Understanding

Adult ART
regimens
SIMKONDA Twambilire
 Learning Objectives
After this lecture, students should be able to:
• Describe the ARV drug classes
• Identify the common side effects of ARVs
• Explain the ART treatment regimens
• Explain the rules for prescribing and dispensing ART

• Pediatric ART will be discussed in the next session 2

Understanding ART Regimens Key
Facts (1)
• Effective antiretroviral therapy requires combining 3
different ARVs that act differently to avoid
development of drug-resistant HIV.
• Use the standard ARV regimens for the specified
patient groups shown in the guidelines.
• Do not change the drugs in the ART regimens without
clear medical indication
3
 Understanding ART Regimens Key
Facts (2)
• 1st Line regimens are often the first treatments people start. Patients
can remain on the same 1st line regimen for many years if they are
fully adherent.
• 1st line regimens:
• Are usually easier to prescribe and easier to take
• Have a lower risk of side effects
• Require no routine lab monitoring for toxicity
• Regimens 4, 5, 9, 13, 14, 15, 16 & 17 are the current 1st line
regimens
4
 Understanding ART Regimens Key Facts
(3):
8 different 1st line regimens:
• Two are standard for initiating ART depending on patient age and
weight
• A standard initiation regimen (5, 9, 13 or 15) is chosen based on
patient weight and age

• Immediately move all patients with significant side effects to an

alternative 1st line regimen
• Alternative regimens are chosen by substituting only the ARV
responsible for the side effects 5
 Understanding ART Regimens Key
Facts (4)
2nd Line regimens:
• For patients who have confirmed treatment failure on 1st line
regimen
• Contain a different class of ARVs than first line
• Are more complicated to prescribe and take
• Can have more side effects
• Moving from 1st to 2nd line ART due to treatment failure is
called switching
Integrated ART-PMTCT-TB Training-
Session 15 6
 Understanding ART Regimens Key
Facts (5)
• 8 different 2nd line regimens
• Some 1st line regimens are also used as 2nd line regimens
(Regimens 9, 13, 14 & 15)
• The appropriate 2nd line regimen is determined by the 1st
line regimen that the patient was taking when
failure occurred

• Changing from 1st to 2nd line requires changing 2 or more

ARVs 7
 Understanding ART Regimens Key
Facts (6)
3rd Line regimen:
• For patients who fail on 2nd line despite good adherence
• Requires confirmation of drug resistant virus using
genetic analysis in the lab
• Needs a Specialist Clinician or 3rd line committee to
switch
• Are very expensive; have more side effects, and are
more difficult to take 8
Classification of individual ARVs
• Main classification is based on mode of action against HIV
replication
• Sub-classification is based on biochemical structure of the
drug
• Only ARVs with the same dosing interval are available as
fixed-dose combinations.
 Classification of
Antiretroviral medicines
• NRTI (Nucleoside Reverse Transcriptase Inhibitors)
• NtRTI (Nucleotide Reverse Transcriptase Inhibitors)
• NNRTI ( Non-Nucleoside Reverse Transcriptase
Inhibitors)
• PI (Protease Inhibitors)
• Entry Inhibitors
• Integrase Inhibitors
NRTIs PIs
• Abacavir (ABC) • Atazanavir (ATV)
• Durunavir (DRV)
• Didanosine (DDI)
• Fosamprenavir (f-APV)
• Emtricitabine (FTC)
• Indinavir (IDV)
• Lamivudine (3TC) • Lopinavir (LPV)
• Stavudine (D4T) • Nelfinavir (NFV)
• Zidovudine (AZT) • Ritonavir (RTV)
• Saquinavir (SQV)
• Tenofovir (TDF) • Tripranvir (TPV)
-an NtRTI NNRTIs
http://www.nejm.org/doi/pdf/10.1056/NEJMoa1311274 • Efavirenz (EFV)
Other ARVs
• Nevirapine (NVP)
• Entry inhibitors: Enfuvirtide, Maraviroc • Etravirine
• Integrase inhibitors: Raltegravir, Elvitegravir,
Dolutegravir • Rilpivirine
• Maturation inhibitors: Beviramat
 CCR5
Inhibitors
HIV Life Cycle Proteas
e
inhibitor
Fusion s (PIs)
Inhibitors

NRTIs and
NNRTI
 Classification of ARV’s
Mode of action Biochem. structure Abbrev. ARVs Dosing interval

AZT 12-hourly

Nucleosides NRTI 3TC, ABC 12- or 24-hourly

Reverse Transcriptase ETV 24-hourly
Inhibitors
Nucleotide NtRTI TDF 24-houry
NVP 12-hourly
Non-Nucleosides NNRTI
EFV 24-hourly
ATV/r 24-hourly
Protease Inhibitors PI DRV 12-hourly
LPV/r 12-hourly
DTG 24-hourly
Integrase Strand
INSTI
Transfer Inhibitor RAL 12-hourly
13
 Regimen names
• ART regimens and formulations are numbered and coded
to ease M&E and supply management:
• Most PI- and INSTI-based regimens may be used as 1st or
2nd line.
• It is therefore no longer possible to distinguish 1st and
2nd line regimens without knowing the patient’s regimen
history.
• The 4 remaining NNRTI-based regimens are only used as
alternative 1st line (Regimen 4, 5, 16, 17).
 START REGIMENS

• Starting 1st line regimen for males & females from 30kg+
= Regimen 13A
• Starting 1st line regimens for children under 30kg =
Regimen 9 and Regimen 15P/15A.
• This will be reviewed in paediatric ART session

• Start on alternative 1st line regimen if the patient has any

contraindications for Regimen 9, 13 and 15.
15
• ART regimen formulation codes
• “A” is added to the regimen number for adult
formulations (e.g. Regimen 13A)
• “P” is added for paediatric formulations (e.g. Regimen 9P)
• “PP” is added for regimens that are made up of 2
separate tablets when both tablets are paediatric
formulations. For example, Regimen 15PP contains ABC
120mg/3TC60mg (paediatric) + DTG 10mg (paediatric).
• “PA” is added for regimens that are made up of 2 separate tablets when
one is paediatric and the other is adult formulation. For example, Regimen
15PA contains ABC 120mg/3TC60mg (paediatric) + DTG 50mg (adult).
• Fixed dose combinations (FDC) are shown with a slash (e.g., TDF / 3TC /
DTG).
• Combinations made up of separate tablets are shown with + (e.g.,
AZT/3TC + EFV)
• 3TC (Lamivudine) is the backbone in ALL 1st and 2nd line regimens
because it is extremely well tolerated and remains effective even when
drug-resistant HIV is present
• Fixed dose combinations (FDC) are shown with a slash
(e.g. TDF/3TC/DTG)
• Combinations made up of separate tablets are shown with
+ (e.g. AZT/3TC+EFV)
 Use of DTG or EFV in women of
reproductive age

• DTG is of particular benefit to Women of Child-

bearing potential and adolescents (sub-optimal
adherence, EFV side-effects, triple class failure)

• DTG is safe in very early pregnancy though

associated with a minimal risk of causing neural
tube defects. 19
 Use of DTG or EFV in women of
reproductive age
 Women should be provided with information about benefits
and risks regarding the use of DTG or other ART
 There is a very small risk of birth defects when taking DTG in early
pregnancy (3/1000 deliveries in women on DTG vs 1/1000 deliveries in
women not on DTG)

 For many women, the benefit of taking DTG outweighs the risk

20
 Use of DTG or EFV in women of
reproductive age
 SRH and HIV Integration should be encouraged at client
and facility levels

 Use of contraceptive method is encouraged but not a pre-

requisite for prescribing DTG
 Offer 5A as an alternative for women with contraindications to
13A or those who prefer not to take 13A.
21
 START REGIMENS summary
Weight (kg) Regimen Conditions / Instructions
Under 3kg - No routine ART. Consult DHA in special cases.

3 – 20kg 9P Use LPV/r granules for children unable to swallow whole paediatric LPV/r tabs.
LPV/r tabs must not be broken, crushed or dissolved.

20.0 – 24.9kg 15P Use paediatric ABC/3TC tablet + regular (adult) dose DTG 50mg. Use paediatric
patient card (blue)

25.0 - 29.9kg 15A Use adult ABC/3TC tablet + regular (adult) dose DTG 50mg. Use adult patient card
(yellow)

30kg + 13A
22
Standard ART Regimens: 1st line
Adult Regimen Paediatric
4A AZT/3TC + EFV 4P
5A TDF/3TC/EFV -
9A ABC/3TC + LPV/r 9P
13A TDF/3TC/DTG -
14A AZT/3TC + DTG 14P
15A ABC/3TC/DTG 15P
16A ABC/3TC + RAL 16P
17A ABC/3TC + EFV 17P
23
 Initiating regimens
Regimen Start Reg. Regimen/Frequency

4 NO AZT/3TC+EFV, 12 + 24hrly

5 Alternative for 13A TDF/3TC/EFV, 24hrly

9 YES ABC/3TC+LPV/r

13 YES TDF/3TC/DTG, 24hrly

14 NO AZT/3TC + DTG, 12 + 24hrly

15 YES ABC/3TC/DTG, 24hrly

16 NO ABC/3TC + RAL, 24hrly + 12hrly

17 NO ABC/3TC + EFV, 24hrly 24

 Giving a Tail
• NVP and EFV remain in the body much longer than other
ARVs. Stopping any 1st line regimen due to side-effects (or due
to patient’s decision, etc.) requires a 7-day ‘tail’ of the other
2 ARVs to avoid exposing HIV to monotherapy (only NVP or
EFV)
• Do NOT give the ‘tail’:
• With severe or life-threatening side effects
• Lactic Acidosis
• Pancreatitis
• STOP all ARVs immediately 25
 Absolute contraindications:

• Patients who developed severe toxicity to any

specific ARV:
• Hepatitis or Stevens-Johnson Syndrome from NVP or EFV
or DRV
• Severe anaemia from AZT
• Hypersensitivity from ABC

• NEVER give a regimen containing the

responsible ARV to the patient who has had a
severe toxicity
26
 Side effects
• Chose the appropriate alternative regimen from Alternative
1 Column for patients with:
• Contraindications
• Significant side-effects (immediately)
• Troubling side effects that did not improve within 2
months with symptomatic treatment.
• Use Alt. 2 if Alt. 1 can’t be used due to previous toxicity or
other specific contraindications
27
Table 11 – Standard ART regimens
 Possible Alternati
Adverse ve
Reaction Regimen
s s

Integrated ART-PMTCT-TB Training- Session 15 29

 Substitution in case of side effect

• Do not use TDF-containing regimens in severe renal

failure (creatinine clearance <50ml/min)

• Possible adverse event / If confirmed:

• Chose the appropriate alternative 1st line regimens for patients
with contraindications or with moderate to severe side-effects

30
 Switching to 2nd line

• The appropriate 2nd line regimen depends on the 1st line

regimen the patient was on when confirmed with
treatment failure.

• Only certified Level 2 & 3 ART providers can initiate 2nd

line.

31
Standard ART Regimens: 2nd line

Integrated ART-PMTCT-TB Training- Session 15 32

 Standard ART Regimens:
3rd line
Adult Regimen Paed.
DTG + DRV + r (±
12A NRTIs) -
 DRV must always be administered together
with ritonavir to be effective
34
 Dosing and Frequency
• Weight-groups are used to determine the number of
tablets to be given

35
 Dosing and Frequency

• Some formulations are tablets that cannot be crushed as they will not
work well.
• Examples are:
• LPV/r for children who cannot swallow a tablet WHOLE
(usually < age 4-5) requires oral pellets or granules
• LPV/r and ATV/r tablets must be given whole (not split or
crushed)
• If these formulations are split or crushed they DO NOT WORK. It is
almost worse than not taking them as resistance develops if they
are crushed or split or chewed 36
 Key Points

• Classification of ARVs is based on mode of action targeting

specific viral enzymes in the infected cells
• ART requires combining 3 different ARVs that act differently
in order to avoid development of drug-resistant HIV
• Do NOT give a ‘tail’ with EFV and NVP containing regimen
case of severe potentially life-threatening side effects (lactic
acidosis, pancreatitis), but stop all ARVs immediately
• Adults 30kg + = 13A with 5A as alternate regimen
37