VERTICAL TRANSMISSION OF HIV/AIDS ( mother/parent to child transmission-PTCT)

Dr. Matin. A. Khan

MBBS, PhD (Public Health USA)

Fellowship in HIV Medicine (School of Tropical Medicine & Medical College Kolkata)
American Academy of HIV Medicine Specialist (AAHIVS-USA) MGM Medical College , Jamshedpur mak5962@hotmail.com

VERTICAL TRANSMISSION : Explained

I. Vertical transmission, also known as mother-to-child transmission, is the transmission of an infection or other disease from mother to child immediately before and after birth during the perinatal period. II. A pathogen's transmissibility refers to its capacity for vertical transmission. III. The concept of vertical transmission is also used in population genetics to describe inheritance of an allele or condition from either the father or mother. IV. Vertical transmission tends to evolve benign symbiosis. It is therefore a critical concept for evolutionary medicine V. Because a pathogen's ability to pass from parent to child depends significantly on the hosts' ability to reproduce, pathogens' transmissibility tends to be inversely related with their virulence. In other words, as pathogens become more harmful to and thus decrease the reproduction rate of their host organism, they are less likely to be passed on to the hosts' offspring, since there will be fewer offspring VI. Although AIDS is sometimes transmitted through perinatal transmission, its virulence can be accounted for by the fact that its primary mode of transmission is not vertical. Moreover, medicine has further decreased the frequency of vertical transmission of AIDS

UNAIDS VISION :Getting to Zero is the theme selected by the

World AIDS Campaign (WAC) to commemorate World AIDS Day on 1st December. From 2011 to 2015, echoes the UNAIDS vision of achieving : Zero new HIV infections. Zero discrimination. Zero AIDS-related deaths.

MCH PROFILE OF INDIA Total Population 1027 Millions

Crude Birth Rate

Sex Ratio (F:M) Annual Pregnancies ANC Coverage Institutional Deliveries

25/1000
933 27 Millions 65.4 % [12.1% to 79.3%] 35.6 % 42.3 %

Deliveries attended by skilled birth attendants

OBJECTIVE OF NACP III

The National AIDS Control Programme (NACP) III 2007-2012 has the overall goal of halting and reversing the epidemic in India. Over 99 per cent of the population in the country is free from infection. NACP III places highest priority on prevention while seeking to integrate care, support and treatment for those affected by HIV/ AIDS.

FAST FACTS (I) Global, Regional & India Estimates An estimated 33.4 million people worldwide were living with HIV (2008). Approximately 2.1 million children under 15 were living with HIV (2007). An estimated 2.1 million people died of AIDS-related causes (2007). An estimated 290,000 children under 15 died of AIDS-related causes

(2007)

IAPSM Conference 2004

FAST FACTS(II) Prevention of parent-to-child transmission (PPTCT) In India, the transmission of the virus from the mother-to-child during pregnancy, labour and delivery or breastfeeding is called parent-to-child-transmission to emphasize the role of the father in both the transmission of the virus and management of the infected mother and child. Nearly five per cent of infections are attributable to parent-to-child-transmission. It is estimated that out of 27 million pregnancies every year, nearly 49,000 occur in HIV-positive mothers. As of December 2008, only 16 per cent of pregnant women were tested for HIV, while 22 per cent of the children born to the estimated 49,000 HIV-positive women were receiving anti retroviral prophylaxis.The number of facilities offering HIV testing and counseling went up from 4,269 in 2007 to 4,817 in 2008 and stands at 4,987 as of March 2009. In 2009, only 11489 of an estimated 49,000 pregnant women living with HIV received anti-retroviral treatment to prevent parent-to-child transmission. This is because of multiple factors including social customs, lack of family support and financial barriers, which constrain women from availing of institutional care necessary for administering treatment. PPTCT services have also not been scaled up in remote areas with lower HIV prevalence. One of the best practices in PPTCT in India is the outreach approach, used by the ICTC to ensure that HIV-positive women who are tested are followed up before, during and after an institutional delivery, and provided with anti-retroviral prophylaxis. The core principle of this approach rests on the continuum of care for women, children and their families a chain of interventions that begin before pregnancy and continue through pregnancy, labour and delivery and subsequently as part of routine or specialized chronic care services for after the child is born.

It is estimated that 70,000 children below the age of 15 are living with HIV in India and 21,000 children are infected every year through parent-to-child transmission. A small proportion are also infected by unsafe injections and infected by blood transfusions. Most children are infected with the virus while still in the womb, during birth or while breastfeeding. The National Pediatric Antiretroviral Treatment (ART) Initiative was launched in 2006. A total of 40,000 children living with HIV will be provided ART by the end of NACP-III. A total of 375 ART centres shall be equipped to offer pediatric ART in the country. Follow up of HIV exposed infants, according to the Indian Guidelines, begins at six weeks. The Road to Health card for these children includes information on maternal HIV status, cotrimoxazole prophylaxis, infant HIV diagnosis and infant feeding information. To reach more mother-infant pairs, the Reproductive and Child Health (RCH) programme is linked to the PPTCT and Pediatric HIV programme in order to provide for and incorporate HIV care into the package of services for mothers and children.

Pediatric care and treatment:(FAST FACTS III)

Preventing infection among young adolescents and young people: In India, the prevalence of HIV among 15-19-year-olds is 0.04 per cent and that among 2024 year olds is 0.18 per cent By the end of the NACP III, about 25 million students will have been reached through the Adolescent Education Programme The NACP III will also bring HIV prevention skills education programmes and related services to 70 million young people who are not in school, including, street children, children of CSWs, children in institutions, child labourers and other vulnerable youth. Protection, care and support for children affected by AIDS: In the short term, NACP III will reach out to as many children living with HIV as possible to provide them with the treatment and the care and support services that they need.

FAST FACTS (IV)

India has a low HIV prevalence of 0.34 per cent. Yet in terms of individuals infected, India is home to the third largest number of people living with HIV in the world. The vast majority of HIV infections in India occur through sexual transmission (85.6 per cent). Nearly five per cent of infections are attributable to parent-to-child transmission. Paediatric HIV due to MTCT -- 90% The epidemic disproportionately affects women, who account for 40 per cent of the total infections in the country. In India, the epidemic is more pronounced in urban areas than rural ones and decreases with increasing education levels

RISK FACTORS FOR MTCT

HIV STATUS OBSETRIC FACTORS Viral load Pre term labour Low CD4 counts Premature ROM . Advanced disease Invasive fetal monitoring Drug resistance Uterine Manipulation MATERNAL FACTORS Episiotomy Malnutrition Forceps, Vacuum Vitamin A Deficiency Emergency C S Cigarette Smoking & Drugs FACTORS IN STD Breast feeding Irregular ANC Premature baby Lesions of skin &or mucus embrane (oral thrush) including GIT

Mother-Infant HIV Transmission in Hypothetical Cohort of 100 Children of HIV+ Mothers

Children Infected Children at Risk

15

30 infected

100

98

95

80

75

70 uninfected

Early Late antenatal antenatal

Late Early postpartum postpartum

36 wks
Labor & Delivery

6 months

Main Risk factor for postnatal transmission: ---Maternal immune status

HIV transmission from 6 w - 24 mo in West Africa by maternal baseline CD4
transmission (%) Cumulative HIV
15 10 5 0 CD4 < 500 1.4 CD4 >= 500 14

Leroy et al 2002

Human Immunodeficiency Virus: Paediatric Immune Category Classification System Based on Age-Specific CD4+ T Cell Count and Percentage In adult CD4< 200 /mm3 = AIDS Initiation of ART = CD4 Count of < 350/mm3
Immune category /class Degree of Immune Suppression

Age < 12 months 1500 or >25% 750-1499 or 15-24 %

Age 1-5 yrs >1000 or >25%

Age 6-12 yrs >500 or >25%

1 2 3

None/mild Moderate Severe

500-999 or 15- 200-499 or 24% 15-24 %

<750 or <15% <500 or <15% <200 or <15 %

PPTCT : The Four Component Strategy

I II III IV

Prevention of HIV in Young People Prevention of HIV infection in women of child bearing age

Prevention of Unintended pregnancies in HIV positive women

Prevention of transmission from a HIV infected woman to her infant

Care & Support for the mother and her family

Rationale for PPTCT in India

27 million pregnancies per year*

0.7% prevalence **
1,89,000 infected pregnancies

30% transmission
Annual Cohort of 56,700 infected newborns
*Derived from population estimates (SRS) & Crude Death Rate adding 10% pregnancy wastage

**Weighted average of estimates of rural and urban HIV prevalence amongst women 15-19 years

 WHO has introduced a 4-pronged model for PMTCT Prong I

Primary prevention of HIV infection women among women of child bearing age
Behaviour change interventions in general population and couples Information, education and counselling on HIV prevention and care child-bearing age Better STI management, reduction of unsafe transfusions
Addressing contextual factors that increase womens vulnerability,i.e., stigma and discrimination Promoting condoms and safer sex practice
Encouraging partners involvement in safer sex discussions and couples VCT Providing counselling to either HIV negative or serodiscordant couples has been shown to be a highly effective primary intervention strategy.

 Prong II:
Prevention of unintended pregnancy among HIV Infected

Women

Increase the number of women who know their HIV sero- status pregnancy among HIV through information, education and counselling on HIV prevention and infected women care, including approach to MTCT prevention. Step up counselling of women and their partners to enable informed choice with regard to potential future pregnancy. Promote condoms as a valuable family planning tool. Set up referrals to family planning and other counselling services as essential ingredients (knowledge of locally available counselling resources is therefore essential). Women who test HIV positive in early pregnancy can make the decision either to continue with the pregnancy or to elect for termination where this is legal and safe.

 Prong III:
Prevention of perinatal HIV transmission among HIV infected

women

Ensure that HIV positive women have access to antenatal care transmission among HIV system and PMTCT services. infected women Provision of antiretroviral drugs to HIV infected pregnant women and their newborns with counselling and support for drug adherence. Safer delivery practice. Counselling and support for safer infant feeding practice.

Prong IV:
MTCT plus provide care and support for HIV-infected women and

their families

Medical and nursing care: VCT, OI prevention therapy, highly activeantiretroviral treatment (HAART) and palliative care. Psychosocial support: counselling, spiritual support, follow up counselling and community support. Human rights and legal support: PLHA participation and stigma/discrimination reduction. Socioeconomic support: material support, micro-credit and food support

Some Lessons Learnt:

Reduced transmission of HIV from mother to infant
Proportion of infants of HIV (+) mothers who acquired HIV

40 30 % 20 10 0
No ARV

33

8
With ARV
IAPSM Conference 2004

Some Lessons Learnt:

Increased knowledge about how to prevent HIV/AIDS
Proportion of women who know how to avoid: acquiring HIV/AIDS transmitting HIV/AIDS to baby

100 85.1 87.8 50 0 50.3 35.7

After counselling

Before counselling

PPTCT: Goals & Objectives

UNGASS ( UN General Assembly Special Session) Target 54
a) By 2010, reduce by 50% the proportion of infants infected by HIV by ensuring that: b) Eighty(80%) per cent of pregnant women accessing antenatal care have HIV information, counselling and other HIVprevention services available to them.

Millennium Development Goals (MDGs) and targets MDG 4: reduce child mortality target 4.A: Reduce by two-thirds, between 1990 and 2015, the under-five mortality rate. MDG 5: Improve maternal health target 5.A: Reduce by three quarters, between 1990 and 2015, the maternal mortality ratio. target 5.B: Achieve, by 2015, universal access to reproductive health. MDG 6: combat HIV/AIDS, malaria and other diseases target 6.A: Have halved by 2015 and begun to reverse the spread of HIV/AIDS. target 6.B: Achieve, by 2010, universal access to treatment for HIV/AIDS for all who

Enrollment Procedure
ANC
One-To-One

Group Education HIV Test

Offered HIV test

Post-Test Counseling
HIV + HIV -

Pre-Test Counseling
One-To-One

Enrollment: AZT/NVP

Primary Prevention

Nevirapine Administration Mother: Screened for contraindications

Single Dose Tablet of 200 mg. during First stage of Labour

Baby: Monitored for First 24 Hours Screened for Contraindications Single Dose of suspension 24 to 72 hours

New recommendations from the World Health Organization (WHO) for preventing mother-to-child transmission (PMTCT) for lowering and virtually eliminate paediatric HIV infection, by 2015. The key recommendations are:
Antiretroviral therapy for all HIV-positive pregnant women with a CD4 count below 350 or WHO stage 3 or 4 HIV disease, with treatment to begin without delay using a backbone of AZT and 3TC or tenofovir and either 3TC or FTC. Longer provision of antiretroviral prophylaxis for HIV-positive pregnant women who are not in need of ART for their own health. Where mothers are receiving ART for their own health, infants should receive prophylaxis with nevirapine for six weeks after birth if the mother is breastfeeding, and prophylaxis with either nevirapine or AZT for six weeks if the mother is not breastfeeding. For the first time there is enough evidence for WHO to support giving antiretroviral therapy to the mother or child throughout the breastfeeding period, with the recommendation that breastfeeding and prophylaxis should continue until twelve months of age if the infant is either HIV-negative or of unknown status. Where mother and infant are both HIV-positive, breastfeeding should be encouraged for at least the first two years of life, in line with recommendations

WHO MOST RECENT GUIDELINES for PPTCT(2009)

The new guidelines recommend : lifelong antiretroviral treatment for all pregnant women with serious or advanced disease or with a CD4 count at or below 350 regardless of symptoms. In women who do not need antiretroviral therapy for their own health (ie, with a CD4 count above 350), antiretroviral therapy is to start earlier in the pregnancy, at 14 weeks or as soon as possible thereafter, and should continue through to the end of the breastfeeding period Daily AZT for the mother during pregnancy, single dose nevirapine at the onset of labour, AZT/3TC during labour and for seven days post-partum. If a mother has taken AZT for at least four weeks prior to delivery AZT/3TC and single-dose nevirapine can be ommitted. Infant prophylaxis with nevirapine or AZT should be continued until the end of the breastfeeding period or for six weeks after birth in non-breastfeeding infants OR. A three-drug regimen for the mother taken during pregnancy and throughout the breastfeeding period, as well as infant prophylaxis as in option A. The recommended regimens are AZT/3TC plus efavirenz, abacavir (Ziagen) or lopinavir/ritonavir (Kaletra/Aluvia).

WHO New advice on infant feeding(I)

WHOs international expert review panel decided that there is now enough evidence for WHO to recommend antiretroviral treatment during breastfeeding. Mothers are faced with choosing between the benefits of breastfeeding but exposing their children to the risk of HIV transmission or not breastfeeding and increasing the childs risk of death from other diseases. Here are two choices for HIV-positive women who breastfeed and are not taking ART: If a woman received zidovudine during pregnancy, daily nevirapine is recommended for her child from birth until the end of the breastfeeding period. Or If a woman received a three-drug regimen during pregnancy, a continued regimen of three-drug prophylaxis is recommended for the mother until the end of the breastfeeding period.

WHO New advice on infant feeding(II)

Recommendations for infant feeding practices in the first 24 months of life: Mothers known to be HIV-infected (and whose infants are HIVuninfected or of unknown HIV status) should exclusively breastfeed their infants for the first six months of life, introducing appropriate complementary foods after that, and continue breastfeeding for the first twelve months of life. Breastfeeding should then only stop once a nutritionally adequate and safe diet without breast milk can be provided. If infants and young children are known to be HIV-infected, mothers are strongly encouraged to exclusively breastfeed for the first six months of life and continue breastfeeding as recommended for the general population, that is up to two years and beyond.

Diagnosis of HIV Exposed children

To exclude infection in the child < 18 mo. age: 2 negative ELISA (antibody) tests beyond 6 months of age with interval of 1 mo. between tests Negative virologic assays (HIV DNA PCR or RNA RT-PCR or HIV viral culture) until > 4 mo. age in the absence of breastfeeding To confirm infection in the child > 18 mo. Age: Positive HIV ELISA + Western Blot

WHO staging system for HIV infection and disease in children

Clinical Stage 1 Asymptomatic /PGL

Clinical Stage 2

Hepatosplenomegaly ,Papular pruritic eruptions,Seborrhoeic dermatitis, Extensive human papilloma virus infection ,Extensive molluscum contagiosum ,Fungal nail infections ,Recurrent oral ulcerations Lineal gingival erythema (LGE),Angular cheilitis Parotid enlargement,Herpes zoster ,Recurrent or chronic RTIs (otitis media, otorrhoea, sinusitis)
Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations : Moderate unexplained malnutrition not adequately responding to standard therapy ,Unexplained persistent diarrhoea (14 days or more ) Unexplained persistent fever (intermittent or constant, for longer than one month),Oral candidiasis (outside neonatal period ), Oral hairy leukoplakia, Acute necrotizing ulcerative gingivitis/periodontitis Pulmonary TB, Severe recurrent presumed bacterial pneumonia

Clinical Stage 3

WHO staging system for HIV infection and disease in children (II)
Clinical Stage 3 Conditions where conrmatory diagnostic testing is necessary
Chronic HIV-associated lung disease including brochiectasis Lymphoid interstitial pneumonitis (LIP) Unexplained anaemia (<8g/dl), and or neutropenia (<1000/mm3) and or thrombocytopenia (<50 000/ mm3) for more than one month

Clinical Stage 4

Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations

Unexplained severe wasting or severe malnutrition not adequately responding to standard therapy,Pneumocystis pneumonia Recurrent severe presumed bacterial infections (e.g. empyema, pyomyositis, bone or joint infection, meningitis, but excluding pneumonia) Chronic herpes simplex infection; (orolabial or cutaneous of more than one months duration), Extrapulmonary TB ,Kaposis sarcoma,Oesophageal candidiasis CNS toxoplasmosis (outside the neonatal period),HIV encephalopathy

Clinical stage 4

Conditions where conrmatory diagnostic testing is necessary

CMV infection (CMV retinitis or infection of organs other than liver, spleen or lymph nodes(onset at age one month or more) ,Extrapulmonary cryptococcosis including meningitis,Any disseminated endemic mycosis (e.g. extrapulmonary histoplasmosis, coccidiomycosis, penicilliosis) Cryptosporidiosis Isosporiasis Disseminated non-tuberculous mycobacteria infection Candida of trachea, bronchi or lungs, Visceral herpes simplex infection

WHO recommends 2 equally-effective options for provision of PMTCT ARVs

OPTION A Mother: If CD4 >350 Antepartum AZT (from 14 weeks) sdNVP + AZT/3TC at delivery AZT/3TC for 7 days postpartum If CD4 350: Lifelong ART Infant If breastfeeding: daily NVP from birth until one wk after breastfeeding has stopped If not breastfeeding or mother on ART: NVP for 6 wks OPTION B Mother If CD4 >350 HAART from 14 weeks of pregnancy until 1 week after breastfeeding has Stopped If CD4 350: Lifelong ART Infant NVP for 6 weeks (regardless of whether mother is breastfeeding)

 When replacement feeding is AFASS ,i.e. Acceptable, Feasible, Affordable, Sustainable and Safe, avoidance of all breastfeeding is recommended. Otherwise EBF is recommended for the first (6) months of life with early and abrupt cessationweaning.

Recommendations on feeding by HIV-positive mothers: WHO consultation Oct.2000

Counselling should include information about the risks and benefits of various infant feeding options, and guidance in selecting the most suitable option

Reducing risk of HIV transmission through breastfeeding

Shorter duration 6 months Exclusive breastfeeding during 1st 6 months Safe sex practices of mother during lactation period to prevent infection or re-infection Good lactation management (attachment, positioning, frequency) to avoid mastitis No feeding from cracked nipple ARVs?

BF transmission of HIV: Ghent meta-analysis (Read et al, 2002). - Early cessation can reduce BF transmission with about 60%
20 Cumulative rates of late postnatal HIV infection (> 4 wks) 16 15 10 5 0 4 w to 6 mo up to 12 mo up to 18 m 4 9

Early cessation is possible but:

Early, rapid cessation is possible (Uganda, Zambia, Botswana) Problems encountered
breast engorgement; mastitis; babies crying, trouble sleeping, appetite loss, diarrhea; financial constraints with replacement feeding; family objections more problems when cessation < 6 months (Botswana)

Trained counselors were able to help mothers overcome problems Provision of replacement feeds, family support facilitated process Impact on HIV transmission, survival not yet known

PPTCT: Challenges,Issues,Concerns
How to maintain QA going to scale? (Training,

Counselling). Counsellors based programme. PPTCT only for institutional deliveries? ( Out reach, District Model)
Completion of the PPTCT package with Primary Prevention and continuum of care: Infant Feeding dilemma Integration into the National Reproductive & Child Health programme. Stigma, Discrimination, Attitude of health care providersCommunication Strategy, Male Involvmentwhile