Crossroads Hotel

7th January 2010

All adolescents & adults with HIV infection & CD4 counts less than/equal to 350 cells/mm3, including pregnant women, should be started on ART immediately regardless of whether they have clinical symptoms

Individuals with severe or advanced clinical disease (WHO clinical stage 3 or 4) should start ART irrespective of CD4 cell count

Target Population

When to Start ART

Malawi ART Guidelines (2008)

2009 ART Guidelines

HIV+ asymptomatic ARV naive individuals

(WHO clinical stage 1)

CD4 count ≤250 cells/mm3 CD4 count ≤350 cells/mm3

HIV+ symptomatic ARV naive individuals(WHO clinical stages 2, 3 and 4)

Mild to moderate clinical disease (WHO clinical stage 2 ) and CD4 count ≤250 cells/mm3 or TLC <1200mm3. orAdvanced or severe clinical disease (WHO clinical stage 3 or 4) irrespective of CD4 cell count

Mild clinical disease (WHO clinical stage 2) if CD4 cell count ≤ 350 cells/mm3

orAdvanced or severe clinical disease (WHO clinical stage 3 or 4) irrespective of CD4 cell count

HIV+ pregnant ARV naive women

Asymptomatic or mild clinical disease (WHO clinical stage 1 or 2) and CD4 ≤ 350 cells/mm3

orAdvanced or severe clinical disease (WHO clinical stage 3 or 4) irrespective of CD4 cell count

CD4 ≤350 cells/mm3 irrespective of clinical symptomsor Advanced or severe clinical disease (WHO clinical stage 3 or 4) irrespective of CD4 cell count

HIV/TB co-infection naive individuals

PTB pts(stage 3) with CD4<350 and Stage 4 (EPTB) irrespective of CD4 cell count

Presence of active TB disease, irrespective of CD4 cell count

HIV/HBV co-infection naive individuals

No specific recommendation Presence of chronic active hepatitis B disease, irrespective of CD4 cell count

Clinical Situation ART initiation Recommendations

Quality of Evidence

Strength of Recommendation

WHO clinical stage 3 or 4 Start ART irrespective of CD4

Moderate to High

Strong

WHO clinical stage 1 or 2 Need CD4 to decide Very Low Strong

CD4 < 350 cells/mm3 Start ART irrespective of WHO stage

Moderate Strong

Active TB Start ART irrespective of CD4

Moderate Strong

Pregnancy Start ART for stage 3/4 or CD4 < 350/mm3

Moderate Strong

Active chronic hepatitis B Start ART irrespective of CD4

Low Strong

First line therapy should consist of an NNRTI + two NRTIs, one of which should be AZT or TDF.

Countries using D4T in first line regimens should start phasing it out because of its long term toxicity

Recommended regimens: AZT + 3TC + EFV AZT + 3TC + NVP TDF + 3TC or FTC + EFV TDF + 3TC or FTC + NVP

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. Start ART in all pregnant women with HIV and WHO clinical stage 3 or 4, irrespective of CD4 count.

◦ Benefits of NVP for women with CD4 cell count between 250 to 350/mm3 likely to outweigh risk of not treating.

◦ EFV regimens preferred but the low risk of NTD (<1%) means should avoid starting in first trimester.

◦ AZT regimens preferred in pregnancy but TDF acceptable.

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.

Patients who require treatment for hepatitis B virus co-infection, should start ART immediately, regardless of CD4 cell count or WHO clinical stage. First and second line regimens for this group should contain TDF and either 3TC or FTC i.e.- TDF+3TC/FTC+ EFV or - TDF+3TC/FTC+ NVP

Regardless of their CD4-cell counts, patients co-infected with HIV and TB should be started on ART as soon as possible after starting TB treatment

◦ EFV based regimens preferred initial options.◦ All active TB pts start ART as soon as tolerable.◦ Rifabutin in TB regimen if using concomitant PI regimen

Regimen options:

- AZT+3TC+EFV or - TDF+3TC/FTC+EFV

Target Population

Preferred 1st Line ART

Malawi ART Guidelines (2008)

2009 ART WHO Guidelines

HIV+ ARV adults and adolescents NVP+3TC+D4T AZT/TDF+3TC+NVP/EFV

HIV+ naive pregnant women NVP + 3TC + D4T

AZT preferred but TDF acceptable EFV included as a preferred NNRTI option(but do not initiate EFV during 1st trimester)

NVP still acceptable where CD4 250-350 cells/mm3

HIV/TB co-infection

NVP+3TC+D4TAZT+3TC+EFV

TDF+3TC/FTC/EFV

HIV/HBV co-infection

No specific recommendation NNRTI regimens that contain both TDF + 3TC or FTC required

(1) d4T phase out plan towards AZT or TDF is recommended in settings where d4T regimens are used as the principal option to start ART.

(2) ART should be initiated as soon as possible in all HIV/TB coinfected patients with active TB (within 8 weeks after start TB treatment).

Second line ART should consist of a Ritonavir-boosted PI plus two NRTIs (one of which should be AZT or TDF, considering what was used in 1st line)

Ritonavir-boosted Atazanavir and Lopinavir/ritonavir are the preferred PIs

Regimens: TDF + 3TC/FTC + LPV/r/ATZ/r or AZT + 3TC/FTC + LPV/r/ATZ/r

All patients should have access to CD4 cell count testing to optimize Pre-ART and ART management. Viral load testing is recommended to confirm treatment failure.

Symptom directed or targeted use of lab tests is the preferred approach for drug toxicity monitoring

Phase of HIV Management Recommended Test Desirable Test

At HIV diagnosis CD4 HBsAg, anti-HCV?

Pre ART CD4

At start of ART CD4 Hb for AZT1

Creatinine clearance for TDF2

ALT for NVP3

On ART CD4Hb for AZT1

Creatinine clearance for TDF2

ALT for NVP3

At clinical failure CD4 Viral load

At immunological failure Viral load1 Recommended test in patients with high risk of adverse events associated with AZT (low CD4 or low BMI).

2 Recommended test in patients with high risk of adverse events associated with TDF (underlying renal disease, older age group, low BMI, diabetes, hypertension and concomitant use of a boosted PI or nephrotoxic drugs).

3 Recommended test in patients with high risk of adverse events associated with NVP ( ART naive HIV+ women with CD4 > 250 cells/mm3, HCV co-infection)

Pregnant women who don't need ART for their own health should start taking prophylaxis as soon as possible from 14 weeks gestation.

Either three-drug ART or infant prophylaxis should be given throughout the breastfeeding period if mothers do not need ART for their own health.

Mother Infant Infant

Option A: Maternal AZT & Daily infant NVP

Antepartum AZT (14 weeks), sdNVP at onset of labour +AZT/3TC during labour & deliveryAZT/3TC for 7 days postpartum

Breastfeeding: daily NVP till 1 week after all exposure to breast milk has ended

Non-breastfeeding:AZT or NVP for 6 weeks

Option B: Maternal Triple ARV prophylaxis:AZT/3TC/LPV/rAZT/3TC/ABCAZT/3TC/EFVAZT/FTC/EFV

Triple ART (from 14 weeks) until 1 week after all exposure to breast milk has ended

Breastfeeding: daily NVP for 6 weeks

Non-breastfeeding:AZT or NVP for 6 weeks

Infant First 6 months

Beyond 6 months

Mother HIV infected

HIV uninfected/ unknown

Exclusively breastfeed

Introduce complementary foods & continue breast feeding till 12 months, then stop if adequate & safe nutrition is guaranteed without breast milk

Mother HIV infected

HIV infected Exclusively breast feed

Continue breast feeding as recommended in the general population up to 2 years and beyond

I Thank you,

Dr Zengani Chirwa – T/A Care Treatment & Support, HIV & AIDS Department - MOH

Department of HIV &AIDS

Crossroads hotel

7th January 2010

To reduce mortality & morbidity in adults and children due to HIV and AIDS and mitigate the impact of HIV and AIDS in Malawi

The eligibility criteria in Malawi includes: CD4 <250 irrespective of WHO staging TLC <1200mm3 for WHO stage 2 patients WHO clinical stage 3 or 4 irrespective of CD4 CD4 < 350 for pregnant women irrespective of

WHO clinical stageMalawi current ART regimensFirst line regimen: Nevirapine+Stavudine+

Lamivudine (Triomune)Alternative first line includes: AZT & EFV based

regimens

Through the scale up plan 2006-2010 the programme had cummulatively by end September 2009:

253,154 patients ever started on ART Out of which 183,147 are alive and on

treatment representing 56% of those in immediate need

ART services are provided at 236 static sites which support over 100 mobile and outreach sites

Access: over 60% of the patients are female, while children make up 10% (<15yrs)

Current ART regimen: 94% are still on 1st line – NVP+3TC+D4T 5% are on one of the alternative first lines –

AZT or EFV or both less than 1% are on second line While 1% are on non-standard regimens

Human resources-HCW, lab technicians etc Infrastructure: more sites required for

service delivery and current sites require expansion/renovation

Equipment and reagents including DNA-PCR and CD4 machines

Funding to meet the extra cost of the recommendations

Sample transportation system (CD4 & DBS)

Thank you

Issues Resources others

Early start: deals with mortality & morbidity

Lack of CD4 capacity

CD4 machines & reagents, Technicians,

Quality assurance for CD4, systems strengthening

Regimen change: deals more with quality of care

Standardised regimen, FDC, No need for baseline tests and monitoring

Cost of drugs,Supply chain management

Few side effects, use in pregnancy

Early start vs Regimen change

May need to implement in phases i.e. priorities

Options

D4T phase out plan

1. No change, but low threshold for alternative

3. Change all new patients and have a low threshold for changing old patients

2. Change all patients > 6-12 months (? Also new ones)

4. Change all patients new & old at same time(costly & wasteful of D4T)

NB: changing after 6 months deals with anemia if changing to AZT

A phased change will reduce wastage of D4T

Forecasting and quantification will be crucial to the phase out plan

AZT TDF NVP EFV

cost Relatively cheaper

Relatively expensive

Relatively cheaper

Relatively expensive

FDC Available Available as atripla - expensive

Available Available as atripla - expensive

Use in pregnancy

safe acceptable safe Teratogenic contraindicated in 1st trimester

Side effects Anaemia Renal insufficiency

Hypersensitivity rxn especially with CD4>250

teratogenicity

Point of care CD4 and Viral load when available will enable early initiation of ART using CD4 and VL monitoring for ART failure

- Currently more feasible to roll out VL for ART failure than CD4 testing due to DBS for VL

Monitoring of patients for ART failure currently will entail >200,000 viral loads per year

Sample transportation systems will need to be strengthened /established

4 groupsGroup 1 – Earlier start & regimen changeGroup 2 – Phase out plan for D4T, lab

monitoring, baseline, monitoring and ART failure

Group 3 – ART in Pregnancy, HIV/TB, HIV/HBVGroup 4 - PMTCT

Trends:◦ Encourage earlier diagnosis ◦ Treat earlier◦ Promote less toxic/ more friendly regimens◦ Monitor more strategically◦ But Will cost more

The major operational question is not if these recommendations should be followed or not, but how to do it safely, with equity… and how to fund it!!

Thank you

Dr Zengani Chirwa