Technological methods to measure adherence to antiretroviral therapy and preexposure prophylaxis.

Purpose Of Review: The WHO's Consolidated Guidelines (2016) call for research on improved methods to proactively monitor adherence and identify those individuals who have the greatest needs for adherence support. This review aims to elucidate the latest technologies available to measure adherence to HIV antiretroviral therapy and preexposure prophylaxis against HIV infection and present their utility in various settings and populations.

Recent Findings: Within the last few years, advances have been made in the features of existing technology to measure adherence (real-time electronic adherence measurements), additional approaches have been developed (digital medicine systems) and improved (short message service surveys), and point of care testing for pharmacokinetic measures are under development.

Systematic review and meta-analysis of the adolescent HIV continuum of care in South Africa: the Cresting Wave.

Context: South Africa has the most HIV infections of any country in the world, yet little is known about the adolescent continuum of care from HIV diagnosis through viral suppression.

Objective: To determine the adolescent HIV continuum of care in South Africa.

Data Sources: We searched PubMed, Google Scholar and online conference proceedings from International AIDS Society (IAS), International AIDS Conference (AIDS) and Conference on Retrovirology and Opportunistic Infections (CROI) from 1 January 2005 to 31 July 2015.

Cooking fuel and respiratory symptoms among people living with HIV in rural Uganda.

Household air pollution (HAP) and chronic HIV infection are each associated with significant respiratory morbidity. Little is known about relationships between HAP and respiratory symptoms among people living with HIV. The objective of this study was to investigate the relationship between cooking fuel type and chronic respiratory symptoms in study participants from the Uganda AIDS Rural Treatment Outcomes Study.

The Technology Acceptance Model for Resource-Limited Settings (TAM-RLS): A Novel Framework for Mobile Health Interventions Targeted to Low-Literacy End-Users in Resource-Limited Settings.

Although mobile health (mHealth) technologies have shown promise in improving clinical care in resource-limited settings (RLS), they are infrequently brought to scale. One limitation to the success of many mHealth interventions is inattention to end-user acceptability, which is an important predictor of technology adoption. We conducted in-depth interviews with 43 people living with HIV in rural Uganda who had participated in a clinical trial of a short messaging system (SMS)-based intervention designed to prompt return to clinic after an abnormal laboratory test.

Immunologic Pathways That Predict Mortality in HIV-Infected Ugandans Initiating Antiretroviral Therapy.

The plasma kynurenine/tryptophan (KT) ratio, a marker of adaptive immune defects, strongly predicts mortality during treated human immunodeficiency virus (HIV) disease in Ugandans as compared to US-based populations. Here, the KT ratio and T-cell and plasma biomarkers of immune activation were measured among 535 HIV-infected Ugandans prior to ART initiation and at month 6 of viral suppression. The month 6 KT ratio (adjusted hazard ratio [aHR], 2.

Brief Report: Medication Sharing Is Rare Among African HIV-1 Serodiscordant Couples Enrolled in an Efficacy Trial of Oral Pre-exposure Prophylaxis (PrEP) for HIV-1 Prevention.

Sharing of pre-exposure prophylaxis (PrEP) medications is a concern for PrEP implementation. For HIV-1 serodiscordant couples, sharing may undermine the HIV-1 prevention benefit and also cause antiretroviral resistance if taken by HIV-1 infected partners. Within a PrEP efficacy trial among HIV-1 serodiscordant couples, we assessed the occurrence of PrEP sharing by self-report and plasma tenofovir concentrations in HIV-1 infected partners.

Identifying barriers to and facilitators of tuberculosis contact investigation in Kampala, Uganda: a behavioral approach.

Background: The World Health Organization recommends routine household tuberculosis contact investigation in high-burden countries but adoption has been limited. We sought to identify barriers to and facilitators of TB contact investigation during its introduction in Kampala, Uganda.

Methods: We collected cross-sectional qualitative data through focus group discussions and interviews with stakeholders, addressing three core activities of contact investigation: arranging household screening visits through index TB patients, visiting households to screen contacts and refer them to clinics, and evaluating at-risk contacts coming to clinics.

Impact of a clinical program using weekly Short Message Service (SMS) on antiretroviral therapy adherence support in South Africa: a retrospective cohort study.

Background: In randomized controlled trials, short message service (SMS) programs have improved adherence to HIV antiretroviral therapy (ART). In response, the World Health Organization recommended use of SMS programs to support ART. However, there is limited data on real-world implementations of SMS programs.

Factors that Motivated Otherwise Healthy HIV-Positive Young Adults to Access HIV Testing and Treatment in South Africa.

The World Health Organization recommends early initiation of HIV antiretroviral therapy (ART) for all those infected with the virus at any CD4 count. Successfully reaching individuals with relatively high CD4 counts depends in large part on healthy individuals seeking testing and treatment; however, little is known about factors motivating this decision. We conducted a qualitative study to explore this issue among 25 young HIV-positive adults (age 18-35) with a CD4 count >350 cells/mm who recently started or made the decision to start ART in Gugulethu, South Africa.

Counseling Framework for HIV-Serodiscordant Couples on the Integrated Use of Antiretroviral Therapy and Pre-exposure Prophylaxis for HIV Prevention.

Background: For HIV-serodiscordant couples, integrated delivery of antiretroviral therapy (ART) for HIV-positive partners and time-limited pre-exposure prophylaxis (PrEP) for negative partners virtually eliminates HIV transmission. Standardized messaging, sensitive to the barriers and motivators to HIV treatment and prevention, is needed for widespread scale-up of this approach.

Methods: Within the Partners Demonstration Project, a prospective interventional project among 1013 serodiscordant couples in Kenya and Uganda, we offered ART to eligible HIV-positive partners and PrEP to HIV-negative partners before ART initiation and through the HIV-positive partner's first 6 months of ART use.

Markov Mixed Effects Modeling Using Electronic Adherence Monitoring Records Identifies Influential Covariates to HIV Preexposure Prophylaxis.

Adherence is a major factor in the effectiveness of preexposure prophylaxis (PrEP) for HIV prevention. Modeling patterns of adherence helps to identify influential covariates of different types of adherence as well as to enable clinical trial simulation so that appropriate interventions can be developed. We developed a Markov mixed-effects model to understand the covariates influencing adherence patterns to daily oral PrEP.

Optimizing Pre-Exposure Antiretroviral Prophylaxis Adherence in Men Who Have Sex with Men: Results of a Pilot Randomized Controlled Trial of "Life-Steps for PrEP".

Antiretroviral pre-exposure prophylaxis (PrEP) has been demonstrated to decrease HIV acquisition in multiple efficacy trials, but medication adherence is critical, and was suboptimal in several studies. Fifty HIV-uninfected at risk men who have sex with men (MSM) were randomized to a cognitive behavioral intervention condition or a time and session-matched comparison counseling intervention. The experimental intervention entailed four nurse-delivered initial and two booster sessions based on Life-Steps, an ART treatment adherence intervention.

Real-time electronic adherence monitoring plus follow-up improves adherence compared with standard electronic adherence monitoring.

The impact of real-time electronic monitoring on antiretroviral therapy adherence warrants further study. We conducted an analysis of cohort participants that initially involved standard electronic adherence monitoring (EAM), followed by real-time EAM and home visits for sustained at least 48-h adherence interruptions. Immediately after switching between the two types of EAM, mean adherence among 112 participants increased from 84% to 93% and remained elevated for 6 months (P < 0.

D-Dimer Levels and Traditional Risk Factors Are Associated With Incident Hypertension Among HIV-Infected Individuals Initiating Antiretroviral Therapy in Uganda.

Objectives: We sought to describe blood pressure (BP) changes after antiretroviral therapy (ART) initiation and evaluate the association of markers of inflammation with incident hypertension in a cohort of HIV-infected individuals in Uganda.

Methods: We used mixed effects linear regression to model changes in systolic BP over time among a cohort of HIV-infected individuals initiating ART in Uganda. After exclusion of participants with preexisting hypertension, we identified participants with normal BP throughout follow-up (controls) and those with elevated BP on ≥3 consecutive visits (cases).

The Acceptability and Perceived Usefulness of a Weekly Clinical SMS Program to Promote HIV Antiretroviral Medication Adherence in KwaZulu-Natal, South Africa.

Short message service (SMS) text messages have been used to remind and encourage patients to take ART in research studies. However, few studies have assessed the feasibility and acceptability of SMS in routine clinical practice. We report patient perspectives on a weekly SMS adherence support program after implementation into clinical care at an HIV clinic in KwaZulu-Natal, South Africa.

Does Adherence Change When No One is Looking? Comparing Announced and Unannounced Tenofovir Levels in a PrEP Trial.

Differences between unannounced and announced tenofovir levels as measures of PrEP adherence are not well understood. In an ancillary adherence study involving one urban site (Kampala) and two rural sites (Kabwohe and Tororo) from the Partners PrEP study, 268 specimen pairs from chronologically proximal clinic and home visits were tested for plasma tenofovir levels. Comparing clinic and home specimens, 89 versus 89 % were classified as detectable (>0.

Understanding Patterns of Social Support and Their Relationship to an ART Adherence Intervention Among Adults in Rural Southwestern Uganda.

SMS is a widely used technology globally and may also improve ART adherence, yet SMS notifications to social supporters following real-time detection of missed doses showed no clear benefit in a recent pilot trial. We examine the demographic and social-cultural dynamics that may explain this finding. In the trial, 63 HIV-positive individuals initiating ART received a real-time adherence monitor and were randomized to two types of SMS reminder interventions versus a control (no SMS).

Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1-Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda.

Background: Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.

Methods And Findings: Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study.

Population Pharmacokinetics of Tenofovir in HIV-1-Uninfected Members of Serodiscordant Couples and Effect of Dose Reporting Methods.

Antiretroviral preexposure prophylaxis (PrEP) with once-daily dosing of tenofovir and tenofovir-emtricitabine was shown to be effective for preventing HIV-1 infection in individuals who had HIV-1-seropositive partners (the Partners PrEP Study). We developed a population pharmacokinetic model for tenofovir and investigated the impacts of different dose reporting methods. Dosing information was collected as patient-reported dosing information (PRDI) from 404 subjects (corresponding to 1,280 drug concentration records) from the main trial and electronic monitoring-based adherence data collected from 211 subjects (corresponding to 327 drug concentration records) in an ancillary adherence study.

Duration of Viral Suppression and Risk of Rebound Viremia with First-Line Antiretroviral Therapy in Rural Uganda.

Little is known about associations between viral suppression, adherence, and duration of prior viral suppression in sub-Saharan Africa. Study participants were from the UARTO study in Mbarara, Uganda. We fit regression models to characterize relationships between average adherence, treatment interruptions, and rebound viremia (>400 copies/mL) following a previously undetectable result.

Intimate Partner Violence and Adherence to HIV Pre-exposure Prophylaxis (PrEP) in African Women in HIV Serodiscordant Relationships: A Prospective Cohort Study.

Background: Intimate partner violence (IPV) is associated with higher HIV incidence, reduced condom use, and poor adherence to antiretroviral therapy and other medications. IPV may also affect adherence to pre-exposure prophylaxis (PrEP).

Methods: We analyzed data from 1785 HIV-uninfected women enrolled in a clinical trial of PrEP among African HIV serodiscordant couples.

Wireless Vital Sign Monitoring in Pregnant Women: A Functionality and Acceptability Study.

Objective: To test the functionality and acceptability of a wireless vital sign monitor in an inpatient obstetric unit.

Materials And Methods: Pregnant women at a U.S.

The Meanings in the messages: how SMS reminders and real-time adherence monitoring improve antiretroviral therapy adherence in rural Uganda.

Objective: To understand how a pilot intervention combining SMS reminders with real-time adherence monitoring improved adherence to HIV antiretroviral therapy (ART) for adults initiating treatment in rural Uganda.

Design: Qualitative study, conducted with a pilot randomized controlled trial.

Methods: Sixty-two pilot intervention study participants took part in qualitative interviews on: preferences for content; frequency and timing of SMS adherence reminders; understandings and experiences of SMS reminders; and understandings and experiences of real-time adherence monitoring.

Comparison of subjective and objective adherence measures for preexposure prophylaxis against HIV infection among serodiscordant couples in East Africa.

Background: Preexposure prophylaxis (PrEP) efficacy is highly dependent on adherence. Yet, it is unclear which adherence measures perform best for PrEP.

Methods: We compared three types of self-reported adherence questions (rating of ability to adhere, frequency of doses taken, percentage of doses taken) and three forms of objective adherence measurement [unannounced pill counts (UPC), electronic monitoring, plasma tenofovir levels] using data from an ancillary adherence study within a clinical trial of PrEP among East African serodiscordant couples (Partners PrEP Study).