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Home > Topics > Emerging Issues > ART & Breast-feeding
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Antiretroviral Treatment, Breast-Feeding, and Mother-to-Child Transmission of HIV

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Introduction
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triangle The Benefits of Breast-Feeding
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triangle Breast-Feeding and HIV: the Dilemma
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triangle Figure 1. Timing of MTCT, Breast-Feeding Population, No ARV: Breast-Feeding Accounts for Up to 40% of All MTCT
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triangle Antiretroviral Treatment: A Way Out of the Dilemma?

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Antiretroviral Drugs and Viral Load Suppression in Breast Milk
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ARV Drug Levels in Breast Milk
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triangle Toxicity in the Infant
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triangle ARV Treatment for the Breast-Feeding Mother and the Development of Resistant Virus

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Challenges of Treating the Mother
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triangle Figure 2. Women Eligible for ARV Treatment Also Most at Risk of Infecting Their Infants

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Concluding Points
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References
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Introduction

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The Benefits of Breast-Feeding

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Exclusive breast-feeding for the first months of life is widely recognized as the best way to feed infants.( 1 , 2 ) Breast milk provides complete and appropriate nutrition in the first months of life as well as antibodies to protect infants against infections.( 3 ) Breast-feeding also can postpone a mother's return to fertility, helping her to space her pregnancies.( 4 , 5 ) The protection breast-feeding provides against malnutrition as well as diarrheal and respiratory illnesses, the major causes of infant mortality in resource-poor countries, is particularly important in settings where many infants are at risk of illness and death because of poor sanitation, high incidence of bacterial infections, and lack of adequate nutrition.

Because of the benefits of breast-feeding for mother and child, the promotion of exclusive breast-feeding for the first months of life has been at the center of maternal and child health initiatives in resource-poor countries for several decades. The advent of the HIV epidemic, and the identification of breast-feeding as a major source of HIV transmission, however, has complicated this clear and consistent message.( 3 )

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Breast-Feeding and HIV: the Dilemma

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HIV is present in breast milk and can be transmitted to infants through breast-feeding. It is estimated that HIV transmission through breast-feeding--also known as postnatal transmission--is responsible for up to 40% of mother-to-child transmission (MTCT) of HIV worldwide.( 6 , 7 ) Research suggests that the first 6-8 weeks of breast-feeding is the high-risk period for postnatal transmission.( 8 , 9 , 10 ) However, HIV transmission through breast milk can occur at any point during lactation, and the risk of infection through breast-feeding is cumulative, increasing with duration of breast-feeding.( 11 , 12 , 13 , 14 ) The risk of postnatal infection therefore is especially high in settings where women tend to breast-feed for long periods of time.

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Figure 1. Timing of MTCT, Breast-Feeding Population, No ARV: Breast-Feeding Accounts for Up to 40% of All MTCT

Figure 1. Timing of MTCT, Breast-Feeding Population, No ARV: Breast-Feeding Accounts for Up to 40% of All MTCT
Source: Mofenson LM. HIV Transmission through Breast-Feeding. March 2006 [In press].
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A study in Kenya has suggested that breast-feeding is associated with increased maternal mortality in HIV-infected women. However, this has not been confirmed in other studies, including a large metaanalysis of research on prevention of MTCT.( 15 , 16 )

Risk factors for HIV transmission through breast-feeding include the following:

  • High levels of HIV in the mother's blood and breast milk (high viral load) related to either advanced HIV disease or mother becoming infected during lactation ( 17 , 18 , 19 , 20 , 21 )

  • Poor maternal immune status (low CD4 count) ( 17 , 18 , 21 )

  • Longer duration of breast-feeding ( 22 )

  • Poor breast health:

    • Mastitis--clinical and subclinical ( 17 , 21 , 23 )

    • Breast abscess ( 17 , 18 )

    • Cracked or bleeding nipples ( 17 , 18 )

  • Oral thrush in the infant ( 28 )

  • Mixed infant feeding ( 24 , 25 )

It has been shown that formula feeding reduces the risk of HIV transmission through breast-feeding,( 8 , 10 ) and most HIV-infected mothers in resource-rich countries formula feed their infants to avoid the risk of postnatal transmission. Unfortunately, most women in resource-poor countries cannot formula feed safely: They have inadequate access to clean water, proper sanitation, and a reliable, sustainable supply of formula milks. In these situations, formula feeding may lead to increased infant mortality. In addition, breast-feeding usually is the norm in resource-poor settings. Formula feeding therefore may be culturally unacceptable, and may indirectly reveal a mother's HIV status and expose her to stigma.

The World Health Organization recommends formula feeding when it is "acceptable, feasible, affordable, sustainable, and safe" for the mother and child. If these conditions cannot be met, exclusive breast-feeding is recommended during the first months of life and should be stopped as soon as the conditions for safe formula feeding have been met.( 4 ) Mixed feeding is to be avoided by all HIV-infected women as it increases the risk of HIV transmission. These guidelines recommend that health care workers provide individualized counseling to HIV-infected women that is specific to their particular social, financial, and health circumstances. Central to this counseling is the education of women on the risks and the benefits of all infant feeding options.

This type of personalized, nuanced counseling is not easy to implement at short-staffed, overburdened health care facilities, particularly as health care workers in those settings often have little time to meet with clients individually. In South Africa, there are reports that the quality of the infant feeding counseling for HIV-infected women is poor and that counseling messages are inconsistent.( 26 ) In Côte d'Ivoire, health care workers report that they have difficulty counseling HIV-infected women and that the long-term infant feeding options for these women seem inadequate.( 27 ) Complicating infant feeding policy-making is the fear that counseling about formula feeding with HIV-infected mothers may "spill over" into the larger community and undermine efforts to promote exclusive breast-feeding in the general population. Women themselves may not be receptive to infant feeding messages that emphasize exclusive breast-feeding and early weaning. Whereas most HIV-infected women in resource-poor settings will choose to breast-feed because they lack safe alternatives, feeding infants other foods even when they are very young is common in many settings and many women have difficulty breast-feeding exclusively or weaning their children early.( 28 , 29 )

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Antiretroviral Treatment: A Way Out of the Dilemma?

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In light of the difficulties implementing current infant feeding recommendations, researchers have been looking for interventions that would allow HIV-infected women in resource-poor countries to breast-feed their infants while minimizing the risk of transmitting HIV to their infants. Some basic interventions already are being practiced, such as training mothers to:

  • breast-feed exclusively in order to avoid the risks of mixed feeding

  • wean their infants early in order to avoid the risks of prolonged breast-feeding

  • practice proper breast-feeding technique in order to avoid transmission risk associated with mastitis, engorgement, and nipple fissures

The risk of HIV transmission through breast-feeding is directly related to maternal HIV viral load in breast milk and blood. Giving mothers antiretroviral (ARV) drugs during pregnancy, labor, and delivery decreases MTCT by reducing maternal viral load in the mother's blood and genital fluids.( 30 , 31 , 32 , 33 , 34 , 35 ) It is hypothesized that, by decreasing viral load in breast milk, providing ARV treatment to HIV-infected mothers in the postpartum period could reduce postpartum transmission significantly. Although a recent study conducted in Botswana raises hopes about the use of maternal ARV treatment as an intervention to prevent postnatal transmission, there are several serious, interrelated concerns about this strategy that will be discussed in this paper:

  1. The ability of ARV drugs to effectively lower viral load in breast milk

  2. The ability of ARV drugs to penetrate into breast milk and thereby provide postexposure prophylaxis to the infant

  3. The chance of low levels of ARV drugs in breast milk leading to resistant virus that will be transmitted to the infant

  4. The potential short- and long-term toxicities in the infant caused by long-term ARV drug exposure through breast milk

  5. Which ARV treatment regimens to choose for mothers, particularly those who are not clinically eligible for treatment

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Antiretroviral Drugs and Viral Load Suppression in Breast Milk

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The most comprehensive investigation to date of the potential of ARV treatment to reduce postnatal HIV transmission is the Mashi Study in Botswana. The study was conducted among women who had been taking a combination of nevirapine (NVP), lamivudine (3TC), and zidovudine (ZDV) for at least 2 months. Researchers evaluated maternal viral loads in plasma and breast milk, and ARV concentrations in breast milk and the infant's blood, and compared HIV transmission rates in the women who received treatment with those of women who had been given ZDV alone from 34 weeks' gestation plus single-dose NVP during labor. The mothers' breast milk was evaluated at 2 and 5 months after delivery. None of the children born during the study period became HIV infected.( 36 )

In the study, 23 of the 26 women (88%) who received ARV treatment had breast milk HIV RNA viral loads <50 copies/mL, compared with only 9 of the 25 (36%) women receiving ZDV prophylaxis (p = .0001). When the women's baseline viral load and CD4 count was taken into account, the difference between the groups remained statistically significant.( 41 ) Although this finding is encouraging, there is one serious caveat; the study found that ARV treatment lowered HIV RNA (cell-free virus) but not HIV DNA (cell-associated virus) in breast milk--there was no statistically significant difference in the levels of cell-associated HIV between the two groups of mothers.( 41 )

  • Cell-free virus refers to "free-floating" virus or the parts of the virus (virions) not associated with a cell. It is measured as HIV RNA. Most standard viral load tests measure HIV RNA.

  • Cell-associated virus refers to HIV that is inside a cell; it is measured as HIV DNA.

Source: WHO, UNICEF, UNAIDS, UNFPA. HIV transmission through breast-feeding: a review of available evidence. Geneva: World Health Organization; 2004.

It also must be noted that neither HIV RNA nor DNA polymerase chain reaction assays actually detect infectious virus, a more precise determinant of infectivity. Detecting the level of infectious virus requires culture and quantification of virus from the blood.

It is not known whether HIV RNA or HIV DNA levels in breast milk are more important as risk factors in postnatal HIV transmission. A recent study in Tanzania suggests that HIV DNA levels in breast milk may play a greater role in HIV transmission during the first few months of breast-feeding whereas HIV RNA levels in breast milk influences HIV transmission in later months.( 37 ) The Tanzanian case-control study examined viral load in breast-milk samples from HIV-infected women: 61 who had transmitted HIV to their infants through breast-feeding (the cases) and 61 who had not (the controls). Each 1 log10 increase in breast-milk HIV RNA or DNA was associated with a 3-fold increased risk of MTCT. However, no lower HIV RNA or DNA threshold for MTCT was determined.

  1. Cell-free virus (HIV RNA) was a significant predictor of postnatal transmission only after 9 months postpartum.

  2. Cell-associated virus (HIV DNA) was predictive of transmission both before and after 9 months postpartum.

It is worth noting that certain ARV drugs may be better than others at suppressing viral loads in breast milk. NVP may be powerful particularly in the short run. A recent study of viral load in breast milk conducted in Kenya found that found that, at 2-3 weeks after childbirth, women receiving single-dose NVP had lower viral load and lower MTCT rates than those who had received ZDV from week 34 of pregnancy and during labor.( 38 ) This is similar to the effect of NVP on maternal viral load following single-dose NVP.( 38 )

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ARV Drug Levels in Breast Milk

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One of the basic questions about the feasibility of using ARV treatment solely to prevent postnatal HIV transmission is how well ARV drugs penetrate into breast milk. Drug concentration in the breast milk of mothers taking medication usually is lower than drug concentration in blood and it is recommended generally that mothers on most medications, including ARV medications, continue breast-feeding.( 39 )

Despite these general guidelines, it is difficult to predict how drugs will transfer into breast milk. In addition, because different ARV drugs have different half lives, some will persist in breast milk more than others.( 40 ) Nucleoside reverse transcriptase inhibitors (NRTIs) have a tendency to concentrate in breast milk and, unlike other ARV drugs, are present in breast milk at higher levels than in maternal blood (see Table 1).( 45 ) Levels of NVP and some protease inhibitors (PIs) are lower in breast milk than in serum.( 45 ) However, intracellular concentrations of ARV drugs may be more important than fluid levels.

Table 1. Transfer of ARVs into Breast Milk
Drug Animal Studies Human Studies Comments
Abacavir (ABC) Yes (rats) Unknown
Zidovudine (ZDV) Yes BM 2-3 times higher than serum
Didanosine (ddI) Yes (rats) Unknown
Emtricitabine (FTC) Unknown Unknown
Lamivudine (3TC) Yes BM 2-3 times higher than serum
Stavudine (d4T) Yes (rats) Unknown
Tenofovir (TDF) Yes (primates) Unknown Peak 3%, AUC 20% of serum
Efavirenz (EFV) Yes Unknown
Nevirapine (NVP) Yes Yes BM/plasma ratio 61-71%
Amprenavir (APV) Yes (rats) Unknown
Atazanavir (ATV) Yes (rats) Unknown
Indinavir (IDV) Yes (rats) Unknown BM/plasma ratio: 90-540%
Lopinavir (LPV) Yes (rats) Unknown
Nelfinavir (NFV) Yes (rats) Yes BM/plasma ratio: 6-24%
Saquinavir (SQV) Yes (rats) Unknown

Abbreviations:
BM = breast milk
AUC = area under the curve (a measure of drug concentration)

Source: Mofenson LM. HIV Transmission through Breast-Feeding. March 2006 [In press].

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Toxicity in the Infant

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Although ARVs usually are considered safe in pregnancy, it is still not clear whether exposing the infant to ARVs through breast milk causes developmental delays or severe side effects. There is little information about the long-term safety of breast-feeding when mothers are receiving ARV treatment. Most information on the safety of ARVs for pregnant women and infants comes from research in resource-rich settings where most HIV-infected women do not breast-feed.

The risk of ARV exposure for the infant depends on the duration of infant exposure, the timing of exposure, and the type and number of drugs to which the infant is exposed.( 45 ) Combination ARV treatment regimens may be more effective at preventing MTCT than shorter, less-complex ARV prophylaxis regimens, but they also expose the infant to more drugs and increase risks of toxicity.( 45 ) Although there are potential short- and long-term risks to uninfected infants who are exposed to high levels of drugs, several follow-up studies have failed to find long-term toxicity or impaired growth and development in infants born to HIV-infected women who received combination ARV treatment during pregnancy. In utero exposure to ARVs, however, has been found to increase the risk of preterm birth.( 44 , 45 , 46 , 47 )

According to Gaillard et al in their review of breast-feeding and ARV treatment, the daily dosage of ARV drugs ingested by the infant is approximately 10-20 times lower than the usual therapeutic dosage. The authors conclude that the risk of most toxicities also is likely to be low.( 48 ) It is important to note that Stevens-Johnson syndrome in reaction to NVP is not dosage dependent and infants therefore are at risk of a reaction even when they are exposed to low levels of NVP in breast milk.( 53 ) In the Mashi Study, there was 1 case of severe rash, 3 cases of serious neutropenia, and 1 case of anemia.( 48 )

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ARV Treatment for the Breast-Feeding Mother and the Development of Resistant Virus

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Despite perinatal interventions to reduce MTCT, some infants will become infected in utero or during labor and delivery, even when the mother has an undetectable viral load. Unless HIV-infected infants are given parallel ARV treatment while breast-feeding, replication of maternally transmitted virus may not be suppressed adequately and resistance may develop. The chance that resistant virus would be transmitted is increased because ARV levels in breast milk are lower than those required to suppress the virus fully.

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Challenges of Treating the Mother

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When mothers need ARV treatment for their own health during pregnancy and lactation, the health benefits to the mother outweigh any potential risks to the infant and the mother should receive treatment. Women who need treatment (ie, those who are symptomatic or who have low CD4 cell counts and high viral loads) are also the ones most likely to transmit HIV to their infants through breast-feeding.

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Figure 2. Women Eligible for ARV Treatment Also Most at Risk of Infecting Their Infants

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Figure 2. Women Eligible for ARV Treatment Also Most at Risk of Infecting Their Infants
Source: Mofenson LM. HIV Transmission through Breast-Feeding, March 2006 [In press]. Data source: Piwoz E, Iliff P, Tavengwa N, et al. Early introduction of non-human milk and solid foods increases the risk of postnatal HIV-1 transmission in Zimbabwe. In: Program and abstracts of the XV International AIDS Conference; July 11-16, 2004; Bangkok. Abstract MoPpB2008.
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Mothers who are receiving treatment still should be counseled to formula feed if they can do so safely and to breast-feed exclusively if they cannot, weaning their infants as soon as it safe to do so.

If the mother does not require treatment for her own health, she should receive ARV prophylaxis during pregnancy, labor, and delivery. Despite the concerns raised above about the use of ARV drugs to prevent postnatal infection, it would seem logical to extend prophylaxis during the breast-feeding period. However, there are significant difficulties in choosing an appropriate ARV prophylaxis or treatment regimen for these women. NVP is a part of the first-line ARV treatment regimens in most resource-poor countries. Long-term use of NVP for treatment has been associated with higher rates of NVP hypersensitivity, severe rash, and acute liver toxicity, including death, in women with CD4 counts >250 cells/µL.( 49 ) Although data from resource-poor countries show generally low rates of NVP-related hepatic toxicity, concerns about NVP toxicity in these settings remain.( 45 ) Patient monitoring in these settings may be less rigorous than it is in resource-rich settings and there may be differences in the ability of various populations to clear the drug.( 47 , 50 ) In the United States, NVP is not recommended to be used in women with CD4 counts >250 cells/µL unless the benefits clearly outweigh the risks.( 51 )

Efavirenz is a nonnucleoside reverse transcriptase inhibitor that often is used as an alternative to NVP in most first-line ARV treatment regimens, but it is not recommended for use in women of childbearing age who do not have reliable access to contraception because it may cause birth defects. The other alternative would be a regimen using PIs. But this also poses problems. The expense of PIs and the necessity of maintaining a cold chain for transport and storage make it unlikely that they will be widely available to HIV-infected mothers in the near future.

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Concluding Points

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  • There is not yet enough evidence on the effectiveness of ARV treatment in preventing HIV transmission through breast-feeding to recommend changing current infant feeding strategies or counseling guidelines.

  • In pregnant and breast-feeding women who require ARV treatment for their own health, the calculation of risks and benefits clearly is in favor of treating the mother.

  • Women who need treatment usually are clinically symptomatic and have high viral loads and low CD4 counts; these are precisely the women at highest risk of transmitting HIV through breast milk. Providing ARV treatment to these women during pregnancy, lactation, and beyond not only will help mothers control their HIV infection but also could reduce the risk of MTCT through breast-feeding.

  • The benefit/risk ratio of providing ARV treatment for women who do not require ARV treatment for their own health is unknown.

  • It is not clear that combination ARV treatment is more effective than the recommended prophylaxis regimens of ZDV plus single-dose NVP in preventing postnatal MTCT by breast milk in women with higher CD4 counts and lower viral loads.

  • Formula feeding still is recommended for HIV-infected women when it is acceptable, feasible, affordable, sustainable, and safe. It remains the only way to avoid the risk of HIV transmission through breast-feeding completely.

  • When women cannot meet the criteria for safe formula feeding, exclusive breast-feeding is recommended during the first months of life and should be stopped as soon as the conditions for safe formula feeding have been met.

  • Clinical trials are required before making universal recommendations to provide ARV treatment to breast-feeding women in order to prevent postnatal MTCT.

    • Studies are needed to assess the safety of maternal ARV treatment on the breast-fed infant.

    • Studies also are needed to understand the pharmacokinetics of ARVs in breast milk and the development of viral resistance in breast milk, specifically whether resistance develops differently in breast milk than it does in plasma.

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References

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1. transparent gif World Health Assembly. Infant and Young Child Nutrition. The 54th World Health Assembly; May 18, 2001; Geneva. Resolution WHA 54.2.
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2. transparent gif World Health Organization. The Optimal Duration of Exclusive Breast-Feeding. Report of an Expert Consultation. Geneva: World Health Organization; March 28-30, 2001.
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3. transparent gif World Health Organization Collaborative Study Team. Effect of breast-feeding on infant and child mortality due to infectious diseases in less developed countries: a pooled analysis. WHO Collaborative Study Team on the Role of Breast-feeding on the Prevention of Infant Mortality. Lancet. 2000 Feb 5;355(9202):451-5.
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4. transparent gif World Health Organization. New Data on the Prevention of Mother-to-Child Transmission of HIV and Their Policy Implications--Conclusions and Recommendations . WHO Technical Consultation on Behalf of the UNFPA/UNICEF/WHO/UNAIDS Inter-Agency Task Team on Mother-to-Child Transmission of HIV. Geneva: World Health Organization; October 11-13, 2000. Accessed May 16, 2006.
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5. transparent gif World Health Organization. Improving Access to Quality Care in Family Planning: Medical Eligibility Criteria for Contraceptive Use; 2nd ed. Geneva: World Health Organization; 2000.
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6. transparent gif Newell M-L, Read J, Leroy V, et al. Mortality among HIV-infected mothers and children's feeding modality: the Breast-Feeding and HIV International Transmission Study (BHITS). In: Program and abstracts of the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment; July 13-16, 2003; Paris. Abstract 221.
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7. transparent gif Alioum A, Cortina-Borja M, Dabis F, et.al. Estimating the efficacy of interventions to prevent mother-to-child transmission of human immunodeficiency virus in breast-feeding populations: comparing statistical methods . Am J Epidemiol. 2003 Sep 15;158(6):596-605.
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8. transparent gif Nduati R, John G, Mbori-Ngacha D, et al. Effect of breast-feeding and formula feeding on transmission of HIV-1: a randomized clinical trial . JAMA. 2000 Mar 1;283(9):1167-74.
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9. transparent gif Dunn DT, Tess BH, Rodrigues LC, et al. Mother-to-child transmission of HIV: implications of variation in maternal infectivity . AIDS. 1998 Nov 12;12(16):2211-6.
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10. transparent gif Moodley D, Moodley J, Coovadia H, et al. South African Intrapartum Nevirapine Trial (SAINT) Investigators. A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1 . J Infect Dis. 2003 Mar 1;187(5):725-35.
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11. transparent gif Miotti PG, Taha TE, Kumwenda NI, et al. HIV transmission through breast-feeding: a study in Malawi . JAMA. 1999 Aug 25;282(8):744-9."
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12. transparent gif Leroy V, Karon JM, Alioum A, et al; West Africa PMTCT Study Group. Twenty-four month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission of HIV-1 in West Africa . AIDS. 2002 Mar 8;16(4):631-41.
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13. transparent gif Petra Study Team. Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial . Lancet. 2002 Apr 6;359(9313):1178-86.
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14. transparent gif Read J, Newell M-L, Dabis F, et al. Late postnatal transmission of HIV in breastfed children: an individual patient data meta-analysis (The Breast-feeding and HIV International Transmission Study). In: Program and abstracts of the 10th Conference on Retroviruses and Opportunistic Infections; February 10-14, 2003; Boston. Abstract 97.
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15. transparent gif Nduati R, Richardson BA, John G, et al. Effect of breast-feeding on mortality among HIV infected women: a randomised trial . Lancet 2001 357: 1651-5.
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16. transparent gif Breastfeeding and HIV International Transmission Study Group. Mortality among HIV-1-infected women according to children's feeding modality: an individual patient data meta-analysis . J Acquir Immune Defic Syndr. 2005 Aug 1;39(4):430-8.
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17. transparent gif John GC, Nduati RW, Mbori-Ngacha DA, et al. Correlates of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission: association with maternal plasma HIV-1 RNA load, genital HIV-1 DNA shedding, and breast infections . J Infect Dis. 2001 Jan 15;183(2):206-212.
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18. transparent gif Fawzi W, Msamanga G, Spiegelman D, et al. Transmission of HIV-1 through breast-feeding among women in Dar es Salaam, Tanzania . J Acquir Immune Defic Syndr. 2002 Nov 1;31(3):331-8.
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19. transparent gif Rousseau CM, Nduati RW, Richardson BA, et al. Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease . J Infect Dis. 2003 Mar 1;187(5):741-7.
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20. transparent gif Pillay K, Coutsoudis A, York D, et al. Cell-free virus in breast milk of HIV-1-seropositive women . J Acquir Immune Defic Syndr. 2000 Aug 1;24(4):330-6.
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21. transparent gif Semba RD, Kumwenda N, Hoover DR, et al. Human immunodeficiency virus load in breast milk, mastitis, and mother-to-child transmission of human immunodeficiency virus type 1 . J Infect Dis. 1999 Jul;180(1):93-8.
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22. transparent gif Coutsoudis A, Dabis F, Fawzi W, et al. Breast-Feeding and HIV International Transmission Study Group. Late postnatal transmission of HIV-1 in breast-fed children: an individual patient data meta-analysis . J Infect Dis. 2004 Jun 15;189(12):2154-66.
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23. transparent gif Embree JE, Njenga S, et al. Risk factors for postnatal mother--child transmission of HIV-1 . AIDS. 2000 Nov 10;14(16):2535-41.
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24. transparent gif Coutsoudis A, Pillay K, Kuhn L, et al. South African Vitamin A Study Group. Method of feeding and transmission of HIV from mothers to children by 15 months of age: Prospective cohort study from Durban, South Africa . AIDS. 2001 Feb 16;15(3):379-87.
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25. transparent gif Iliff PJ, Piwoz EG, Tavengwa NV, et al. ZVITAMBO study group. Early exclusive breast-feeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival . AIDS. 2005 Apr 29;19(7):699-708.
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26. transparent gif Smart T. Safer infant feeding. HIV & AIDS Treatment in Practice #54; San Francisco: HIV InSite, UCSF Center for HIV Information; September 9, 2005. Available at: http://hivinsite.ucsf.edu/InSite?page=pa-hatip-54 . Accessed May 16, 2006.
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27. transparent gif Becquet R, Ekouevi DK, Sakarovitch C, et al. Knowledge, attitudes, and beliefs of health care workers regarding alternatives to prolonged breast-feeding (ANRS 1201/1202, Ditrame Plus, Abidjan, Côte d'Ivoire) . J Acquir Immune Defic Syndr. 2005 Sep 1;40(1):102-5.
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28. transparent gif Becquet R, Ekouevi DK, Viho I, et al. Acceptability of exclusive breast-feeding with early cessation to prevent HIV transmission through breast milk, ANRS 1201/1202 Ditrame Plus, Abidjan, Côte d'Ivoire . J Acquir Immune Defic Syndr 2005 Dec 15;40(5):600-8.
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29. transparent gif Coutsoudis A. Infant feeding dilemmas created by HIV: South African experiences . J Nutr. 2005 Apr;135(4):956-9.
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30. transparent gif Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment . N Engl J Med 1994; 331: 1173-1180.
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31. transparent gif Lallemant M, Jourdain G, Le Coeur S, et al. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand . N Engl J Med 2004; 351: 217-28.
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32. transparent gif Wiktor SZ, Ekpini E, Karon JM, et al. Short-course zidovudine for prevention of mother-to-child transmission of HIV in Abidjan, Côte d'Ivoire: a randomised trial . Lancet 1999; 353: 781-785.
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33. transparent gif Guay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV in Kampala, Uganda: HIVNET 012 randomised trial . Lancet 1999; 354: 795-802.
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34. transparent gif Lallemant M, Jourdain G, Le Coeur S, et al. A trial of shortened zidovudine regimens to prevent mother-to-child transmission of human immunodeficiency virus type 1 . N Engl J Med 2000; 353: 982-991.
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35. transparent gif Shaffer N, Chuachoowong R, Mock PA, et al. Short-course zidovudine for perinatal HIV transmission in Bangkok, Thailand: a randomised controlled trial . Lancet 1999; 353: 773-780.
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36. transparent gif Shapiro RL, Ndung'u T, Lockman S, et al. Highly active antiretroviral therapy started during pregnancy or postpartum suppresses HIV-1 RNA, but not DNA, in breast milk . J Infect Dis 2005 Sep 1;192(5):713-9.
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37. transparent gif Koulinska IN, Villamor E, Chaplin B, et al. Transmission of cell-free and cell-associated HIV-1 through breast-feeding . J Acquir Immune Defic Syndr. 2006 Jan 1;41(1):93-9.
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38. transparent gif Chung MH, Kiarie JN, Richardson BA, et al. Breast milk HIV-1 suppression and decreased transmission: a randomized trial comparing HIVNET 012 nevirapine versus short-course zidovudine . AIDS. 2005 Sep 2;19(13):1415-22.
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39. transparent gif American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk . Pediatrics. 2001 Sep;108(3):776-89.
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40. transparent gif Mofenson L. Antiretroviral toxicity in the context of PMTCT . In: Program and abstracts of the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment; July 24-27, 2005; Rio de Janeiro. Abstract TuFo0201.
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41. transparent gif Lee EJ, Kantor R, Zijenah L, et al. HIVNET 023 Study Team. Breast-milk shedding of drug-resistant HIV-1 subtype C in women exposed to single-dose nevirapine . J Infect Dis. 2005 Oct 1;192(7):1260-4.
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42. transparent gif Bulterys M, Weidle PJ, Abrams EJ, et al. Combination antiretroviral therapy in African nursing mothers and drug exposure in their infants: new pharmacokinetic and virologic findings . J Infect Dis. 2005 Sep 1;192(5):709-12.
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43. transparent gif Shapiro RL, Holland DT, Capparelli E, et al. Antiretroviral concentrations in breast-feeding infants of women in Botswana receiving antiretroviral treatment . J Infect Dis. 2005 Sep 1;192(5):720-7.
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44. transparent gif Briand N, Le Coeur S, Traisathit P, et al. Growth of human immunodeficiency virus-uninfected children exposed to perinatal zidovudine for the prevention of mother-to-child human immunodeficiency virus transmission . Pediatr Infect Dis J. 2006 Apr;25(4):325-32.
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45. transparent gif Lambert JS, Watts DH, Mofenson L, et al. Risk factors for preterm birth, low birth weight, and intrauterine growth retardation in infants born to HIV-infected pregnant women receiving zidovudine . Pediatric AIDS Clinical Trials Group 185 Team. AIDS. 2000 Jul 7;14(10):1389-99.
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46. transparent gif Culnane M, Fowler M, Lee SS, et al. Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women . Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams. JAMA. 1999 Jan 13;281(2):151-7.
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47. transparent gif Newell ML, Borja MC, Peckham C. European Collaborative Study. Height, weight, and growth in children born to mothers with HIV-1 infection in Europe . Pediatrics. 2003 Jan;111(1):e52-60.
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48. transparent gif Gaillard P, Fowler MG, Dabis F, et al. Ghent IAS Working Group on HIV in Women and Children. Use of antiretroviral drugs to prevent HIV-1 transmission through breast-feeding: from animal studies to randomized clinical trials . J Acquir Immune Defic Syndr. 2004 Feb 1;35(2):178-87.
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49. transparent gif U.S. Food and Drug Administration. FDA Public Health Advisory for Nevirapine (Viramune). January 19, 2005.
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50. transparent gif Hosseinipour MC, Kanyama C, Mshali I, et al. Pharmacokinetic comparison of generic and trade formulations of lamivudine, stavudine, and nevirapine in 12 HIV-infected Malawian subjects. In: Program and abstracts of the 12th Conference on Retroviruses and Opportunistic Infections; February 22-25, 2005; Boston. Abstract 631.
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51. transparent gif Viramune (nevirapine) [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals; revised January 11, 2005."
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