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Letters to the Editor

Indian Pediatrics 2001; 38: 680-683  

Mother-to-Child Transmission of HIV Must be Prevented

 

Merchant and colleagues have shown clearly that perinatal transmission of HIV is more common than we expected or suspected, and that it can be prevented, in most cases, at affordable cost, in India(1). Their report is a landmark in our country, for several reasons. This is the first reported experience of a systematic approach to the prevention of vertical (mother-to-child) transmission of HIV in our country. It did not come as a result of any national policy or plan on prevention of vertical transmission, but from the in-house clinical research of a health care institution in the private voluntary sector. This is an important lesson for all of us in the Indian Academy of Pediatrics. We must continue to ask what we can do for our country, to provide leadership where it may be lacking.

The Merchant report inspires us to take prevention of perinatal HIV transmission seriously. How should we proceed, with this, and other recent studies in other countries, to guide us? We had learned, way back in 1986, that the predominant mode of HIV trans-mission in India was via sexual intercourse between men and women, unlike in the West where it was via men having sexual acts with men(2). By 1988 we became aware of the spread of HIV within ordinary house-holds(3,4). In 1993, the disturbing finding of HIV infection among monogamously married women without personal risk behavior, was published(5). This phenomenon was later confirmed and elaborated on, in another study(6). These were signals that the stage was set for mother-to-child transmission of HIV in our country, the magnitude of which would be dictated by our failure to prevent infection in women of child bearing age. In other words, our nation had enough warning that vertical transmission would occur and that it would become a major concern for the health system in general and pediatrics in particular. Unfortunately, until today, there is no guidance on its prevention, from the national agencies concerned with policies on health care and public health.

The problem is already at our doorsteps. There have been several recent publications on the clincial features of HIV disease in childhood, especially among those infected perinatally, showing that the occurrence of mother-to-child transmission is already wide-spread in India(7-9). We can no longer ignore its magnitude, or the gravity of its adverse impact on children in particular and society at large(7-9). The frequency of mother-to-child HIV transmission in India was reported to be 35%(10). There are regions in the country where the frequency of maternal infection is already 2% or more(1). It was recently reported, in the lay press, that the rate is 0.1% in Kerala. If we take an overall national rate as 0.5%, then the annual number of infected women giving birth to infants would be 125,000. The vertical transmission rate in the Merchant study was about 24%; the only other report showed a rate of 35%(10). If we accept the rate as 30% vertical transmission, each year India has the burden of 37,500 infants acquiring HIV infection from mothers.

The method of prevention of vertical transmission in the Merchant study consisted of 5 interventions, namely, counseling and testing, zidovudine 400 mg per day for at least 6 weeks pre-partum, elective caesarian delivery, zidovudine 8 mg/kg per day to the infant for 6 weeks and the exclusion of breastfeeding(1). The success was a reduction by 75% of transmission, from 24% to 5.8%(1). I wish to draw attention to another similar recent experience from Thailand(11). Siri-navin and colleagues reported on their study in which there were 4 groups of pregnant women, all of whom refrained from breastfeeding(11). One group received no zidovudine, and vertical transmission was documented in 11 infants among 48 (22.9%). A second group was given 500 mg zidovudine (in two divided doses) for 4-6 weeks pre-partum; transmission occurred in 10 of 47 infants (21.3%). A third group of 28 women were given the above zidovudine regimen and their infants were given 24 mg zidovudine (oral, syrup form) in 4 divided doses daily for 4-6 weeks; no infant was infected. In the last group of 13 women and their infants, the regimens were like in group 3, but in addition, intra-partum intravenous zidovudine was given again, no infant was infected. Altogether, in the 41 infants who were started on zidovudine soon after birth, and continued for 4-6 weeks, the rate was 0, with a 95% confidence interval of 0-8.6%(11). The Merchant study included neonatal zidovudine at a similar dose of 8 mg/kg, which would be 24 mg for an infant of 3 kg body weight. It would seem to me, that the four most important interventions common in these two studies were: counseling and testing pregnant women with their participation in decision-making; zidovudine treatment of the mother in late pregnancy; early start of neonatal zidovudine and its continuation for 4-6 weeks; and withholding of breast-feeding(1,11). Elective caesarian delivery or additional intra-partum zidovudine did not appear to be critical interventions.

In summary, we have very clear answers to the question of how to prevent vertical transmission of HIV, at affordable cost. Zidovudine is manufactured in India and its cost is much lower here than elsewhere(12). I suggest that the standard obstetric and neonatal/pediatric practice should include the following:

1. Counseling of all antenatal women and their husbands, in a suitable manner, and testing for HIV infection, with consent.

2. Preparing HIV positive mothers not to give breastfeeding at all; giving of lactation inhibiting hormone on request or on advice; and ensuring nutritional adequacy of the infants.

3. Oral zidovudine to the mother, 100 mg 4 times daily, from 32 weeks pregnancy or as soon as possible thereafter; or 250 mg every 12 hours, from 34 weeks pregnancy or as soon as possible thereafter; and to continue the drug right up to the time of actual delivery.

4. Oral zidovudine to the infant, 8 mg/kg body weight/day or 24 mg/day, in 4 divided doses, at intervals of 6 hours, starting immediately after birth, or within 2 hours, and continuing for a minimum of 4 and a maximum of 6 weeks.

With the publication of the above two study reports, the norm of practice has become reasonably clear, as summarized above(1,11). If these suggested interventions are applied, we can expect the transmission rate to be about 5% or even less. The opportunity of counseling must be used to talk about hepatitis B virus infection also, and all mothers should be offered the test for carrier state. Already recommendations are available on the standard practice of active and passive immunization of the infants of hepatitis B virus carrier mothers.

The four steps suggested above should be the minimum standard in routine practice, for preventing vertical HIV transmission, in government sector and private sector clinics and institutions. It is suggested that the National AIDS Control Organization (NACO) should reimburse the total expenses involved in the above 4 interventions, to those mothers who are in financial need, as certified by the attending obstetrician and pediatrician. It is also recommended that NACO may commis-sion a cost-effectiveness study of prevention of vertical transmission of HIV, instead of treatment of infected children. India has the opportunity to lead the developing countries in the systematic prevention of vertical HIV transmission.

Elective caesarian before rupture of membrane or start of labor, may be considered as a possible additional intervention to further reduce transmission, but it cannot be offered as standard practice, in the light of the above review. Intra-partum intravenous zidovudine is of doubtful value, and it is not suggested for further reduction of transmission.

Future research in prevention of vertical transmission must take into account these important components of intervention. For example, if a short course or a single dose of nevirapine given to the mother just before delivery is to be compared with zidovudine as described above, then it is important to keep constant the neonatal zidovudine and exclusion of breastfeeding. If neonatal short course or single dose nevirapine is to be compared with zidovudine as described above, then all other components of intervention must be kept constant. The major reason to stipulate these conditions is the relatively low success rate of prevention of vertical transmission by other interventions and the relatively high success rate of the intervention described in the two recent studies reviewed above.

T. Jacob John,
Advisor, Kerala State Institute of Virology and Infectious Diseases (Ministry of Health),
439 Civil Supplies Godown Lane,

Kamalakshipuram,Vellore, TN 632 002, India

E-mail:
tjjohn@md4.vsnl.net.in

 References

1. Merchant RH, Damania K, Gilada IS, Bhagwat RV, Karkare JS, Oswal JS, et al. Strategy for preventing vertical transmission of HIV: Bombay experience. Indian Pediatr 2001; 38: 132-138.

2. John TJ, Babu PG, Jayakumari H, Simoes EAF. Prevalence of HIV infection in risk groups in Tamil Nadu, India. Lancet 1987; 1: 160-161.

3. John TJ, Babu PG, Pulimood BR, Jayakumari H. Prevalence of human immunodeficiency virus among voluntary blood donors. Indian J Med Res 1989; 89: 1-3.

4. Mathai R, Prasad PVS, Jacob M, Babu PG, John TJ. HIV seropositivity among patients with sexually transmitted diseases in Vellore. Indian J Med Res 1990; 91: 239-241.

5. John TJ, Bhushan N, Babu PG, Seshadri L, Balasubhahmanium N, Jasper P. Prevalence of HIV infection in pregnant women in Vellore region. Indian J Med Res[A] 1993; 97: 227-230.

6. Gangakhedkar RR, Bentley ME, Divekar AD, Gadkari D, Mehendale SM, Shepherd ME, et al. Spread of HIV infection in married monogamous women in India. J Amer Med Assoc 1997; 278: 2090-2092.

7. Daga SR, Verma B, Gosavi DV. HIV infection in children: Indian experience. Indian Pediatr 1999; 36: 1250-1253.

8. Dhurat R, Manglani M, Sharma R, Shah NK. Clinical spectrum of HIV infection. Indian Pediatr 2000; 37: 827-830.

9. Lodha R, Singhal T, Jain Y, Kabra SK, Seth P, Seth V. Pediatric HIV infection in a tertiary care center in North India: Early impressions. Indian Pediatr 2000; 37: 982-985.

10. John TJ. Frequency of mother-to-infant trans-mission of human immunodeficiency virus. Indian Pediatr 2000; 37: 1027-10298.

11. Sirinavin S, Phaupradit W, Taneepanichskul S, Atamasirkul K, Hetrakul P, Takkinstian A, et al. Effect of immediate neonatal zidovudine on prevention of vertical transmission of human immunodeficiency virus type 1. Int J Infect Dis 2000; 4: 148-152.

12. Reddy CR. Cipla stirs pharma world with its AIDS cocktail. The Hindu, Chennai, 23-2-2001, p 19.

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