Compiled by Anne H. Vincent
MD, MPH - UNICEF India Country Office
for Pediatric HIV/AIDS, First National Conference (Held on 3^rd & 4^th November, 2001 at Delhi)

Introduction

Mother-to-child transmission (MTCT) is by far the largest source of HIV infection in children below the age of 15 years. In countries where blood products are regularly screened and clean syringes and needles are widely available, it is virtually the only source in young children.

So far, the AIDS epidemic has claimed the lives of nearly 4.3 million children, and another 1.4 million are living with HIV today. Worldwide, one in eleven of those who became newly infected in 2000 was a child.

Globally, there are around 16.4 million women of childbearing age who are HIV-positive. And the number of infants who acquire the virus from their mothers is rising rapidly in a number of places, notably Africa, India and South-East Asia.

The virus may be transmitted during pregnancy (mainly late), childbirth, or breastfeeding. In the absence of preventive measures, the risk of a baby acquiring the virus from an infected mother ranges from 15% to 20% in industrialised countries, and 25% to 45% in developing countries. The difference is due largely to feeding practices: breastfeeding is more common and usually practiced for a longer period in developing countries than in the industrialised world.

In India, 2000 surveillance data put at 3.86 million the estimated number of Indians infected by the HIV virus. The prevalence rate in the adult group - 15 to 49 years of age, is 0.7%. With 27 million pregnancies a year and a prevalence rate in pregnant women estimated at 0.3%, it is already close to 100,000 HIV positive Indian women that become pregnant every year. Using a conservative vertical transmission rate of 30%, this means a new annual cohort of 30,000 infected infants. With HIV/AIDS being in India a disease of the poor, these 30,000 children will all dye within a few months to a few years.

The effects of the epidemic among young children are serious and far-reaching. AIDS threatens to reverse years of steady progress in child survival, and has already doubled infant mortality in the worst affected countries. In Zimbabwe, for instance, infant mortality increased from 30 to 60 per 1000 between 1990 and 1996. And deaths among one to five year olds, the age group in which the bulk of child AIDS deaths are concentrated, rose even more sharply-from 8 to 20 per 1000-in the same period.

In India, high prevalence States coincide with those States that are doing better in terms of health indicators and development, in general. The less-developed and more populated States, in the northern part of the country are so far classified as "low prevalence States". These States cumulate number of vulnerability factors with regards to an epidemic such as the a HIV epidemic: extreme socio-economic conditions leading to high levels of migration, particularly towards metropolis such as Mumbai where prevalence is high, poor health and social services, illiteracy, low women status, low school enrollment, limited access to information, etc. It is difficult to assess the role of these vulnerability factors - particularly migration, on the spread of the epidemic but it is doubtful that these States remain in the "low prevalence" group. It is not unconceivable to have, in a rather near future, better-off States move backward in terms of health indicators while worst-off States will enter the epidemic.

Mother-To-Child Transmission

Timing of transmission

The timing of the transmission of the HIV virus during and after the pregnancy has obvious implications for strategies to reduce it. The Pediatric Virology Committee of the AIDS Clinical Trials Group in the United States has proposed definitions for determining in utero versus intrapartum transmission. It is considered that a child with a positive PCR within 48 hours of birth has been infected in utero. A PCR negative at 48 hours but positive 7-90 days after delivery indicates an intrapartum infection.

Transmission through breastfeeding

A systematic review of studies done by Dunn et al in 1992 found that the additional risk of transmission through breast milk (over and above the risks of transmission in utero and intrapartum) was 14% when the mother had been infected prenatally and 29% when the mother acquired the HIV virus postnatally.

Nduati in Kenya reported a 16% excess transmission (by 24 months) through breastfeeding in a study where women were randomly assigned to either breastfeeding or to formula milk. This indicates a 44% contribution of breastfeeding to the overall HIV transmission. It is important to note here that full compliance with assigned infant feeding practice was 96% in the breastfeeding group and only 70% in the replacement feeding group.

In an observational study in South Africa, Coutsoudis et al found the extra risk linked to breastfeeding to be 12% at 15 months giving an overall contribution to the transmission of 39% .

Transmission of HIV-1 through breastfeeding varies over time. The risk appears to be greatest during the first six months of life - 0.7% per month, and to decrease over time with a cumulative risk of 10 to 20%.

Prevention strategies

Until recently, countries had only two main strategies for limiting the numbers of HIV-infected infants; today a three-pronged strategy is recommended:

• primary prevention of MTCT-taking steps to protect women of childbearing age from becoming infected with HIV in the first place;
• the provision of family planning services, including pregnancy termination where this is legal, to enable HIV positive women to avoid unwanted births;
• a course of antiretroviral drugs for the mother (and sometimes the child), and where applicable replacement feeding for the infant.

Antiretroviral drugs

Until 1998, only one drug regimen had been proven to reduce the risk of HIV transmission from mother to child. A study called ACTG 076 found that zidovudine (ZDV, also known as AZT) given orally starting in the fourth month of pregnancy, intravenously during labour, and for six weeks to the infant in a non-breastfed population, reduced mother-to-child transmission of HIV by nearly 70%. When combined with elective caesarean section in non-breastfeeding populations, this regimen results in a transmission rate of 2% or less.

A CDC-sponsored trial concluded in Thailand in February 1998 showed that a short course of ZDV pills given to women during the last four weeks of pregnancy and labour cuts the rate of vertical transmission during childbirth by 50% in a non-breastfeeding population. Because the women in the study were also given formula milk, the short treatment reduced MTCT in the study population to 9%, compared with 18% in the control group who did not receive a placebo but did receive replacement feeding (as mentioned, the norm in developing countries is 25-45%). The same regimen in a breastfeeding population cuts the transmission by 37%.

Preliminary results from a number of ongoing studies in breastfeeding populations indicate that a short course of antiretrovirals can still reduce the transmission of HIV from the mother to the baby, though not as well as when mothers do not breastfeed. One of these studies is the PETRA trial (coordinated by the UNAIDS secretariat), which is testing the effectiveness of a number of antiretroviral regimens using two drugs - AZT and lamivudine (3TC) - in combination. When a HIV-positive mother starts taking the two drugs at the time of delivery, and she and her newborn baby continue on the drug regimen for just one week following birth, the risk of the baby becoming infected is reduced to about 11% when measured at 6 weeks of age, as compared with a 17% risk when no antiretroviral drugs at all are given. An even bigger reduction - to 9% - is seen when the drug regimen is started at 36 weeks of pregnancy, around a month before delivery.

In July 1999, the US National Institutes of Health released the results of a joint Uganda-US study comparing the preventive efficacy of a single dose of the antiretroviral drug nevirapine (NVP), given to the mother during labour and to the baby within the first three days of life, with that of AZT given in labour to the mother and administered to the baby for one week after delivery. Measured at 6-8 weeks of age, HIV infection was found in 20% of the infants who received AZT, compared with 12% in those receiving NVP. The transmission rate was 16% (15.7% for Owen) at 12 months in breastfed infants in the NVP group.

Concerns were raised in 2000 on the risk of resistance development (K103N NVP resistance mutation) after a single dose of NVP. In a phase II study HIVNET 006, 3 out of 14 women had NVP-resistant virus at 6 weeks postpartum. WHO convene in October 2000 a meeting of a group of Technical Experts and concluded that "the benefit of decreasing mother-to-child HIV transmission with antiretroviral drug prophylaxis regimens greatly outweighs any theoritical concerns related to development of drug resistance.

Other interventions targeting pregnancy, labour and delivery

Other interventions to prevent MTCT include:

• Delivery by elective caesarean section: There is a relatively high risk of transmission during delivery due to presence of the virus in blood and mucus in the birth canal. Delivery by elective caesarean section reduces the child's exposure to the mother's body fluids during birth and has been shown to lower the risk of HIV infection: 1.8% of transmission as opposed to 10.5% (p<0.001). In resource-poor settings these benefits need to be weighed with costs, logistical requirements and risk of post-operative complications.
• Cleansing the birth canal during labour and delivery: To reduce exposure to HIV in the birth canal, various methods of vaginal washing (lavage) before and during delivery are being investigated. In a trial performed in Malawi, lavage using chlorhexidine showed no overall difference in rates of MTCT, but did show a significant reduction in cases where membranes were ruptured for more than four hours; it also resulted in significant reduction of infant mortality and morbidity.
• Other obstetrical modifications can reduce contact between the infant and the mother's infected body fluids. These involve avoiding episiotomy, unnecessary artificial rupture of membranes, fetal scalp electrodes and other invasive procedures.
• Vitamin A supplements: A deficiency of vitamin A in HIV-infected mothers is associated with a higher risk of transmission from mother to child. However, trials in Malawi and South Africa have shown no effect of vitamin A supplementation on the risk of MTCT.

Counselling and voluntary testing

For women to take advantage of measures to reduce MTCT they will need to know and accept their HIV status. Voluntary counselling and testing services therefore need to be widely available and acceptable. Ideally, everyone should have access to such services since there are clear advantages to knowing one's serostatus. People who know they are HIV-infected are likely to be motivated to look after their health, perhaps with behaviour and lifestyle changes, and to seek early medical attention for problems. They can make informed decisions about sexual practices, childbearing, and infant feeding, and take steps to protect partners who may still be uninfected. Those whose test results are negative can be counselled about how to protect themselves, and their children from infection. Furthermore, voluntary counselling and testing has an important role to play in challenging denial of the epidemic: it helps societies which are currently only aware of people who are ill with AIDS to recognise that there are many more people living with HIV and who show no outward signs.

Sweat demonstrated that VCT is highly cost effective in high prevalence urban settings in East Africa. This cost effectiveness, measured in terms of HIV-1 infections averted, is highest if VCT is targeted at populations with high HIV prevalence, particularly HIV-1 positive women receiving VCT as individuals or together with their sexual partner.

However, providing voluntary counselling and testing for the whole population might not necessarily be justified in low HIV-prevalence areas where resources are scarce. And even where justified on the basis of prevalence, it might not be a realistic option in some places because the health infrastructure is not sufficiently strong to support the service. For, besides the cost and practical requirements of providing counselling and testing itself, there must be an efficient referral system to a range of other basic services that people need once they have received their test results. These include family planning, prevention and treatment of sexually transmitted diseases (STDs), mother-and-child health services, and health care for infected people including prevention and treatment of opportunistic infections, counselling, and psychological support.

Taking local conditions into account, policy-makers need to decide what kind of counselling and testing services are most appropriate and feasible, and what action, if any, is required to strengthen the health system that supports them. In particular, decisions need to be made about whether to make counselling and testing available to the whole population (comprehensive VCT); or to target the service at women or couples making use of reproductive health services in areas where the HIV prevalence is especially high (targeted antenatal VCT); or to offer counselling and testing to all women attending antenatal services as part of a programme to reduce MTCT of HIV (routine antenatal VCT).

Health Care systems

A PMTCT programme can only be set up where there is an efficiently functioning health system with certain key services. Mother-and-Child health services, including widely available and acceptable antenatal, delivery and postnatal services, are essential. Counselling services, family planning and medical care for HIV-positive women and their children should also be part of the basic health care provision. Pre-requisites to PMTCT interventions include:

• easy access and privacy for clients attending services. This will require assessment of the physical environment of clinics, and perhaps rearrangement of activities
• adequate laboratory services with quality assurance system
• continuity of care and a good flow of information while respecting strict confidentiality between the various units involved in the management of HIV-positive clients
• technical supervision of services to enhance quality
• opportunities for clients to express their needs and their views

Where the basic services are already in place and operating efficiently, the cost of providing counselling and testing and antiretroviral drugs is likely to be well distributed across the health system and relatively easy to absorb. However, in places where the health infrastructure needs considerable strengthening and perhaps even building from scratch to support the new programme, the additional cost will assume greater significance. Since expansion and improvement of the health system benefit the whole of society, it is important that the MTCT programme is not expected to bear an undue and perhaps crippling proportion of the costs and responsibility. If the provision of VCT services and antiretroviral drugs is to be sustainable over the long term, the financial burden must be fairly distributed across the health services. Policy-makers may also want to seize the opportunity brought by additional funds provided for HIV initiatives to strengthen services dedicated to women and children.

Replacement feeding

The issue of infant feeding in the context of the HIV epidemic is probably the most difficult dilemma faced by those involved, particularly pediatricians.

Breastfeeding is associated with a significant additional risk of HIV transmission from mother-to-child. In untreated women breastfeeding beyond 12 months, the absolute risk of transmission through breastfeeding is 10-20%.

It is during the first four to six months of life that exclusive breastfeeding carries its maximum benefits in terms of nutrition, prevention of infections others than HIV, and decreased fertility for the mother. There is evidence that exclusive breastfeeding in the first three months of life carries a lower risk of HIV transmission than mixed feeding.

The WHO Technical Consultation in October 2000 issued recommendations that confirm that issued in 1998 in the WHO/UNAIDS/UNICEF Policy Guidelines themselves endorsed by the Breastfeeding Promotion Network of India (BPNI) in 1999.

Pilot Projects

Beside numerous clinical trials and country programmes like that of western countries and Thailand, many less-developed countries (Africa, India, South-East Asia, the Carribean, Central and Eastern Europe) are implementing pilot projects for prevention of mother-to-child transmission of HIV within the public health sector.

All these projects are based on: 1) voluntary counselling and testing of pregnant women at ANC clinics; 2) provision of either zidovudine (AZT) (according to the CDC-Abidjan protocol) or nevirapine (NVP) (following the HIVNET 012 protocol); 3) informed choice with regards to infant feeding.

In India, the National AIDS Control Organization is implementing, with the support of UNICEF, a Feasibility Study or piloting of PMTCT interventions using AZT/NVP in 11 centers in the five States with the highest HIV prevalence (Maharashtra (5), Andhra Pradesh (1), Karnataka (1), Tamil Nadu (3), and Manipur (1)).

This pilot project aims at 1) identifying strengths and weaknesses of the Indian public health sector in implementing PMTCT, 2) identification of a strategy for scaling up through integration into the national Reproductive and Child Health Programme, 3) development of a National Policy for PMTCT.

Implementation started on 1st March 2000 and as of August 2001 (18 months):

• 192,474 women attended ANC
• 171,471 (89.1%) benefited from "HIV group education"
• 103,681 (60.5%) were tested for HIV
• 1,724 (1.7%) tested positive for HIV-1 (from 0.4 to 5%)
• 726 (42.1%) of live births to positive pregnant women benefited from AZT prophylaxis

Lessons learned from these pilot projects throughout the world are:

• A consistent drop for counselling (65% of women attending ANC in Africa; 89% in India). This drop is attributed mainly to understaffed health centers, poorly motivated health workers or both.
• Secondly, a consistent drop for HIV testing (67% of women counseled in Africa and 60.5% in India). This drop is attributed mainly to poor quality of counselling, lack of trust in the health care system, stigmatization, and low levels of community awareness and mobilization.
• Finally for women who have been HIV tested and found to be HIV positive, there is a significant drop in terms of appropriate utilization of antiretrovirals (AZT or NVP). This last drop is mainly attributed to late coming to ANC clinics, particularly for those countries using AZT.

Nevertheless, some sites are able to achieve high levels of counselling (close to 100%) and of acceptance of HIV testing (75 to 80%), included in India.

What seems to be the keys to success for these sites:

• A well managed health care center where workers are regularly paid, given feedback, and asked to participate in the management of their center and where supplies and services are consistently available thereby ensuring trust of the community in the health care center and its staff
• An upgraded ANC delivery system integrating HIV prevention interventions
• An effective communication strategy to raise community awareness and mobilization
• A model for counselling that provides adequate information in the most time effective manner, be it appropriate group counselling with Q/A session, use of lay counselors, use of group counselling with video or short one on one individual session with health workers
• The use of rapid testing kits with immediate results provided to the patients
• A support system for HIV infected individuals and families, including nutritional, psychosocial and clinical support

UN goals set a 25% reduction in MTCT by 2005 (including prevention of infections among pregnant women and a 14 to 15% reduction in MTCT per se) and a 50% reduction by 2010 (again including prevention of infections among pregnant women and a 25 to 30% reduction in MTCT per se). So, there is a need for an urgent scaling up of the interventions with much improved levels of counselling, acceptance of HIV testing, and compliance with intervention.

Priority Actions:

• Integrate MTCT within MCH/RCH
• Scale up where MCH services are satisfactory in terms of quality, staffing and supplies. Wherever these conditions exist, scaling up is possible now. Elsewhere, MTCT should be seen as an opportunity to improve the overall quality of MCH services.
• Implement behavior communication strategy that integrates all aspects of HIV prevention (i.e. ensure that a comprehensive, research-based and strategic communication and community participation component is fully integrated within MTCT as well as with the whole HIV/AIDS national intervention).

A Decision Tree

Clearly, national and local circumstances will have a major influence on decisions regarding the adoption of voluntary counselling and testing, antiretroviral drugs and replacement feeding. The following "decision tree" is proposed as a means of assisting those involved in national and local policy-making to decide on: a) the appropriate levels of provision, and b) the best model of operation of the strategy.

The influencing factors:

• seroprevalence of HIV in the country or community will determine the costs of inaction and the relative cost-effectiveness of different screening strategies
• attitudes towards HIV in the country or community will determine the risk of discrimination against women found to have HIV, the likelihood of infringement of their rights, and the expected acceptability of the intervention
• the risks associated with replacement feeding will determine whether or not the intervention can be introduced or whether exclusive breastfeeding should be favoured
• the state of the existing health system and Mother-and-Child Health services (including family planning) will determine the expenditure of effort and resources required to strengthen them sufficiently to support the new programme
• the maturity of the epidemic and level of social support that has developed to cope with it will determine how big a burden will be imposed upon the MTCT programmes by increased demand for health care and counselling
• the wider benefits to society will have to be taken into account when balancing costs and benefits of the intervention
• available financing for MTCT interventions and associated services will be a major consideration in decision-making.

These factors will vary a great deal from one place to another. The following table proposes a decision-making process to assist policy-makers who wish to consider adopting an antiretroviral drug and replacement feeding strategy that is suited to their situation, and that reflects the local HIV prevalence, available resources, health system performance and expected risks associated with replacement feeding.

Combination of appropriate services for different circumstances Local HIV prevalence

Key: VCT = voluntary counselling and testing; ARV = antiretroviral drugs; RF = replacement feeding
Source: Prevention of HIV transmission from mother to child: Strategic Options