Indian J Med Res 121, April 2005, pp 489-501
489
The HIV epidemic is showing a shift towards
women and young people. In India, 39 per cent of
adults living with HIV/AIDS are women 1. The
increasing HIV prevalence among women will show
an increase in mother-to-child transmission of HIV.
Until 2002, over 4.3 million children have succumbed
to the AIDS epidemic worldwide and in 2003 an
estimated 7,00,000 children under the age of 15 yr
became infected with HIV 2. The vast majority
(>90%) acquired the infection from their mother
through mother-to-child transmission (MTCT). In the
absence of any intervention, rates of MTCT of HIV
can vary from 15 to 30 per cent in the developed
countries and can reach as high as 30 to 45 per cent
in developing countries. This difference is mainly
attributable to infant feeding practices in the
developing world 3. Transmission during the
peripartum period accounts for one to two-thirds of
the overall transmission rate, depending on whether
breastfeeding occurs or not. The peripartum and
breastfeeding period has thus become the focus for
efforts to prevent MTCT. The discovery of successful
interventions that interrupt this transmission has been
one of the greatest successes in AIDS research.
Currently 95 per cent of vertical transmission occurs
in the developing countries and the challenge in these
Prevention of mother-to-child transmission of HIV - An overview
Rashid H. Merchant & Mamatha M. Lala*
Nanavati Hospital & Asian Heart Institute & B.J. Wadia Hospital for Children, Mumbai, India
Accepted March 8, 2005
With the human immunodeficiency virus (HIV) epidemic showing a shift towards women and
young people, the increasing seroprevalence among women will result in an increase in the
mother-to-child transmission of HIV. The vast majority of HIV-positive children worldwide
acquire the infection through vertical transmission. The discovery of successful interventions
that interrupt this transmission has been one of the greatest successes in AIDS research. The
transmission of HIV from an infected mother to her child can be reduced to less than 2 peer
cent by intensive interventions in the antenatal, intranatal and postnatal periods. To achieve
this low rate, primary prevention of HIV infection in parents-to-be, early identification of
seropositivity in pregnant women, prevention of unwanted pregnancies, prevention of mother-
to-child transmission of HIV by appropriate antiretroviral therapy, special interventions in
maternal management during labour, appropriate care and follow up of the newborn, all play
an important role. However, these approaches are not always possible in developing countries
wherein currently 95 per cent of vertical transmission occurs. Several questions and challenges
remain. These include choice, availability, affordability, duration, long-term safety of optimal
antiretroviral agents to be used during pregnancy and early neonatal life and the issue of
transmission via breastfeeds in situations where alternatives to breastfeeding are not available.
The challenge is to find the most cost-effective and feasible intervention to achieve zero per
cent transmission of HIV from an infected mother to her child.
Key words  Interventions - paediatric HIV - preventing mother-to-child transmission - vertical transmission
490 INDIAN J MED RES, APRIL 2005
settings is to find the most cost-effective and feasible
intervention to prevent MTCT. The transmission of HIV
from an infected mother to her child can be reduced to
less than 2 per cent by intensive interventions that
include combination therapy of potent antiretrovirals,
obstetrical interventions including elective caesarean
section at 38 wk and complete avoidance of
breastfeeding4-7. Throughout this document, HIV
refers to HIV-1 since cases of mother-to-child
transmission of HIV-2 are extremely rare.
Vertical transmission
Magnitude of the problem: In India, about 28 million
deliveries occur annually, of which 84,000 deliveries
would occur in HIV-positive women considering a
national average of 0.3 per cent prevalence of HIV
in pregnant women8. Without any intervention, about
30-45 per cent of these babies will become infected
with HIV. In the high prevalence states of
Maharashtra, Tamil Nadu, Andhra Pradesh,
Karnataka, Manipur and Nagaland, with more than
1 per cent HIV prevalence amongst pregnant
women, there could be a much higher number of
vertically infected babies being born annually8. In
developing countries, WHO/UNICEF’s child survival
programmes on immunization, oral rehydration
therapy, and effective case management of acute
respiratory infections, promotion of breastfeeding,
good weaning practices, family planning and growth
monitoring achieved much. But the HIV/AIDS
pandemic has reversed these gains to a large extent.
Efficacy of transmission : MTCT is by far the most
significant route of transmission of HIV infection in
children below the age of 15 yr. This can occur during
pregnancy especially in the last trimester, during
delivery, and postnatally during breastfeeding. The
foetus can get infected in utero through maternal blood,
transplacental haemorrhage, and infection via umbilical
cord or via the gastrointestinal mucosa while
swallowing infected amniotic fluid. Contact with the
mother’s blood and/or secretions during labour and
delivery increases the risk of HIV transmission to the
infant. The efficiency of transmission through breast
milk ranges between 16-29 per cent. Of the 30% of
babies who get infected vertically, the relative frequency
of timing of transmission is said to be as follows : 2 per
cent early in gestation, 3 per cent late in gestation, 15
per cent during labour, 5 per cent in early postpartum
period, and 5 per cent in late postpartum period 9. In
the absence of any intervention, rates of  MTCT of
HIV-1 can vary from 15 to 30 per cent in developed
countries and can reach as high as 30 to 45 per cent in
developing countries. This difference can mainly be
attributed to infant feeding practices in the developing
world that comprise almost universally of breastfeeds
for prolonged duration3.
Factors affecting transmission : Maternal factors
like seroconversion during pregnancy, advanced stage
of the disease, concomitant malnutrition, micronutrient
deficiencies, sexually transmitted diseases in the
mother, poor adherence to antiretroviral therapy after
initiation, are some important factors which increase
the transmission in the antenatal period. In the
intranatal period, factors like vaginal delivery,
prolonged contact with maternal blood and cervico-
vaginal secretions, prolonged rupture of membranes,
chorioamnionitis, procedures that increase exposure
of infant to maternal blood like instrumentation during
delivery, episiotomy, foetal scalp electrode, are
associated with increased risk of transmission.
Prematurity is a risk factor for increased transmission
probable due to thin skin, susceptible mucous
membranes, immature immune functions and low
levels of maternal antibodies in the premature infant.
In the postnatal period breast feeding, feeding in the
presence of cracked nipples or mastitis, feeding by
both breast feeds and top feeds, continuation of
breastfeeds for prolonged periods of time,
seroconversion of the mother during postnatal period,
high viral load, low CD4 cell count, all increase the
risk of transmission of HIV. Prolonged breastfeeding
continues to expose the child to HIV, and estimates
of the additional risk of infection after three months
(known as late postnatal transmission) range from is
considerably high10.
Prevention: For the large scale implementation of
prevention of mother-to-child transmission, UNAIDS,
UNICEF and WHO have identified 5 phases11 (Fig.):
Phase 1:  This phase of imparting information in the
antenatal period on voluntary counselling and testing,
family planning measures, option of medical
491
Five Phases of PMTCT
Phase
alpha:
Prevent
Phase1:
Inform
Phase2:
Prophylaxis
Phase3:
Infant
Feeding
Phase
omega:
Support
ANC
VCCT
FP
STIs
Life skills
ARV
Safe
Delivery
RF
EBF
PCPP
Social
Support
MERCHANT & LALA :  VERTICAL TRANSMISSION OF HIV
termination of pregnancy, appropriate infant feeding
recommendations, goes a long way in the prevention
of unintended pregnancies in HIV-positive women and
all women at risk. This requires strengthening of
family planning services. Women considering
pregnancy should be encouraged to determine their
HIV status and the implications of pregnancy when
infected with HIV.
Phase 2 : This consists of antiretroviral prophylaxis
to the mother antenatally and intranatally and to the
baby postnatally. These antiretrovirals act by reducing
the viral load in the mother (a lesser quantity of virus
goes to the infant) and preventing the virus from
“fixating” itself in the child (post-exposure
prophylaxis).
Phase 3 : This phase deals with issues related to
replacement feeds versus breast feeds in the context
of maternal HIV. It supports the mother-infant pair
in conducting a successful method of feeding.
Phase alpha : This phase deals with the primary
prevention of HIV through sex education, family
planning education and avoidance of high risk
behaviour. The best way to prevent MTCT is by
preventing HIV infection in girls and women of
childbearing age and the society at large.
Phase omega : This phase deals with support-care-
protection package to the HIV infected mother, child
and the family. Issues like  Pneumocystis jroveci
pneumonia (PCP) prophylaxis, early detection of
tuberculosis and management, weaning food
supplements, vitamin A supplementation, are considered.
Main interventions for decreasing mother-to-
child transmission:
(i) Antiretroviral therapy
Antiretroviral therapy (ART) recommendations for
HIV infected pregnant women are based on the
principle that therapies of known benefit to women
should not be withheld during pregnancy unless the
risk of adverse effects to the mother, foetus or infant
outweighs the expected benefit to the woman
concerned12. Antiretroviral therapy to the mother
antenatally and intranatally, and to the baby postnatally
has been one of the interventional strategies studied
extensively in prevention of vertical transmission. The
largest body of experience relating to efficacy and
maternal and foetal safety has been gained with
zidovudine (ZDV/AZT). Consequently, first-line
treatment regimens in pregnant women should include
ZDV whenever possible. On World AIDS Day 2003,
WHO and UNAIDS released a detailed and concrete
plan to reach the “3 by 5” target of providing
antiretroviral treatment to three million people living
with AIDS in developing countries and those in
transition by the end of 2005. This is a vital step
towards the ultimate goal of providing universal access
to AIDS treatment to all those who need it. According
to the “3 by 5 initiative” of the WHO, the key
recommendations are13:
(i) Women who need ART for their own health should
receive it, following revised ART  guidelines recently
posted by WHO14. The use of ART when indicated
during pregnancy will improve the health of the mother
and substantially decrease the risk of transmission of
the HIV to the infant.
(ii) Women who do not need treatment, or do not
have access to treatment, should be offered
antiretroviral prophylaxis to prevent MTCT using one
of the drug regimens known to be safe and effective.
Fig. Five Phases of prevention of mother-to-child transmission
(PMTCT).  FP, Family planning; STI, Sexually transmitted
infections. ANC, Antenatal check-up; VCCT, Voluntary
confidential counseling & testing; ARV, Anti retro virals;
RF, Replacement feeds; EBF, Exclusive breastfeeds;
PCPP,  Pneumoystis jeroveci pneumonia prophylaxis.
Source: http://www.dec.org/pdf docs/PNACN748.pdf.
492 INDIAN J MED RES, APRIL 2005
Table. Prophylactic ARV regimens for MTCT prevention (summary of the evidence) (Ref. 21)StudyPrincipleAntenatal /Post-partum infantMedianMode ofVertical transmissionIntrapartummaternalinfantrate (VTR) and efficacyCD4+countfeeding/mm
3 
by armat enrolmentPACTG 076/ZDV vs placeboLong (from 14Long (6 wk)538,560FormulaVTR 7.6% in interventionANRS 024 trialwks), intravenousfeedingarm versus 22.6% inUSA, France
15
intrapartumplacebo arm at 18m (68% efficacy)[363 infants]Bangkok CDCZDV vs placeboShortNone411,427FormulaVTR 9.4% in interventionshort-course ZDV(from 36 wk),feedingarm versus 18.9% intrial Thailand
16
oral intrapartumplacebo arm at 6m (50.1% efficacy)[392 infants]Thai Perinatal HIVZDV differentLong (from 28wk),Long (for 6w),350,380FormulaShort-Short arm wasprevention trialregimens, noShort (for 36 wk)Short (for 3 days)Feedingstopped.VTR 6.5% inThailand
50
placebolong-short arm versus 4.7%in short-long arm at 6 m(statistical equivalence)[1079 infants]Ivory Coast CDCZDV vs placeboShortNone528,548BreastfeedingVTR 15.7% in intervention armshort-course ZDV trial(from 36 wk)versus 24.9% in placebo arm atCote D’Ivoire
23, 51
3m (37% efficacy) [230 infants]DITRAME / ANRSZDV vs placeboShortShort535,568BreastfeedingVTR 18.0% in ZDV arm, 27.5%049a trial(from 36 wk)(1 wk)in placebo at 6 m (38% efficacy),Cote D’Ivoire,(mother only)21.5% versus 30.6% (30%  efficacy)Burkina Faso
22,51
at 15 m; 22.5% versus 30.2%(26% efficacy) in pooled analysiswith other Ivory Coast trialat 24 m [276 infants]PETRA  trialZDV + 3TC in 3Short (from 36wk)Short (7 days)435,475BreastfeedingVTR 14.9% at 18m for antenatal/South Africa,regimens vsMother and Infantintrapartum/neonatal ZDV + 3TC,Tanzania andplacebo18.1% for intrapartum/neonatalUganda
18
ZDV + 3TC, 20.0%  for intrapartumZDV + 3TC only and 22.2% forplacebo[1413 infants]French AZT + 3TC/Open label, nonFrom 32 wk3TC and ZDV for 6 wk426FormulaVTR 1.6% [437 infants]; 5-foldANRS 075 trialrandomisedfeedinglower than in controls receivingFrance
52
ZDV + 3TCZDV only
493
StudyPrincipleAntenatal /Post-partum infantMedianMode ofVertical transmissionIntrapartummaternalinfantrate (VTR) and efficacyCD4+countfeeding/mm
3 
by armat enrolmentThai ZDV + 3TC trialOpen label,Short (from 34wk)Long (ZDV 4 wk),274FormulaVTR 2.8% at 18mThailand
24
non randomisedfeeding[106 infants]ZDV + 3TCPACTG 316 trialNVP vs placebo inNon-study ARTSingle dose 2 mg/kg423,441FormulaTrial stopped early due to very(USA, Europe,women alreadyantenatalwithin 72  h of birth plusfeedinglow VTR in both arms. VTR 1.4%Brazil, Bahamas)
6
receiving ZDV orIntrapartum; singlenon-study ARTin intervention arm versus 1.6% inZDV plus otherNVP dose 200 mg including ZDVplacebo arm [1248 infants]ARTplus ZDC intravenouslyHIVNET 012 trialNVP vs ZDVNo antenatal ARTSingle dose NVP 2 mg/426, 461Breast-Placebo arm was stopped, VTRUganda
25,27
Intrapartum : single dosekg within 72 h of birthfeeding15.7% in NVP arm versus 25.8%NVP 200 mg versusversus short ZDVin ZDV arm (41% efficacy), atoral ZDV  (7 days)18 m [451 infants]SAINT trialNVP versusNo antenatal ARTSingle NVP dose within384,404BreastfeedingVTR 12.3% in NVP arm versusSouth Africa
26
ZDV + 3TCIntrapartum: single48 h of birth versus shortand formula9.3% in ZDV + 3TC arm atdose NVP 200 mgZDV + 3TC (7 days)feeding8 wk [1301 infants]versus ZDV + 3TC (mother and infant)DITRAME Plus/Open label, ZDVZDV from 36 wk,Infant single dose370BreastfeedingVTR at 6 wk 6.4%ANRS 1201.0 trialboosted by singleNVP one dose atNVP, plus oneand  formula[331 infants]Abidjan, Cote D’dose NVP onset of labourweek ZDV feedingIvoire
28
DITRAME Plus/Open label, ZDV +ZDV + 3TC from 32 wkInfant single dose439BreastfeedingVTR at 6 wk 4.6%ANRS 1201.1trial3TC boosted by(stopped at day 3 postNVP, plus one weekand formula[99 infants]Abidjan, Cotesingle dose NVPpartum), NVP one doseZDVfeedingD’Ivoire
30
at onset of labourSIMBA trialNVP vs 3TCZDV + ddI from 36NVP once then twice423, 432BreastfeedingVTR at 6 months 7.8% (noRwanda, Uganda
53
postnatally inwk to 1 wk postpartumdaily versus 3TC twicefor 3-5different between the two arms)nenonates exposeddaily while breastfeedingmonthsPostnatal (6 wk - 6 months)antenatally totransmission rate 0.9%ZDV + ddI[397 infants]NVAZ trialNeonatal NVP vsNone (late comers)Single dose NVPNot reportedBreastfeedingOverall VTR at 6-8 wk, 15.3%Malawi
31
NVP + ZDVright after birth; ZDVin NVP + ZDV arm and 20.9%twice daily for onewith ZDV only. VTR at 6-8 wkweekin infants who were negative atbirth 7.7% and 12.1%,  respectively(36% efficacy) [952 infants]
494 INDIAN J MED RES, APRIL 2005
(iii) The most efficacious regimen among those
recommended for prevention of MTCT for women
with HIV who do not need ART is zidovudine from
28 wk with single dose nevirapine (NVP) at onset of
labour for the mother and single dose NVP plus one
week ZDV for the infant.
(iv) Alternative but less efficacious regimens include
one based on ZDV alone (from 28 wk of pregnancy
and through labour for the mother and for one week
for the infant), one using the combination of ZDV
plus lamivudine (3TC) (from 36 wk of pregnancy,
through labour and one week postpartum for the
mother, and for one week for the infant), and a
regimen comprising a single dose of NVP to the
mother and to the infant (which does not need to be
initiated until labour).
(v) The selection of the ART regimen should be
made at the national level based on issues of
efficacy, safety, drug resistance, feasibility, and
acceptability.
In February 1994, the Pediatric AIDS Clinical
Trials Group (PACTG) Protocol 07615 demonstrated
that a three-part regimen of ZDV could reduce the
risk for mother-to-child HIV-1 transmission by nearly
70 per cent. Studies conducted in Thailand using short
course ZDV regimen for MTCT have indicated that
this regimen could prevent many HIV-1 infections
during late pregnancy and  labour in less-developed
countries unable to implement the full 076 regimen
and can be successful if effectively implemented and
complemented with other preventive interventions16.
However, keeping in mind the practical difficulties of
offering HIV testing and counselling in overcrowded
antenatal clinics in Indian hospitals compounded by
the apprehension that this procedure may expose the
antenatal women to the risk of social discrimination
leading to poor acceptance of the intervention, the
National AIDS Control Organisation (NACO),
Ministry of Health and Family Welfare, Government
of India (GOI), initiated a feasibility study on
prevention of mother-to-child transmission using the
short course regimen of  ZDV17. Between April 2000
and July 2001, intervention for PMTCT was initiated
among consecutive antenatal attendees at 11
institutions selected from the 5 high prevalence states
namely Maharashtra, Tamil Nadu, Karnataka, Andhra
Pradesh and Manipur. During 173 months (average
of 15.7 months at each institution) of the study, active
group education, counselling of women and their
husbands, HIV testing, cost-free ZDV for
seropositive women, intra- and post-partum services
were offered. Out of 103,681 women tested for HIV-
1/2, 1724 (1.7%) tested seropositive. Despite efforts
of project staff at these institutions only 43.6% of
seropositive women took ZDV prophylaxis, the major
reasons for lower recruitment for ZDV being:
intention of women to return to their parents’ town
during the third trimester as is the custom in most
communities, refusal of women/family to take ZDV,
etc. 82 per cent of seropositive women delivered a
full-term normal baby vaginally. Only 18 per cent
women had a lower segment caesarean section
(LSCS) delivery due to indications other than as a
mode of reducing MTCT. Informed choices were
offered at counselling sessions and only 22 per cent
opted for breast feeding at birth and the number
remained consistent even at 2 months of age. The
women who breastfed their babies for 2 months did
not encounter any infant mortality as compared with
those babies who were top fed. The predominant
cause of death among top fed babies was diarrhoeal
diseases. The study showed that the MTCT rate was
reduced to 8.4 per cent at birth or 10.1 per cent at
age two months. The cost effectiveness of the
programme, as measured by the number of HIV
infections averted in the babies born to seropositive
women, may not be high since the prevalence of HIV
in the community in most parts of the country is still
low, hence, the number of new born HIV infections
averted would also be very low. However, as seen in
this study, the programme becomes cost-effective
when primary prevention among 98.3 per cent HIV
seronegative antenatal women is considered as an
important outcome indicator. The cost of the
intervention was determined at Rs.175 per woman.
Since the feasibility study has established that PMTCT
is a cost-effective strategy for prevention and control
of the epidemic, it is recommended that NACO, GOI
should expand the strategy to a programme level
across the country17.
The only combination drug prophylaxis that has
been assessed to date for long-term efficacy at
495
18 months is ZDV + 3TC in three different
regimens18. The antepartum + intrapartum +
postpartum ZDV + 3TC regimen was the only one to
show a sustained  effect. NVP is the only non-
nucleoside reverse transcriptase inhibitor (NNRTI)
that has been studied in pregnancy. In recent years,
the use of nevirapine has attracted considerable
attention because of its demonstrated efficacy in
clinical trials in reducing MTCT, its low cost and ease
of use as also for the fear of high rates of mutations
associated with resistance to NNRTIs following its
use in PMTCT protocols. Further, Boehringer
Ingelheim and FDA have notified healthcare
professionals of new safety information added to the
warnings for viramune (nevirapine) cautioning about
severe, life-threatening, and in some cases fatal
hepatotoxicity, including fulminant and cholestatic
hepatitis, hepatic necrosis and hepatic failure 19.
Women with CD4 counts >250 cells/mm3, including
pregnant women receiving chronic treatment for HIV
infection, are at considerably higher risk of these
events19. Ritonovir (RTV), nelfinavir (NFV), indinavir
(IDV) and saquinavir (SQV) have been studied
pharmacokinetically in pregnant women and shown
to be well tolerated. NFV, followed by SQV, are the
most common protease inhibitors (PI) used to treat
HIV infected pregnant women in resource-rich
countries20. The design and efficacy of the various
short course ARV drug regimens evaluated to date
for the prevention of peripartum MTCT are presented
in Table21.
Short-term efficacy, as determined by infant
infection status at 6-8 wk of life, has been
demonstrated for short course prophylactic to ARV
drug regimens comprising: ZDV alone 16,22,23, ZDV
together with 3TC18,24-26, NVP alone in two single-
dose regimens to the mother and the infant25,27 , ZDV
boosted by single-dose NVP28,29, and ZDV+3TC
boosted by single-dose NVP30.
In a recent trial from Malawi evaluating post-
exposure prophylaxis (PEP) of either single-dose
NVP or single-dose NVP plus 1 wk ZDV given to
infants born to mothers who had not received
antenatal or peripartum ARV prophylaxis, showed
that the combination of NVP+ZDV was significantly
more effective as PEP than NVP alone31. With the
exception of this trial, all other regimens evaluated to
date include an intrapartum component, and varying
durations of antepartum and/or neonatal and
sometimes maternal postpartum prophylaxis. There
are conflicting data as to whether receipt of
combination antiretroviral therapy during pregnancy
is associated with adverse pregnancy outcomes such
as preterm delivery. The potential harm to the foetus
from maternal ingestion of a specific drug depends
not only on the drug itself, but on the dose ingested,
the gestational age of the foetus at exposure, the
duration of exposure, the interaction with other agents
to which the foetus is exposed and to an unknown
extent, the genetic makeup of the mother and foetus.
Because the period of organogenesis (when the foetus
is most susceptible to potential teratogenic effects of
drugs) is during the first 10 wk of gestation and the
risks of antiretroviral therapy during this period are
unknown, it is advisable to delay initiation of therapy
until after the first trimester of pregnancy is over.
Until more information is available, HIV-1 infected
pregnant women who are receiving combination
therapy for their HIV-1 infection should continue their
provider-recommended regimen. They should receive
careful, regular monitoring for pregnancy complications
and for potential toxicities. Although mitochondrial
dysfunction has been found to be associated with
perinatal antiretroviral exposure in rare instances, it
should be compared against the clear benefit of
antiretroviral prophylaxis in reducing transmission of a
fatal infection by 70% or more 4,32,33. Mitochondrial
dysfunction should be suspected in HIV uninfected
children with perinatal antiretroviral exposure who
present with neurologic findings of undetermined
etiology. This emphasizes the importance of long-term
follow up for any child with in utero exposure to
antiretroviral drugs. The clinical significance of the
emergence of resistance in the context of MTCT
prevention programmes is as yet unknown, particularly
with regard to future treatment options for the mother
or the child, or to the outcome of prophylaxis during a
subsequent pregnancy if the same drug is used. The
WHO Technical Consultation in October 2000 carefully
reviewed the available information and concluded that
the benefit of decreasing mother-to-child HIV
transmission with these antiretroviral drug prophylaxis
regimens greatly outweighed concerns related to
development of drug resistance34.
MERCHANT & LALA :  VERTICAL TRANSMISSION OF HIV
496 INDIAN J MED RES, APRIL 2005
(ii) Elective lower segment caesarean section
(LSCS)
Labour and delivery management of HIV infected
pregnant women should focus on minimizing the risk
for both perinatal transmission and the potential for
maternal and neonatal complications. Caesarean
delivery (elective or scheduled) performed before onset
of labour and rupture of membranes has been found to
be associated with a significant decrease in perinatal
HIV-1 transmission. In a prospective study conducted
in the perinatal clinic of a university affiliated maternity
hospital in Mumbai35. which included a four-pronged
intervention consisting of the use of a shorter course
with a lower dose of ZDV (as compared to the original
ACTG 076 protocol15) 400mg/day for the last 6 wk of
antenatal period, coupled with elective caesarian
section before the rupture of membranes, oral ZDV
powder to the infant for 6 wk following delivery (due
to unavailability of oral suspension at the time of the
study) and complete omission of breast milk, a striking
success in reduction of perinatal transmission was
noted7,35. (Transmission rates of 5.8% as against 24%
in those who had not received any form of perinatal
intervention)35. However few centres in the developing
countries will have the capacity to perform safe
operative deliveries on a large scale and hence may
not be justifiable solely for the purpose of preventing
HIV transmission. Nonelective cesarean delivery
(performed after onset of labour or rupture of
membranes) is not associated with a significant
decrease in transmission compared with vaginal
delivery.
Further studies are needed to determine whether
elective cesarean delivery provides significant benefit
in infected women with a low or undetectable viral
load who are receiving combination antiretroviral
therapy. Any benefit must be weighed against the
known increased risks to the woman with cesarean
section compared with vaginal delivery, i.e., a several
fold increased risk of postpartum infections, including
uterine infections and pneumonia, anaesthesia risks,
and surgical complications. Although the risk for
perinatal transmission in women with HIV-1 viral
loads below the level of assay quantitation appears
to be extremely low, transmission from mother-to-
infant has been reported among women with all levels
of maternal HIV-1 viral loads 36. Results of
epidemiologic and clinical trials suggest that women
receiving ART regimens that effectively reduce HIV
RNA to <1,000 copies/ml or undetectable levels have
very low rates of perinatal transmission4,6,37. Given
the variability in quantification of HIV-1 RNA levels
at low copy numbers, the variety of lower limits of
quantification of the tests, and the similarly low levels
of perinatal transmission of HIV-1 at levels <1,000
copies/ml, the American College of Obstetricians &
Gynecologists (ACOG) has chosen 1,000 copies/ml
as the threshold above which to recommend
scheduled caesarean delivery as an adjunct for
prevention of transmission38. However, since
transmission can occur even at low or undetectable
HIV-1 RNA copy numbers, viral load levels should
not be a determining factor when deciding whether
to use ZDV for chemoprophylaxis.
(iii) Infant feeding
Breastfeeding is normally the best way to feed
infants with its benefits going far beyond sound
nutrition, unfortunately, both cell-associated and cell-
free virus has been detected in breast milk from HIV
infected mothers. The efficiency of transmission
through breast milk ranges between 16-29 per cent.
Colostrum has shown to have a higher viral load as
also higher antibody levels. Some of the cellular and
humoral factors are found to be reduced in colostrum
samples obtained from HIV seropositive mothers as
compared to seronegative mothers39. Seroconversion
during lactation, advanced stage of the disease in the
mother, concomitant vitamin A deficiency, breast
conditions like cracked nipples and mastitis, have
shown to increase the risk of postnatal transmission
of HIV through breastfeeds 40. Infant feeding
practices in the developing world that comprises
almost universally of prolonged duration of breastfeeds
contribute to the higher rates of 30-45 per cent of
MTCT as against 15-20 per cent in the developed
countries, in the absence of any intervention3.  The
least common route of vertical transmission in
industrialized nations is breastfeeding. Current WHO/
UNAIDS/UNICEF guidelines recommend that
women with HIV infection should be fully informed
of both the risks and benefits of breastfeeding and be
supported in their decision about feeding practices41.
497
If safe alternatives to breastfeeding are not available
in resource-limited settings, exclusive breastfeeding
for the first several months of life is recommended.
The overall objective is to prevent HIV transmission
through breastfeeding while continuing to protect,
promote and support breastfeeding for HIV-negative
women and those of unknown status. When children
born to women living with HIV can be ensured
uninterrupted access to nutritionally adequate breast-
milk substitutes that are safely prepared and fed to
them, they are at less risk of illness and death if they
are not breastfed. However, when these conditions
are not fulfilled, in particular in an environment where
infectious diseases and malnutrition are the primary
causes of death during infancy, artificial feeding
substantially increases children’s risk of illness and
death41. Replacement-fed infants born to HIV-
infected mothers in India have a high early postpartum
rate of hospitalization42. The risk of giving
replacement feeds must be less than the risk of HIV
transmission through breastfeeding in order to be
justified. Essential requirements include knowledge
and commitment on the part of caregivers, safe water,
assured supplies of affordable fuel, easy access to
quality health care for mothers and infants, and a good
level of support from counselors and/or social
workers. Women choosing not to breastfeed will need
extra support and counselling in order to avert mixed
feeding which can be more hazardous. The time
immediately after delivery was noted as critical for
recounselling about infant feeding and further support
of the woman’s decision, thus lowering the risk of
mixed feeding43. A policy recommendation that HIV
infected mothers be counseled about considering not
breastfeeding can have major implications for birth
spacing, as such women are deprived of protection
from lactational amenorrhoea. If they do not use an
appropriate form of family planning, they may have a
shorter interval between births with adverse
consequences for their own health. Ultimately, a
larger number of potentially HIV infected children
will be born and will need to be cared for. Family
planning information and services need to be made
readily available to mothers and their partners.
Further, ZDV, 3TC and NVP have all been
detected in the breast milk of HIV-infected women
on treatment44,45. This could probably lower the viral
load in breast milk and be associated with a reduced
risk of HIV transmission. However, there is a
possibility of only some drugs penetrating the breast
milk, some only in sub-optimal concentrations that may
not be sufficient to decrease viral replication, probably
promoting the development of drug resistant virus in
the milk, which could be transmitted to the infant.
Moreover, the toxicity of chronic ARV exposure of
infants via breast milk is unknown.
(iv) Other interventions
Vitamin A prophylaxis : Vitamin A is an essential
micronutrient for normal immune function. Vitamin
A deficiency is found to be common among HIV
infected pregnant women and is associated with
higher mother-to-child transmission of HIV-1 and
increased infant mortality46. The biological
mechanisms by which vitamin A deficiency could
influence MTCT include impairment of immune
responses in both mother and infant, abnormal
placental and vaginal pathology and increased HIV
viral burden in breast milk and blood47. However,
there is no conclusive evidence to say that vitamin A
supplementation can reduce MTCT.
Vaginal disinfection: Most HIV infections in children
occur during the time of delivery. Both free and cell
bound viruses have been found in cervical and vaginal
secretions. Theoretically, cleansing the vagina with an
antiseptic or viricidal agent such as chlorhexidine could
reduce this mode of transmission.  Again, there is
scarcity of evidence to conclusively say that inexpensive
modalities like cleaning/disinfection of the birth canal
can reduce MTCT. However, the incidence of neonatal
sepsis is definitely cut down by these strategies.
Immunotherapy: Although ART has significantly
reduced the MTCT of HIV, it has its own drawbacks.
The antiretroviral medications have a relatively short
half-life and therefore have to be administered
throughout the course of breast-feeding, to both the
mother and the infant in order to optimally prevent
infection in the infant. Additionally, the cost, the
potential toxicities and the development of resistance
are likely to limit the long-term efficacy of
antiretroviral prophylaxis. Hence, a safe and effective
active/passive immunoprophylaxis regimen, begun at
MERCHANT & LALA :  VERTICAL TRANSMISSION OF HIV
498 INDIAN J MED RES, APRIL 2005
birth, and potentially overlapping with intrapartum or
neonatal chemo prophylaxis, would therefore pose a
more attractive strategy and might also provide the
basis for a lifetime protection against HIV-1
infection48. Various strategies for stimulating a
protective immune response against HIV infection are
being explored through basic research, animal models,
and clinical trials. Vaccines capable of stimulating the
mother’s and/or infant’s immune response or passive
immunity therapies may be capable of reducing
perinatal transmission49. Vaccines also may serve as
immunomodulators to improve immune function and
diminish disease progression in HIV infected
individuals and may potentially prevent transmission
from the mother to her foetus or from one infected
adult to another. Like Hepatitis B, the use of active,
passive, or active/passive strategies to reduce
transmission has the highest potential for reducing
mother-to-child transmission in developing countries.
Conclusion
Mother-to-child transmission of HIV is a global
problem. HIV can be transmitted from mother-to-
child at various stages of pregnancy, i.e. ante, intra-
and post-partum. A number of interventions have
therefore been aimed at effectively administering
antiretroviral drugs to the mother and to the baby,
limiting the risk of newborn infection by elective
caesarian section as the mode of delivery and
providing alternatives to breastfeeding. However,
these approaches are not always possible in
developing countries wherein currently 95 per cent
of vertical transmission occurs. Several questions and
challenges remain, which include choice, availability,
affordability, duration, long term safety of optimal
antiretroviral agents to be used during pregnancy and
early neonatal life to reduce transmission whilst also
protecting treatment options to women and children
who may need it in future and the issue of transmission
via breastfeeds in situations where alternatives to
breastfeeding are not available. A wider array of
strategies for prevention of mother-to-child
transmission of HIV-1 during breastfeeding including
passive and active immunization, may offer much
needed answers to the problem of continued HIV
transmission. Evaluation of efficacy and tolerance of
preventive interventions complementary to
antiretroviral prophylaxis such as HIV perinatal
vaccine, passive immunoprophylaxis, micronutrient
supplementation and vaginal-cervical disinfection by
means of microbicides should be actively continued
and encouraged. The challenge is to find the most
cost-effective and feasible intervention to achieve
zero per cent transmission of HIV from an infected
mother to her child.
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Reprint requests: Dr Rashid H. Merchant, 501, Rang Mahal, 2, Mount Mary Road, Bandra (West), Mumbai 400050, India
e-mail: deandoc2000@yahoo.co.uk
MERCHANT & LALA :  VERTICAL TRANSMISSION OF HIV