Job Aids on Dolutegravir Transition [Draft]

National HIV, AIDS, STI Prevention and Control Program

Job Aids on Dolutegravir Transition November 2020

National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

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CONTENTS

TLD Eligibility ��������������������������������������������������������������������������������������������������������������������������������������� 1 TLD-related Adverse Events ������������������������������������������������������������������������������������������������������������ 2 Common Adverse Effects and its Management �������������������������������������������������������������������������� 3 Managing Immune Reconstitution Inflammatory Syndrome (IRIS) in TLD Patients ������������ 4 Managing Hypersensitivity Reactions in TLD Patients ���������������������������������������������������������������� 5 Managing TLD related Renal and Liver Diseases ������������������������������������������������������������������������ 6 Management and Reporting TLD Adverse Drug Reactions ������������������������������������������������������ 7 TLD Drug-drug Interactions ������������������������������������������������������������������������������������������������������������ 8 TLD and Supplements ���������������������������������������������������������������������������������������������������������������������� 9 Monitoring on TLD ����������������������������������������������������������������������������������������������������������������������������� 10 Role as a Healthcare Worker ������������������������������������������������������������������������������������������������������������ 11 Reporting through Form BC ����������������������������������������������������������������������������������������������������������� 12 References ������������������������������������������������������������������������������������������������������������������������������������������� 13

TLD Eligibility

All adults, adolescents, and children ≥ 30 kg, not on rifampicin-based regimen Not on ART

1. Newly diagnosed OR 2. Lost-to-follow-up returning to care

On ART

First-line ART with severe side effects* AZT or ABC-based regimens with treatment failure

*Eligible side effects ☐ Dizziness ☐ Insomnia ☐ Vivid dreams ☐ Anxiety, depression ☐ Mental confusion ☐ Convulsions ☐ Liver toxicity ☐ Severe skin reactions ☐ Severe hypersensitivity reactions ☐ Gynecomastia

National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

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TLD-related Adverse Events

Commonly reported AEs

Rare but serious AEs

Nausea

Renal toxicity (Fanconi’s syndrome)

Abdominal Pain

Bone problems

Diarrhea

Lipodystrophy

Headache

Lactic acidosis

Itching or mild rash Body ache

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National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

Common Adverse Effects and its Management

Common DTG related adverse effects

Management

Nausea (2-17%)

Drink lots of water

Headache (1-15%)

Paracetamol as needed

Rash (1%)

Antihistamines as needed

Sleep disorder (Insomnia) (1%)

Take TLD upon waking up

Weight gain

Maintain ideal body weight and 150 minute moderate intensity aerobic exercise per week

National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

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Managing Immune Reconstitution Inflammatory Syndrome (IRIS) in TLD Patients

Adverse Event

Description

Management

Immune Reconstitution Inflammatory Syndrome (IRIS)

Happens to someone who is severely immunocompromised and has undetected or incompletely treated preexisting opportunistic infection. Quick recovery of immune system could lead to worsening of symptoms (eg., enlargement of TB adenitis, difficulty of breathing in Pulmonary TB)

It happens as much as with other ART. If unstable vital signs, manage at emergency care level.

If stable, can prescribe steroids to decrease inflammation at outpatient.

Pictures from: Meintjes G, Lawn SD, Scano F, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis. 2008;8(8):516-523. doi:10.1016/S14733099(08)70184-1

IRIS in a patient with TB adenitis, who presented with enlargement of cervical lymph nodes upon starting ART

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National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

Managing Hypersensitivity Reactions in TLD Patients

Adverse Event

Description

Management

Hypersensitivity Reaction

☐ Severe rash

Stop all drugs until patient recovers.

Identify the drug causing severe hypersensitivity as it should never be used again.

— Severe urticaria, angioedema, with or without anaphylaxis ☐ Constitutional symptoms — Fever, malaise, fatigue, etc., AND / OR ☐ Organ dysfunction — Liver and kidney

Picture from: Walkty A, Smith D, Lopko B, Kasper K. Severe skin rash associated with atazanavir. Can J Infect Dis Med Microbiol. 2009;20(1):e10-e12. doi:10.1155/2009/721956

A patient who experienced generalized rash after starting on ART

National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

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Managing TLD related Renal and Liver Diseases Renal Insufficiency

Liver Disease

Common Signs and Symptoms

Decreased urine output, edema, fatigue

Jaundice, RUQ pain, ascites, nausea, vomiting, malaise, disorientation

Dose adjustment

Mild (eGFR 50-80 mL/ min): No dose adjustment

Mild - Moderate (Child Pugh A / B): No dose adjustment

Moderate Severe (eGFR <50 mL/min): Avoid use. Refer to nephrologist

Severe (Child Pugh C): Use with caution but co-manage with gastroenterologist

Child-Pugh Score (Classification of Liver disease severity) 1 point

2 points

3 points

Total bilirubin (umol/L)

<34

34-50

>50

Serum albumin 9g/L)

>35

28-35

<28

PT-INR

<1/7

1.71-2.30

>2.30

Ascites

None

Mild

Mod Severe

Hepatic Encephalopathy

None

Grade I-II Grade (suppressed III-IV (or with refractory) medications)

SCAN ME

Class A: 5-6; Class B: 7-9; Class C: 10-15

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National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

Compute for your patient’s eGFR through here!

Management and Reporting TLD Adverse Drug Reactions

Mild to Moderate

Manage accordingly

Assessment and Management

Tolerated ADR

Continue ART

Impact on Adherence

Severe

Send to emergency

Restart ART

Follow-up and Releases

Interrupted ART intake Substitute ART

SCAN ME

Report to FDA

National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

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TLD Drug-drug Interactions Interaction requiring dose adjustment

☐ Loperamide ☐ Omeprazole ☐ Pain meds: Paracetamol, ibuprofen ☐ Psychiatric: Valproic acid, Lamotrigine, Anti-depressants ☐ Cardiologic: Most antiarrhythmics, Beta blockers, losartan, amlodipine ☐ Antihistamines ☐ Hormonal therapy: Testosterone, ethinyl estradiol ☐ Hormonal contraceptives ☐ Recreational drugs: Alcohol, methamphetamine ☐ Methadone ☐ Anti-malarials ☐ Rifabutin

☐ Rifampicin (such as in HRZE and HR) - DTG 50 mg BID ☐ Antacids - take 2 hours before or 6 hours after TLD ☐ Supplements: Multivitamins, Calcium, and Iron supplements - take 2 hours before or 6 hours after TLD ☐ Metformin - decreases dose of metformin, monitor glycemic control. ☐ St. John’s Wort - may decrease the efficacy of DTG ☐ Carbamezapine - DTG 50mg BID ☐ Etravine - only use with boosted protease inhibitors

Contraindicated ☐ Phenobarbital ☐ Phenytoin

SCAN ME

No interaction / dose adjustment

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National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

TLD and Supplements

Intravenous (IV) Glutathione

IV Glutathione is not approved for skin whitening. It is only approved for use to protect cancer patients from side effects of their chemotherapy. Its use with DTG, as with other ART, has not been established.

Whey protein

Generally safe taken with TLD

Magnesium and Zinc containing supplements

Should NOT be taken together. Take TLD 2 hours before or at least 6 hours after the supplements.

Calcium, Iron, Magnesium, and Aluminum supplements

May be taken with TLD ONLY if with meals. If not taken with meals, take TLD 2 hours before or at least 6 hours after the supplements.

Slimming tea (Senna)

Generally safe taken with TLD

National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

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Monitoring on TLD

History and PE Clinical Status

General well-being and health status, WHO clinical staging

Adherence

Missed pills; investigate if poorly adherent, probe on experience with TLD, treatment motivation, support group, mental health issues, and drug use.

Possible adverse effects

Probe and manage both common and rare adverse drug reactions

Female who has the intent of having a child.

Counsel female patients on the potential risks of TLD intake during early pregnancy. They should be aware there is a risk of neural tube defects 1 in 1000 pregnancies among patients who took TLD before 12 weeks of pregnancy

Laboratory Work-up Effectiveness

Viral load, CD4 count (only in the absence of VL)

Blood chemistries

Serum creatinine (DTG can increase this slightly but not due to renal toxicity) and other routine labs

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National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

Role as a Healthcare Worker

We have important roles* in ensuring the TLD transition is successful Use

Prescribing TLD to the eligible patients

Product/Supplier selection

Counselling patients regarding the transition Inventory Management

Timely and accurate reporting of stocks and other issues

Inventory Management*

Forecasting

Use*

Procurement

Distribution

National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

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Reporting through Form BC BC

HIV CARE REPORT

VISIT INFO

The Law on Reporting Disease (R.A. 3573) & the Philippine AIDS Prevention and Control Act (R.A. 8504) requires physicians to report all diagnosed HIV infections to the HIV & AIDS Registrar at the Epidemiology Bureau, DOH. Please write in CAPITAL LETTERS and CHECK the appropriate boxes.

HIV Confirmatory Code:

Patient code:

Date of visit:

Physician's name:

(MM / DD / YYYY)

Visit type: ☐ First consult at this facility; trans-in from:

☐ Follow-up ☐ Inpatient

Facility name: (HIV treatment facility)

Facility address: Facility contact #:

If this is the patient's first care visit at this facility , please fill out this section: UIC:

Philhealth No.:

__ __ | __ __ | __ __ | __ __ __ __ __ __ __ __

IF FIRST VISIT

* UIC: First two letters of mother's name, first two letters of father's name, two-digit birth order, birthdate (MM-DD-YYYY)

Sex (at birth): ☐ M

Patient's full name: Current residence:

City/Municipality:

KP Class: ☐ MSM

☐ TGP

☐ SW

☐ IDU

☐ Partner of KP

☐ Yes ☐ No

Already on treatment for current active TB prior to this visit?

☐I

LABORATORY TESTS

Latest results

☐ II

☐ III

☐ IV

Date done

Results

Date done copies/mL

Creatinine

μmol/L

CD4 count

cells/µL

HBsAg

IU/mL

Chest X-ray Gene Xpert HIVDR & Genotype

No active TB

TB INFORMATION

Results

Viral load

Presence of at least one of the following: weight loss, cough, night sweats, fever?

IPT Status: ☐ Started IPT this visit

☐ Ongoing IPT ☐ Not on IPT

☐ Ended IPT this visit

Site: ☐ Pulmonary Drug resistance:

☐ Completed ☐ ☐ Stopped before target end

OI

☐ Hepatitis B ☐ Hepatitis C

TB tx outcome (if ended this visit):

☐ Pneumocystis pneumonia (PCP) ☐ CMV retinitis ☐ Cotrimoxazole prophylaxis ☐ Azithromycin prophylaxis

Currently pregnant: Type of infant feeding:

☐ No ☐ Yes; Age of gestation: ☐ Breastfeeding ☐ Formula feeding

ART Status:

Drug

☐ Enrolling this visit ☐ Continuing

ART REGIMEN

☐ Extrapulmonary ☐ Susceptible ☐ MDR ☐ RR only ☐ Other: ☐ Not on tx

☐ Other:

Currently taking:

☐ Yes ☐ No

With active TB

TB treatment status: ☐ Ongoing

IPT outcome (if ended IPT this visit):

Infections currently present (check all that apply):

OB

History of PreP: ☐

☐ Yes ☐ No

Already diagnosed with current active TB by another facility?

WHO Classification:

☐F

Province:

☐ XDR

☐ Completed ☐ Other:

☐ Cured ☐ Failed ☐ Not yet evaluated ☐ Other: ☐ Oropharyngeal candidiasis ☐ Others (specify)

If delivered, date of delivery:

☐ Mixed feeding

# of pills per day

# pills missed

(past 30 days)

# of pills left

Date discontinued

Reason (D/C code)

☐ Not on ART Reason if not on ART:

Discontinuation codes: 1- Treatment Failure 2-Clinical progression/hospitalization

HACT Physician approval:

PHARMACY

Date Dispensed

Drug

# of pills on hand

3-Patient Decision/Request 4-Compliance difficulties 5-Drug Interaction

6-Adverse Event (Specify) 7-Others (Specify) 8-Death

# of pills dispensed

Dispensed by:

Please send this accomplished form to Epidemiology Bureau - Department of Health, 2/F Rm. 209, Building 19, San Lazaro Compound, Rizal Avenue, Sta. Cruz, 1003 Manila Contact Nos: (02) 310-1452 & (02) 651-7800 loc. 2952 | EB-DOH Form BC (HIV Care Report) v2017

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National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

TDF+3TC+DTG

References

Health Care Worker Training on the Introduction of Dolutegravir for the Treatment of HIV Infection. New York: ICAP at Columbia University; 2018.

Philippines TLD/DTG TRANSITION Operational Plan. Department of Health, Republic of the Philippines; 2020.

Meintjes G, Lawn SD, Scano F, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis. 2008;8(8):516-523. doi:10.1016/S14733099(08)70184-1.

Walkty A, Smith D, Lopko B, Kasper K. Severe skin rash associated with atazanavir. Can J Infect Dis Med Microbiol. 2009;20(1):e10-e12. doi:10.1155/2009/721956.

National HIV, AIDS, STI Prevention and Control Program: Job Aids on Dolutegravir Transition

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