Alberta Reappraising AIDS Society

David Crowe, President
Phone: +1-403-289-6609
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Email: David.Crowe@aras.ab.ca

Kathleen Newell, Treasurer
Box 61037, Kensington Postal Outlet
Calgary, Alberta T2N 4S6
Canada
Office
Phone: +1-403-220-0129
Email: aras@aras.ab.ca
Web: noaids.ca

Transmission of HIV and AIDS

Transmission by Breastfeeding

Babies of HIV-positive mothers are believed to be at great risk of HIV infection if their mothers breastfeed them. Is this true, particularly if exclusive breastfeeding is practiced? And, does a higher risk of HIV infection guarantee a worse health outcome?

“182 infants born to HIV-positive mothers [in Rakai, Uganda] were followed at one, six and twelve months postpartum [after birth]. Mothers were given infant-feeding counseling and allowed to make informed choices as to whether to formula-feed or breast-feed. Eligible mothers and infants received antiretroviral therapy (ART) if indicated. Mothers and their newborns received prophylaxis for prevention of mother-to-child HIV transmission (pMTCT) if they were not receiving ART. Infant HIV infection was detected by PCR…75 infants (41%) were formula-fed while 107 (59%) were breast-fed. Exclusive breast-feeding was practiced by only 25% of breast-feeding women at one month postpartum. The cumulative 12-month probability of infant mortality was 18% among the formula-fed compared to 3% among the breast-fed infants. There were no statistically significant differentials in HIV-free survival by feeding choice (86% in the formula-fed compared to 96% in breast-fed group…Formula-feeding was associated with a higher risk of infant mortality than breastfeeding in this rural population. Our findings suggest that formula-feeding should be discouraged in similar African settings.”
Kagaayi J et al. Survival of Infants Born to HIV-Positive Mothers, by Feeding Modality, in Rakai, Uganda. PLoS ONE. 2008;3(12):e3877.
“Other early studies, which depended on serologic or clinical evidence of infection or estimated the additional risk of HIV-1 infection among breast-fed children by comparing infection rates among children ever breast-fed versus children never breast-fed, were unable to accurately assess the timing of acquisition of HIV-1 infection during breast-feeding…we defined late postnatal transmission as occurring after 4 weeks of age [which is at least as arbitrary as other studies]
Coutsoudis A et al. Late Postnatal Transmission of HIV-1 in Breast-Fed Children: An Individual Patient Data Meta-Analysis. J Infect Dis. 2004 Jun 15;189(12):2154-2166.
“70 children tested positive for HIV-1, giving an overall prevalence of 6%, and an estimated transmission rate of 20%. HIV-1 was not detected in any child born to an HIV-1 negative mother. Infection rates were lowest (14%) in infants younger than 1·5 months (table 2). This rate is probably an underestimate, since 7% of infants were younger than 2 weeks old, a time when diagnostic assays are insensitive. In older children (>1·5 months), infection rates remained stable at 22-23%. Such a stable rate was unexpected in a population in which more than 95% of women breastfeed.3 We expected rates to increase during the first months of life due to transmission of HIV-1 in breastmilk.”
Rollins NC et al. Prevalence, incidence and mother-to-child transmission of HIV-1 in rural South Africa. Lancet. 2002 Aug 3;360(9330):389.
“Following week 6, continued HIV-1 transmission (not taking death into account) was rarely seen among non-breastfed children [but it was found, and how can it be, because breastfeeding is believed to be the only risk factor these babies have]
The 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.
“54 (2%) of women [in the European Collaborative Study] breastfed their infants, with duration of breastfeeding ranging from 6 hours to 38 weeks. These cases were concentrated in the early years of the study, with only four women breastfeeding since the start of 1996. 3 of these women were African and were diagnosed with HIV infection at the time of delivery; two stopped breastfeeding as soon as the positive test result became available (within 24 hours), while the remaining woman continued to breastfeed her infant for 1 week after she received the test result. The fourth woman...was an active IDU [intravenous drug user]...no information was available regarding duration of breastfeeding in this case”
European Collaborative Study. HIV-infected pregnant women and vertical transmission in Europe since 1986. AIDS. 2001 Apr 13;15(6):761-70.
[In response to a report by Nduati et al that breastfeeding, HIV+ mothers had a higher rate of mortality] we were unable to confirm any deleterious effects of breastfeeding on the health of seropositive women. Our assessments of the putative impact of breastfeeding on HIV-infected women included deaths, illnesses, CD4 and CD8 cell counts, and hemoglobin levels. None of these showed significant differences between formula and breastfeeding women.”
Coutsoudis A et al. Are HIV-infected women who breastfeed at increased risk of mortality?. AIDS. 2001 Mar 30;15(5):653-5.
“Among 157 children who were never breastfed, the probability of HIV detection was 0.076 (95% CI 0.042–0.125) at birth, 0.180 (95% CI 0.124–0.245) by 6 weeks, and 0.194 (95% CI 0.136–0.260) by 128 days, after which no new infections were observed.”
Coutsoudis A et al. Method of feeding and transmission of HIV-1 from mothers to children by 15 months of age: prospective cohort study from Durban, South Africa. AIDS. 2001 Feb 16;15(3):379-87.
“Vertical transmission from an infected mother to her child is a special problem. Infection can occur in utero or intrapartum. Postpartum infection can result from the ingestion of breast milk by a nursing infant from an infected mother. It has been estimated by the World Health Organization that up to one-third of all cases of transmission of HIV-1 from an infected mother to her child may occur via breast milk. However, for certain populations where the infant mortality rate is high, the risk of death associated with the lack of breast feeding may be greater than the risk of HIV infection acquired through breast milk.”
Schwartz SA, Nair MP. Current Concepts in Human Immunodeficiency Virus Infection and AIDS. Clin Diagn Lab Immunol. 1999 May;6(3):295-305.
“Although substantial, the incidence of 3.2 per 100 child-years of breastfeeding for late postnatal transmission underestimates infection occurring through breastfeeding”
Leroy V et al. International multicentre pooled analysis of late postnatal mother-to-child transmission of HIV-1 infection. Lancet. 1998 Aug 22;352(9128):597-600.
“mere presence of HIV-1 in a body fluid does not necessarily mean that it is infective...breast feeding can reduce the preventable childhood disease that take a toll several thousand times the effects of perinatal transmission of HIV...Finally, we know of the antiviral activities of breast milk, and possibly an anti-HIV property, present in infant’s saliva”
Kennedy SB. Human Immunodeficiency Virus in Breast Milk. Med Hypotheses. 1998;51(1):75-77.
“An estimated one-third to one-half of vertical transmission of HIV-1 worldwide is due to breastfeeding. The exact frequency of breastmilk HIV-1 transmission is unknown, but it has been estimated to be 14% in the setting of established maternal HIV-1 infection and 29% in the setting of acute maternal infection. The timing of breast milk transmission during the course of lactation also remains unknown, but two studies have found an association between duration of breastfeeding and risk of infant infection. In one such study, prolonged breastfeeding for 15 months or longer was associated with a two-fold increased transmission risk. HIV-1 DNA can be detected in over 50% of breast milk samples and is correlated with CD4 depletion and vit A deficiency. The presence of breast milk HIV-1 provirus is associated with increased transmission risk. Many current intervention strategies to prevent vertical transmission of HIV-1 are aimed at in utero or perinatal transmission. IN developing countries in which breastfeeding by HIV-1 infected women is recommended practice, additional intervention strategies to reduce breast milk transmission warrant evaluation.”
Kreiss J. Breastfeeding and vertical transmission of HIV-1. Acta Paediatr Suppl. 1997 Jun;421:113-7.
“The effect of breastfeeding on HIV disease progression in perinatally HIV-infected infants was examined...As of 6/96, 197 HIV-infected children, evaluated for HIV after 1 month of age, were reported. Breastfeeding status was known for 138 (70%)...At last follow-up, non-breastfed (NBF) children compared to BF were more likely to have AIDS (58% vs. 48%), and PCP (31% vs. 18%) although statistical significance at p<.05 was not reached. Kaplan-Meier estimate of median time to AIDS was 42 mos. for NBF and 74 mos. for BF. Median time to death was 95 mos. for NBF and still undefined for BF with 75% survival probability at 55 months vs. 29 mos. for NBF. Recurrent diarrhea was more frequent in NBF vs. BF (16% vs. 3%, p<.05)...In this cohort of HIV-infected children, breastfeeding was not associated with earlier or more severe disease. Those breastfed had later AIDS onset, less PCP and less chronic diarrhea. Due to HIV transmission risk, however, policies recommending not to breastfeed should not change [huh?]
Frederick T et al. Breastfeeding and Disease Progression Among Perinatally HIV-Infected Children in Los Angeles County (LAC).. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:197 (abstract 720).
“The presence of HIV-1 in genital secretions may be a determinant of vertical HIV-1 transmission. Cervical and vaginal secretions from HIV-1+ pregnant women were evaluated to determine prevalence and correlates of HIV-1 infected cells in the genital tract. HIV-1 DNA was detected by PCR in 32% of 212 cervical and 10% of 215 vaginal specimens. Presence of HIV-1 DNA in the cervix was associated with cervical mucous and a significantly lower absolute CD4 cell count (354 vs 469, P<.001). An absolute CD4 cell count <200 was associated with a 9.6 fold increased odds of cervical HIV-1 DNA detection compared with a count > or = to 500 (95% CI, 2.8-34.2). Detection of vaginal HIV-1 DNA was associated with abnormal vaginal discharge, lower absolute CD4 cell count, and severe vitamin A deficiency. Presence of HIV-1 infected cells in genital secretions was associated with immunosuppression and abnormal cervical or vaginal discharge.”
John GC et al. Genital shedding of HIV-1 DNA during pregnancy: association with immunosuppression, abnormal cervical or vaginal discharge, and severe vitamin A deficiency. J Infect Dis. 1997 Jan;175(1):57-62.
“we were able to detect HIV-1 sequences in the breast milk of 74% of 125 HIV-1 infected women...We found no correlation with maternal clinical status and detection of HIV-1 in breast milk”
Guay LA et al. Detection of human immunodeficiency virus type 1 (HIV-1) DNA and p24 antigen in breast milk of HIV-1-infected Ugandan women and vertical transmission. Pediatrics. 1996 Sep;98(3):438-44.
“How best to advise mothers infected with HIV in developing countries regarding breastfeeding is an important issue that has generated considerable debate. Previous studies have addressed this problem by means of mathematical models, but without considering the issue of the duration of breastfeeding. A mathematical model was developed to compare the age-specific risks of MTCT HIV vs excess mortality due to not breastfeeding. In this model it is assumed that both the the risk of MTCT of HIV through breastmilk and the RR of not breastfeeding do not vary with age. The model indicates that, in HIV+ mothers, the decrease in child mortality afforded by breastfeeding may exceed the risk of MTCT of HIV only during the first 3-7 months of life. Thereafter the risk of HIV-1 transmission probably exceeds the mortality benefit of breastfeeding. Experimental studies of counselling HIV-1 infected mothers to limit their duration of breastfeeding should be considered in the setting of developing countries.”
Nagelkerke NJ et al. The duration of breastfeeding by HIV-1 infected mothers in developing countries: balancing benefits and risks. J Acquir Immune Defic Syndr. 1995 Feb;8(2):176-181.
“Between 1986 and 1991, 365 children of HIV-1-infected mothers and 363 control children were studied in Kenya. The overall risk of transmission from mother to child, determined by serologic evidence of infection by age > or + 12 months and excess mortality in the HIV-1 exposed group was 42.8% (range, 27.6% - 62.6%)... In 44% of children ultimately infected, the pattern of antibody response implied intrapartum or postnatal exposure to HIV-1. Of potential postnatal exposures examined, duration of breastfeeding beyond age 15 months and the mother being married were independently associated with increased risk of infection and seroconversion of children. The percentage of HIV infection attributable to breastfeeding > or + 15 months was 32%. The frequency of mother to child transmission of HIV-1 was high: a substantial proportion of infection occurred postnatally, possibly through breastfeeding.”
Datta P et al. Mother to child transmission of HIV type 1: report from the Nairobi Study. J Infect Dis. 1994 Nov;170(5):1134-40.
“additional transmission risk attributable to BF and the factors that enhance or inhibit transmission are presently unknown. One mechanism by which breastmilk might inhibit HIV 1 transmission is the presence of specific antibodies directed against HIV-1 in breastmilk .... In this study serum and breast milk samples from women in Nairobi Kenya, were tested to determine the prevalence of HIV-1 IgA antibodies.....94 of 63 HIV-1 positive women had anti-HIV-1 IgA in serum and 59% had anti-HIV-1 sIgA in their breast milk. ..... No protective effect of anti-HIV-1 sIgA was seen regarding mother to child transmission...”
Duprat C et al. Human immunodeficiency virus type 1 IgA antibody in breastmilk and serum. Pediatr Infect Dis J. 1994 Jul;13(7):603-60.
“70% (33 of 47) of breast milk specimens collected from HIV-1 seropositive women 0-4 days after delivery were positive for HIV-1 DNA by PCR [which is probably mostly, or even totally, non-infectious]...24% (9 of 37)...contained acid-dissociated p24 antigen...Indicators of more advanced HIV-1 disease in the women did not correlate with either HIV-1 DNA or p24 antigen in breast milk”
Ruff A et al. Prevalence of HIV-1 DNA and p24 antigen in breast milk and correlation with maternal factors. J Acquir Immune Defic Syndr. 1994;7(1):68-73.
“A total of 11 pregnant women who acquired HIV postnatally and who breast-fed were identified...No predelivery sera were available for retrospective testing [i.e. it was assumed that because 10/11 women had no risk factors, they were HIV- at birth]. Of the 11 infants, 3 became infected. Each breast-fed for 2, 3 or 14 months...All 3 infected children were HIV antibody-positive and were either viral-culture positive [without illness] or developed symptoms and signs meeting the CDC criteria for AIDS (P1 or P2 [neither of which involve ongoing clinical symptoms]). 1 died from an AIDS-related illness when the child was 7 years old [illness not specified]...The rate of transmission of HIV in breast-feeding mothers whose primary infection occurs during the breast-feeding period can be estimated as 27% (3/11 infants; 95% confidence interval, 6%-61%).”
Palasanthiran P et al. Breast feeding during primary maternal human immunodeficiency virus infection and the risk of transmission from mother-to-infant. J Infect Dis. 1993 Feb;167(2):441-4.
“No study [used by this meta-analysis] reported an association between risk of infection and duration of breastfeeding, but numbers are too small to establish the absence of such an association.”
Dunn DT et al. Risk of Human Immunodeficiency Virus Type 1 transmission through breastfeeding. Lancet. 1992 Sep 5;340(8819):585-8.
“HIV-positive women were discouraged from breastfeeding. 36 (5%) mothers nevertheless chose to breastfeed, although duration of breastfeeding tended to be short (median 4 weeks). Rate of vertical transmission was significantly higher in breastfed (31%) than in never-breastfed infants (14%), but there was no association with duration of breastfeeding. 6 of 17 (35%) for less than 4 weeks were infected versus 5 of 19 (26%) breastfed for longer”
European Collaborative Study. Risk factors for mother-to-child transmission of HIV-1. Lancet. 1992 Apr 25;339:1007-12.
“Among babies born to HIV-1-seropositive mothers, we were unable to demonstrate a significant dose-response effect between the amount of breast-feeding and HIV-1 infection...Among the 19 children with laboratory evidence of perinatally acquired HIV-1 infection, the development of clinical AIDS did not correlate with the type of infant-feeding practice during their first 3 months of life...Morbidity [illness] during the first year of life as quantified by the incidence of acute diarrhea, fever, lower respiratory tract infection, purulent otitis media [ear infections], and failure to thrive was significantly higher in non-HIV-1 infected children who were not exclusively breast-fed compared with uninfected children who were exclusively breast-fed during the first 6 months of life”
Ryder RW et al. Evidence from Zaire that Breast-feeding by HIV-1-seropositive Mothers is Not a Major Route for Perinatal HIV-1 Transmission but Does Decrease Morbidity. AIDS. 1991 Jun;5(6):709-714.
“Breast-fed [HIV-positive] infants appear to have a longer survival [than those formula fed]…The median incubation time for bottle-fed children was 9.7 months while for breast-fed children it was 19.0 months. It appears that breastfed infants have a slower progression to AIDS, even if ultimately there is an overlap in the latter part of the curves.”
Tozzi AE et al. Does breastfeeding delay progression to AIDS in HIV-infected children?. AIDS. 1990;4(12):1293-1304.
“Three incident HIV cases occurred in the 19 children born to mothers who had seroconversion to HIV during follow-up. All of the infected children had received bacille Calmette-Guérin vaccine at birth...Only one of the three infected children had symptoms of HIV infection (persistent generalized lymphadenopathy [not illness, just low CD4 cell counts]) two years after seroconversion. Of the 634 HIV seronegative women screened at 1 year of follow-up, 19 had become seropositive for HIV [yet not all of them had HIV-positive sex partners, and promiscuity seemed to be very low, as well as other risk factors]...In all of the incident cases of HIV in women, the infection was asymptomatic”
Hira SK et al. Apparent vertical transmission of human immunodeficiency virus type 1 by breast-feeding in Zambia. J Pediatr. 1990;117(3):421-4.
“The role of breast-feeding remains controversial...In our study 5 of the 6 infants (83%) who were breast-fed became infected, as compared with [25/99] 25% of those who were bottle-fed [Note that a 1992 paper by Dunn quotes follow-up data showing that the ratio of HIV+ infected babies among those breastfed dropped to 7/16]
Blanche S et al. A prospective study of infants born to women seropositive for human immunodeficiency virus type 1. N Engl J Med. 1989 Jun 22;320(25):1643-8.
“Three seronegative mothers were given HIV seropositive blood during caesarean section...The two children born to the mothers transfused at delivery were seronegative when tested at 6 and 9 months of age. Both were breastfed almost exclusively for 9 months. The child breastfed by the third mother seroconverted during breastfeeding.”
Colebunders R et al. Breastfeeding and transmission of HIV. Lancet. 1988 Dec 31;1487.
“We found no evidence that mother's clinical status at delivery, mode of delivery, or breastfeeding influenced transmission rates, but the small sample size and other confounding variables made accurate risk estimates impossible”
European Collaborative Study. Mother to child transmission of HIV infection. Lancet. 1988 Nov 5;2:1039-43.
“The third child of a previously healthy woman was delivered by caesarean section. Because of intraoperative blood loss, a blood transfusion was given after the delivery. The baby was breast-fed for 6 weeks. One unit of blood came from a male in whom the acquired immunodeficiency syndrome (AIDS) developed 13 months later. On recall, the mother proved to have lymphadenopathy, serum antibody to the AIDS virus, and a reduced T4/T8 ratio [but “is well”]. The infant, who failed to thrive and had atopic eczema from 3 months, has likewise proved to have antibody to the AIDS virus [but he later recovered, except for continuing eczema]. [Table I shows that Father, Brother and Sister were all antibody negative]
Ziegler J et al. Postnatal transmission of AIDS-associated retrovirus from mother to infant. Lancet. 1985 Apr 20;1(8434):896-897.

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