introduction, roll out and pharmacovigilance of dolutegravir in … · 2019. 12. 6. · hiv program...

Introduction, Roll out and Pharmacovigilance

of Dolutegravir in the Zambia National HIV

Program

LLOYD MULENGA, MBChB, PhD

Director: Infectious Diseases Division, University Teaching Hospital

National Coordinator: HIV Treatment & Care

Best Practice Symposium

20th November, 2019

ART COVERAGE

Introduction, Roll out and Pharmacovigilance of Dolutegravir in the Zambia National HIV Program

• ART Coverage September 2019

1,070,628 on ART

1,017,477 Adults

53,151 Pediatrics

Zambian HIV Guidelines

4

• Tenofovir Disoproxil Fumarate/

Lamivudine/Dolutegravir (TLD) or

Tenofovir Alafenamide Fumarate/

Emtricitabine/Dolutegravir TAFED

listed as the preferred first line (1L)

regimen for adults and adolescents

– Replacing TLE or TLN

Zambian Preferred First-Line ART &

Alternative Regimens by Specific Population

New

Table 11 page 29_ZCG_2018

Specific Populations Description Preferred 1st line cART Alternative regimen

Pregnant & Breastfeeding

Women

ARV naïve or Sure of tail

coverageTDF + XTC + DTG

TDF + XTC + EFV400 or

TDF + XTC + ATV-r (or LPV-r) or

ABC + 3TC + ATV-r (or LPV-r)

ABC + 3TC + DTG

Previous sdNVP exposure; or

NVP monotherapy exposure

(NVP without 7 days of AZT +

3TC cover); or unsure of tail

coverage

TDF + XTC + DTG

TDF + XTC + ATV-r (or LPV-r) or

ABC + 3TC + ATV-r (or LPV-r)

Children (0-2 weeks) AllAZT + 3TC + NVP

Consult or refer to exper t opinion

Children (2 weeks to < 5 years old)

All ABC + 3TC + LPV-r AZT + 3TC + LPV-r

HIV and TB co-infection

AZT + ABC + 3TC

(if < 3 months)

ABC + 3TC + EFV

(3 months to < 5yrs)

After completion of ATT, substitute to

preferred 1st line with LPV-r

Children (5 to <10 years old) ARV naïve ABC + 3TC + EFV AZT + 3TC + EFV or

ABC + 3TC + NVP

History of maternal sdNVP;

maternal or infant NVP

monotherapy; mother unsure of tail

coverage

ABC + 3TC + LPV-rAZT + 3TC + LPV-r or

AZT + 3TC + ATV-r

Adolescents (10 to <19 years old)

weighing ≥35kg

With or without history of maternal

or infant NVP exposure

TDF (or TAF) + XTC + DTG

TDF (or TAF) + XTC + EFV400 or

ABC + 3TC + EFV

ABC + 3TC + DTGAdults All

KEY


HIV Program Priority Areas for 2019-2020

• TLD and TAFED scale up in

adult and pediatric population

• Gradual phase out of EFV & NVP

• Introduction of TLD & TAFED in

paediatric population

• Extension of LPV/r based regimen

2 weeks to 10 years (<20kg)

• Introduction of LPVr/ granules

• Phase out of LPV/r suspension

• Setting up of the ARV active

pharmacovigilance (PV) system

• HIV Testing using screening tool

• HIV Recency Testing

• 30-day LTFU introduction

• TB Preventive Therapy with

introduction of 3HP

• Scale up Cervical Cancer

Screening for WLHIV

• POC for EID & VL

• Treatment & VL literacy

• EMTCT of HIV & Syphilis


TLD Transition Steering Committee

Members from

• Ministry of Health

• USG Agencies

– CDC, USAID

• Implementing Partners

– CHAZ, CIDRZ, CRS, EQUIP, SAFE, UoM, UTH, GHSC-PSM, CHAI

• Zambian Government Medical Supplies Limited

• Regulatory Agencies

– ZAMRA

• Civil Society

– TALC, AFROCAB, NZP+

• Private Sector –Faculty of GPs

7

Transition Protocol (1)

Initiate all ARV naïve HIV patients on TLD as 1L

• Males (>10 years and > 35kg in weight)

• Females (>49 years and those without pregnancy potential)

• New patients with HIV-1 or HIV2 or mixed HIV1/ HIV2

• Patients on 1L TLE/TLN for less than 6 months

Transition all existing virally suppressed patients on 1L TLE/N to TLD

• Virally suppressed* males (>10 years and > 35kg in weight)

• Virally suppressed females( +/- contraception )

8

* Viral suppression is defined as HIV-1 RNA < 1,000 copies/ml

VL result must not be more than 12 months old

If VL result is more than 12 months, order a fresh VL test

TLD TRANSITION ELIGIBILITY CRITERIA

Transition existing virally suppressed patients on alternate 1L to TLD or TAFED

• Patients on TDF + 3TC + LPV/r as their first line (e.g. HIV-1 & 2 or HIV – 2)

• Children aging out from pediatric regimens such as:

• ABC + 3TC + LPV-r; ABC + 3TC + EFV; AZT + 3TC + NVP

9

Patients on AZT + 3TC + LPV/r as their 2nd LINE SHOULD

NOT be transitioned to TLD (due to the risk of keeping

them on monotherapy DTG)

Transition Protocol (2)

Zambia TLD Prescribing Algorithm -

Males

Already on ART?

Yes

On TLE?

No

No

Manage as suspected

treatment failure

Continue on current

treatment

NoYes

Viral Load <1,000 copies/ ml* ?

TLD TLD

On ART <6 months? On ART ≥6 months

Yes

The test must have been done not more than 12 months ago, otherwise recommend for a new viral load test

Zambia TLD Prescribing Algorithm –

Females (during the NTD alarm period)

Zambia TLD/TAFED Prescribing Algorithm

l Publication Date: August 2019 l

OverviewThese prescribing algorithms are intended to help healthcare workers determine a patient’s eligibility for TLD and TAFED and should beinterpreted in the context of additional guidance. The algorithm has been revised to reflect the latest evidence on the use of dolutegravir(DTG) and tenofovir alafenamide (TAF). For circumstances not covered here or for any questions, please consult expert opinion (toll freenumber 7040 or through the ZamCGs mobile app).

Adults and Paeds (>25kg)

Manage as suspected treatment failure

No

Yes

Adults on Anti-TB Treatment (ATT)

Already on ART?

On TLD?

Yes

Use TLE400

during ATT5

Able to take EFV (no previous EFV failure

or intolerance) ?

No

Is DTG 50mg tablet

available?

TLD recommended3

Yes

Use LPV/r during ATT6

Yes

TLD + DTG

50mg7

No

No

5 Remember to switch TLE400 patients to TLD or TAFED after TB therapy if eligible6 LPV/r when given with rifampicin should be dosed at 600/150mg (3 tabs) twice daily for the first two weeks and then increased to 800/200mg (4 tabs) twice daily for duration of TB treatment. Remember to switch back to standard dosing after TB therapy, and if the patient is eligible, switch to TLD or TAFED7 DTG should be dosed at 50mg twice daily (i.e., 1 pill of TLD daily then 1 pill of DTG 50mg after 12 hours). Remember to switch back to standard dosing after TB therapy

For additional information on DTG or treatment of HIV, see the latest Zambia Consolidated Guidelines or ZamCGs mobile app

Yes

Yes No

1The test must have been done not more than 12 months ago, otherwise recommend for a new viral load test 2 Refer to ‘Key DTG Counseling Messages’ below 3 TLD = TDF+3TC+DTG; TLE400 (TDF+3TC+EFV400 ) is the preferred alternate 4 TAFED=TAF+FTC+DTG; ABC+3TC+ EFV is the preferred alternate to TAFED alternate

Counsel on

benefits and risks of DTG2

1. Documented creatinine clearance test>50mls/min?

2. Women less or equal to 45 years3. Men less than 50 years

Already on ART?No

No

Key DTG and TAF Counseling Messages

Inform of benefits and risks of DTG• DTG, a key component of TLD and TAFED, offers many benefits including a

higher genetic barrier to resistance, minimal side effects and druginteractions, and more rapid achievement of viral suppression

Inform of potential side effects of TLD• As with all ARVs, it is common to have side effects when taking TLD. Many

side effects from HIV medicines like TLD and TAFED, such as nausea, occasional dizziness, and insomnia, are manageable and usually go away after 1-2 months.

• All side effects and adverse events should be reported to the Pharmacovigilance (PV) Unit at ZAMRA [email protected] using the recommended PV reporting forms or Mobile App “WEBRADR”.

• DTG effectiveness can be diminished by antacids, some multivitamins, iron supplements, TB medicines, and epilepsy medicines such as phenytoin and carbamazepine. DTG also increases metformin (diabetes medicine) levels.

Provide family planning counselling • Women should always be informed that family planning is voluntary and is

not required for them to receive ART. Women of childbearing potential (WOCBP) who choose not to use contraception but opt for DTG should still be offered DTG because of the potential benefits to their health

• As is the routine practice, all women of childbearing potential seeking HIV treatment services should have access to a broad range of contraception methods and be able to choose the method that best suits their specific needs and health situation, or to choose no contraception method

Provide guidance on pregnancy • Pregnant women are recommended to take TLD given benefits of rapid viral

suppression and preventing transmission of HIV• Do not use TAFED in pregnancy

TAFED recommended4

Viral load <1,000 copies/ml?1Yes

Detectable VL is first sign of drug

resistance

13

Slideshare

Risk of DTG Monotherapy in TLD

Transition

14

TDF 3TC DTG

TDF 3TC EFV

TDF 3TC EFVPatient on

Detectable Viral Load

? Drug resistance

Transitioned to TLD

This is effectively

DTG

monotherapy

DTG in Special Populations

15

Pregnant/BF women:contraception advised before

conception (but not mandatory)

HIV-associated TB: need to double dose if rifampin is

used

Infants and children: use from 25kg as TAFED

National Uptake of TLD in Zambia (Actual vs. Targets)


DTG & TAF Active Pharmacovigilance

• No active PV exists

• Currently setting up active PV

• Mandatory reporting of specific

data elements

• Specific options to be selected

from a drop down list

• Patients to be given a paper

based form which they may

complement and submit at

subsequent visit

• Pharmacist to be specifically

assigned to the follow-up and

reporting of the data

• Introduction, Roll out and Pharmacovigilance of Dolutegravir in the Zambia National HIV Program

Data elements to be collected

• Additional

– Weight

– BMI

– Blood sugar

– Lipids (Cholesterol)

– Creatinine

• Pregnancy Module

– Infant Status

• Alive Vs Dead

• Congenital anomalies


Criteria for selecting sites for active PV

• High volume ART sites

• Availability of electronic medical records ( smart care)

– Model Sites

• Human Resource Availability

• Strong Community Linkage system


Integrating PV into the National Electronic

System (Smart Care)

ARV Pharmacovigilance Framework

ART site completes the ADR form

enters data into the Electronic System (Smart

Care)

WHO

ARV Pharmacovigilance of the MOH Collates, analyses and report to National HIV Program

Zambia Medicines

Regulatory Authority

Senior Management

of the MOH

INSULIN RESISTANCE AND SYSTEMIC INFLAMMATION AMONG HIV-POSITIVE, ANTIRETROVIRAL THERAPY (ART)-

TREATED ZAMBIAN ADULTS

HIV Unit of the MOH report to various stake holders

HIVDR

• Introduced Routine HIVDR testing for

– all individuals with VL>1,000 copies/mL on DTG based

therapy after enhanced adherence counselling

– Includes first and second line failure

• HIVDR Surveys

– Pretreatment Drug Resistance Survey

• Adults and Children

– Acquired Drug Resistance Survey

• Children and Adults


introduction, roll out and pharmacovigilance of dolutegravir in … · 2019. 12. 6. · hiv program...

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