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Didactic Series

DHHS Guideline Update: Low-Level Viremia and Virologic Failure

Kirsten Balano, PharmD, AAHIVP

University of California, San Francisco January 25, 2018

Disclosure

• No Financial Disclosures

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Learning Objectives

1) Define low-level viremia and virologic failure.

2) Counsel patients regarding significance of detectable virus.

3) Apply DHHS guidelines when considering changes to ARV in patients with viremia.

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Poll Question A patient who has been undetectable (VL<75) Truvada (TDF/emtricitabine) and Isentress (raltegravir) for 7 years is now showing a VL of 30 and repeated 2 mo later again 55 copies/ml. How would current DHHS guidelines describe this patient’s response to ARV therapy? A: Virologic Failure B: Virologic Blip C: Virologic Suppression D: Low-Level Viremia E: Incomplete Virologic Response

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Incomplete Virologic Response:

Virologic Rebound

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Virologic Blip

Low-Level Viremia

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Risk of Virologic Failure: Inability to maintain HIV VL < 200 copies/ml on ARV Treatment

• HIV VL > 500 copies/ml • Persistent VL > 200 copies/ml • ARV change recommended

Highest Risk of Resistance and Viral Evolution

• HIV VL between LLOD – 200 copies/ml • Controversy regarding need to change ARV

Low Risk

• Virologic Blips • Virologic Suppression

Not Usually Associated with

Resistance 8

Causes of Viremia

• Patient/Adherence-Related Factors • HIV-Related Factors • ARV Regimen Related Factors

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Patie

nt F

acto

rs

• Comorbidities • Unstable

Housing • Mental Health • Missed Clinic

Appointment • Interruption Med

Access • Cost/Affordability • Adverse Effects • High Pill

Burden/Dosing

HIV

Fac

tors

• Resistance Documented

• Prior Treatment Failure

• Tropism or HIV-2 infection/co-infection

• Higher baseline VL

Med

icat

ion

Fact

ors • Suboptimal PK

• Suboptimal virologic potency

• Low Genetic Barrier to resistance

• Reduced efficacy due to Prior Exposure to suboptimal regimens

• Food Requirements

• DDI • Rx Errors

Counseling for Viremic Patient • Adherence Assessment

– Use Validated Tools with Motivational Interviewing and Strength-Based Counseling Skills

• Drug-Drug Interactions • Food Requirements • Recent illness (Vomiting or Diarrhea) • Adverse Effects/Challenges • Insurance/Pharmacy Access of Meds

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Drug-Drug Interactions

• Review concomitant medication list • http://hiv-druginteractions.org • Review OTC medication use

– Divalent Cations (Iron, Zinc, Magnesium, Calcium) can chelate with Integrase Inhibitors if administered together

– Antacids/PPI can interfere with rilpivirine absorption

– St. John’s Wort avoided with most regimens 12

Food Requirements

• Must Be Taken with Food: – Rilpivirine-containing regimens

• Improved Absorption with Food: – Elvitegravir-containing regimens

• Best if taken on empty stomach: – Efavirenz-containing regimens to avoid CNS

effects

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Poll Question A patient who has been undetectable (VL<75) Truvada (TDF/emtricitabine) and Isentress (raltegravir) BID for 7 years is now showing a VL of 30 and repeated 2 mo later again 55 copies/ml. Brief history of PI-based regimen switched due to GI SE, no resistance. Counseling shows no significant DDI (Rx or OTC). “Almost always take my medicines” – some challenges with second dose raltegravir when travel for work (approx once/mo). Good tolerance and access with strong pharmacy services. Would you change her ARV? A: No – work on adherence when travel. B: Yes – Goal is undetectable virus. C: Yes – but need Archived Genotype Resistance Test first D: I am unsure

When to change

• Low-Level Viremic Patients and Viral Blips – Often adherence related – Counsel and support

• Change ARV if needed and no resistance – Monitor VL Carefully (no more than 3 mo)

• Sustained VL > 200 after counseling interventions – Resistance Testing – Review ARV History

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DHHS Panel Recommendations • New regimens should include at least two, and

preferably three, fully active agents (A1). – Fully active has uncompromised activity based on

ART hx and current/past resistance – May have novel mechanism of action

• Adding a single ARV to failing regimen is not recommended

• Continue ARV drugs active against HBV for patients living with coinfection

• Discontinuation in setting of virologic failure not recommended

• Table 10 provides guidance on ARV options

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ARV Change after First Regimen Failure “Take Home”

• Subsequent regimens depend upon initial regimen and if M184V alone or multiple resistance mutations

• ARV with low genetic barrier to resistance (i.e. NNRTI, Elvitegravir, Raltegravir) avoided in new regimen options

• Dolutegravir BID recommended in new regimen if INSTI resistance

• Goal is always resuppression

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See nccc.ucsf.edu for more information.

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Pregnant women with HIV or at-risk for HIV & their infants

Pre-exposure prophylaxis for persons at risk for HIV

Occupational & non-occupational exposure management

Case Discussion 55 yo man living with AIDS for over 20 years. Current CD4 7, VL 65,000 off meds for 3 mo. Debilitating COPD and care for aging family members are significant barriers for patient to attend clinic visits as scheduled. Active methamphetamine use. Multiple ARV regimens over decades, however current and past resistance test only show M184V and K103N mutations. Was undetectable on Atazanavir/r/tenofovir/emtricitabine regimen in 2005 - 2010, but has not been suppressed when come in for visits over past 7 years – primarily poor access and adherence to medications and visits. Most recent regimen (first rx 2012) was using as many active drugs with darunavir, ritonavir (BID), etravirine, raltegravir – treating possibly resistant virus given history even though not seen on resistance tests. Pt motivated to improve adherence and improve CD4, but cannot swallow large tablets. Provider considering Descovy (TAF/emtricitabine) and Tivicay (dolutegravir).

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Summary • All patients with viremia, including low-level viremia,

need counseling and likely adherence support • ARV history, current and past resistance tests are

important in assessing options for ARV changes • Change ARV regimens for patients with consistent VL >

200 copies/ml to a regiment with at least 2 and preferably 3 fully active agents.

• Support adherence through ARV changes

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References • Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines

for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of Health and Human Services. Available at http://info.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Section accessed Jan 24, 2018

• Ryscavage P, Kelly S et al. “Significance and Clinical Management of Persistently Low-Level and Very-Low-Level Viremia in HIV-1-Infected Patients. Antimicrobial Agents and Chemotherapy p 3585-3598 July 2014, Vol 58(7).

• Tiera R, Vidal F et al. “Very low level viraemia and risk of virological failure in treated HIV-1-infected patients.” HIV Medicine (2017), 18 196-203.