Mobile Text Messaging to Improve Medication Adherence and Viral Load in a Vulnerable Canadian Population Living With Human Immunodeficiency Virus: A Repeated Measures Study.

BACKGROUND: Combination antiretroviral therapy (cART) as treatment for human immunodeficiency virus (HIV) infection is effective and available, but poor medication adherence limits benefits, particularly in vulnerable populations. In a Kenyan randomized controlled trial, a weekly text-messaging intervention (WelTel) improved cART adherence and HIV viral load (VL). Despite growing evidence for short message service (SMS) text-message interventions in HIV care, there is a paucity of data utilizing these interventions in marginalized or female cohorts. OBJECTIVE: This study was undertaken to assess whether the standardized WelTel SMS text-message intervention applied to a vulnerable, predominantly female, population improved cART adherence and VL. METHODS: We conducted a repeated measures study of the WelTel intervention in high-risk HIV-positive persons by measuring change in VL, CD4 count, and self-reported adherence 12 months before and 12 months after the WelTel intervention was introduced. Inclusion criteria included VL ≥200 copies/mL, indication for treatment, and meeting vulnerability criteria. Participants were given a mobile phone with unlimited texting (where required), and weekly check-in text messages were sent for one year from the WelTel computer platform. Clinical data were collected for control and intervention years. Participants were followed by a multidisciplinary team in a clinical setting. Outcomes were assessed using Wilcoxon signed ranks tests for change in CD4 and VL from control year to study end and mixed-effects logistic regressions for change in cART adherence and appointment attendance. A secondary analysis was conducted to assess the effect of response rate on the outcome by modeling final log10 VL by number of responses while controlling for mean log10 VL in the control year. RESULTS: Eighty-five participants enrolled in the study, but 5 withdrew (final N=80). Participants were predominantly female (90%, 72/80) with a variety of vulnerabilities. Mean VL decreased from 1098 copies/mL in the control year to 439 copies/mL at study end (P=.004). Adherence to cART significantly improved (OR 1.14, IQR 1.10-1.18; P<.001), whereas appointment attendance decreased slightly with the intervention (OR 0.81, IQR 0.67-0.99; P=.03). A response was received for 46.57% (1753/3764) of messages sent and 9.62% (362/3764) of text messages sent were replied to with a problem. An outcome analysis examining relationship between reply rate and VL did not meet statistical significance (P=.07), but may be worthy of investigating further in a larger study. CONCLUSIONS: WelTel may be an effective tool for improving cART adherence and reducing VLs among high-risk, vulnerable HIV-positive persons. TRIAL REGISTRATION: Clinicaltrials.gov NCT02603536; https://clinicaltrials.gov/ct2/show/NCT02603536 (Archived by WebCite at http://www.webcitation.org/6qK57zCwv).

Endocrine abnormalities in HIV-infected women are associated with peak viral load - the Children and Women: AntiRetrovirals and Markers of Aging (CARMA) Cohort.

OBJECTIVES: To investigate the prevalence of endocrine disturbances in a group of HIV-positive (HIV+) women and to identify factors affecting presence of these disorders. To examine specifically whether cellular ageing, as measured by leukocyte telomere length (LTL), is correlated with the presence of endocrine disturbance. DESIGN: A cross-sectional retrospective substudy of an ongoing prospective cohort study. PATIENTS: Adult HIV+ (≥19 years) women enrolled in the CARMA (Children and Women: AntiRetrovirals and Markers of Aging) cohort study (N = 192). Prevalences of T2DM, glucose intolerance, dyslipidaemia, thyroid disorders, adrenal insufficiency, hypogonadism, primary ovarian insufficiency (POI), demographics, HIV and hepatitis C virus (HCV) infection status, baseline LTL, combined antiRetroviral therapy (cART) and substance exposures were collected. Statistical analysis included univariable followed by multivariable Poisson regression and step-wise reduction to refine the multivariable model. RESULTS: Prevalence of any endocrine abnormality was 58% (dyslipidaemia 43%, glucose intolerance/T2DM 13%, thyroid disorders 15%). In multivariable analysis, age was associated with number and type (any, glucose, lipid) of abnormality, while increasing body mass index (BMI) was associated with number of diagnoses and with glucose metabolism disorders. Interestingly, peak HIV pVL ≥100 000 copies/ml was associated with any abnormality, total number of disorders and presence of a thyroid disorder, while any disorder, glucose abnormalities and dyslipidaemia were negatively associated with alcohol use. LTL was not associated with number or type of endocrine abnormalities in this study. CONCLUSION: Further studies examining the relationship between duration and extent of exposure to HIV viraemia in relation to developing abnormal endocrine function are warranted.

Preterm Birth and Antiretroviral Exposure in Infants HIV-exposed Uninfected.

BACKGROUND: Infants HIV-exposed and uninfected (IHEU) who are born to women living with HIV are at an increased risk of preterm birth (PTB). Antenatal exposure to certain maternal antiretroviral therapy (ART) regimens has been associated with PTB, although existing studies in this domain are limited and report discordant findings. We determined odds of PTB among IHEU by antenatal ART regimens and timing of exposure, adjusting for maternal risk factors. METHODS: We retrospectively studied IHEU born in British Columbia (BC), Canada between 1990 and 2012 utilizing provincial health administrative databases. We included data from a control group of infants HIV-unexposed and uninfected (IHUU) matched ~3:1 for each IHEU on age, sex and geocode. RESULTS: A total of 411 IHEU and 1224 IHUU were included in univariable analysis. PTB was more frequent among IHEU (20%) compared with IHUU (7%). IHEU were more often antenatally exposed to alcohol, tobacco, as well as prescription, nonprescription, and illicit drugs (IHEU: 36%, 8% and 35%; vs. IHUU: 3%, 1% and 9%, respectively). After adjusting for maternal substance use and smoking exposure, IHEU remained at increased odds of PTB [adjusted odds ratio (aOR) (95% CI): 2.66; (1.73, 4.08)] compared with matched IHUU controls. ART-exposed IHEU (excluding those with NRTIs only ART) had lower adjusted odds of PTB compared with IHEU with no maternal ART exposure, regardless of regimen [aOR range: 0.16-0.29 (0.02-0.95)]. Odds of PTB between IHEU exposed to ART from conception compared with IHEU exposed to ART postconception did not differ [aOR: 0.91 (0.47, 1.76)]; however, both groups experienced lower odds of PTB compared with IHEU with no maternal ART [preconception: aOR: 0.28 (0.08, 0.89); postconception: aOR 0.30 (0.11, 0.83)]. CONCLUSIONS: BC IHEU were over twice as likely to be born preterm compared with demographically matched controls. Maternal substance use in pregnancy modulated this risk; however, we found no adverse associations of PTB with exposure to antenatal ART.

Health Care Provider Utilization and Cost of an mHealth Intervention in Vulnerable People Living With HIV in Vancouver, Canada: Prospective Study.

BACKGROUND: Improving adherence to combined antiretroviral therapy (cART) can be challenging, especially among vulnerable populations living with HIV. Even where cART is available free of charge, social determinants of health act as barriers to optimal adherence rates. Patient-centered approaches exploiting mobile phone communications (mHealth) have been shown to improve adherence to cART and promote achievement of suppressed HIV plasma viral loads. However, data are scarce on the health care provider (HCP) time commitments and health care costs associated with such interventions. This knowledge is needed to inform policy and programmatic implementation. OBJECTIVE: The purpose of this study was to approximate the resources required and to provide an estimate of the costs associated with running an mHealth intervention program to improve medication adherence in people living with HIV (PLWH). METHODS: This prospective study of HCP utilization and costs was embedded within a repeated measures effectiveness study of the WelTel short-message service (SMS) mHealth program. The study included 85 vulnerable, nonadherent PLWH in Vancouver, Canada, and resulted in improved medication adherence and HIV plasma viral load among participants. Study participants were provided mobile phones with unlimited texting (where required) and received weekly bidirectional text messages to inquire on their status for one year. A clinic nurse triaged and managed participants' responses, immediately logging all patient interactions by topic, HCP involvement, and time dedicated to addressing issues raised by participants. Interaction costs were determined in Canadian dollars based on HCP type, median salary within our health authority, and their time utilized as part of the intervention. RESULTS: Participant-identified problems within text responses included health-related, social, and logistical issues. Taken together, management of problems required a median of 43 minutes (interquartile range, IQR 17-99) of HCP time per participant per year, for a median yearly cost of Can $36.72 (IQR 15.50-81.60) per participant who responded with at least one problem. The clinic nurse who monitored the texts solved or managed 65% of these issues, and the remaining were referred to a variety of other HCPs. The total intervention costs, including mobile phones, plans, and staffing were a median Can $347.74/highly vulnerable participant per year for all participants or Can $383.18/highly vulnerable participant per year for those who responded with at least one problem. CONCLUSIONS: Bidirectional mHealth programs improve HIV care and treatment outcomes for PLWH. Knowledge about the HCP cost associated, here less than Can $50/year, provides stakeholders and decision makers with information relevant to determining the feasibility and sustainability of mHealth programs in a real-world setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT02603536; https://clinicaltrials.gov/ct2/show/NCT02603536 (Archived by WebCite at http://www.webcitation.org/70IYqKUjV).

Neurodevelopmental outcomes and in-utero antiretroviral exposure in HIV-exposed uninfected children.

OBJECTIVES: To assess and compare neurodevelopmental disorders in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children in British Columbia, Canada. To determine associations between these outcomes and in-utero exposure to antiretroviral drugs. DESIGN: Retrospective controlled cohort study. METHODS: Data were collected on 446 HEU children and 1323 HUU children (matched ∼1 : 3 for age, sex, and geocode) born between 1990 and 2012. Multivariable logistic regressions determined odds ratios of neurodevelopmental disorder diagnoses. RESULTS: HEUs had three times higher odds of being born preterm (P < 0.0001), and a more than two-fold increase in odds for autism, disturbance of emotions, hyperkinetic syndrome, and developmental delay compared with matched HUUs (P < 0.02) in unadjusted analysis. This association was reduced [adjusted neurodevelopmental disorder odds ratio (AOR) = 1.67; 95% confidence interval: 1.12-2.48; P = 0.011] after adjusting for maternal substance use and/or smoking (children born after April 2000). Regardless of antiretroviral exposure type (i.e. none, treatment with one or multiple drug classes), HEUs had higher odds of any neurodevelopmental disorders compared with matched HUUs; however, there was no evidence suggesting any specific classes of antiretroviral drugs or exposure durations increased their likelihood of neurodevelopmental disorders. CONCLUSION: The results suggest no adverse associations between antiretroviral drugs and neurodevelopmental disorders within antiretroviral-exposed HEU children in our cohort. Prevalence of neurodevelopmental disorders is higher in HEUs; however, maternal substance use plays a role, as could other environmental factors not captured. These findings highlight a need for holistic support for pregnant women as well as careful developmental monitoring of HEUs past infancy, and access to early interventions, particularly among those born preterm and those exposed to addictive substances.