hiv vertical transmission and pregnancy

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Discussion

Epidemiology of Mother-to-Child Transmission (MTCT) in Resource-Limited

Settings

In 2011, there were an estimated 330,000 new pediatric HIV infections globally, approximately

half the number of new pediatric HIV infections recorded in 2003 (Figure 1) [1]. This

remarkable progress in reducing HIV incidence among children can be attributed primarily towidespread implementation of universal HIV screening policies for pregnant women and

improved linkage to prevention of mother-to-child transmission (PMTCT) services. In 2011,

57% of pregnant women with HIV in low- and middle-income countries received effectiveantiretroviral drugs to prevent HIV transmission to their child (Figure 2), continuing a trend of

improved access to PMTCT [1].

Timing of Perinatal HIV Infection

Transmission of HIV from a mother to her infant can occurin utero, during delivery, and by

breastfeeding (Figure 3)[2]. Among breastfeeding populations with no antiretroviral therapy

given, the risk of mother-to-child transmission of HIV is approximately 20 to 45% [3]. MaternalHIV RNA level is the strongest predictor of HIV transmission in utero [4]. Co-infections, such

as herpes simplex virus, malaria, tuberculosis, and syphilis, have also been associated with

increased risks of antepartum HIV transmission[2,5].

Antenatal PMTCT Options in Resource-Limited Settings

The WHO recommends that countries adopt one of three approaches (Option A, B, or B+)

for managing HIV-infected pregnant women (Figure 4)[6]. For pregnant HIV-infected womenwho meet clinical and/or immunologic criteria for receipt of antiretroviral therapy (such as WHO

stage III or IV disease, or an absolute CD4 count less than 350 cells/mm 3), all three options

endorse immediate initiation of triple antiretroviral therapy for the mother. The options differwith respect to management of the pregnant woman who does not meet criteria to receive

antiretroviral therapy for her own health:

Option A. Zidovudine monotherapy started at 14 weeks gestation (or as soon as possible

thereafter), followed by single-dose nevirapine and initiation of zidovudine-lamivudinecombination therapy at onset of labor. A tail of zidovudine-lamivudine is continued for

one week postpartum in order to reduce the risk of HIV developing resistance to

nevirapine. The single-dose nevirapine and zidovudine-lamivudine tail can be omitted ifthe mother received at least four weeks of zidovudine monotherapy prior to delivery.

Option B. Triple antiretroviral therapy started at 14 weeks gestation (or as soon as

possible thereafter), continued throughout labor and delivery and continuing until one

week after cessation of breastfeeding, at which time antiretroviral therapy for the motheris discontinued.
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Option B+. Triple antiretroviral therapy started as soon as HIV infection is diagnosed (or

as soon as possible thereafter), continued throughout labor and delivery and indefinitely

postpartum.

In each scenario, the infant receives daily nevirapine antiretroviral prophylaxis following

delivery (Figure 4)[6]. Women and infants who did not receive antiretrovirals prior to labor anddelivery follow separate guidelines.

Comparison of Options

When implemented properly, the three options listed above have roughly equal efficacy in

preventing perinatal HIV transmission[3,6] but differ in cost and operational complexity. The2010 PMTCT Guidelines issued by the WHO recommended that countries adopt either Option A

or Option B depending upon local circumstances. In contrast, some countries, such as Malawi,

adopted a variation, Option B+, in which triple antiretroviral therapy is started for all pregnant

women and continued for life following labor and delivery. The success of this approach in

Malawi prompted the WHO to release an update to its PMTCT guidelines in 2012 that promotedOption B+ based on its operational simplicity and other advantages (Figure 5)[6] . The WHO

now recommends all three options as reasonable choices for national PMTCT programs whilehighlighting the relative advantages of the B+ approach.

Choice of Antiretroviral Treatment Approach during Pregnancy

The selection of the PMTCT regimen for a pregnant woman will depend on her health and which

option (A, B, or B+) is being implemented in her country (Figure 4)[6].

Zidovudine Monotherapy: This PMTCT treatment approach is indicated only for

women who are living in countries where Option A has been adopted and who do notmeet criteria for antiretroviral therapy for their own health (if CD4 count testing is not

readily available for a pregnant woman in an Option A country, it may be preferable to

initiate triple antiretroviral therapy instead of zidovudine monotherapy). Zidovudine

dosed at 300 mg twice daily is started at 14 weeks gestational age (or as soon as possiblethereafter) and continued throughout pregnancy. A single 200 mg dose of nevirapine is

administered at the start of labor to further reduce the risk of HIV transmission during

delivery. In order to reduce the likelihood that the mothers strain of HIV will developresistance to nevirapine, oral zidovudine plus lamivudine should also be started during

labor and continued for seven days postpartum. If, however, the mother received more

than four weeks of zidovudine monotherapy prior to the onset of labor, the single-dose

nevirapine and seven day zidovudine/lamivudine tail may be omitted; in this scenario,oral zidovudine dosed at 300 mg twice daily is continued throughout labor and

discontinued after delivery.

Triple Antiretroviral Therapy: Triple antiretroviral therapy is indicated for pregnant

women who need HAART for their own health, and for all pregnant women living in

countries in which the Option B or B+ approach is implemented. Recommended triple

antiretroviral therapy regimens for most pregnant women in resource-limited settingsnow align with guidelines for non-pregnant adults and adolescents, consisting of two
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nucleoside reverse-transcriptase inhibitors (NRTIs) paired with a non-nucleoside reverse-

transcriptase inhibitor (NNRTI) (Figure 6)[3]. For most pregnant women, a fixed-dose

combination of tenofovir plus lamivudine (or emtricitabine) plus efavirenz will be themost appropriate antiretroviral option, given the efficacy, convenience, and low toxicity

profile of this regimen. Alternative regimens may be indicated for women with

compromised renal function or prior exposure to PMTCT regimens, as described below.

o Use of Efavirenz in Pregnancy: In 2012, the WHO included efavirenz in the

recommended first-line antiretroviral triple drug regimens for all, includingpregnant women and non-pregnant women who may become pregnant[7].

Although concerns exist regarding possible teratogenicity of efavirenz, an

accumulation of clinical experience with efavirenz in pregnancy has notdocumented an increase in the rates of birth defects among infants born to women

taking this drug.[8,9]. In addition, clinical trials data suggest that efavirenz-based

regimens are associated with less toxicity and better long-term outcomes for

mothers as compared with nevirapine-based regimens (Figure 7) [7,10,11,12].Finally, the cost of efavirenz has declined dramatically (Figure 8), and efavirenz

is now available in convenient once-daily fixed dose combination tablets, co-

formulated with tenofovir and either lamivudine or emtricitabine[7]. For all ofthese reasons, the WHO now recommends that unless specifically

contraindicated, pregnant women should receive efavirenz-based antiretroviral

therapy regimens[7].

o Use of Nevirapine in Pregnancy: Nevirapine remains an option for inclusion in

first-line antiretroviral therapy regimens for pregnant women, but the WHO doesnot recommend this agent for women with CD4 counts greater than 350 cells/mm3

due to an increased incidence of severe nevirapine-related toxicity in women with

high CD4 counts[13,14]. Data are conflicting and limited regarding the risk of

hepatic toxicity in women with CD4 counts between 250 and 350 cells/mm3.Accordingly, the WHO guidelines recommend close clinical monitoring (and

laboratory monitoring, if feasible) during the first 12 weeks of therapy,

particularly when NVP is initiated in women with CD4 counts of 250 to 350cells/mm3. To decrease toxicity, reduced lead-in dosing (200 mg once daily) is

recommended for the first 2 weeks when starting NVP[3].

o Use of Tenofovir in Pregnancy: Although there is more experience with the use

of zidovudine in pregnancy, tenofovir offers important advantages over

zidovudine in that it is generally better tolerated and is available in a once-daily,fixed-dose combination pill paired with efavirenz and lamivudine (or

emtricitabine). Safety data regarding the use of tenofovir in pregnancy have beenreassuring to date, failing to identify any increased risk of fetal or maternal

complications[15,16]. Tenofovir should be avoided in pregnant women with renaldisease

o Use of Zidovudine in Pregnancy: Zidovudine has an extensive record of safety

and efficacy in pregnancy and is widely used for PMTCT. Zidovudine is

equivalent to tenofovir, but it requires twice-daily dosing. Zidovudine should be
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used in pregnant women with renal disease or other contraindications to tenofovir.

Zidovudine should be avoided in pregnant women with moderate or severe

anemia (defined as a hemoglobin level less than 8 mg/dL).

o Emtricitabine (FTC) versus Lamivudine (3TC): These two agents are virtually

identical in terms of safety profile, efficacy, and resistance considerations. Thedecision regarding which one to use will typically depend upon which one is

included in locally available fixed-dose combinations of antiretrovirals.

o Regimens for Women with Prior Exposure to PMTCT Prophylaxis:

Substitution of a ritonavir-boosted protease inhibitor (such as lopinavir-ritonavir)

for the NNRTI component is recommended for women who received single-dosenevirapine without an NRTI tail within the past twelve months (Figure 9)[3].

Mothers who receive intrapartum single-dose nevirapine, alone or with

antepartum zidovudine, may acquire resistance to non-nucleoside reverse

transcriptase inhibitor drugs due to the long serum half-life of nevirapine.Administration of additional antiretrovirals for one week (typically zidovudine

plus lamivudine) immediately after single-dose nevirapine significantly reducesthe risk of developing NNRTI resistance[17,18,19], and mothers who receive thisone-week tail of zidovudine plus lamivudine after single-dose nevirapine may

be prescribed NNRTI-based triple antiretroviral therapy in subsequent

pregnancies, though checking a viral load six months into therapy isrecommended in this scenario (Figure 9)[3]. NNRTI-based triple antiretroviral

therapy may also be prescribed to pregnant women who received single-dose

nevirapine, with or without a tail, more than one year prior to their currentpregnancy, because the risk of NNRTI resistance wanes with

time[20,21,22,23,24,25].
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Case 3: Discussion

Background

The last two decades has seen significant improvements in the therapeutic options for HIV-

infected individuals, resulting in increased longevity and improved quality of life. Concomitantwith these improvements in therapy, there has been an increase in the number of perinatally

HIV-infected girls anticipating the birth of their own children[1]. The case history presented here

illustrates some of the challenges in managing an HIV-infected pregnant adolescent. Although

reducing the risk of vertical transmission is a primary concern, it is important to keep inperspective the patient's commitment to taking the medications, her likely adherence while

taking antiretroviral medications, and the potential long-term implications of non-adherence. If

effective highly active antiretroviral therapy (HAART) is taken during pregnancy, the risk ofmaternal-to-child HIV transmission is very low (Figure 1)[2]. Unfortunately, in some situations,

such as with this 15-year-old girl, pregnant HIV-infected mothers may go through pregnancy

without taking antiretroviral therapy. In such scenarios, efforts to prevent HIV transmission at

the time of delivery are of paramount importance. Indeed, it is estimated that among newbornswith perinatally-acquired HIV, approximately 60% become infected during labor and

delivery[3]. The mother-to-child transmission of HIV that occurs during labor and delivery isbelieved to result from transplacental maternal-fetal microtransfusion of blood during uterine

contractions and fetal exposure to maternal cervicovaginal secretions and blood during

delivery[4]. Investigators have identified a number of factors prior to and during delivery that

may affect the risk of HIV transmission (Figure 2). The remaining discussion will focus on theimpact, indications, timing, and complications of cesarean section delivery in HIV-infected

mothers, as well as use of antiretroviral therapy administered during delivery.

Impact of Cesarean Section on Perinatal HIV Transmission

Prior to the widespread use of viral load testing and the use of combination antiretroviral therapy

during pregnancy, several studies clearly established that cesarean section, if performed before

the onset of labor and rupture of membranes, significantly reduces perinatal transmission of HIVwhen compared with other modes of delivery[5,6]. In 1999, the International Perinatal HIV

Group published the findings of a meta-analysis of 15 prospective cohort studies that addressed

the impact of elective cesarean section versus vaginal delivery on the risk of mother-to-childHIV transmission[6]. These studies involved a cumulative total of 8533 mother-child pairs, and

the data were adjusted for receipt of antiretroviral therapy, maternal stage of disease, and infant

birth weight. The investigators found that elective cesarean section decreased the risk oftransmission by approximately 50%, with a transmission rate of 8.4% for women who underwent

elective cesarean section versus 16.7% for those with any other mode of delivery (Figure 3)[6].For those mother-child pairs who received antiretroviral therapy during the prenatal, intrapartum,

and neonatal periods, transmission occurred in 4 (2%) of the 196 women who underwent electivecesarean-section delivery compared with 92 (7.3%) among the 1255 with other modes of

delivery (Figure 4).

In a separate article published in 1999, the European Mode of Delivery Collaboration group

reported findings from their trial involving 436 HIV-infected pregnant women randomized to
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undergo elective cesarean section at week 38 or vaginal delivery at term[7]. The study was

performed between 1993 and 1998. In an analysis of 346 infants followed to 18 months, 7

(3.5%) of 196 infants whose mother had undergone cesarean section acquired HIV comparedwith 17 (10.2%) of 150 those delivered vaginally (Figure 5). The overall benefit of cesarean-

section delivery occurred with elective cesarean section, but not with emergent cesarean section

(Figure 6)[7]. Among those mothers who received zidovudine (Retrovir

) during pregnancy,cesarean section did not appear to provide any benefit (Figure 7). In addition, studies have not

demonstrated additional reduction in the risk of vertical transmission following cesarean section

if the near term maternal HIV RNA level is less than 1000 copies/ml[5].

Indications for Cesarean Section

In May 2000, the American College of Obstetricians and Gynecologists (ACOG) revised itsrecommendations regarding the management of HIV-infected pregnant women. These revised

guidelines, as well as the current 2005 Public Health Task Force guidelines, recommend that

women with viral loads above 1,000 copies/ml near term should undergo scheduled cesarean

section at 38 completed weeks of gestation, prior to the onset of labor or the rupture ofmembranes[4,5]. In addition, intravenous zidovudine should be started 3 hours prior to delivery

and continued throughout delivery[4]. For women with a near term HIV RNA level less than

1,000 copies/ml, cesarean section probably does not significantly reduce the risk of HIVtransmission and thus most experts would not recommend scheduled cesarean section in that

situation[5]. If a near term viral load has not been performed, decisions regarding cesarean

section should be made based on the most recent HIV RNA level. Women taking antiretroviraltherapy should remain on therapy through delivery and continue therapy after delivery if

indicated for maternal purposes.

Timing of Planned Cesarean Section

For women scheduled to undergo cesarean section, the ACOG and the US Public Health Task

Force guidelines recommend that it take place at 38 completed weeks of gestation (determined

by best clinical estimate), prior to the onset of labor or the rupture of membranes. The ACOGrecommends performing a scheduled cesarean section delivery at 38 completed weeks of

gestation, as opposed to the 39 weeks recommended for persons not infected with HIV, because

of the substantially higher risk of entering labor or rupturing membranes after 38 weeks of

completed gestation. On the other hand, performing a cesarean delivery at 38 versus 39completed weeks of gestation confers a small increased risk of infant respiratory distress

possibly requiring mechanical ventilation. Although it would be ideal to know the status of the

fetal lung maturity prior to cesarean section, the ACOG recommends avoiding amniocentesis,

primarily to avoid fetal exposure to maternal blood[4].

Scheduled Cesarean Section and Woman Presents in Labor

When a woman is scheduled to undergo cesarean section, but presents early in labor (or shortly

after rupture of membranes), the benefit of cesarean section is unknown and decisions regarding

the approach to delivery should be individualized. If the woman has minimal cervical dilatationand is likely to have extended labor, one option is to immediately give the loading dose of
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intravenous zidovudine and then proceed to cesarean section[5]. Alternatively, one could

immediately give the loading dose of intravenous zidovudine and then start oxytocin (Pitocin) to

expedite delivery, with vaginal delivery performed as long as rapid labor ensues[5]. For anyvaginal delivery, the duration of ruptured membranes should be as short as possible, given the

increased risk of HIV transmission with longer duration of membrane rupture. Rupture of

membranes for longer than 4 hours doubles the risk of HIV transmission[5,6,8]. For any vaginaldelivery, the clinician should, if possible, avoid using scalp electrodes or other invasive

monitoring devices, forceps, or the vacuum extractor.

Complications of Cesarean Section

Although limited data exist regarding maternal morbidity following cesarean section in HIV-

infected women[9], several studies have suggested that HIV-infected women who undergocesarean section have higher complication rates than women who deliver vaginally[10,11]. Post-

delivery complications most frequently consist of hemorrhage, postpartum fever, cesarean

wound infection, endometritis, urinary tract infection, and sepsis[4,7,10,12]. Among HIV-

infected women who deliver via cesarean, those with CD4 counts less than 200 cells/mm3

have agreater rate of complications[10]. Because of the increase in infectious complications, the PHS

guidelines recommend that following cord clamping with a cesarean delivery, the mother should

receive prophylactic antibiotics, which reduces the risk of postpartum maternal infection[5].

Discussion

Overview
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In resource-limited settings, HIV-infected mothers of HIV-uninfected infants often confront a

difficult dilemma with regard to infant feeding: breastfeeding risks transmitting HIV to their

infants, but formula feeding may not be a viable option due to high cost, lack of clean water, orstigma associated with not breastfeeding. Fortunately, recent clinical studies have established

that HIV-infected mothers can breastfeed with minimal risk of HIV transmission to their infants,

as long as the mother and the infant receive appropriate antiretroviral prophylaxis.

Epidemiology of HIV Acquisition from Breastfeeding

In the absence of any antiretroviral prophylaxis for either the mother or the infant, the risk ofHIV transmission from mother to infant is 30 to 45% for breastfeeding infants and 15 to 30% for

infants who are not breastfed (Figure 1)[1]. Globally, up to 40% of HIV infections in infants

have resulted from breastfeeding[2]. The risk of HIV transmission is highest in the first fewmonths of breastfeeding[3,4,5], but risk continues throughout the breastfeeding period; infants

who are breastfed the longest have the highest risk of acquiring HIV[6,7]. Both maternal factors

(high HIV viral load, mastitis, or maternal illness) and infant factors, such as oral candidiasis,

can increase the infant's risk of acquiring HIV from breastfeeding[1,8].

Mortality and Morbidity in Non-breastfed Infants in Resource-limited Settings

Formula feeding, as a replacement for breastfeeding, reduces the risk of HIV transmission toinfants of HIV-infected mothers, but it is associated with high morbidity and mortality rates in

resource-limited settings[9,10,11,12,13,14]. The increased mortality associated with formula

feeding in these settings is likely due to the absence of key breast milk-associated antibodies that

provide protection against infectious diseases. In addition, the water used for formula preparationmay be contaminated, resulting in severe gastrointestinal infections. Furthermore, infant formula

may not be affordable, and formula feeding in some settings may carry a social stigma and imply

that the mother is infected with HIV. For these reasons, the WHO guidelines endorse formulafeeding over breastfeeding only in situations where six specific conditions are met (Figure 2)

[15].

Extended Daily Infant Nevirapine to Prevent HIV Transmission via

Breastfeeding

Although single-dose nevirapine given to the infant is effective in preventing peripartum and

early breastmilk transmission of HIV, its effect does not extend beyond the first few weeks of

life[16]. Several studies have evaluated longer-term daily nevirapine prophylaxis given to theinfant, and all show that extended nevirapine prophylaxis for breastfeeding infants is more

effective than single-dose nevirapine in reducing both HIV infection and infant mortality,particularly for those infants whose mothers are not receiving antiretroviral therapy. Extendedinfant nevirapine has been studied for 6 weeks (Figure 3)[17], 14 weeks (Figure 4)[18], and 6

months (Figure 5)[19]; the benefit to the infants continued for as long as nevirapine was given.

Extended zidovudine, alone or in combination with nevirapine, is also effective at reducing HIV

transmission, but has been associated with high rates of infant anemia and neutropenia[11,18].For breastfeeding infants of HIV-infected mothers not receiving a triple antiretroviral drug

regimen, the WHO therefore recommends the use of daily nevirapine from birth and until 1 week
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after all exposure to breast milk has ended (or for a minimum of 4 to 6 weeks if breastfeeding

ceases prior to 6 weeks)[20]. Antiretroviral prophylaxis recommendations for infants of mothers

receiving a triple-drug antiretroviral regimen are discussed below.

Maternal Antiretroviral Drugs to Prevent HIV Transmission via Breastfeeding

Multiple studies have established that administration of a triple-drug antiretroviral regimen toHIV-infected pregnant women who breastfeed reduces the risk of HIV transmission to their

infants[19,21,22,23,24,25,26]. This finding applies to women who meet antiretroviral therapy

eligibility criteria based on low CD4 count and/or advanced HIV disease, as well as to womenwith less advanced HIV disease who do not meet antiretroviral therapy eligibility criteria. The

success of this approach derives from the effectiveness of triple-drug antiretroviral regimen in

reducing maternal serum and breast milk HIV viral load, the strongest determinants of HIVtransmission via breast milk[9]. Rates of transmission are lowest when women initiate drugs

early in pregnancy[27], underscoring the importance of promoting early antenatal care and

prompt HIV diagnosis and management during pregnancy. The most impressive results were

seen in the Mma Bana ("mother of the baby") study (Figure 6), where prophylaxis began as earlyas the second trimester and the overall rate of HIV transmission was 1.1%[24]. The HIV

transmission rates in most other studies of triple-drug antiretroviral prophylaxis, where antenatal

prophylaxis was not initiated until mid-to-late third trimester, have ranged from 5 to 8% (Figure7). If the HIV-infected mother is breastfeeding and receiving a triple-drug antiretroviral regimen

only for prophylaxis (e.g., she doesn't require treatment for her own health) and plans to stop the

regimen after breastfeeding cessation, she should continue the antiretroviral drugs until 1 weekafter all infant exposure to breastmilk has ended.

Antiretroviral Prophylaxis for Infants of Mothers Receiving Triple-Drug

Regimens

Administration of daily nevirapine or twice-daily zidovudine to the infant is recommended forthe first 4 to 6 weeks of life, even if the mother is receiving a triple-drug antiretroviral regimen

for treatment or prophylaxis. Infant antiretroviral prophylaxis is particularly important in infants

of mothers who either received no antepartum antiretroviral drugs or started drugs late inpregnancy: nevirapine or zidovudine given directly to the infant provides prophylaxis against

HIV that might persist in the mother's breast milk due to insufficient maternal exposure to

antiretroviral drugs prior to delivery. Continuing the infant prophylaxis beyond 6 weeks whenthe mother is receiving a triple-drug antiretroviral regimen does not appear to provide any

additional benefit[28].

Importance of Exclusive Breastfeeding

Exclusive breastfeeding, in which the infant receives no supplemental fluids or foods apart from

breast milk during the first 6 months of life, is associated with a lower risk of HIV transmission

from breast milk when compared with mixed feedings[29,30]. It is hypothesized that mixed

feedings disrupt the integrity of the gut endothelium, and facilitate HIV entry via thegastrointestinal tract[31]. Current WHO Guidelines therefore recommend that HIV-infected

mothers of infants who are not HIV-infected (or whose HIV status is unknown) should avoid
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mixed feedings. Mothers should instead exclusively breastfeed for the first 6 months of life,

gradually introducing mixed feedings thereafter, while continuing to breastfeed for the first 12

months of life "or until a nutritionally adequate and safe diet without breast milk can beprovided"[14].

Importance of Breastfeeding for at Least 1 Year

Previous guidelines endorsed weaning infants from breast milk by 6 months of age in order to

reduce the risk of HIV transmission, but clinical studies (Figure 8) and (Figure 9) have

subsequently established that, in resource-limited settings, weaning infants at 4 to 6 months ofage is associated with marked increases in mortality, hospitalizations, and growth compromise

[11,32,33]. The WHO breastfeeding guidelines therefore recommend that after exclusively

breastfeeding for 6 months, infants should continue to breastfeed for the first 12 months of life.Since rapid weaning has also been associated with HIV transmission and mastitis[35], weaning

should take place gradually over 1 month. For infants and mothers who are on antiretroviral

prophylaxis to prevent HIV transmission, the antiretroviral drugs should continue for 1 week

following complete weaning[15]. Mothers who are receiving antiretroviral therapy for maternalhealth (antiretroviral treatment is indicated) should continue to do so for life.

Use of Heat-treated, Expressed Breast Milk

The WHO has endorsed heat-treated, expressed breast milk as an interim feeding strategy that

may enable women to continue breastfeeding under certain conditions. Heat treatment of breast

milk inactivates HIV, but does not adversely affect the nutritional quality of breast milk[36]. The

use of heat-treated expressed breast milk as a temporary strategy to continue breastfeedingwithout putting the infant at risk may be considered under certain circumstances, such as low

birthweight newborns who cannot breastfeed, women with conditions that may temporarily

interrupt breastfeeding (such as mastitis), women whose supply of antiretroviral therapy orprophylaxis is interrupted, or as an adjunct to weaning practices[15]. Under these circumstances,

infants should continue nevirapine prophylaxis since they will be consuming breastmilk.

Current WHO Recommendation for Breastfeeding HIV-Infected Mothers

The WHO has issued recommendations for feeding of infants born to HIV-infected mothers[14]

and for the use of maternal and infant antiretroviral prophylaxis to prevent HIV transmissionfrom HIV-infected mothers to their infants who are breastfeeding[20]. The key points of these

recommendations are summarized as follows:

Mothers known to be HIV infected should exclusively breastfeed their infants for the first6 months of life, introducing complementary food thereafter, and continue breastfeeding

for the first 12 months of life. Breastfeeding should then only stop once a nutritionallyadequate and safe diet without breast milk can be provided.

Mothers known to be HIV infected that decide to stop breastfeeding at any time should

stop gradually over a 1-month period. Abrupt weaning is not advisable. Mothers orinfants who have been receiving antiretroviral prophylaxis should continue prophylaxis
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for 1 week after breastfeeding has completely stopped. Mothers receiving antiretroviral

therapy for their own health should continue their antiretroviral therapy regimen.

When an HIV-infected mother decides to stop breastfeeding, the infant should be

provided with safe and adequate replacement feeds to enable normal growth and

development. For infants less than 6 months of age, commercial infant formula (if WHOsafe formula feeding criteria are met) or expressed heat-treated breast milk are considered

acceptable. Animal milk is not recommended as a replacement food in the first 6 months

of life. For children older than 6 months of age, commercial infant formula or boiledanimal milk are acceptable. Meals should include complementary foods and should be

provided 4 to 5 times per day.

If infants are known to be HIV infected, mothers are strongly encouraged to exclusively

breastfeed for the first 6 months of life and continue breastfeeding as per the

recommendations for the general population, that is, up to 2 years or beyond.

If antiretroviral prophylaxis is not available (for example, in an emergency situation), or

health services are unavailable, women with HIV or unknown status are stronglyencouraged to breastfeed their children.

The infant prophylaxis will depend on whether the mother is eligible to receive

antiretroviral therapy for her own health, or, if the mother does not need treatment for her

own health, the mothers antiretroviral regimen used to prevent mother-to-childtransmissionWHO Option A or Option B (Figure 10) [20]:

o Mother eligible for treatment for her own health: If the mother received

antiretroviral therapy for her own health during the pregnancy and delivery (andwill continue on antiretroviral therapy), the infant should receive daily nevirapine

or twice daily zidovudine from birth until 4 to 6 weeks of age, irrespective of the

mode of feeding.

o Mother does not need treatment for her own healthOption A: If the mother

received zidovudine monotherapy antepartum for preventing mother-to-childtransmission, the breastfeeding infant should receive daily nevirapine for a

minimum of 4 to 6 weeks and until 1 week after all exposure to breast milk has

ended. Infants receiving replacement feeding only should receive daily nevirapineor single dose-nevirapine plus twice-daily zidovudine from birth until 4 to 6

weeks of age.

o Mother does not need treatment for her own healthOption B: If the mother

received a triple-drug antiretroviral regimen during pregnancy (and continues thisregimen post-partum if she breastfeeds), the infant should receive daily nevirapine

or twice daily zidovudine from birth until 4 to 6 weeks of age, irrespective of themode of feeding.

The nevirapine (Figure 11) and zidovudine (Figure 12) dosing for the infant is based on

the birth weight and age of the infant.
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hiv vertical transmission and pregnancy

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