The NEW ARV Guidelines

FAQs
Dr Madeleine Muller
MBChB (Pret).MRCGP(Lon).Dip Hiv Man

IYDSA Clinical Advisor

Acknowledgments
IYDSA for materials and support
NDOH for slides
CDC our funder
HIV Clinician Society
HIV Hotline -Prof Gary Maartens
Dr Rob Freercks Specialist nephrologist, LVH
Where we were - < 2010
2009: Centralized doctor-led ARV program
CD4 <200
D4T still part of first line regimen
5-8% PMTCT transmission rate.

NGOs provided direct care in under-serviced

areas and busy ARV units.
April 2010 March 2013
2010: We will have the biggest ARV
program in the world
CD4<350 for Pregnant women and TB
2011: PMTCT transmission rate down to 3.5%
TDF introduced into first line regimen
NIMART: nurse led, clinic based ARV
programs
IYDSA shift to Technical support
April 2013 The New ARV guidelines
ZERO MTC transmission
ZERO New HIV Infections
ZERO AIDS related deaths
Zero discrimination
Action Framework No Child Born with HIV by 2015

The most dramatic changes

Around PMTCT
Introduction of FDC
Guideline implementation
Scope of Guidelines determined by
NSP2012- 2016, Millennium Goals 4, 5, 6 and
the NSDA
A balance between
Evidence based medicine
Public resources
Feasibility of Implementation
FDC
Introduced into the public sector on 1st April
2013
Tenders awarded to three companies
Cipla Medro, Aspen and Mylan
Combination of TDF / FTC / EFV

Roll out: SA has close to 2 million patients on

ART: phased approach to roll out
 Priority groups
PG 1: All HIV-positive patients newly initiating ART
PG 2: HIV-positive pregnant women and breastfeeding
mothers

PG 3: Virologically suppressed patients on a d4T containing

regimen
PG 4: TB co-infected patients, stable on 3TC + TDF + EFV
PG 5: Patients with co-morbidities (e.g. hypertension, diabetes),
and stable on 3TC + TDF + EFV

PG 6: Patients receiving individual 3TC + TDF + EFV who

request switch to FDC
PG 7: Patients receiving individual 3TC + TDF + EFV
who, after counseling, agree to switch to FDC
S Afr J HIV Med 2013;14(1 Suppl):41 - 43
Case 1
A patient has been on an FDC (TDF/FTC/EFV)
for a year in private practice in East London.
She now presents at my clinic for ARV
collection. Do I give her the FDC or do I
prescribe the individual ARVs?
Case 1: Discussion
Does not fall into priority group 1 or 2, and
therefore must be switched to the individual
drugs (TDF + 3TC + EFV)
This patient falls into priority group 6
Not enough FDC available to keep this group
on the FDC currently
Private practitioners need to advise their
patients accordingly
Case 2
A 22 year old patient is tested at the clinic
and found to be 18 weeks pregnant. She is
booked and receives full counselling for HIV
testing.
 17

HIV negative test

If negative, repeat 12 weeks after first test or at
32 weeks gestation or later
Consent at initial counselling includes consent for
all follow up tests
Consider re-testing at delivery, at 6/52 post natal
EPI visit, 3 monthly while breastfeeding and then
at least annually
3 monthly testing whilst breastfeeding should be
aligned with EPI visits where possible (10wk, 6m,
12m, 18m)

p5 (2.2 Antenatal Care) & p46, PMTCT Guidelines

 18

HIV positive test

If positive
Baseline bloods (CD4, creatinine)
Initiate ART with the FDC on the same day
regardless of CD4 cell count or gestational age.
Do not wait for blood results to initiate
Exceptions: Start AZT whilst awaiting bloods
Ensure patient has a negative TB screen
Ensure no proteinuria on U-dipsticks (renal risk)
Active Psychiatric patients
Bring client back within 7 days for CD4 and
creatinine results (within 2 days if GXP pending)

p8 Figure 2 PMTCT Algorithm 1, PMTCT

Guidelines
 19

HIV positive
All pregant women get triple therapy ART
In fixed dose combination (FDC)

If CD4 >350
If CD4 350 cells/mm
cells/mm
or WHO 3/4
and WHO 1/2

Lifelong ART for duration of pregnancy

and FOR ONE WEEK AFTER
ART cessation of breastfeeding

p8, Figure 2: PMTCT Algorithm 1, PMTCT Guideline

FDC Prophylaxis or AZT
Most women are eligible for FDC
TDF +FTC +EFV
Active Psychiatric disease cannot use EFV
Active Renal disease cannot use TDF
If patient dx with TB start TB treatment first
and ARVs 2 weeks later
If patient does NOT qualify for FDC for
treatment (CD4>350): use AZT monotherapy
 21

Screen for neuropsychiatric illness

Efavirenz may be contraindicated in active
psychiatric illness
Any woman with an active psychiatric illness
should not receive an EFV-containing
antiretroviral regimen without consultation
Mild depression is not a contraindication to
efavirenz

p9, Figure 3: PMTCT Algorithm 2 & pp26-27, PMTCT

Guidelines
Use of nevirapine
Only consider NVP in patients with a
baseline CD4 count <250 cells/mm3 in
women (<400 cells/mm3 in men)
Note: pregnancy puts patients at a higher
risk for NVP toxicity
Counsel patient well on early symptoms of
toxicity and ensure adequate follow up
 24

Screen for renal disease

Renal Risk:
diabetes or hypertension
a previous kidney condition requiring hospitalisation
2+ proteinuria on urine dipstix testing
A serum creatinine of >85 mol/L is considered
abnormal in pregnancy
If patient history/ U-dipstix suggests renal
disease, dispense AZT at 1st ANC visit and
review with creatinine result at 7 days

p10, Figure 4: PMTCT Algorithm 3, PMTCT

Guidelines
Case 3
I have a 24 year old pregnant patient with a
creatinine of 90 mol/L and a CD4 of 180
cells/mm3. She is 22 weeks pregnant and
weighs 76kg. As indicated in the guidelines, I
cannot give TDF and will be giving her AZT +
3TC + EFV. Do I adjust the dosages of the
ARVs?
Pregnant women already on ART
Does one change the following stable
pregnant women on ART to FDC?
A patient on TDF + 3TC + EFV
A patient on d4T + 3TC + EFV
A patient on AZT + 3TC + EFV or TDF + 3TC +
NVP
A patient on TDF, 3TC and Aluvia
Case 3
Any pregnant patient with possible renal
disease MUST be referred to a doctor
investigated and monitored
Doctors may still use the Cockcroft- Gault
formula (creatinine clearance) to adjust the
applicable ARV dosages in renal disease
Use ideal or baseline weight in the calculation
All medication excreted by the kidneys must
have the dose adjusted according to the
creatinine clearance level
EFV in Pregnancy?
EFV still has a FDA pregnancy class D
classification
Risk with EFV of congenital defects: 2.7%
NVP: 2.5%
AZT: 3.3%
2011 Pregnancy register: 17 / 623
Although reassuring, numbers still too small
to change FDA classification.
The Infant
Three phases where we intervene
Use FDC in all women during pregnancy
6 weeks Post Exposure prophylaxis to the
infant: daily NVP
FDC to all breast feeding mothers

Regular HIV testing of mother during

pregnancy and breast feeding
 31

Monitoring bloods FDC - Pregnant

women
Creatinine (lifelong and prophylaxis)
Baseline, 3 months, 6 months, 12 months then
annually
CD4
Lifelong: baseline and at 1 year
Prophylaxis: baseline and 6 months after FDC
stopped
VL (only if on lifelong)
6 months, 12 months and then annually
 32

Discontinuing FDC (prophylaxis)

If breastfeeding, continue until 1 week after
cessation of breastfeeding
If woman chooses not to breastfeed
Assess WHO and baseline CD4 count was >350
Send HBsAg
Baby still gets 6/52 NVP syrup
Always check HBsAg BEFORE DISCONTINUING
If HBsAg positive, DO NOT discontinue FDC:
woman qualifies for LIFELONG ART (p31, PMTCT
guideline)
ART Eligibility
CD4 count <350 cells/mm3 irrespective of WHO
clinical stage
WHO stage 3 or 4 irrespective of CD4 count

Irrespective of CD4 count

All types of TB
All pregnant and breast feeding
women
 Standardised ART regimen A
adults: 1st line
Category Recommended regimen
All new patients eligible for treatment, TDF + (FTC / 3TC) + EFV
including pregnant women or FDC formulation
Contraindications to EFV TDF + (FTC / 3TC) + NVP
Contraindication to TDF AZT+ 3TC + EFV (or NVP)
Contraindication to TDF and AZT d4T + 3TC + EFV (or NVP)
Contraindication to TDF, AZT and d4T ABC + 3TC + EFV (or NVP)
Currently on d4T based regimen TDF + FTC / 3TC + EFV
FDC preferred
All HIV naive patients initiated on treatment must be initiated on FDC based regimen
unless there are documented contraindications
Use NVP based regimen in patients with significant psychiatric comorbidity, intolerance to
EFV and where the neuropsychiatric toxicity of EFV may impair daily functioning, e.g. shift
workers.
Standardised ART regimen adults: 2nd line
Category Recommended regimen
Failing on a TDF-based 1st line regimen AZT + 3TC + LPV/r
Failing on a d4T -based 1st line regimen TDF + 3TC / FTC and LPV/r
Dyslipidaemia or severe / intolerable Switch LPV/r to ATV/r
diarrhoea associated with LPV/r

Management of virological failure:

-If plasma HIV RNA >1000 copies/mL
-Check for adherence, compliance, tolerability and drug- drug interaction
- Assess psychological issues
-Continue with first line treatment.
- Repeat VL test 2 months later
-If plasma VL confirmed >1000copies/mL
- change regime to second line therapy, provided adherence >80%
Standardised clinical monitoring: At initiation

WHO clinical staging

Screen for pregnancy
Screen for TB symptoms

CD4 count / HB / Creat

If considering NVP ALT
CrAG if CD4 <100 cells/mm3
Standardised clinical monitoring:
Patients on ART
CD4 at 1 year on ART
VL at month 6 and 1 year on ART and then every 12
months
ALT only if on NVP and develops rash or symptoms of
hepatitis
HB or FBC at month 3 and 6 if on AZT
Creatinine at month 3 and 6, 1 year then every 12
months if on TDF
Fasting cholesterol and triglycerides at month 3 if on
LPV/r
 ART considerations in older patients
or those with co-morbidities
Co morbidities can affect ART regimen selection and
tolerability
Examples
High cholesterol avoid lipid-elevating regimens
Cardiovascular disease may consider avoiding abacavir
Diabetes may avoid tenofovir or boosted PIs
Fragile bones avoid tenofovir
Renal failure avoid fixed-dose combinations; consider
avoiding tenofovir
 Guidelines for initiating ART in
TB/HIV co-infected patients
Clinical scenario Recommendation
CD4+ count <50 cells/mm3 Start ART within 2 wks of starting TB
therapy
CD4+ count 50 cells/mm3 with Start ART within 2-4 wks of starting
clinical disease of major severity* TB therapy
Other patients with CD4+ count Can delay ART initiation until 2-8
50 cells/mm3 wks after starting TB therapy
Drug-resistant TB Start ART within 2-4 wks after
confirmation of resistance, initiation
of second-line TB therapy
HIV-infected pregnant women with Start ART as early as feasible
active TB
*Low Karnofsky score, low body mass index, low
hemoglobin, low albumin, organ system dysfunction, extent
of disease
Guidelines for initiating
INH in HIV positive patients
NB: Revisions to policy will be phased in. Continue with current policy until
systems are in place for Mantoux testing
Pre- ART(CD4 >350) on ART

TST not done* IPT for 6 months IPT for 6 months

TST negative IPT for 6 months IPT for 12 months

TST positive IPT for 36 months IPT for 36 months

Case4: Problem
A pregnant HIV positive women presents at the clinic.
Her baseline urine dipstick is NAD and she is otherwise
well. You initiate her on FDC, take the creatinine and
CD4, and ask her to return a week later.
When she comes back her creatinine is normal but her
CD4 is 86 cells/mm3. As her CD4 is <100 cells/mm3, you
test for Cryptococcal Antigen (CrAg), which is
positive.
Should you continue FDC? Should you start
fluconazole?
For the doctor: CrAg positive
Continue the FDC in all cases
asymptomatic in the first trimester of pregnancy
do not initiate fluconazole due to adverse effects on the foetus
counsel the patient to report any symptoms suggestive of cryptococcal
meningitis IRIS ASAP
headache, confusion, fever, neck stiffness
initiate fluconazole after first trimester of pregnancy
asymptomatic in the second/third trimester of pregnancy
initiate fluconazole as per the CrAg algorithm.
counsel the patient to report any symptoms suggestive of CM IRIS ASAP
symptomatic for cryptococcal meningitis
urgent LP and treat for CM accordingly

(Reference: Prof Gary Maartens, Western Cape HAST

Committee)
2013
ARV Eligibility
All children <5 years old irrespective of CD4
count
Children >5: CD4 <350 or WHO Stage 3 & 4

Children <1 years old must be initiated in 7

days of HIV test.
ARV Regimens
First Line Regimen

All infants and children under 3 ABC + 3TC + LPV/r

years (and <10kg)

Children 3 years (and 10kg) ABC + 3TC + EFV

Currently on d4T-based regimen Change d4T to ABC if viral load is undetectable

If viral load >1000 copies/mL manage as treatment failure
If viral load between 50 1000 copies/mL consult with
expert for advice

Children 3 years and exposed to NVP for 6 weeks or

longer (PMTCT) should be initiated on ABC + 3TC + LPV/r
2nd line regimens
2nd line regimen
Failed 1st line protease inhibitor (PI) based regimen

Failed 1st line PI based regimen Recommended 2nd line regimen

ABC + 3TC + LPV/r
D4T + 3TC + LPV/r Consult with expert for advice*
Unboosted PI based regimen
Failed 1st line NNRTI based regimen
(discuss with expert before changing)
Failed 1st line NNRTI Recommended 2nd
based regimen line regimen
ABC + 3TC + EFV (or NVP) AZT + 3TC + LPV/r
d4T + 3TC + EFV (or NVP) AZT + ABC + LPV/r
Advice for the expert
Recommended 2nd line regimen under expert advice
ABC + 3TC + LPV/r No previous daily NVP for PMTCT
AZT + 3TC + EFV* + LPV/r
* Use NVP if <3 years or <10kg

Previous Daily NVP for PMTCT

Treat with 3rd line regimen

d4T + 3TC + LPV/r No previous daily NVP for PMTCT

AZT + ABC + EFV* + LPV/r
* Use NVP if <3 years or <10kg

Previous Daily NVP for PMTCT

Treat with 3rd line regimen

Previously on a regimen with Must be managed by an expert on basis of genotype resistance

unboosted PI (e.g. RTV alone), or testing to confirm PI susceptibility
with rifampicin while on LPV/r
3rd line
Third line regimens

Failing any 2nd line Refer for specialist opinion Regimen based
regimen on genotype resistance testing, expert
opinion and supervised care.
Access to third line ART will be managed
centrally by the NDOH
Most likely: Raltegravir / Darunavir / Etravirine
Investigations at dx
Document weight and height (head
circumference <2years old)
Screen for TB
WHO staging

Baseline CD4 & HB or FBC

HIV Viral load
Cholesterol and TG if on LPV/r regimen
(creatinine if using TDF, ALT if using NVP)
Monitoring: treatment response
On ART Purpose
Height, weight, head circumference To monitor growth and development
(<2yrs) and development stages
Clinical assessment To monitor response to ART and
exclude adverse effects
CD4 at 1 year into ART, and then To monitor response to ART, stop
every 12 months cotrimoxazole prophylaxis as per
national guideline
VL at month 6, 1 year into ART, To monitor viral suppression response
then every 6 monthly in children to ART
<5 years / 12 monthly in children 5 - To identify treatment failure and to
15 years identify problems with adherence
Monitoring: adverse events
On ART Purpose

Hb or FBC at month 1, 2, 3 and To identify AZT-related anaemia

then annually if on AZT

Cholesterol and triglyceride at 1 To monitor for PI-related metabolic side-

year, and then every 12 months effects
if on PI based regimen

Clinical drug-related adverse To identify drug-related adverse events

events If develops jaundice or rash on EFV or NVP
do liver function tests and refer to specialist
Case 5
A sexually active 17yr old is found to be HIV
positive and eligible for ARVs.
Which regimen would you initiate?
Case 5: Discussion
ABC +3TC + EFV
TDF is not the preferred treatment in adolescents
may predispose to hypophosphataemia and osteoporosis in
adolescents (rare complication)
TDF and FDC are not licensed for use <18 years of age in SA
ABC is therefore first choice in all children and adolescents
under 18 years of age
Children at age 18 can be changed to FDC if
virally suppressed
no risk factors and
ONLY once the DOH has extended FDC to other priority groups
this patient does not fall into priority group 1 or 2 so will not yet be
eligible for FDC when she turns 18
For the doctor
Some doctors would consider TDF if
approaching 18 years
past Tanner Stage 2
weighs >35 kg
ie, TDF can be used if the child is physically mature
enough
FDC is NOT licensed for children <18 years old
ABC based regimen must be used when ART is
initiated by NIMART trained nurses
Case 6
A 16 year old pregnant teenager presents at
the clinic. Which regimen do I use?
Case 6: Discussion
This is NOT defined in the new guidelines
FDC is not yet licensed in SA for use in children <18 years
cannot be prescribed by NIMART nurses to pregnant
teenagers
If the child is pregnant and under 18 years the following
is recommended:
If CD4 <350 cells/mm3: ABC + 3TC + EFV
If CD4 >350 cells/mm3 and does not qualify for lifelong ART:
AZT monotherapy
ALL OF THESE CASES MUST BE DISCUSSED WITH A DOCTOR
AS LEGISLATION MIGHT CHANGE IMMINENTLY
Key Messages
FDC roll out GO SLOW and stick to priority
groups.
HIV negative pregnant women test every
12 weeks
ALL pregnant women are eligible for FDC
irrespective of CD4 count
Centralized procurement of drugs for
salvage therapy