Real-time ART adherence monitoring in rural Uganda

Duration of antiretroviral therapy adherence interruption is associated with risk of virologic rebound as determined by real-time adherence monitoring in rural Uganda.

Haberer JE, Musinguzi N, Boum Y, 2nd, Siedner MJ, Mocello AR, Hunt PW, Martin JN, Bangsberg DR. J Acquir Immune Defic Syndr. 2015 Jun 24. [Epub ahead of print]

Background: Antiretroviral therapy (ART) adherence interruptions have been associated with viral rebound; however, the true risk is unknown because HIV RNA has never been measured during ongoing interruptions.

Methods: The Uganda AIDS Rural Treatment Outcomes Study is an observational longitudinal cohort of adults initiating ART. We monitored adherence with device that wirelessly transmits records of device openings, and routinely assessed HIV RNA quarterly. When 48+ hour lapses between device openings were detected, we made unannounced visits to participants to investigate the cause and assess HIV RNA. Generalized estimating equation logistic regressions were used to assess factors associated with viral rebound.

Results: We followed 479 participants (median 25 months per participant). Most were female (72%), median age was 36 years, median pre-ART CD4 count was 198 cells/µL, median pre-ART HIV RNA level was 5.0 log10 copies/ml, and median duration of prior viral suppression was 13 months. A total of 587 adherence interruptions followed confirmed prior viral suppression, of which 13 (2%) had detectable viral rebound. Viral rebound was associated with duration of adherence interruption (OR 1.25 for each day beyond 48 hours, p=0.007) and 30-day adherence prior to the interruption (OR 0.73, p=0.02).

Discussion: This paper is the first demonstration of HIV RNA rebound during adherence interruptions objectively measured in real-time. Odds of viral rebound increased by 25% with each day beyond 48 hours. Real-time adherence monitoring was feasible in a sub-Saharan African setting. Further research should assess the potential for real-time adherence interventions to sustain adherence to affordable first-line regimens.

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Editor’s notes: As the number of people taking antiretroviral therapy grows, the challenge of supporting retention and adherence to treatment becomes greater. Measuring adherence to treatment is difficult, particularly in resource-constrained settings. It is often based on self-report of missed pills, which lacks sensitivity. This paper reports a study in which adherence was monitored using a battery-operated pill box which electronically monitors each time the box is opened. Box opening is “reported” by short message service (SMS) either immediately or whenever the cellular network is next available. In this study, if the box was not opened for more than 48 hours, an unannounced home visit was made to investigate the cause and take blood for HIV viral load measurement.

Adherence of less than 80%, as measured by the adherence monitoring device, was associated with detectable viral load at the next routine clinic visit. Longer treatment interruptions were associated with increasing risk of HIV viral load being detectable in blood taken at the home visit. These results, based on a very small number of individuals with detectable viral load, are not unexpected. However the methodology is interesting in that these medication monitors have the potential to provide health care providers with real-time alerts concerning individuals missing doses. Medication monitors have previously been too expensive to be used outside research studies. However, there is interest in developing monitors which could be mass-produced at low cost. Such monitors have the potential to assist health workers in identifying individuals with poor adherence much more rapidly than is currently possible, and allowing additional adherence support to be targeted. As such they could play an important role in improving treatment outcomes. 

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