Revised Guidelines for PMTCT and Infant

Feeding in the Context of HIV

PresentedBY

DR. A. K. GUPTA MD(PEDIATRICS)Additional Project Director

Delhi State AIDS Control SocietyGovt of Delhi

“We have effective drugs.

There is no reason why any mother should die of AIDS.

There is no cause for any child to be born with HIV

If we work hard enough we can virtually eliminate mother-to-child

transmission.”

Risk of Mother-to-Child HIV Transmission

Background transmission risk: 15-45%15-30% Risk during pregnancy and delivery10-20% Additional risk postpartum via breastfeeding

35% Average risk without any intervention

Transmission risk with interventions:19.8% Sd NVP to MB Pair ( Study by DSACS)<5% 2010 interventions, BF

<2% 2010 interventions, no BF

ANC HIV prevalence HSS

2005 2006 2007 2008-09 2010-11

0.310000000000002

0.1

0.2 0.2

0.3

ANC

2007-08 2008-09 2009-10 2010-11 2011-12 UPTO DEC 2012

2007-08 2008-09 2009-10 2010-11 2011-12 UPTO DEC 2012

PRE TEST

82673 152894 176062 166704 208728 159727

TEST

72469 146469 170941 161043 204241 154494

POST TEST

60077 137381 162971 151294 190870 146839

POSITIVE

167 334 386 329 356 258

MB PAIR

81 162 228 222 224 234

% POSIVIVE

0.23 0.23 0.23 0.20 0.17 0.17

25000

75000

125000

175000

225000

0.03

0.08

0.13

0.18

0.230.23 0.23 0.23 0.200.17 0.17

TREND OF ICTC ANC POSITIVITY RATE IN NACP III

PMTCT & Early Infant Diagnosis programme (April 11 -Dec’ 12)

Total Number of ANC Screened for HIV 154494

Total Number of ANC Detected Positive for HIV 258 (0.17%)

Total Number of HIV Positive ANC Delivered 232 (90%)

Total no. of ANC registered at ARTC 229 (89%)

Total Number of CD4 done in registered ANC 217 (95%)

Total Number of ANC eligible for ART (CD4 <=350) 100 (46%)

Total Number of ANC initiated on ART 82 (82%)

DBS Test done in HIV exposed infants 237

DBS HIV-1 DNA Positive 30 (12.7%)

DBS HIV-1 DNA Negative 186 (78.5%)

DBS Report Awaited 21

No. of DBS positive infants tested by WB HIV-1 DNA PCR 28 (93%)

WB DNA PCR Positive 19 (68%)

WB DNA PCR Negative ie false positive DBS tests 9

Number of HIV Infected Infant started on ART 17 ( 90%)

The 2010 revised PMTCT recommendations are based on two key approaches

:

1. Lifelong ART for HIV-infected women in need of treatment for their own health, which is also safe and effective in reducing MTCT- CD4 ≤ 350 ( 40% PW)2. ARV prophylaxis to prevent MTCT during pregnancy, delivery and breastfeeding for HIV-infected women not in need of treatment- CD4 > 350 (60% PW)

9

WHY ART to Pregnant Women with CD4 <350?

• MTCT risk: > 75%

• Account for >80% of postpartum transmission (BF)

• Account for 85% of maternal deaths within 2 years of delivery

• Strong benefit from initiating ART for maternal health and PMTCT during pregnancy, labour and delivery and breastfeeding

1. When is ART indicated In pregnant women with confirmed HIV infection Indicated for all women with CD4 cell counts of ≤350 cells/mm , irrespective of the WHO clinical staging, and for all women in WHO clinical stage 3 or 4, irrespective of the CD4 cell count.2. When to start ART in pregnancyHIV-infected pregnant women in need of ART for their own health should start ART as soon as feasible regardless of gestational age 3. What ART regimen to initiateIn pregnant women in need of ART for their own health the preferred first-line ART regimen is AZT + 3TC + NVP /or EFV . Alternative recommended regimens are TDF + 3TC + EFV/ or NVP. Avoid the use of EFV in the first trimester and use NVP instead.4. What ARV prophylaxis to give infants of HIV-infected women receiving ARTAll HIV exposed infants (regardless of whether breastfeeding or receiving only replacement feeding) should be given daily NVP from birth or as soon as feasible thereafter until 6 weeks of age.

ART Regimens

1st Line

Preferred AZT 300 mg BD+3TC 150 mg BD +NVP 200 BD (or EFV 600 mg OD)

Alternative TDF 300 mg OD +3TC 150 mg BD+NVP 200 mg BD(or EFV 600 mg OD)

If anemic (Hb<8 Gm/L), replace the AZT-containing regimen with TDF (10% cases) . If 1st trimester, do not use EFV-containing regimen: Use NVP

Should be initiated on lifelong ART as soon as possible

1. Pregnant Women Eligible for ART (CD4<350)

Baby receives daily NVP for 6 weeks after birth

2. ARV Prophylaxis to PW (CD4 > 350)Option-B WHO PMTCT Guideline of adapted by NACO

ARV Prophylaxis and dosing

Ante-partum Intra-partum Post-partum

TDF 300mg once daily +3TC 300 mg once daily +EFV 600mg once daily

Start at 14 weeks or as soon as possible thereafter

Continue triple ARV prophylaxis

• Continue triple ARV prophylaxis until 1 week after all infant exposure to breast milk has ended

Infant ARV Prophylaxis with NVP

• 15 mg once daily (if birth weight >2500 g) or

• 10mg once daily (if birth weight ≤2500 g) from birth until 4 to 6 weeks of age

ARV prophylaxis for women presenting directly in labour

• Start Triple ARV Prophylaxis (same as option B) to all HIV positive PW presenting directly in labour

• Continue prophylaxis postpartum throughout breast feeding until 1 week after BF is stopped

• Do CD4 count at the earliest to assess eligibility for lifelong treatment

• Infant is given NVP once daily for 6 weeks.

Increased NVP Hepatotoxicity in women with higher CD4 counts

1. CD4 > 350- NVP is not recommended in such women

2. CD4 250-350: There may or may not be an increased risk of hepatotoxicity, benefits of using NVP outweigh the risks of not initiating ART, Close clinical /Lab monitoring during the first 12 weeks of therapy in women with a CD4 cell count of 250 to 350 cells/mm

Potential Teratogenicity of EFV-

EFV rarely can cause neural tube defects. Potential risk (probably <1%) of neural tube defect with use of EFV in first month of pregnancy (before 6 weeks of gestation) Neural tube closure occurs by approximately 28 days of gestation and very few pregnancies are recognized by this time, the potential risk with the use of EFV is primarily in women who become pregnant while already receiving the drug.EFV should not be initiated in the first trimester of pregnancy but may be initiated in the second and third trimesters.

Toxicity of TDF

• Risk of Nephro-toxicity with use of TDF• Limited data available on potential for maternal and infant bone toxicity

PI Inhibitors in cases of Sd NVP Exposure

LPV/r-based regimen is recommended for women who require ART for their own health who have received SdNVP within 12 months of initiating ART.

This regimen is available only at COE, MAMC.

Women receiving ARTand planning to become pregnant

• Fully suppressive ART before conception and that it be maintained during pregnancy, labour, delivery and breastfeeding.

• Preferred ART regimens in such situations should have minimal teratogenic potentials for infants (does not include EFV in first 28 days of gestation)

• For women receiving an EFV-based regimen and who plan to become pregnant, substitution of NVP in the place of EFV for at least the peri-conception period

Women receiving ART who become pregnant

• If a Woman receiving EFV is recognized as pregnant before 28 days of gestation, EFV should be stopped and substituted with NVP or a PI.

• If a woman is diagnosed as pregnant after 28 days of gestation, EFV should be continued.

• There is no indication for abortion in women exposed to EFV in the first trimester of pregnancy

Clinical and laboratory monitoring of pregnant women receiving ARV

prophylaxis and their infants

• CD4 cell counts X every 6 months • Clinical and laboratory monitoring of adverse

reactions related to the antiretroviral drugs should be based on the potential adverse reactions of the drugs use

Women with HIV-2 infection• Testing for both HIV-1 and HIV-2 before initiating a PMTCT ARV intervention. • HIV-2 may also progress to AIDS, although progression is generally much

slower• HIV-2 has the same modes of transmission as HIV-1 but has been shown to

be much less transmissible from mother to child (transmission risk 0−4%). • NNRTI drugs, such as NVP and EFV are not effective against HIV-2 • First-line ART regimen for women who are infected with HIV-2 alone-and

eligible for treatment (based on the same eligibility criteria as for HIV-1)- AZT + 3TC + ABC)

• ARV Prophylaxis- Pregnant women living with HIV-2 alone who are not eligible for treatment for their own health should receive an ARV prophylaxis intervention consisting of AZT from 14 weeks of pregnancy (or as soon thereafter as possible) and continuing during labour and delivery. This maternal intervention should be coupled with twice-daily AZT given to infants from birth until 4 to 6 weeks of age. In

Women with active tuberculosis

• HIV-infected pregnant women with active TB should start ART, irrespective of the CD4 cell count.

• The TB treatment should be started first, and followed by ART as soon as clinically possible ( between rifampicin and some of the antiretroviral drugs (i.e. the boosted protease inhibitors)

• As for all adults, EFV is the preferred NNRTI for HIV/TB co-infected pregnant women (starting after the first trimester).

• For those HIV/TB coinfected women not able to tolerate EFV, an NVP-based regimen or a triple NRTI regimen (e.g. AZT + 3TC + ABC or AZT + 3TC + TDF) can be used.

Adverse Effects

• Nevirapine- Nevirapine is associated with systemic symptoms (e.g. nausea, vomiting, malaise, fatigue, anorexia, jaundice, liver tenderness and hepatomegaly) ,increases in hepatic transaminase enzymes and skin rash, mainly in the first 18 weeks after starting treatment.

NVP-related rash and hepatotoxicity can be life-threatening, particularly among pregnant women with CD4 counts of >250 cells/mm

• Efavirenz: EFV is primarily associated with toxicities related to the central nervous system (CNS), rash and possible Teratogenicity (if taken during the first trimester of pregnancy). The rash is generally mild and self-resolving and usually does not require discontinuation of therapy.

The CNS symptoms are common. While they typically resolve after 2 to 4 weeks, they can persist for months and require discontinuation of the drug. EFV should be avoided in

(i) Patients with a history of psychiatric illness, (ii) When there is a potential for pregnancy (unless

effective contraception can be assured) and (iii) During the first trimester of pregnancy

• LPV/r- The most frequent side-effects of LPV/r consist of

- Weakness, headache and moderate digestive-disorders (diarrhoea, nausea, abdominal pain, vomiting),

- Fat mal-distribution and Dyslipidaemia - Pancreatitis, Hepatotoxicity• TDF- Nephrotoxicity, Fetal Bone defect and

LBW

The counseling messages given to mothers during antenatal changes with the new

guidelines

In the new guidelines (2010):

HIV+ mothers are strongly encouraged to breastfeed their

exposed infants for 12 months while on ARV’sExclusive BF until 6 months, complementary from 6-12

months

Breastfeeding is no longer Just “necessary” but “critical”

because of the nutritional need and because ARV prophylaxis

now limits the risk of transmissionHowever, if the mother still prefers to replacement feed after

counseling, she can do so if AFASS criteria is met

Successful implementation of the new guidelines depends on:• Scale up HIV testing and counseling for pregnant women• Availability of CD4 testing and ARVs at ANC/ICTC/PPTCT level• Integration of PMTCT and MCH; PMTCT and ART• Improved follow-up of pregnant women antenatally and of

mothers and HIV-exposed infants after birth• Ability to provide prophylaxis to the mother or baby throughout

breastfeeding• Health systems strengthening• Enhanced M&E, including impact assessment

Implementation Challenges

Existing facilities in Delhi

• ANC Testing Sites (PPTCTs/ICTCs)- 46• CD4 Testing labs- 5 (NICD, AIIMS, SJH, MAMC, RML)• ART centres-9 (8 for PPTCT programme, except

ARTC LRS Institute)• EID Test Lab for DNA-PCR testing-1 (AIIMS, New

Delhi)• EID sample collection sites- 27 ICTCs• Whole Blood Collection for DNA-PCR sites (ART

centers)- 7

Dr.A.K.Gupta,New Delhi

Profile of Existing ANC Testing Sites as per HIV Positive ANC Client Load/ Annuum

• >20 - 4 sites (BSAH, LHMC, SJH, SGMH )

• 10-19- 8 sites (GTBH, SDNH, Kasturba, DDU,LBS, LNH, RML,BJRM)

• 5-9- 13 sites (AIIMS, GGSH, Hindu Rao, DHAS, Rest all- 5 clients: JPCH, BMH, PMM Malviya Ngr, Rao Tularam, SGMH, SRHC Narela, MCWC Madipur, DAD Ashok Vihar, DAD Khajuri Khas)

• 1-<5 – 26 sites• 0 -22 sites

Dr.A.K.Gupta,New Delhi

Setting up F-ICTCs at 50 ANC sites through ANMs

DSACS trained 572 ANMs in Feb- March 12 on whole blood single prick test for screening of Pregnant women, for tracking of HIV positive women and HIV exposed infants. In Nov’12, 74 ANMs were given refresher hands on training on WB HIV screening test and provided test kits and reporting formats and IEC material. These FICTCs are placed in Govt. dispensaries where no ICTC center was functioning nearby. After screening, the suspected HIV positive ANC will be linked to nearest ICTC for confirmatory testing. It is expected that these centers will cover an additional number of 11000 ANC per year besides improving referral linkages of ICTCs with ARTCs. In addition to above 50 FICTs, one at Naraina Maternity Home is also doing HIV screening of ANC.

CD4 Testing –Revised Strategy

CD4 sample is now drawn at ICTC/PPTCTC for testing directly at NCDC (except ICTC/PPTCTCs with CD4 Labs who will send sample to their labs)No prior ART registration is done to:1. Save time &2. Segregate HIV positive ANC with CD4 < 350 & > 350 to prioritize further action of ART or ARV prophylaxis. ART will be started at nearest ART centre & ARV prophylaxis will be given at PPTCTC/ICTC.

PMTCT software

PPTCT software has been installed at all 45 ICTC/ PPTCT centers catering to ANC which will be useful to track mother and her baby till EID enrollment & up to 18 months.

Mainstreaming Pvt. Sector

Assessment of 100 leading Private hospital on PMTCT Programme through survey is being undertaken in March-April 2013 to help in mainstreaming National PMTCT Protocol in Pvt Sector of Delhi during 2013-14 and setting up PPP ICTCs.

ANC Target 2013-14

• 2,75,000 ANC to be counseled & tested

• 500 ANC HIV +ve expected• ANC Expected ARV Prophylaxis

(Option B) - 60% with CD4 Count > 350= 300

• ANC expected eligible for ART-40%= 200

Dr.A.K.Gupta,New Delhi

Sites of Emergency Labour Room Testing-75 sites

• Hospitals – 37 (Delhi Govt- 21, DGHS/GOI Hospitals-3, AIIMS, ESI-4, Rly-2, Army-3, MCD -4)- ICTC services available in all hospitals

• Maternity homes- 37 (33-MCD, 2-NDMC, CGHS-2)- ICTC services available in 11/37.

• RHTC, Nazafgarh- ICTC services available.

Dr.A.K.Gupta,New Delhi

Nominations TOT for Master Trainers

• 4 days training programme by NACO in Delhi in April-May 2013

• Regional TOT Master Trainers (PPTCT)(a) Doctors (O&G )-30(b) Paramedical staff (ANMs, Counselors, Staff nurses)-

30• Slot for 10 O&G M.O./ specialists available

Dr.A.K.Gupta,New Delhi