have a risk of preterm birth (PTB) that is twice that among uninfected women, and treatment with antiretroviral therapy (ART) may further increase this risk. Progesterone supplementation reduces the risk of preterm delivery in women who have a shortened cervix in the midtrimester. We propose to study the feasibility of a trial of vaginal progesterone (VP) to prevent PTB among HIV-infected women receiving ART in pregnancy. Given low adherence among women self-administering vaginal study product in recent microbicide trials, we plan to investigate whether adequate adherence to VP can be achieved prior to launching a full-scale efficacy trial. METHODS AND DESIGN: One hundred forty HIV-infected pregnant women in Lusaka, Zambia, will be randomly allocated to daily self-administration of either VP or matched placebo, starting between 20 and 24 gestational weeks. The primary outcome will be adherence, defined as the proportion of participants who achieve at least 80% use of study product, assessed objectively with a validated dye stain assay that confirms vaginal insertion of returned single-use applicators. Secondary outcomes will be study uptake, retention, and preliminary efficacy. We will concurrently perform semi-structured interviews with participants enrolled in the study and with women who decline enrollment to assess the acceptability of VP to prevent PTB and of enrollment to a randomized controlled trial. DISCUSSION: We hypothesize that VP could prevent PTB among women receiving ART in pregnancy. In preparation for a trial to test this hypothesis, we plan to assess whether participants will be adherent to study product and protocol. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02970552.

2017 HIV Medicine Association of Infectious Diseases Society of America Clinical Practice Guideline for the Management of Chronic Pain in Patients Living With Human Immunodeficiency Virus.

Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population.It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

2017 HIVMA of IDSA Clinical Practice Guideline for the Management of Chronic Pain in Patients Living With HIV.

Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population.It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Common Herbal Dietary Supplement-Drug Interactions.

Nearly 25% of U.S. adults report concurrently taking a prescription medication with a dietary supplement. Some supplements, such as St. John's wort and goldenseal, are known to cause clinically important drug interactions and should be avoided by most patients receiving any pharmacologic therapy. However, many other supplements are predicted to cause interactions based only on in vitro studies that have not been confirmed or have been refuted in human clinical trials. Some supplements may cause interactions with a few medications but are likely to be safe with other medications (e.g., curcumin, echinacea, garlic, Asian ginseng, green tea extract, kava kava). Some supplements have a low likelihood of drug interactions and, with certain caveats, can safely be taken with most medications (e.g., black cohosh, cranberry, ginkgo, milk thistle, American ginseng, saw palmetto, valerian). Clinicians should consult reliable dietary supplement resources, or clinical pharmacists or pharmacologists, to help assess the safety of specific herbal supplement-drug combinations. Because most patients do not disclose supplement use to clinicians, the most important strategy for detecting herb-drug interactions is to develop a trusting relationship that encourages patients to discuss their dietary supplement use.

A randomized clinical trial on the effects of progestin contraception in the genital tract of HIV-infected and uninfected women in Lilongwe, Malawi: Addressing evolving research priorities.

Hormonal contraception is central in the prevention of unintended pregnancy; however there are concerns that certain methods may increase the risk of HIV acquisition and transmission. Hormonal contraceptives may modify the genital mucosa in several ways, however the mechanisms are incompletely understood. Few studies have examined genital HIV shedding prospectively before and after initiation of hormonal contraception. The effects of hormonal contraception on genital HIV shedding in the setting of antiretroviral therapy (ART) are also unknown. We designed a pilot clinical trial in which HIV-infected and uninfected women were randomized to either depot medroxyprogesterone acetate (DMPA) injectable or levonorgestrel (LNG) implant in Lilongwe, Malawi. The objectives were to: 1) assess the effect and compare the impact of type of progestin contraception (injectable versus implant) on HIV genital shedding among HIV-infected women, 2) assess the effect and compare the impact of type of progestin contraception on inflammatory/immune markers in the genital tract of both HIV-infected and uninfected women, and 3) assess the interaction of progestin contraception and ART by examining contraceptive efficacy and ART efficacy. An additional study aim was to determine the feasibility and need for a larger study of determinants of HIV transmissibility and acquisition. As injectable contraception is widely used in many parts of the world with high HIV prevalence, this study will provide important information in determining the need for and feasibility of a larger study to address these questions that can impact the lives of millions of women living with or at risk for HIV.

Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women.

BACKGROUND: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings. OBJECTIVE: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based nutrient supplements (LNS) with concentrations of selected micronutrients in HIV-infected Malawian women at 24 wk postpartum. METHODS: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor-based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. RESULTS: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: -27%, P < 0.001; without LNS: -12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: -12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present (-18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. CONCLUSION: The association of HAART with lower folate, iron deficiency, and higher RBP plus the attenuation of LNS effects on folate and vitamin B-12 when combined with HAART has implications for the health of lactating HIV-infected women taking HAART in prevention of mother-to-child transmission programs. This trial was registered at clinicaltrials.gov as NCT00164736.

Total daily pill burden in HIV-infected patients in the southern United States.

The need for antiretroviral therapy coupled with treatment of chronic co-morbidities places HIV-infected patients at risk for polypharmacy. However, few studies have described overall pill burden among HIV-infected patients. HIV-infected outpatients of the UNC Infectious Diseases Clinic were enrolled in this cross-sectional study. Subjects were contacted prior to a scheduled appointment and asked to bring all their medications to the visit. Daily total pill burden and medication type were recorded. 151 subjects were recruited: 76% male, 58% African American, 97% receiving antiretrovirals (ARVs). Median age was 48 (IRQ: 42-54) years. The median number of medications per subject was 8 (IQR: 6-11), and the median individual daily pill burden was 8 pills (IQR: 5-15): 3 pills (range: 2-5) for ARVs and 6 (range: 3-12.5) pills for non-ARVs. Duration of ART (per 2 years increase) and more than 3 co-morbidities was significantly associated with high pill burden (over 10 pills per day) with adjusted OR of 2.09 (95% CI, 1.14-3.84) and 8.04 (95% CI, 2.30-28.15), respectively. As patients with HIV age, strategies to reduce pill burden and number of medications will become increasingly critical to maintaining adherence, preventing medication errors, and serious drug-drug interactions.

Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post-partum: results of the BAN Study.

BACKGROUND: An intensive, prospective, open-label pharmacokinetic (PK) study in a subset of HIV-infected mothers and their uninfected infants enrolled in the Breastfeeding, Antiretroviral and Nutrition (BAN) Study was performed to describe drug exposure and antiviral response. METHODS: Women using Combivir(®) (zidovudine [ZDV] + lamivudine [3TC]) +Aluvia(®) (lopinavir/ritonavir [LPV/RTV]) were enrolled. Breast milk (BM), mother plasma (MP) and infant plasma (IP) samples were obtained over 6 h after observed dosing at 6, 12 or 24 weeks post-partum for drug concentrations and HIV RNA. RESULTS: A total of 30 mother/infant pairs (10 each at 6, 12 and 24 weeks post-partum) were enrolled. Relative to MP, BM concentrations of ZDV and 3TC were 35% and 21% higher, respectively, whereas LPV and RTV were 80% lower. Only 3TC was detected in IP with concentrations 96% and 98% lower than MP and BM, respectively. Concentrations in all matrices were similar at 6-24 weeks. The majority (98.3%) of BM concentrations were >HIV(wt) IC50, with one having detectable virus. There was no association between PK parameters and MP or BM HIV RNA. CONCLUSIONS: ZDV and 3TC concentrated in BM whereas LPV and RTV did not, possibly due to protein binding and drug transporter affinity. Undetectable to low antiretroviral concentrations in IP suggest prevention of transmission while breastfeeding may be due to antiretroviral effects on systemic or BM HIV RNA in the mother. Low IP 3TC exposure may predispose an infected infant to HIV resistance, necessitating testing and treating infants early.