Carol A. Bova

Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of ‘covert’ virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.

Psychometrics of a Brief Acculturation Scale for Hispanics in a Probability Sample of Urban Hispanic Adolescents and Young Adults

This article presents data in support of the reliability and validity of afour-item measure of acculturationfor Hispanics. The study has three strengths. First, this brief measure is evaluated with a probability sample of Hispanic adolescents and young adults (ages 15-24 years) living in urban, low-income households. Second, the sample contains both second-and third-generation Puerto Rican and Mexican American adolescents and young adults. Third, the acculturation measure was administeredas part ofaface-to-face interview. The four-item acculturation scale correlated highly with generation, length of time in the United States, subjective evaluation of acculturation, country of birth, and language chosen for the interview. The psychometric properties of this brief scale are comparable to those obtained for other published scales. Results support the use of this four-item measure of acculturation as a simple, inexpensive measure that involves minimal respondent burden.

Use of Electronic Monitoring Devices to Measure Antiretroviral Adherence: Practical Considerations

The purpose of this paper is to describe electronic monitoring device (EMD) (e.g., MEMS caps) use among HIV-infected adults enrolled in a randomized clinical trial and to make explicit some of the benefits and caveats of using electronic monitoring device technology. This is a descriptive, exploratory study of EMD use among 128 HIV-infected adults treated with at least three antiretroviral agents. Thirty-six percent of the sample admitted that they did not use the EMD consistently. Forty-one percent of the subjects reported taking out more than one dose at a time and 26% reported opening the EMD but not taking the medication. Special subject-related issues accounted for only a small percentage of all reported problems with EMD use (e.g., transient housing, incarceration, substance abuse relapse and drug treatment). Results of this study suggest that EMDs may underestimate antiretroviral adherence among HIV-infected adults. Recommendations for improving EMD data quality are presented.

A Proposal for Quality Standards for Measuring Medication Adherence in Research

A decade after widespread recognition that adherence to medication regimens is key to antiretroviral effectiveness, considerable controversy remains regarding a “gold standard” for adherence measurement. Each adherence measurement approach has strengths and weaknesses and each rests on specific assumptions. The range of assumptions regarding adherence measurement and the diversity with which each approach is implemented strongly suggest that the evaluation of a particular measure outside of the context in which it was used (e.g. the study’s operational protocol) may result in undeserved confidence or lack of confidence in study results. The purpose of this paper is to propose a set of best practices across commonly used measurement methods. Recommendations regarding what information should be included in published reports regarding how adherence was measured are provided to promote improvement in the quality of measurement of medication adherence in research.ResumenUna década después del reconocimiento generalizado que la adherencia a los regímenes de medicación es fundamental para la efectividad del tratamiento antirretroviral (ARV), se mantiene una gran controversia con respecto al “patrón oro” para la calculación de adherencia. Cada método de calculación de adherencia tiene fortalezas y debilidades y cada uno se basa en suposiciones específicas. La variedad de suposiciones sobre la calculación de adherencia y la diversidad con la cual cada método es implementado, encarecidamente sugiere que la evaluación de un método en particular fuera del contexto del cual se utiliza (por ejemplo el protocolo operativo del estudio) puede resultar en confianza inmerecida o falta de confianza en los resultados del estudio. El propósito de este manuscrito es proponer una serie de las mejores prácticas de métodos de calculación comúnmente utilizados. Las recomendaciones respecto a la información que se debe incluir en los informes publicados acerca de cómo la adherencia fue calculada, son proporcionados para promover mejoría en la calidad de la calculación de adherencia al régimen de medicación en estudios de investigación.

Pharmacokinetics of nevirapine: initial single-rising-dose study in humans.

Nevirapine, a nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, was administered for the first time to humans in a pilot study designed to investigate the pharmacokinetics and tolerance of the drug following single-dose administration to 21 HIV-1-infected individuals. The study followed a parallel design. Different groups of three subjects each were given one of seven dose levels (2.5 to 400 mg) in sequential order, starting with the lowest dose. Each subject received only one dose. Nevirapine was rapidly absorbed at all doses from a tablet formulation. Peak concentrations in plasma were generally achieved within 90 min of dose administration. Secondary peaks were also noted between 3 and 12 h or between 24 and 28 h, the latter being noted mainly in subjects receiving the higher doses. After 24 h, concentrations in plasma declined in a log-linear fashion. The terminal half-life and mean residence time exceeded 24 h in all but one subject, indicating a prolonged disposition time in this population. Both peak concentrations in plasma and areas under the plasma concentration-time curves increased proportionally with increasing dose from 2.5 to 200 mg; however, the increase in the peak concentration in plasma and the area under the plasma concentration-time curve appeared to be less than proportional at the 400-mg dose level in this small number of subjects. This observation may be due to increased clearance or decreased absorption at the highest dose or population differences in absorption or clearance between doses. Studies with a cross-over design are planned to resolve these issues. The pharmacokinetic characteristics of nevirapine are appropriate for once-daily administration. A daily 12.5-mg dose is predicted to achieve trough concentrations in plasma in the range required to totally inhibit replication of wild-type HIV-1 in human T-cell culture.

Home visits to improve adherence to highly active antiretroviral therapy : A randomized controlled trial

Background: Few rigorously designed studies have documented the efficacy of interventions to improve medication adherence among patients prescribed highly active antiretroviral. Data are needed to justify the use of limited resources for these programs. Methods: A 2-arm, randomized, controlled trial evaluated the efficacy of a community-based, home-visit intervention to improve medication adherence. Participants were 171 HIV-infected adults prescribed a minimum of 3 antiretroviral agents. The majority had a past or current history of substance abuse. Subjects were randomly assigned to receive home visits for 1 year or usual care. Medication adherence was assessed with Medication Event Monitoring stem caps at 3-month intervals from randomization through 3 months after the conclusion of the intervention. Results: A larger proportion of subjects in the intervention group demonstrated adherence greater than 90% compared with the control group at each time point after baseline. The difference over time was statistically significant (Extended Mantel-Haenszel test: 5.80, P = 0.02). A statistically significant intervention effect on HIV-RNA level or CD4 cell count was not seen, but there was a statistically significant association between greater than 90% adherence and an undetectable HIV-RNA over time (P < 0.03). Conclusion: Home visits from a nurse and a community worker were associated with medication adherence greater than 90% among a cohort of socially vulnerable people living with HIV/AIDS in northeastern United States.

Sexual Functioning among HIV-Infected Women

The influence of HIV on sexual activity and functioning presents a unique set of issues. HIV transmissibility, partner disclosure, potential vertical transmission and, for some HIV-infected women, problems associated with illicit drug use, may affect sexuality. Few studies have examined HIV-infected womens sexuality and none have studied the relationship between HIV symptoms, HIV illness stage, quality of life, meaning of illness and sexual functioning. This descriptive study examines sexual activity, sexual functioning and safer sex behavior among 101 HIV-seropositive women. Results indicate that (1) the majority of women continue to be sexually active after testing HIV positive, (2) sexual functioning does not change as a result of HIV disease progression, and (3) few women report that HIV itself caused worsening of their sexual functioning. Those women with better mental health, more positive meaning attributed to life with HIV infection, better quality of life, fewer HIV-related symptoms and who never used injection drugs had higher levels of sexual functioning. Greater focus on sexual functioning as an integral part of clinical assessment is needed. Patterns of sexual behavior among HIV-infected women require continued study as we search for more effective means to prevent secondary HIV transmission.

Social Support to Empower Parents (STEP) An Intervention for Parents of Young Children Newly Diagnosed With Type 1 Diabetes

Purpose The purpose of this study was to test the efficacy of a social support intervention with parents of children <13 years old newly diagnosed with type 1 diabetes mellitus (T1DM). Methods For this randomized, controlled clinical trial, 10 parent mentors of children diagnosed with T1DM ≥1 year and 60 parent participants were recruited from 2 pediatric diabetes centers. Mentors were trained to provide social support (home visits and phone calls) for 12 months to families in the experimental arm (32 mothers). Control group parents (28 mothers) received the phone number of an experienced parent (not trained to give social support) to call as needed. Findings Mothers in the experimental and control arms differed at baseline only in birth order of the child with T1DM. The 2 groups did not differ significantly at 3, 6, or 12 months in parent concern, confidence, worry, impact on the family, or perceived social support. Mothers in the experimental arm identified the parent mentor as someone they would seek for advice and issues regarding growth and development, sleep, eating habits, and identification of community agencies. Parent mentors consistently referred mothers to health care providers for advice on medications and treatments but helped them incorporate this advice into day-to-day management. Conclusion Mothers in the experimental arm valued the mentors’ help in adjusting to the diagnosis, but this value was not measured by the study instruments. Focus group research is under way to clarify the concept of parent mentor social support and to develop a social support measurement tool.

Parents of children newly diagnosed with type 1 diabetes: experiences with social support and family management.

Purpose The purpose of this mixed-methods descriptive study with parents of children newly diagnosed with type 1 diabetes was to explore their experiences with peer social support following the Social Support to Empower Parents (STEP) intervention and the usefulness of the Family Management Measure (FaMM) in this population. Methods Parents who were in the experimental arm of STEP were recruited. Qualitative interviews were conducted (n = 21), and 11 parents completed the FaMM, a quantitative family-functioning measure. Qualitative content data analysis was conducted and compared to the descriptive measure analysis. Findings Three themes were identified: availability, practical tips, and common ground. Five FaMM subscales were reliable (α > .80) in this small sample. Conclusions The findings illustrate that the STEP intervention is helpful, providing the participants with emotional, affirmational, and informational social support. The use of the FaMM is a first step in assessing family management in families with children with type 1 diabetes.

Home-based study of anti-HIV drug regimen adherence among HIV-infected women: Feasibility and preliminary results

Collection of antiretroviral medication adherence data in the homes of HIV-infected people may have methodological advantages that can improve data quality. However, the feasibility of this approach has not been established. In addition, data on adherence, and its predictors, among HIV-infected women have been limited. Sixty-three HIV-positive women who were prescribed at least one antiretroviral drug in the last month were interviewed in their homes. A standard instrument was used to collect data on all antiretroviral medications prescribed and taken in the three days prior to the interview. Data were also collected on factors thought potentially to affect the ability to be adherent. The results of this study suggest that it is feasible to conduct home-based adherence research. Sixty-seven per cent reported taking all prescribed antiretroviral medication doses. One-third took a sub-optimal dose putting themselves at increased risk of treatment failure and the selection of resistant HIV strains. Unintentional reasons for missing doses were most commonly reported. An ability to describe the intended effect of antiretroviral therapy on HIV viral load was the best predictor of adherence. This finding is consistent with other research suggesting that adherence is associated with an understanding and belief in the effectiveness of antiretroviral therapy.