June 2004

HITCH TrainingSlide Set #3

Special Considerations in Antiretroviral Therapy

ObjectivesThis lecture will provide information on the following subjects:

Tuberculosis (TB) and antiretroviral (ARV) drug therapy

Immune reconstitution syndrome Adherence Clinical and laboratory monitoring for patients

in South Africa on antiretroviral treatment (ART) regimens

Concomitant Tuberculosis

Concomitant Tuberculosis

Evaluate patients for TB before starting ART Suspect TB if 2 or more of the following are

present: Observed weight loss of ≥1.5 kg over the past 4

weeks Cough >2 weeks Night sweats >2 weeks Fever >2 weeks If patient has symptoms suggestive of TB, collect 2

sputum specimens for 2 smears and a TB culture

Patient Presents with TB before Commencing ART

If no history of WHO Stage IV illness, and CD4 count >200 cells/µL, ART is not yet needed.

Start TB treatment and reassess need for ART after completion of TB treatment.

If history of WHO Stage IV illness and/or CD4 count <200 cells/µL:

Complete 2 months of TB therapy before commencing ART.

Patient Presents with TB before Commencing ART (cont.)

If CD4 count is <50 cells/µL or other serious HIV-related illness is present, make sure that the patient is tolerating TB treatment before initiating ART.

Complete at least 2 weeks of TB treatment before initiating ART.

Start patient on first-line therapy consisting of stavudine (d4T), lamivudine (3TC), and efavirenz (EFV).

Patient Develops TB while on ART

ART should be continued throughout TB treatment, with:

monitoring of clinical status changes to drug regimens as needed to

compensate for drug-drug interactions

Patient Taking TB Medication and ARVs Concurrently

Avoid nevirapine (NVP) in ARV drug regimen.

ARV drug concentrations may decrease as a result of TB medication.

There will be an increased risk for hepatotoxicity.

Patients on TB medication and ARVs are taking a large number of tablets: do proactive counseling to improve adherence.

If TB Patient Is on ARV Regimen 1b

Change NVP to EFV whenever possible. If not possible (eg, EFV intolerance or

significant risk of pregnancy), NVP may be continued in selected cases, with monthly liver enzyme monitoring.

Discuss these cases with an ARV expert.

If TB Patient Is on ARV Regimen 2

Change lopinavir/ritonavir dosage to 400/400 mg (3 extra caps of ritonavir) every 12 hours.

Continue until 2 weeks after completion of TB treatment, when the extra ritonavir can be stopped.

Immune Reconstitution Syndrome

Immune Reconstitution Syndrome

As immune system is strengthened by ART, it may begin to aggressively fight coexisting opportunistic infections (OIs).

If immune system response is too vigorous, it causes inflammation of tissues involved in the infection.

This response makes coexisting OIs worse. This is called immune reconstitution syndrome or

immune reconstitution disease.

Immune Reconstitution Syndrome (cont.)

Can occur with TB, cryptococcosis, and cytomegalovirus (CMV), among other infections.

Symptoms: fever, sweats, weight loss, cough, decreased visual sharpness (in CMV), enlarged lymph nodes (in TB).

Often seen in patients with advanced HIV disease: low CD4 T-cell count (<50 cells/µL).

Develops in the initial weeks of ART.

Immune Reconstitution Syndrome (cont.)

Immune reconstitution syndrome is not a sign of treatment failure.

Not a reason to switch therapy but should be evaluated thoroughly to exclude treatment failure or infections.

In severe cases, patients should be referred to an expert. There are no clear guidelines for the management of

immune reconstitution syndrome. Approaches include stopping ARVs or using systemic

corticosteroid treatment in severe cases.

Prophylaxis of Opportunistic Infections

Prophylaxis of Opportunistic Infections Cotrimoxazole to prevent Pneumocystis jiroveci

pneumonia (PCP) and toxoplasmosis must be continued in all patients on ART until CD4 count remains >200 cells/µL.

Also recommended if CD4 count drops to <200 cells/µL, as in cases of treatment failure.

Fluconazole for patients who have had cryptococcal meningitis should continue until CD4 count remains >200 cells/µL.

Patients on isoniazid TB prophylaxis who start ARVs should complete isoniazid treatment.

Adherence

Adherence Overview

Treatment success depends on tablet-taking behavior.

Ideal adherence means patient takes >95% of doses.

Should miss <3 doses/month

If patient is taking <95% of doses: Increased risk of developing viral resistance Decreased viral suppression Increased risk of long-term treatment failure

Adherence Overview (cont.)

Difficult to predict which patients will be adherent.

Important to provide all patients with a comprehensive plan that utilizes multiple strategies to support adherence.

Involve members of the health care team, family, and community in developing plan.

Strategies to Promote Adherence Spend time with patients and have several meetings to explain goals of therapy.

Negotiate treatment plans that patients can understand. Provide tools such as calendar of medications and pillboxes.

Ask patients about other medications they may be taking. Develop links with community-based organizations to support adherence.

eg, home-based care organizations

Pretreatment: Promoting Adherence before Starting ART

Give patients pretreatment information and education per visit schedule.

Introduce patients to therapeutic counselor and patient advocate.

Do cotrimoxazole pill count for 1 month prior to commencing ART.

This reinforces daily medication-taking behavior and helps identify potential problems before starting ART.

At Each Treatment Visit: Do ARV tablet count to calculate adherence.

(Ideal, but depends on clinic staff and workload) Goal: >95% doses taken Patient with adherence <80% requires additional

support Tablet count may done before patient is seen by

doctor Address missed/late appointments. Evaluate for possible side effects of treatment and manage appropriately.

Allow time for questions with therapeutic counselor. Encourage participation in a support group. Arrange regular community visits by patient advocates.

Additional Adherence Support Additional adherence support is needed when adherence

is <80% with or without viral or clinical failure. Therapeutic counselor/nurse or doctor must reeducate

patient. Emphasize long-term benefits of treatment. Supply memory aids such as pillboxes or daily dosing diaries. Insist on participation in a support group. Check family situation. Check psychological profile of patient. Increase home visits by counselors or patient advocates. Consider directly observed therapy for a specific amount of

time.

Calculating Monthly Adherence

Monthly adherence = (tablets dispensed -tablets returned) / (tablets prescribed)

30-5/28 = 25/28 25/28 = 0.9 0.9 x 100% = 90% Adjust for actual number of days in a given

month

Clinical and Laboratory Monitoring

Types of Clinical/Lab Monitoring

Monitoring for: Side effects Treatment failure (viral load, CD4 count)

Common tests for monitoring side effects: FBC (full blood count): to test for anemia from

zidovudine (ZDV) ALT: to test liver function Triglycerides, fasting cholesterol, fasting glucose:

to test for elevated cholesterol levels from protease inhibitors

Routine Monitoring for ARV Regimens

Regimen Drugs Monitoring Tests Frequency 1a d4T/3TC/EFV CD4 count Staging, every 6 months Viral load Baseline, every 6 months ALT Symptomatic

1b d4T/3TC/NVP CD4 count Staging, every 6 months Viral load Baseline, every 6 months

ALT

Baseline; weeks 2, 4, and 8; every 6 months thereafter

Staging: Initial testing for all patients when being referred for ART.

Baseline: Testing for ARV-eligible patients at initiation of ART.

Routine Monitoring for Regimen 1

Routine Monitoring for Regimen 2 Summary of Adult ARV Regimen 2 and Routine Monitoring Regimen Drugs Monitoring Tests Frequency 2 ZDV/ddI/LPV/r

CD4 count FBC Fasting

cholesterol, triglycerides

Fasting glucose

Staging, every 6 months

Baseline, monthly for 3 months, then every 6 months (with CD4 count and viral load)

Baseline, 6 months, and every 12 months thereafter

Every 12 months

Clinical and Laboratory Monitoring for Patients on Regimen 1a or 1b Patients attend monthly to collect medications. Seen by a professional nurse to monitor drug

tolerance, adverse events, and adherence. If possible, have clinic nurse, doctor, pharmacist, or

therapeutic counselor count drugs. Patients should be seen by doctor at 4, 8, and 12

weeks, and every 3 months thereafter. CD4 count and viral load measured every 6 months. If patient is not doing well, see patient more

frequently as determined by doctor or nurse.

Special Monitoring for Patients on Regimen 1b

Patients need to be seen by nurse at 2 weeks of treatment.

In addition to monthly visits, to check for adverse effects.

Need to check ALT levels at baseline; at 2, 4, and 8 weeks; and every 6 months thereafter.

Adjust dosing as needed.

Clinical and Laboratory Monitoring for Patients on Regimen 2

Patients must come in monthly for first 3 months to see doctor.

Thereafter, must see doctor every 6 months or as required.

Drugs should be collected every month.

Special Monitoring for Patients on Regimen 2

There is no viral load monitoring for patients in regimen 2.

FBC will be measured monthly for 3 months and every 6 months thereafter.

In addition, monitor for elevated cholesterol. Check:

Fasting cholesterol Triglycerides Fasting glucose

Viral Load Monitoring

If viral load is <400 copies/mL: Monitor viral load every 6 months Provide routine adherence support

Viral Load Monitoring (cont.)

If viral load count is 400 to 5,000 copies/mL: Repeat viral load check in 6 months. Begin stepped-up adherence package. Review at next 6-

month viral load check. If <400 copies/mL, return to monitoring at 6-month intervals

and resume adherence support. If still between 400 and 5,000 copies/mL, continue stepped-

up adherence package, repeat viral load check at 6 months. If >5,000 copies/mL despite stepped up adherence support,

switch to second-line therapy only if adherence is >80%.

Viral Load Monitoring (cont.)

If viral load count is >5,000 copies/mL: Repeat viral load check in 3 months. Begin stepped-up adherence package. Review at next 6-

month viral load check. If <400 copies/mL, return to monitoring at 6-month intervals

and resume adherence support. If between 400 and 5,000 copies/mL, continue stepped-up

adherence package, repeat viral load check at 6 months. If >5,000 copies/mL despite stepped-up adherence support,

switch to second-line therapy only if adherence is >80%.

Unscheduled Visits

Assess whether additional safety bloods are required if patient presents with adverse event.

No extra CD4 count or viral load test should be performed.

Only exception is when repeating viral load test after previous count of >5,000 copies/mL.

Treatment Failure

Patients who experience virologic failure on regimen 1 despite adherence may be changed to regimen 2.

Prior to changing, patients should undergo readiness and education process again.

Determine whether patients are hiding their nonadherence.

Patients who experience failure on regimen 2 should receive increased adherence support.

Treatment Failure with Regimen 2

If failure occurs despite demonstrated adherence, continue ARVs until the patient ceases to derive any clinical benefit from treatment.

If adherence is consistently <80%, the patient requires ongoing education and counseling.

If the patient has a WHO Stage IV illness on regimen 2, consult with an expert about stopping therapy and starting palliative care.