Prevention of Mother-to-child Transmission(PMTCT) 2011 Ashraf Coovadia Department Of Paediatrics & Child Health Rahima Moosa Mother and Child Hospital University of The Witwatersrand

Overview Statistics Timing of Transmission Risk Factors for MTCT History of pMTCT Interventions Revised SA pMTCT policy 2010

Antenatal Prevalence - SA

Antenatal Prevalence - SA

Just under a third of pregnant women (29 Just under a third of pregnant women (29.3%) in South Africa are HIV Positive

Mother to Child Transmission One out of four babies (25%) born to all HIV positive mothers will acquire HIV from their mother ( if no intervention is offered ) That means at least 75% of babies are uninfected at birth!

Background 55% of all HIV-1 positive adults are women of child bearing age. Seroprevalence rates among pregnant women exceeds 30% in many urban populations in sub-Saharan Africa

MTCT Rates ~10 - 30% in non-breastfeeding population of HIV-1 positive women in more developed countries 25 -45% in breast-feeding populations in Africa

Timing of transmission in Non breast-feeding

Timing of transmission Breastfeeding

Risk Factors for MTCT Pregnancy Labour and Delivery Breastfeeding High maternal VL Placental infection STIs Maternal malnutrition ROM >4 hours before labour begins Invasive delivery procedures First infant in multiple birth Chorioamnionitis Duration of breastfeeding Early mixed feeding Breast abscesses, nipple fissures, mastitis Poor maternal nutritional status Oral disease in the baby

History of PMTCT and ARV interventions ACTG 076 1994, AZT to mother from 2nd trimester, IV during labour and delivery, 6 weeks to infant; transmission reduced from 25%-8% Shorter course therapies sought Thai regimen PETRA HIVNET 012 Nevirapine one dose to mother and one dose to baby (transmission reduced to 13%)

What did we know and when did we know it What did we know and when did we know it? Perinatal HIV Clinical Trial Results 1994 2004 1994 U.S. AZT Trial ACTG 076 67% reduction in transmission 2004 Thailand PHPT 1.9% AZT + NVP 1998 Thai Bangkok short AP/IP AZT trial 50% reduction in transmission 2003 DITRAME + 1201.1 4.7% TR with AZT/3TC & IP/PP NVP 1998 Cote d‘Ivoire short AP/IP AZT trials 37% reduction in transmission (breastfeeding) 2002 Cote d’Ivoire DITRAME + 6.2% TR with AZT & IP/PP NVP 2000 Thailand Long vs short AZT regimens 4% TR in LL (non BF) 1999 PETRA AZT/3TC trial (6 wk results) 50% reduction with longest arm. 38% reduction with the IP/PP arm 1999 Uganda 2-dose IP/PP NVP trial (HIVNET 012) 47% reduction in transmission (breastfeeding)

MTCT: The four-pronged strategy Primary prevention of HIV in parents-to-be Prevention of unwanted pregnancies Prevention of transmission from HIV-infected mother to infant Appropriate treatment and care

Interventions Before conception Antenatal Peripartum Postnatal Primary prevention of HIV in parents-to-be Prevention of unwanted pregnancies Antenatal Identification of women requiring HAART or PMTCT ARV course Avoidance of unprotected sex with HIV+ partner Peripartum Good obstetric practice Elective Caesarian section ARV – Nevirapine given in labour Postnatal Avoidance of breastfeeding – where safe, feasible, acceptable

Standard ANC procedure Group pre-test counselling – PMTCT information Individual counselling Obtain verbal consent and proceed to test Test results Post-test counselling and further PMTCT information

Screening HIV test NB! Retest at 32 weeks or Screening Negative Screening positive Negative Confirmatory HIV test NB! Retest at 32 weeks or ( 6 weeks after initial test ) Confirmatory positive Confirmatory negative According to new protocol women diagnosed in pregnancy (window period) should be given ART immaterial to CD4 count due to increased viral load and risk of transmission. CD4 to be repeated at 6 wks post partum and ART will be stopped if CD4 >350.NB retest all negative women Indeterminate Final result positive Send for HIV ELISA Indeterminate Elisa send for PCR DNA test (diagnostic PCR) Positive /Negative final result

HIV-infected pregnant women: 1ST visit Haemoglobin CD4 cell count U&E (with weight) ALT (if ALT abnormal do HepB Sag) TB screening – clinical HIV staging WHO stage 1, 2 – PMTCT protocol Stage 3 and 4, initiate AZT regardless of CD4 count – refer for urgent ART Staging knowledge may be problematic Those with stage III disease have advanced HIV disease and may need ART soon.

Staging – highly simplified Stage 1 - healthy Stage 2 – skin conditions Stage 3 – oral conditions and pulmonary TB Stage 4 – other opportunistic infections

Zidovudine (AZT) Dual therapy – antenatal AZT and intrapartum sd-NVP – introduced in February 2008 Addition of antenatal AZT further decreases transmission to 5% Timing of initiation of AZT changed now to be in line with new WHO guidelines – from 14 weeks gestation

AZT cont... According to president Zuma’s mandate on 1 December 2009, AZT for PMTCT should be started from 14 weeks of pregnancy instead of 28 weeks All HIV-infected pregnant women seen at antenatal clinics at 14 weeks of pregnancy and above must be started on AZT while awaiting CD4 cell count result

AZT cont... If the CD4 cell count is above 350 cells/mm3, AZT is continued until labour begins. During labour, sd-NVP is issued in labour ward together with AZT 300mg 3 hourly until delivery. The women is then given TDF + FTC (acts as the tail cover) If the CD4 cell count is less than 350 cells/mm3, the pregnant woman qualifies for ART). AZT is stopped once ART is started, no additional AZT during labour nor tail required. AZT 3hourly as per national protocol

AZT AND ANAEMIA IN PREGNANCY Haemoglobin monitoring AZT AND ANAEMIA IN PREGNANCY Anaemia is common in pregnancy Various causes: nutritional (iron deficiency), HIV-related are common AZT may exacerbate an existing anaemia, or cause the haemoglobin to drop Prescribe adequate doses of haematinics – for all women and advise on how to take iron

Haematinics and monitoring (BANC) Iron Supplementation Hb <8g/dl Ferrous sulphate 200mg tds/Folic acid 5mg daily Urgent referral for investigation Hb ≥ 11g/dl Ferrous Sulphate 200mg daily/ Folic acid 5mg daily Hb >8g/dl <10g/dl Ferrous Sulphate 200mg tds/Folic acid 5mg daily Repeat Hb weekly For women on AZT 4 weekly Hb monitoring Consider initiating ART

Hb, TB screen,CD4, Stage, Start FeSO4 and Folic Acid 1st Visit – HIV Infected Hb, TB screen,CD4, Stage, Start FeSO4 and Folic Acid >14weeks <14 weeks Stage 3, 4 (any gestation) Hb > 8 Hb < 8 Stage 4 can start AZT at any stage preferably by 14 weeks but can be started earlier in special circumstances e.g.Karposis Return 1 week, ART/AZT from 14weeks Start AZT results 1 week Refer for anaemia start AZT when Hb >8 AZT immediately refer for ART

Management in labour Single dose Nevirapine + AZT 300mg 3 hourly To reduce intrapartum transmission (esp. unbooked mothers presenting in labour) Reduces transmission to around 10% by 6 weeks testing TDF + FTC stat after delivery Combination therapy reduces resistance due to sdNVP

Check CD4 cell count result Subsequent ANC visits AZT started at 1st visit Check CD4 cell count result ALT if abnormal – HebBSag U&E + Weight (creatinine clearance) CD4 > 350 Stage 1 & 2 CD4 ≤ 350 or stage 3 & 4 AZT 300 mg 12 hourly Give 4 weeks supply Same day referral to ARV clinic for ART, AZT stopped once ART initiated

PMTCT and ART initiations NEW ANC Booking Case finding do a CD4 cell count Less than 14 weeks (NVP,TDF,3TC) Continue AZT CD4 <350 HIV staging CD4 result within 1week Start AZT from 14 weeks From 14 weeks, initiate ART (EFV,TDF,3TC) CD4 < 350 CD4>350

PMTCT and ART initiation outline: ANC booking visit Rapid HIV test positive HIV staging and CD4 cell count Gestational age from 14 wks to 42 wks - initiate AZT same day CD4 count result within 1 week A. CD4 >350 – continue AZT B. CD4: <350 or stage 3 or 4 – initiate ART: TDF, 3TC and NVP/EFV

Labour and delivery AZT 300mg 3 hourly plus 200mg sd NVP stat If Nevirapine already taken with false labour do not repeat, neonate receives standard post exposure prophylaxis. Continue AZT 300mg 3 hourly at the usual times until the neonate is delivered. Mother on ART, continue treatment as usual during labour. Gauteng administers 600mg of AZT stat during labour then reverts to 12hourly dosing . Nationally AZT 300mg 3hrly during labour

Labour and delivery Minimize number of PV exams to decrease risk of infection Avoid prolonged labour Avoid artificial rupture of membranes Avoid traumatic vaginal delivery

Labour and delivery Avoid routine episiotomy Suction baby only when indicated, i.e. no routine suctioning Wipe baby clean immediately after delivery to remove blood & liquor

Continue ART regimen 12 hourly throughout labour At onset of labour NEW HIV infected mother on PMTCT regimen or no treatment NVP stat AZT 300mg 3 hourly during labour Infant NVP 6 weeks* Delivery Tail cover FTC/TDF stat dose post delivery At onset of labour mother on ART Continue ART regimen 12 hourly throughout labour Mother continue ART lifelong . Truvada after delivery

Caesarian section Routine C/S for HIV neither indicated nor feasible in government hospitals. Elective C/S (Obstetric indication): give sd NVP at least 4 hours before surgery If patient on ART, continue medication at usual times Emergency C/S, antiretroviral treatment / prophylaxis should be given stat Tail cover post C/S ARV ( can be given within an hour of C/S)

Feeding practices SAFE FEEDING PRACTICES For all HIV positive women Either exclusive replacement feeding or exclusive breast feeding AFASS must be assessed on an individual basis

Feeding choices for HIV infected women Mixed feeding strongly discouraged BREAST FEEDING: exclusive breastfeeding recommended for 1st 6 months of life . If she wants to stop at 6 months AFASS must be reassessed Cessation of breastfeeding before 6 months not recommended. Introduce complementary foods from 6 months in addition to continuing with breastfeeding

Feeding choices for HIV infected women REPLACEMENT FEEDING: If women chose not to breast feed, exclusive formula feeding (i.e. no breast milk) should be practiced Provision of free formula for at least 6 months Complementary foods should be introduced from 6 months

If the mother is known to be HIV positive – the infant is referred to as HIV EXPOSED AVOID MISLABELING

Post natal care All women of unknown HIV status should be offered HIV testing and counseling prior to discharge All HIV exposed infants to receive NVP daily for 6 weeks *All abandoned infants considered to be in their first 72 hours of life, provide NVP daily for six weeks or until HIV ELISA confirms no HIV exposure

Switch to EBF if possible . Exclusive formula fed Identify HIV -exposed infant 6 weeks: Start CTX Do PCR Stop NVP Prompt referral for ART. Continue CTX Switch to EBF if possible PCR PCR positive PCR negative *HIV negative Stop CTX If infant is ill test earlier. All HIV exposed infants not on ART should have an HIV ELISA or rapid test at 18 months of age to confirm HIV status conferred by the 6-week PCR test

Infants of Breastfeeding mothers Breastfeeding mothers on ART Breastfeeding mothers not on ART Stop infant NVP at 6 weeks Continue infant NVP until breastfeeding cessation or max 1year Infants on NVP should continue with NVP for 1 week after breastfeeding has been stopped. All positive infants should continue breastfeeding and referred for ART within a week.

Proposed Extended Simplified Infant NVP Dosing Recommendations (dosing required to sustain exposure in infant of > 100 ng/ml with least dose changes) 50mg / 5 ml Birth -6 weeks Birth Weight < 2,500 gram Birth Weight >2,500 gram 10 mg/daily = 1ml 15mg/daily =1,5ml >6 weeks to 6 months 20mg/daily = 2ml >6 to 9 months 30mg/daily =3ml >9 months to end of BF 40mg/daily =4ml

Blood collection CAPILLARY VENOUS V 500 ul (0.5 ml) 1ml The old Guthrie card has been crossed out because it should no longer be in circulation (but may be at some clinics). The reason for the new card is that it is framed which is required for the automated punch in the laboratory to grip the card and punch out the blood spots automatically The ‘adult’ EDTA tubes require a MINIMUM volume of 1ml (because there is EDTA diluent in the tube that will dilute out a smaller volume) and the microtainers a MINIMUM volume of half a ml. 44

Confirm HIV infection in infants . PCR Positive Do Viral load on separate blood sample Repeat DNA PCR Initiate ART while waiting for VL results VL ≥ 10000 copies/ml (4log) Continue ART If infant is ill test earlier. All HIV exposed infants not on ART should have an HIV ELISA or rapid test at 18 months of age to confirm HIV status conferred by the 6-week PCR test If VL test <10 000 copies per ml, repeat HIV DNA PCR If can’t perform blood sampling for VL (not done on DBS), refer to CCMT site for confirmatory testing and treatment initiation VL ≤10000 copies/ml

Testing breastfed infants 6 week PCR (as for all HIV-exposed infants) BEFORE breastfeeding is stopped, do HIV test: if positive, continue breastfeeding, refer for initiation if negative, stop breastfeeding AFTER breastfeeding is stopped, do HIV test: if positive, try to re-initiate breastfeeding refer for initiation if negative, currently HIV-uninfected HIV test to be done is age-appropriate e.g. if younger than 18 months, do HIV PCR and if older than 18 months, use rapid test or ELISA

Rapid test at 18 months " All HIV-exposed infants should have a rapid test at 18 months to confirm their status unless they are already on ART" Traditionally we need TWO tests with the same results to confirm an HIV status. In all cases, except for 2 positive PCR tests in HIV-infected infants, infants only have a single test to establish their HIV status therefore the 18 month rapid test acts as a confirmatory test 12 - 18month olds that are diagnosed on PCR for the first time will NOT be on HAART but will need their HIV status confirmed on rapids in case they slip through the gap on a confirmatory viral load test. Final HIV tests will have to occur after 18 months in instances where infants are breastfed for longer than 18 months

The provision of a “tail” to prevent Nevirapine resistance for women receiving sdNVP in labour Dispensing daily NVP to the baby for 6 weeks (instead of AZT). For breastfed infants NVP continues daily for 1 week after breastfeeding stops preferably no more than 12 months if mother not on ART.

pMTCT and feeding choices HIV is present and transmitted via breast milk Formula feeding is difficult in many areas especially rural Women should be fully informed about choices and supported in their decision by health care workers (WHO)

Exclusive Breastfeeding (for 4 months) RISKS Transmits HIV BENEFITS Optimal nutrition Saves time, money and effort Reduced exposure to germs Better immunity Less allergy Socially acceptable Bonding

Exclusive Formula feeding BENEFITS No transmission of HIV through breast milk RISKS Cost- may have higher risk of poor growth Infectious diseases, such as diarrhoea and pneumonia if hygiene, sanitation and access to clean water is poor

PMTCT RATES Of all HIV Infected Women > 95% HIV Negative Babies ! 25 % HIV Infected Babies Where no intervention < 5% Infected

Take Home Messages All women have a right to receive PMTCT All babies have a right to be protected through PMTCT Testing of all women is key to the realization of these rights Provision of appropriate and timely interventions is critical to diminishing MTCT risk Feeding choice needs to be an informed one Paediatric Diagnosis is a key component of PMTCT Paediatric HIV is ERADICABLE