ANTIRETROVIRAL THERAPY

JULIUS OPWONYA
ROSE NAMPEERA
Outline
1. Classes of ARVs
2. When to start
3. Specific populations
4. What to start
5. When to switch
6. Causes of Rx failure
7. Second line regimens
8. Third line regimens
Classes of ARVs
There are 3 main classes
1. Nucleoside reverse transcriptase inhibitors-
ABC,ddI,3TC,D4t,AZT,FTC
2. Protease inhibitors-IDV, LPV/r,NFV
3. Non-nucleoside reverse transcriptase inhibitors-
EFV,NVP
Others -Enfuvirtide,Maravirov
When to start
1. It is recommended to treat all patients with CD4
counts of ≤350 cells/mm3 irrespective of the WHO
clinical stage.
2. It is recommended that all patients with WHO clinical
stage 1 and 2 should have access to CD4 testing to
decide when to initiate treatment.
3. It is recommended to treat all patients with WHO
clinical stage 3 and 4 irrespective of CD4 count.
Specific populations
1. HIV-infected pregnant women
2. Women with prior exposure to antiretroviral for
PMTCT
3. HIV/HBV co-infection
4. HIV/tuberculosis coinfection
HIV-infected pregnant women
1. Start ART in all pregnant women with HIV and a CD4
count of ≤350 cells/mm3, irrespective of clinical
symptoms.
2. CD4 testing is required to determine if pregnant
women with HIV and WHO clinical stage 1 or 2
disease need to start ARV treatment or ARV
prophylaxis for PMTCT.
3. Start ART in all pregnant women with HIV and WHO
clinical stage 3 or 4, irrespective of CD4 count.
HIV-infected pregnant women
4. Start one the following regimens in ART-naive
pregnant women eligible for treatment:
• AZT + 3TC + EFV;
• AZT + 3TC + NVP;
• TDF + 3TC (or FTC) + EFV;
• TDF + 3TC (or FTC) + NVP.
5. Do not initiate EFV during the first trimester of
pregnancy.
Previous ARV exposure for PMTCT
Option A
Antepartum AZT (from as early as 14 weeks
of gestation) sdNVP at onset of labour AZT +
3TC during labour and delivery AZT + 3TC
tail for 7 days postpartum sd-NVP and AZT +
3TC can be omitted if mother receives >4
weeks of AZT Antepartum
All triple ARV regimens (including Option
B),irrespective of duration of exposure and
time since exposure
Option B
Triple ARV from 14 weeks gestation until
after all exposure to breast milk has ended AZT
+ 3TC + LPV/r ,AZT + 3TC + ABC
AZT + 3TC + EFV,TDF + [3TC or FTC] +
EFV
Recommendations for initiation of
ART when needed for treatment
of HIV for maternal health
Initiate an NNRTI regimen
If possible, check viral load at 6 months
and if >5000 copies/ml, switch to secondline
ART with PI.If no sdNVP was given, start
standard NNRTI (viral load does not need to be
checked unless clinically indicated as no
sdNVP received)
Initiate standard NNRTI regimen.If EFV-based
triple ARV was used for prophylaxis and no tail
(AZT + 3TC; or TDF + 3TC; or TDF + FTC)
was given when triple ARV was discontinued
after cessation of breastfeeding (or delivery if
formula feeding), check viral load3 at 6 months
and if >5000 copies/ml, switch to second-line
ART with PI
HIV/HBV coinfection
1. Start ART in all HIV/HBV-coinfected individuals who
require treatment for their HBV infection, (chronic
active hepatitis), irrespective of the CD4 cell count or
the WHO clinical stage.

2. Start TDF and 3TC (or FTC)-containing antiretroviral

regimens in all HIV/HBV coinfected individuals
needing treatment.
HIV/TB coinfection
1. Start ART in all HIV-infected individuals with active
TB, irrespective of the CD4 cell count.
2. Start TB treatment first, followed by ART as soon as
possible afterwards (and within the first eight weeks).
3. Use efavirenz (EFV) as the preferred NNRTI in
patients starting ART while on TB treatment.
What to start
Start one of the following regimens in ART-naïve
individuals eligible for treatment.
I. AZT + 3TC + EFV
II. AZT + 3TC + NVP
III. TDF + 3TC or FTC + EFV
IV. TDF + 3TC or FTC + NVP
ART for HIV/TB co-infection
1. Start ART in all HIV-infected individuals with active
tuberculosis (TB) irrespective of CD4 cell count.
2. Start TB treatment first, followed by ART as soon as
possible after starting TB treatment.
3. Use efavirenz (EFV) as the preferred non-nucleoside
reverse transcriptase inhibitor (NNRTI) in patients
starting ART while on TB treatment.
ART for HIV/HBV co-infection
1. Start ART in all HIV/HBV co-infected individuals
who require treatment for their HBV infection,
irrespective of CD4 cell count or WHO clinical stage.
2. Start TDF and 3TC or FTC containing antiretroviral
regimens in all HIV/HBV co-infected individuals
needing treatment.
ART for pregnant women
1. Start ART in all pregnant women with HIV and CD4
count <350 cells/mm3, irrespective of clinical
symptoms.
2. CD4 testing is required to identify if pregnant women
with HIV and WHO clinical stage 1 or 2 disease need
to start antiretroviral treatment or prophylaxis.
3.Stage 3 or 4, irrespective of CD4 count.
ART for pregnant women
4. Start one the following regimens in ART-naïve
pregnant women eligible for treatment.
AZT + 3TC + EFV
AZT + 3TC + NVP
TDF + 3TC or FTC+ EFV
TDF + 3TC or FTC + NVP
5. Do not start EFV during the first-trimester of
pregnancy.
When to switch ART
1. Where available, use viral load (VL) to confirm
treatment failure.
2. Where routinely available, use VL every 6 months to
detect viral replication.
3. A persistent VL above 5 000 copies/ml confirms
treatment failure.
4. When VL is not available, use immunological criteria
to confirm clinical failure.
Switching criteria
Failure Definition Comments
Clinical failure New or recurrent WHO Condition must be
stage 4 condition differentiated from
immune reconstitution
inflammatory
syndrome (IRIS)
Certain WHO clinical
stage 3 conditions
(e.g. pulmonary TB,
severe bacterial
infections), may be an
indication of
Treatment failure
Failure Definition Comments

Immunological Fall of CD4 count to Without concomitant

failure Baseline (or below) OR infection to cause
50% fall from on-treatment transient CD4 cell decrease
peak value OR
Persistent CD4 levels
below
100 cells/mm3

Virological Plasma viral load above The optimal viral load

failure 5000 copies/ml threshold for defining
virological failure has not
been determined. Values of
>5 000 copies/ml
are associated with clinical
progression and a decline
in the CD4 cell count
Causes of Rx failure
 Inadequate adherence
 Drug side effects and toxicity leading to poor
adherence and toxicity
 Baseline patient factors
 Drug-drug interactions btn ARV drugs and other
concomitantly administered drugs
 Suboptimal potency of the ARV regimen
Second-line ART
1. A boosted protease inhibitor (PI/r) plus two nucleoside
analogues (NRTIs) are recommended for second-line
ART.
2. ATV/r and LPV/r are the preferred boosted PI’s for
secondline ART.
3. Simplification of second NRTI options is recommended.
• If d4T or AZT has been used in first-line, use TDF + 3TC
or FTC as the NRTI backbone in second-line.
• If TDF has been used in first-line, use AZT + 3TC as the
NRTI backbone in second-line.
Preferred second line options
1.Adults and adolescents (including pregnant women)
If d4T or AZT used in first-line therapy
TDF + 3TC or FTC + ATV/r or LPVr
If TDF used in first-line therapy
AZT + 3TC + ATV/r or LPVr
Preferred second line options
2. TB/HIV coinfection
If rifabutin available
Same regimens as recommended above for
adults and adolescents
If rifabutin not available
Same NRTI backbones as recommended for adults and
adolescents plus LPVr or SQV/r with superboosted
dosing of RTV (LPV/r 400 mg/400 mg twice daily or
LPV/r 800 mg/200 mg twice daily or SQV/r 400
mg/400 mg twice daily)
Third-line regimens
1. National programmes should develop policies for third-
line therapy that consider funding, sustainability and
the provision of equitable access to ART.

2. Third-line regimens should include new drugs likely to

have anti HIV activity such as integrase inhibitors and
second generation NNRTIs and PIs.

3. Patients on a failing second-line regimen with no new

ARV options, should continue with a tolerated regimen.