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 to widespread 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 effective antiretroviral 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 occur in 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]. Maternal HIV 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 women who 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/mm3), all three options endorse immediate initiation of triple antiretroviral therapy for the mother. The options differ with 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-lamivudine combination 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 if the 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 mother is discontinued.

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 and delivery 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. The 2010 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 promoted Option 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 while highlighting 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 not meet 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 possible thereafter) 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 develop resistance 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 settings now align with guidelines for non-pregnant adults and adolescents, consisting of two

nucleoside reverse-transcriptase inhibitors (NRTIs) paired with a non-nucleoside reversetranscriptase inhibitor (NNRTI) (Figure 6)[3]. For most pregnant women, a fixed-dose combination of tenofovir plus lamivudine (or emtricitabine) plus efavirenz will be the most 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, including pregnant 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 not documented 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, coformulated with tenofovir and either lamivudine or emtricitabine[7]. For all of these reasons, the WHO now recommends that unless specifically contraindicated, pregnant women should receive efavirenz-based antiretroviral therapy regimens[7]. Use of Nevirapine in Pregnancy: Nevirapine remains an option for inclusion in first-line antiretroviral therapy regimens for pregnant women, but the WHO does not 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 350 cells/mm3. To decrease toxicity, reduced lead-in dosing (200 mg once daily) is recommended for the first 2 weeks when starting NVP[3]. 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 been reassuring to date, failing to identify any increased risk of fetal or maternal complications[15,16]. Tenofovir should be avoided in pregnant women with renal disease 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

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. The decision regarding which one to use will typically depend upon which one is included in locally available fixed-dose combinations of antiretrovirals. 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-dose nevirapine 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 reduces the risk of developing NNRTI resistance[17,18,19], and mothers who receive this one-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 is recommended 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 current pregnancy, because the risk of NNRTI resistance wanes with time[20,21,22,23,24,25].

Case 3: Discussion
Background
The last two decades has seen significant improvements in the therapeutic options for HIVinfected individuals, resulting in increased longevity and improved quality of life. Concomitant with 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 in perspective 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 of maternal-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 newborns with 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 is believed 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 the impact, 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 HIV when 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-child HIV 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 of transmission 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 elective cesarean-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

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 compared with 17 (10.2%) of 150 those delivered vaginally (Figure 5). The overall benefit of cesareansection 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 its recommendations 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 of membranes[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 HIV transmission 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 antiretroviral therapy 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 ACOG recommends 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 39 completed 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 dilatation and is likely to have extended labor, one option is to immediately give the loading dose of

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 any vaginal 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 vaginal delivery, 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 HIVinfected women[9], several studies have suggested that HIV-infected women who undergo cesarean section have higher complication rates than women who deliver vaginally[10,11]. Postdelivery complications most frequently consist of hemorrhage, postpartum fever, cesarean wound infection, endometritis, urinary tract infection, and sepsis[4,7,10,12]. Among HIVinfected women who deliver via cesarean, those with CD4 counts less than 200 cells/mm3 have a greater 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

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, or stigma 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 of HIV 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 few months 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 to infants 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 preparation may 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 formula feeding 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 the infant, 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. Extended infant 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

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 to HIV-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 women with 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 HIV transmission 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 early as 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% (Figure 7). 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 week after 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 for the 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 in pregnancy: 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 when the 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 the gastrointestinal 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

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 be provided"[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 of age 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 maternal health (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 breastfeeding without 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 or prophylaxis 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 transmission from 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 first 6 months of life, introducing complementary food thereafter, and continue breastfeeding for the first 12 months of life. Breastfeeding should then only stop once a nutritionally adequate 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 or infants who have been receiving antiretroviral prophylaxis should continue prophylaxis

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 WHO safe 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 boiled animal 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 strongly encouraged 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-child transmissionWHO 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 (and will 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. Mother does not need treatment for her own healthOption A: If the mother received zidovudine monotherapy antepartum for preventing mother-to-child transmission, 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 nevirapine or single dose-nevirapine plus twice-daily zidovudine from birth until 4 to 6 weeks of age. Mother does not need treatment for her own healthOption B: If the mother received a triple-drug antiretroviral regimen during pregnancy (and continues this regimen 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 the mode 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.