HIV MTCT IN ZIMBABWE

BURDEN OF DISEASE
• 15% - 30% HIV Seroprevalence in antenatal attendees in
both urban and rural areas.
• Estimated 30% MTCT HIV rate without intervention
• 25% of neonatal deaths attributable to HIV infection.
• 70% of deaths from sepsis in mothers and neonates are
in HIV + patients
• Increasing PNMR, MMR and IMR largely attributable to
HIV infection
• Estimated 50% of perinatally HIV-infected infants die in
the first 2 years of life if untreated.
 Strategic Timing of Antiretroviral Treatment
(START)
• Large RCT AT 215 sites, 35 countries since
2011
• 4685 asymptomatic HIV infected adults CD4
≥500 cells/cmm, ART naïve. 27% women
• Early ART vs Delayed ART when CD4 ≤ 350
• Premature release of results mandated by
DSMB
 RESULTS
• Early ART associated with lower risk of AIDS,
serious AIDS and non-AIDS illnesses, death
from all causes
• 41 events of AIDS events, serious non-AIDS
events or death events in Early ART group vs
86 events in delayed ART group ( HR 0.47)
• WHO now recommends ART for all HIV
infected adults
 ZIMBABWE BURDEN OF HIV
• Estimated 1.1 million people living with HIV
2015
• 15% adult HIV prevalence
• 18% HIV vertical transmission rate in 2012
• Rates falling with introduction of Option B+ to
5%
 HIV AND PREGNANCY
COUNSELING ISSUES
• Impact of HIV on pregnancy course/outcome
• Impact of pregnancy on HIV progression
• Other issues based on maternal factors e.g. co-
existing drug/alcohol use, medical disorders.
• Long term health of mother
• Perinatal transmission
• Use of ARV and other medications in pregnancy
 INTERVENTIONS TO PREVENT
PERINATAL HIV TRANSMISSION
• Prevention of new infections in reproductive age
women.
• Prevention of unwanted pregnancies in HIV positive
women – EFFECTIVE CONTRACEPTION
• Termination of unwanted pregnancies
• Behavioural interventions e.g. Condom use during
pregnancy and breastfeeding.
 HIV TRANSMISSION FROM
MOTHER TO INFANT
• Antenatal
- In utero by transplacental passage
• Intranatal
- Exposure to maternal blood and vaginal secretions
during labour and delivery.
• Postnatal
- Postpartum through breastfeeding
• 25 – 35% of all infants born to HIV –infected women in
developing countries become infected.
• 90% of HIV-infected infants and children were infected by
mother.
 MTC TRANSMISSION

* Estimated transmission rates

* 20- 30% in utero
* 35-50% intrapartum
* 20-30% postpartum
Evidence
In utero transmission: HIV-11 detected in fetal and placental tissue.
• P24 antigen found in fetal serum.
• HIV virus has been isolated from 20-60% of infected infants at birth.
• Bimodal distribution of symptoms in children.
• 50% of infected infants are negative to viral isolation studies at time of
birth.
• HIV demonstrated in cell-free and cellular portions of breast milk.
 2010 WHO Antiretroviral Drugs Use for Treating
Pregnant Women and Preventing MTCT

Antenatal Postpartum
Early Late Early Late

Pregnancy Labor- Breastfeeding

10-25% Delivery 35-40%
35-40%
<28 wks >28 wks 0-1 mo 1-6 mos 6-24 mos
 CLINICAL COURSE OF HIV IN PREGNANCY

• Meta analysis of 7 prospective cohort studies (French

1998):
• No significant differences in death.
• No significant differences in disease progression.
• No significant fall in CD4 counts.
 DETERMINANTS OF MTC TRANSMISSION

1. Viral load
2. Stage of HIV Disease
3. Maternal Immunological Status
- Low CD4 counts
- High CD4/CD8 ratios
- Neutralising antibodies
4. Maternal nutritional factors
- Vitamin A (Semba et al. 94):
- Women with low Vit. A levels were 4 times more
likely to transmit HIV to their infants
 OBSTETRIC RISK FACTORS FOR
MTC TRANSMISSION
• Amniocentesis and Amnioscopy
• Premature rupture of membranes
• Preterm labour
• Sexually transmitted disease during pregnancy
• Antepartum haemorrhage
• Bloody amniotic fluid
 COMPLICATIONS OF HIV IN PREGNACY

• Anaemia
• Intrauterine growth retardation
• Bacterial infections
• Preterm labour
• Low birth weight
• Perinatal mortality
• Infant mortality
• Increased Stillbirth rate
 STRATEGIES FOR PREVENTION OF HIV MTCT

• Reduction of viral load.

• Reduction of fetal viral exposure.
• Identification of treatable/modifiable risk factors.
• Stimulation of immune system: active or passive
immunization.
• Improve general nutrition.
 THERAPEUTIC INTERVENTIONS

• Antiretroval therapy
 AZT alone
 Nevirapine alone
 Combinations of ARV
 HAART recommended
• Treatment of STI in pregnancy.
• Caesarean section depending on viral load
 THERAPEUTIC INTERVENTIONS II

• Immunotherapy
• Nutritional supplementation

¤ Multivitamins
¤ Micronutrients
 ANTENATAL CARE

• Treatment of Anaemia.
• Screening and treatment of STI.
• Close monitoring for IUGR.
• Avoidance of invasive procedures (amniocentesis,
amnioscopy, external cephalic version).
• Nutritional counselling.
 INTRAPARTUM CARE
UNIVERSAL PRECAUTIONS
• Gowns
• Double gloving
• Eye protection
• Recommended in all procedures likely to result in
splashing of blood or amniotic fluid.
 INTRAPARTUM CARE

• Delayed amniotomy
• Avoidance of invasive monitoring procedures:
 Scalp electrodes.
 Fetal blood sampling
• Avoidance of episiotomy.
• Avoidance of instrumental delivery.
 VAGINAL VS CAESAREAN SECTION

• In absence of ARV caesarian section reduces HIV

MTCT by 55-80%.
• Effect best in patients with high viral loads.
• Morbidity and mortality high in AIDS patients
generally.
• CS after HAART or in patients with undetectable viral
loads is not necessary.
TABLE 7.7 REGIMEN ZIDOVUDINE PERINATAL TRANSMISSION PROPHYLAXIS

ANTEPARTUM INITATION AT 14-34 WK GESTATION AND CONTINUED

THROUGHOUT PREGNANCY
a. PACTG 076 REGIMEN: ZDV 100MG 5 TIMES DAILY
b. ACCEPTABLE ALTERNATIVE REGIMEN:
- ZDV 200MG 3 TIMES DAILS
OR
- ZDV 300MG 2 TIMES DAILY
INTRAPARTUM DURING LABOR, ZDV 2MG/KG INTRAVENOUSLY OVER 1 HR
FOLLOWED BY A CONTINUOUS INFUSION OF 1MG/KG
INTRAVENOUSLY UNTIL DELIVERY.
POSTPARTUM ORAL ADMINISTRATION OF ZDV TO THE NEWBORN (ZDV
SYRUP, 2MG/KG EVERY 6HR) FOR THE FIRST 6WKS OF LIFE,
BEGINNING AT 8-12 HR AFTER BIRTH.
 TABLE 3 NEVIRAPINE

Pregnancy Nil

Labour Single dose 200mg orally at onset of labour.

Baby Single dose 200mg/kg orally at 48-72 hours after birth. If mother
receives NVP less than one hour prior to delivery, give baby
2mg/kg as soon as possible after birth and repeat same dose 48-
72 hours after birth.

Comments Efficacy 47% at 3/12 in breast feeding babies. Very cheap,

adverse effects minimal.
 ANTIRETROVIRAL THERAPY TO PREVENT
PERINATAL TRANSMISSION
TABLE 1. THAI LONG COURSE (ZDV)

Pregnancy Initiate oral ZDV 300mg bd at 28 weeks until labour

Labour Oral ZDV 300MG 3 hourly until delivery

Baby Suspension ZDV 2mg/kg every 6 hours for 6 weeks beginning

8-12 hours after birth

Comments Efficacy over 60% in non breast feeding

 Evolution of WHO PMTCT ARV
Recommendations

2001 2004 2006 2010 Launch

July 2013
4 weeks AZT; AZT from 28 AZT from 28wks Option A Option B or B+
PMTCT

AZT+ 3TC, or wks + SD NVP + sdNVP (AZT +infant NVP) Moving to ART
SD NVP +AZT/3TC 7days Option B for all PW/BF
(triple ARVs)

No CD4 <200 CD4 <200 CD4 <350 CD4 <500

ART

recommendation

Move towards:
Move towards: more
more effective
effective ARV
ARV drugs,
drugs, extending
extending coverage
coverage
throughout MTCT
throughout MTCT risk
risk period,
period, and
and ART
ART for
for the
the mother’s
mother’s health
health
 Pregnancy Initiate oral ZDV 300mg bd at 36 weeks
gestation until labour.

Labour Oral ZDV 300mg 3 hourly until delivery

Baby Nil or give for 6 weeks as above

Comments
Efficacy 51% in non breast feeding and without AZT to
baby. Efficacy improves with dosing baby. Efficacy 37% at 3
months in breast feeding babies.
 B/B+: Issues of concern
• Readiness and willingness to adhere to lifelong ART
• Inconvenience of lifelong treatment
• Cost to the program
• Risks of ART-toxicity, resistance, drug interactions
• However, improvements in potency, toxicity and
tolerability, and reduction in pill burden allow for
durable viral suppression for most patients
• Male involvement and Option B+M
 TABLE 4 – INFANTS DOSING WHEN MOTHER
HAS RECEIVED NO ARV OR SUBOPTIMAL ARV
ZDV 2mg/kg per dose QDS for 6 weeks. Should be initiated as
soon as possible after birth within 12-24 hours.

ZDV + 3TC ZDV as above. 3TC 2mg/kg per dose 12 hourly for 6 weeks.
Initiate as soon as possible after birth.

Nevirapine Give baby 2mg/kg as soon as possible after birth and repeat
same dose 48-72 hours after birth.
 MTCT AND BREASTFEEDING RISK FACTORS

¨ High maternal viral load

¨ Advanced HIV infection: CD4, clinical symptoms
¨ Acquisition of HIV during breastfeeding
¨ Duration of breastfeeding
¨ The volume of breast milk ingested
¨ Breast pathology: mastitis, abcesses, fissures
¨ Infant oral thrush
¨ Infant feeding type: mixed worse than exclusive BF
 SAFETY OF ARV PROPHYLAXIS

¨ In clinical trials ARV has not been associated with an

excess of adverse events.
¨ Normal growth, neurologic development and
immunologic parameters have been demonstrated in
uninfected children.
¨ HIV progression in mothers has not been altered.
¨ Prognosis for infected children NOT affected.
 SAFETY OF ARV PROPHYLAXIS

® In RCTs the only adverse effect attributed to drug

exposure was mild transient anaemia following AZT
treatment.
® Benefit strongly outweighs the potential adverse
effects of ARV drug exposure.
 PATTERNS OF INFANT FEEDING AND MTCT
CUMULATIVE TRANSMISSION RATES

Birth 6W 3M 6M 12M 15M

No. BF 7.6 18.0 18.7 19.4

Exclusif BF 6.8 15.0 16.0 19.4 22.1 24.7

Mixed BF 6.9 21.9 24.4 26.1 33.3 35.9

 OPTION B

• FOR all HIV-infected mothers who are not eligible for

ART , ARV prophylaxis option B is TRIPLE ARV drugs
from 14 weeks gestation using regimens:
• AZT+ 3TC+LPV/r
• AZT+3TC+ABC
• AZT+3TC (or FTC ) + EFZ
• INFANT : Similar to option A
% T r a n s m is s i o n T h r o u g h A g e 1 4 D a
MTCT Through Age 14 Days
Significantly Lower in Triple ARV Arms
1.8%

2
ZDV (Arm A)
Triple ARV (Arms B+C)

1.5

ZDV +
1
sdNVP +
FTC-TDF tail
(Arm A)
25 infections/ 0.56% 9 infections/
0.5
1,326 Triple ARV 1,710
(Arms B & C
Combined)
0

Difference in MTCT Risk (Repeated Confidence Interval):

-1.28% (95% CI -2.11%, -0.44%) 33

 Women Eligible for ART Are At Highest Risk for Mother to Child HIV
Transmission and Mortality
Kuhn L et al. AIDS 2010;24:1374-7
Not Not eligible
Eligible Eligible for ART
for ART
31.9% MTCT by 6 wk (K-M) 16.7% 5.0%

Eligible Proportion of MTCT by 6 87.5% 12.5%

wks
68.1%
(54% due to MTCT after 6 wks (K-M) 17.0% 4.2%
CD4 <350)
Proportion of MTCT 87.5% 12.5%
after 6 wks

13.4% 2.4%
% maternal death @ 24 mos (K- (69/698) (6/327)
M)

 1,025 pregnant women and their infants Proportion maternal 92% 8%

mortality 24 mo post
in Zambia prior to HAART availability, delivery
followed for 24 mos
 Analyzed MTCT/mortality by eligibility for
ART with current WHO criteria (CD4 <350
or WHO Stage 3 or 4)
 FUTURE PMTCT STRATEGY 2014
• MOH reviewed national guidelines following
2013 WHO GUIDELINES
• OPTION B + adopted and being rolled out
• HAART for all pregnant women on diagnosis
for life
• FD TDF based HAART-TDF/FTC/EFV
• Roll-out 98% complete