How do you grade antiretroviral drug adherence in Human Immunodeficiency Virus (HIV) patients?

Grading Antiretroviral Drug Adherence in HIV Patients

Adherence should be monitored at every clinic encounter using patient self-report combined with objective measures, with optimal adherence defined as taking ≥90-95% of prescribed doses to achieve viral suppression. 1

Primary Measurement Methods

Patient Self-Report (First-Line Assessment)

• Conduct short-term assessment of each dose taken during the recent past (≤3 days) and general inquiry regarding adherence since the last visit 1
• Patient self-reporting is unreliable for predicting optimal adherence, but a patient's estimate of suboptimal adherence is a strong predictor and should be strongly considered 1
• Ask explicitly about circumstances of missed doses and possible measures to prevent further missed doses 1
• Have patients bring medications and medication diaries to clinic visits 1

Objective Measures (Supplementary)

• Pharmacy refill records: Track prescription refill dates to calculate medication possession ratio 1, 2
• Pill counts: Count remaining pills at clinic visits, though this can be manipulated by patients 1, 2
• Electronic monitoring systems (MEMS caps): Computer chips record each bottle opening, but due to complexity and cost, these are primarily useful for research rather than routine clinical settings 1
• Pharmacologic measures: Hair drug concentrations and dried blood spots provide objective cumulative adherence data over weeks to months 3

Adherence Thresholds for Grading

Optimal Adherence

• ≥90-95% of doses taken is required for optimal viral suppression 1
• Meta-analysis shows no significant difference in virologic outcomes between ≥95%, ≥98-100%, or ≥80-90% thresholds, suggesting the threshold may be wider than traditionally cited 4

Suboptimal Adherence

• <90% adherence is associated with virologic failure and development of drug resistance 1
• One-third of patients miss doses within 3 days in surveys, indicating suboptimal adherence is common 1

Clinical Monitoring Strategy

Frequency of Assessment

• Monitor adherence at every clinic encounter without exception 1
• Adherence wanes over time even among initially adherent patients (pill fatigue or treatment fatigue) 1

Virologic Monitoring as Adherence Indicator

• Measure HIV RNA at 4-6 weeks after starting ART, then every 3 months until viral suppression maintained for ≥1 year 5
• Persistent detectable viral load despite reported adherence suggests either true non-adherence or drug resistance 5

Important Clinical Caveats

Clinician Estimates Are Unreliable

• Clinicians overestimate patient adherence by an average of 8.9% and have poor sensitivity (24-62%) for detecting non-adherent patients 6
• Never rely solely on clinical impression; always use structured assessment methods 6

Predictors of Poor Adherence to Monitor

• Lack of trust between clinician and patient 1
• Active substance abuse or mental illness (especially depression) 1
• Lack of patient education and inability to identify medications 1
• Medication side effects or fear of metabolic/morphologic effects 1
• Lack of reliable access to primary care or medications 1

Response to Declining Adherence

• Increase intensity of clinical follow-up, shorten follow-up intervals, and recruit additional health team members 1
• Consider pharmacist-based adherence clinics, peer educators, and behavioral interventions 1
• For patients with persistent adherence difficulties despite support, consider long-acting injectable cabotegravir plus rilpivirine (Cabenuva) 7

Practical Implementation Algorithm

1. At every visit: Ask about doses missed in past 3 days and since last visit 1
2. Review pharmacy refill records: Calculate medication possession ratio 1, 2
3. Check viral load results: Detectable virus suggests adherence problem or resistance 5
4. Grade adherence: ≥90-95% = optimal; <90% = suboptimal requiring intervention 1
5. If suboptimal: Intensify monitoring, involve multidisciplinary team, address barriers 1