Prevention of mother to child transmission of HIV Kapoor A, Kapoor A, Vani SN - Indian J Pediatr
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In this article
» Abstract
» Timings of Trans...
» Strategies for PMTCT
» Counseling and V...
» Antiretroviral D...
» Use of Nevirapin...
» Benefits of Usin...
» Optimizing the O...
» Elective Cesarea...
» Changing the Lif...
» Reducing Exposur...
» Early Diagnosis ...
» Timing of HIV Te...
» Treatment of New...
» Conclusion
» Acknowledgement
» References
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SYMPOSIUM
Year : 2004 | Volume : 71 | Issue : 3 | Page : 247-251
Prevention of mother to child transmission of HIV
Kapoor A, Kapoor A, Vani SN
Departments of Pediatrics, P.S. Medical College, Karamsad, Anand, Gujarat
Correspondence Address:
Departments of Pediatrics, P.S. Medical College, Karamsad, Anand, Gujarat
anilanjukapoor@yahoo.com
» Abstract
Perinatal transmission is the most common cause of HIV infection in pediatric population below the age of 15 years. Much progress has been made to decrease the risk of transmission than just offering the option of medical termination of pregnancy to the mother. Future research is needed not only to develop the simple preventive program, but also to make it more cost effective, acceptable and accessible to the general population. Following review article focuses on the factors affecting the transmission of HIV, strategies for prevention of MTCT with special reference to use of nevirapine and breast-feeding practices in HIV positive mother. The role of counseling and voluntary testing is also stressed upon.
How to cite this article:
Kapoor A, Kapoor A, Vani SN. Prevention of mother to child transmission of HIV. Indian J Pediatr 2004;71:247-251
How to cite this URL:
Kapoor A, Kapoor A, Vani SN. Prevention of mother to child transmission of HIV. Indian J Pediatr [serial online] 2004 [cited 2005 Dec 28];71:247-251. Available from: http://www.ijppediatricsindia.org/article.asp?issn=0019-5456;year=2004;volume=71;issue=3;spage=247;epage=251;aulast=Kapoor
The global HIV/AIDS epidemic killed more than 3 million (2.5 -3.5 million) people in 2003, and an estimated 5 million (4.2-5.8 million) acquired human immuno­deficiency virus (HIV), 7 lakhs (5.9 - 8.1 lakhs) of them children, bringing to 40 million (34-46 million) the number of people living with the virus around the world. Out of this, about 2.5 million (2.1-2.9 million) are children. [1] So far, the AIDS epidemic has claimed the lives of nearly 4.3 million children. Mother-to-child transmission (MTCT) is the largest source of HIV infection in children below the age of 15 years and affects approximately 5,00,000 infants per year all over the world, majority of which are in developing countries.
According to HIV surveillance by National AIDS Control Organization (NACO) in India, seropositive rate in high-risk population has increased from 5.25 per 1000 population in 1995 to 25.84 per 1000 population in 1999. MTCT was the probable source of infection in 1.8% cases reported in India between 1986-2001. [2] In the year 2003 upto 30th November, out of 57781 AIDS cases reported to NACO, 1551(2.68%) cases are due to MTCT. [3]
In India, MTCT rate of 48% has been reported by Kumar et al, and 36% by Dongaonkar et al. [4] Recent survey done in Maharashtra has shown seroprevalence rate of 0.25%-4%, averaging 1% among pregnant ladies. Considering 25 million births per year in the country and the seroprevalence rate among pregnant ladies of 1% and vertical transmission rate of 30%, we would expect to have 75000 HIV infected neonates born every year.
Apart from posing the burden of HIV positive children on the society, MTCT is causing great social problems by producing orphans after the death of one or both parents due to AIDS.
Factors Affecting MTCT
Various factors that affect the rate of MTCT are summarized in [Table - 1] .
» Timings of Transmission of Virus from Mother to Infant
Rate of perinatal transmission without prophylaxis varies in different geographical areas. In developed countries, it is about 14%-33%, [13] while in developing countries it is higher up to 43%. [14] Knowledge of timing of transmission helps in developing the protective measures.
(1) During Pregnancy
(a) Antepartum: 25%-35% of total transmission, occurring mainly in the late pregnancy. [15]
(b) Intrapartum: 70%-75% of total transmission. The postulated mechanisms are:
Ž Micro transfusion from constant massage the placental bed gets from uterine contractions.
Ž Exposure of the baby's mucocutaneous surface to maternal blood and cervical secretions.
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 and a PCR negative at 48 hours but positive 7-90 days after delivery indicates an intrapartum infection.
(2) After Delivery- Breast-Feeding (BF) Accounts for 5-15% of infants getting infected after delivery. The risk varies depending on the duration of BF, associated breast abscess, cracks in nipple, mastitis and mixed feeding. High perinatal transmission rate in developing countries is due largely to prolonged BF, practiced more commonly than in industrialized world. 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 HIV virus postnatally. [16]
» Strategies for PMTCT
(1) Primary prevention of HIV among parents to be.
(2) Prevention of unwanted pregnancy among HIV positive females.
(3) Prevention of HIV transmission from HIV infected females to their infants through antiretroviral therapy to pregnant females and infants, and where applicable, replacement feeding for the infant.
Primary Prevention of HIV Infection in “Would be Mothers/Parents”- is the only 100% effective method in preventing the HIV transmission to the infants. It includes HIV education, safe-sex practices, avoidance of intravenous drugs and sharing contaminated needles, early treatment of STDs and change in moral behavior and attitude of the community. In the developing countries like India, most of the mothers are getting infection from their husbands through sexual route; i.e. fathers are equally responsible for the transmission of HIV to their children. Hence, in order to ensure that mothers alone should not be blamed for MTCT, PMTCT has been renamed as PPTCT (prevention of parent to child transmission) in India.
» Counseling and Voluntary Testing
Every pregnant woman attending antenatal clinic (ANC) should be enrolled in the program and counseled. Use pre-test counseling session to explore her knowledge of HIV/AIDS, impart education regarding the routes of transmission, importance of HIV testing and its implication, help her in decision making, ensure her for confidentiality, tell her for partner notification, and make her understand the impact of positive result on herself, her spouse, baby and the family. Explain the importance of window period and need to repeat the test after 3-6 months, if she has high-risk behavior and HIV test is negative.
During post- test counseling session, she should be given enough time to accept the result, if it is positive. Hold the first discussion maintaining confidentiality. After a period of preliminary adjustment, give a clear factual explanation of what the result means. How fast the disease will progress or probable time left to live, should not be discussed at this stage. It is the time to encourage positive thinking and it should be emphasized that 'HIV infection is not AIDS'. Educate and motivate her to take care of her general health, avoid infecting others by abstinence or engaging in safer sex (must use condom for every sexual act). Do family counseling after reviewing the advantages and disadvantages of informing husband / sexual partners and key persons in her life.
Do preventive counseling for those tested negative, to avoid them from engaging into high-risk behavior.
A known HIV infected woman should be encouraged for contraception, but if she gets pregnant, the decision to choose between MTP and continuation of pregnancy with other options should be left to her after proper counseling. These options are-
» Antiretroviral Drugs (ARV)
ARV decrease the risk of MTCT by two mechanisms-
(1) By reducing the viral load in the mother.
(2) By preventing the virus from fixing itself in the infant.
The risk reduction through ARV given in the antenatal period and during delivery persists through the breast-feeding period. Continuing ARV during breast-feeding period is a promising new intervention.
Efficacy of different regimes using ARV is summarized below [Table - 2] .
In India, a feasibility study of short term AZT to HIV infected mothers was conducted in 11 centers located in high prevalence states from April 2000 to July 2001. [4] Total ANC attendance during this period in all the centers was 1,92,474. Pre-test counseling (group education) was done in 1,71,471 mothers, thus educating 89.1% women for primary prevention. After obtaining the consent, HIV testing could be done only in 1,03,681 (60%) mothers mainly because of a lag period in developing the infrastructure and completing the training of counselors. There were 3-5% women across institutions that refused to take the test. Among the tested, 1724 (1.7%) mothers came out to be positive. Of these, 751 mothers were given 300 mg of AZT twice a day from 36 weeks onwards till labour started, followed by 300 mg 3 hourly till delivery. After undergoing counseling for advantages and disadvantages of BF (informed choice), 22% opted to breast feed their babies. 658 mothers were followed and PCR on the baby was done at day 2 and 2 month of life. At day 2, out of 457 PCR done, 38 were positive (8.3%) and at 2 month, out of 228, 23 were positive (10.1%). Thus the study showed that MTCT rate was reduced significantly.
After the success of the HIVNET-012 study, NACO had started the feasibility study using single dose of NVP to both the mothers and their infants in the same 11 centers selected in India. Seeing very encouraging preliminary results, NACO has started to implement the program in all the states beginning with the states with high prevalence of HIV.
» Use of Nevirapine (NVP) for PMTCT
Recently, NVP has attracted a lot of attention for its use in PMTCT. It is a non-nucleoside reverse transcriptase inhibitor (NNRTI), which binds to the HIV-1 reverse transcriptase directly, inhibits the synthesis of viral DNA and thus inhibits the viral replication. It rapidly gets absorbed and crosses the placenta efficiently after a single oral dose of 200 mg to the mother. It has got a very long elimination half-life of 40 hours. In infants, median half-life ranges from 45-72 hours for elimination of maternal NVP and 37-46 hours for a single 2 mg/kg of neonatal dose (HIVNET - 012 regimen). Metabolism of NVP to hydroxylated compounds occurs via cytochrome P450 in liver, which are further metabolized by glucuronide conjugation. Elimination of NVP and its metabolites are mainly through urine.
» Benefits of Using NVP for PMTCT
It is a simple two-dose regimen (one dose each to mother and the newborn) to be taken by mouth (under supervision), thus making it easier to maintain confidentiality. It is inexpensive, does not require refrigeration and no significant side effects, clinical or laboratory, have been noticed after single dose administration. Single dose administration is unlikely to develop drug resistance.
Acute adverse reactions to NVP that have been observed are allergic reactions, rash, erythema multiforme, vomiting, diarrhea, hyperkalemia or hypokalemia, tachycardia, systolic hypertension and hepatotoxicity. At present, there are no indications that a single dose NVP will have any long-term side effect in infant.
» Optimizing the Obstetric Practices to Decrease the Viral Exposure at Birth
Avoid prolonged rupture of membrane especially when it exceeds more than 4 hours. Avoid invasive procedures like episiotomy and forceps application as they increase the risk of transmission by exposing the neonate to maternal blood, but their judicious use to shorten the duration of labor especially with ruptured membranes may decrease the transmission. Avoid fetal blood sampling or application of fetal electrode because they increase the exposure to maternal blood and cervical secretions. [21] 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, chlorhexidine lavage 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.
» Elective Cesarean Section Versus Vaginal Delivery
Elective cesarean section (CS) at 38 weeks of pregnancy before the onset of labor or rupture of membrane decreases transmission by 50%-80%. [22] , [23] However, it is not clear, whether CS offers any benefit to those mothers who have undetected viral load or receiving HAART (Highly Activated Anti-Retroviral Therapy). Rate of transmission is reduced to 2% when elective CS is combined with AZT prophylaxis. The decision of elective CS should be individualized.
» Changing the Life Style and Dietary Habits
Improving nutritional status of the mother especially diet containing lots of fruits, vegetables and grains but low in fat will help in decreasing the MTCT. Vitamins and mineral supplementation like iron and calcium is required. However, Vitamin A supplement has not shown to decrease the risk of MTCT. Use of tobacco and other hard drugs should be stopped.
» Reducing Exposure to Virus Through Breast Feeding
There is no doubt that BF provides various benefits to both the infant and the mother like nutritional completeness, ecofriendly, provides immunity, prevents from infection and improves bonding between the two, but the breast-milk also contains HIV virus and a study done recently had shown cumulative risk of HIV transmission with increasing duration of BF. The incidence per month was 0.7% in first 5 months, 0.6% during 6 to 11 months and 0.3% between 12-17 months. [24]
WHO recommendation to the developed world is not to breast-feed. But in developing countries where mortality is more due to malnutrition and infection as compared to AIDS itself, choice of BF can be offered after proper counseling. Option of alternative feed can be given to the mother, provided, it is acceptable, affordable, feasible, sustainable and safe. Otherwise, exclusive BF that helps to maintain the physiological barrier intact, followed by early and rapid weaning between 4-5 months should be advised. Mixed feeding should not be allowed, as mixed fed children are probably more likely to acquire HIV than exclusively breast-fed children. Another option is Modified BF, where breast milk is expressed manually or by a breast-pump and subjected to pasteurization by boiling at 65[0] Celsius for 30 minutes, which kills the virus. Though this cannot be used at individual level, it is important for breast milk banks to avoid HIV infection.
» Early Diagnosis of HIV Infection in Newborn
Ž HIV IgG (ELISA) can't be used for the diagnosis of HIV infection in the newborn because of passive transfer of IgG from mother to fetus, which can persist for 18 months in the baby.
Ž Viral culture- is the gold standard test but is costly and takes 2-4 weeks for the result to be available and sensitivity varies with the time. One study has reported 33% sensitivity in first 2 weeks, 70% between 1-2 months and 100% at 5-7 months.
Ž HIV DNA PCR- test is being used for the early diagnosis of HIV infection in newborn with sensitivity of 30-35% within first week after birth, which increases upto 100% by 1 month of age.
Ž HIV RNA PCR- test is being used for monitoring the efficacy of the therapy.
Ž HIV p24 antigen-sensitivity of this method ranges between 60-98%, with very low sensitivity just after birth (15-30%). False positive results are also possible after birth.
ELISPOT (Enzyme Linked Immuno Spot Assay), HIV specific IgA and HIV specific IgM tests were tried earlier prior to the PCR technique but are not being used now because of their less sensitivity and nonspecificity.
» Timing of HIV Testing in Newborn
Current recommendation is to test the newborn within first 2 days of birth, at 1-2 months of age and then at 4-6 months of age; some also favor testing at age 14 days to maximize early detection. [25]
» Treatment of Newborn with ARV Drugs
All HIV exposed infants should be started with ARV, preferably within 12-24 hours of birth, even when mother had not taken any ARV drug during pregnancy. Commonly used regimes are: AZT 2mg/kg 6 hrly for 6 weeks, NVP 2mg/kg single dose or a combination of both. Once infection is documented, HAART should be considered.
» Conclusion
Pediatric AIDS is likely to become another major public health problem in coming years. MTCT is the major route of acquisition of HIV in children, so developing and implementing a comprehensive MTCT prevention program in our country is the need of hour. There are three main mechanisms that are essential for achieving maximum effective reduction of MTCT: (1) reduce maternal viral load with ARV drugs, (2) prevent avoidable exposure to maternal virus at birth through improved obstetric practices and (3) reduce exposure to HIV through BF. Emphasis should be given equally on all the components of the PMTCT/PPTCT program - viz -Information, Education and Counseling; Condom promotion; Voluntary counseling and testing; Treatment of STDs; Good antenatal care; Prevention of transmission with anti-retroviral therapy; Safe delivery practices; Counseling and support for safe infant feeding practices and Community action to decrease social stigma.
In order to make the program successful, and to safeguard our future generation, women and their husbands should participate actively in PMTCT. Intervention strategies for PMTCT can be integrated into pre-existing maternal and child health (MCH) clinics along with consistently available drug supplies and services for better and cost effective coverage. It is crucial for regional institutions and health care centers to mobilize resources, national and state governments to commit themselves to make PMTCT a priority in order to reduce the incidence of pediatric HIV infection and improve child survival.
» Acknowledgement
The authors are grateful to Dr.K.K. Sharma (Dean), P.S. Medical College and Mr. Sandeep Desai (CEO) H. M. Patel Centre for Medical Care & Education for granting permission to publish the article.
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