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National TLD transition

NASCOP

NASCOP September 2018


OPTIMIZATION AND ITS PRINCIPLES
• Optimization refers to making the best or most effective use of a
resource
Key Principles of ARV Drug Optimisation
a) Reduce toxicity
b) Improve palatability/pill burden
c) Increase resistance barrier
d) Reduce drug interactions
e) Safe use across different age groups and populations
(“Harmonization”)
f) Reduce cost
NASCOP September 2018
OVERVIEW OF DOLUTEGRAVIR
Dolutegravir (DOLUTEGRAVIR) is an Integrase Strand Inhibitor (INSTI)
Benefits of DTG
• It is better tolerated
• Has higher antiretroviral potency
• Achieves faster viral suppression
• Has a high genetic barrier for resistance
• It is available in fixed dose combination as TDF/3TC/DTG (TLD)
• Has fewer drug-to-drug interactions
Transition from NVP to DTG began in 24 high volume facilities

NASCOP September 2018


DRUG INTERACTIONS
• Significant drug interactions
a) Rifampin: use DTG 50 mg BD
b) Rifabutin: no dose adjustment required
c) Antacids and multivitamins/minerals: Administer DTG at least 2 hours
before or 6 hours after taking supplements or antacids containing Mg, Al,
Fe, Ca and Zn. For Ca or Fe, if DTG is taken with a meal then dose
separation is not required
d) Metformin: use lower dose of metformin and monitor glycemic control
e) Anti-seizure medications: consult, may need alternative anticonvulsants
• Contraindications
a) Hypersensitivity to DTG
b) End-stage renal disease; end-stage liver disease (not studied)
(Refer to 2018 ART guidelines Annex 13 C for more information) NASCOP September 2018
DTG: ADVERSE EVENTS (AEs)
• Generally well tolerated

• Most common AEs are insomnia, headache, nausea, diarrhea

• CNS AEs are common in older age (> 60 years), co-administration


with ABC, and higher plasma drug levels

• Insomnia may improve if administered with low-fat meal or on an


empty stomach (theoretical)
Note: Advise patient to take DTG in the morning and preferably with low fat diet to
minimize the AEs

NASCOP September 2018


TRANSITIONING TO TLD
Eligible population:

a) Adolescents and Adults ≥ 15 years including adolescent girls


and women of child bearing potential on effective
contraception who are on TDF/3TC+NVP, AZT/3TC+EFV,
AZT/3TC/NVP, TDF/3TC/EFV, AND PI -Based first line

b) Adolescents and Adults ≥ 15 years including adolescent girls


and women of child bearing potential on effective
contraception newly initiating 1st line ART
c) Next slides shows the transition algorithm which can be found in the 2018
guidelines on page 105 figure 6.1
NASCOP September 2018
NASCOP September 2018
MANAGEMENT OF PATIENTS CURRENTLY
ON DTG BASED ART
•Pregnant and breast feeding women on DTG based
regimen should continue their current regimen until
complete cessation of breastfeeding
•Women and adolescent girls of child bearing potential
who are NOT on effective contraceptives should be put
on Efavirenz based regimen (TDF/3TC/EFV400MG)
•Women and adolescent girls of child bearing potential
who are NOT on effective contraceptives should be
counselled on choosing an appropriate contraceptive
option and offered their choice NASCOP September 2018
DTG DURING PREGENANCY

NASCOP September 2018


DTG During Pregnancy:Studies
Botswana (DTG initiated in 1st trimester, after conception)

The preliminary findings from Botswana identified 4 babies born with a neural
tube defect among 426 women who got pregnant while taking DTG. This neural
tube defect rate is approximately 0.9 percent, compared to a rate of 0.1 percent
among women who became pregnant while taking non-DTG-based regimens.

Antiretroviral Pregnancy Registry2


• 2/110 congenital abnormalities; no neural tube defects (NTD)

• Equivalent to population-expected rates

European Cohorts3
• 3/42 congenital abnormalities; no NTD
NASCOP September 2018

2. Antiretroviral Pregnancy Registry Interim Report, Dec 2017; 3. Thorne, IAS Conference 2017
NEURAL TUBE DEFECTS
22 -26 day old embryo

Anencephaly

Spina Bifida

These are congenital deformities involving the coverings of the nervous


system
NASCOP September 2018
TIMING OF DRUG EXPOSURE

Neural tube closes


Conception

LMP 4 weeks 8 weeks 12 weeks

1st trimester: embryogenesis 2nd and 3rd trimester:


fetal development
NASCOP September 2018
INTERNATIONAL ADVISORIES, 18-MAY-2018
• World Health Organization, President’s Emergency Plan for AIDS Relief, US Food
& Drug Administration (US FDA), European Medicines Agency (EMA), Southern
African HIV Clinicians Society (SAHCS)
• DTG should not be used for women of childbearing age who are intending to
become pregnant or are not on effective contraception
• Pregnant women who are currently on DTG should continue, but consult their
HCW

• Other points
• Exclude pregnancy before starting DTG (EMA, FDA, SAHCS)
• If pregnancy is confirmed in the first trimester, switch to a non-DTG
containing regimen (EMA, SAHCS)
NASCOP September 2018
VIRAL LOAD MONITORING

NASCOP September 2018


VIRAL LOAD MONITORING
• Before switching ensure you have adequately counselled the
patient on the TLD transition

• Review the recent VL results (within the last 6 months).


• If VL is undetectable – change to TDF/3TC/DTG. Follow up in
2 weeks and repeat viral load after 3 months of new ARV
regimen
• If VL is detectable or ≥1000copies/ml – do not change current
regimen. Follow the viral load monitoring algorithm

NOTE: Viral load monitoring for clients with single drug


substitution OR regimen modification is performed at 3 months.
NASCOP September 2018
Monitoring TLD transition
•Facility and IPs accountability during transition
•Submit monthly reports on the TLD transition using a standard
template provided by NASCOP
•Monthly monitoring of transition plan at facility, main areas of focus;
•Commodities stock levels in ARV ordering points and satellites
•Numbers of PLHIV transitioned
•Adverse drug reaction reports
•Treatment outcomes
•Patient literacy among PLHIV
NASCOP September 2018
NASCOP September 2018

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