Karen
You asked about the reliability of HIV testing in
pinpointing breastfeeding as the route of
transmission. This is one of the many
difficulties in this very problematic topic. I
think we cannot rule out yet that a tiny
percentage of infection during birth may be
missed, and erroneously attributed to
breastfeeding. Even a tiny percentage of
false-negative results in the early postpartum
can translate to life or death policy decisions
for hundreds of thousands of babies in the
HIV-prevalent countries, coincidentally those
which are not able to support safe formula
feeding. I'm setting out below a few refs. I'd
be grateful for any input from the paediatrician,
or anyone on Lactnet on HIV testing of infants to
more accurately determine when transmission
occurs. I'm always looking for more
info/refs/opinions so if anyone has anything to
add, I would love to hear it, please.
1. Working definitions of early vs late infection
were developed to determine that transmission
would have occurred at birth if diagnostic tests
were negative in the first 2-7 days of life, but
became positive between 30 – 90 days of age.
Bryson YV, Luzuriaga K, Wara DW 1992, Proposed
definitions for in utero versus intrapartum
transmission of HIV-1. N Eng J Med 327:1246-1247,
Dickover RE, Dillon M Gillette SG, Deveikis A,
Keller M, Plaeger-Marshall S, Chen I, Diagne A,
Steihm ER, Bryson Y. Rapid increases in load of
human immunodeficiency virus correlate with early
disease progression and loss of CD4 cells in
vertically infected infants. J Infect Dis. 1994;170(5):1279-84,
Bagasra O 1998, Is infection with HIV-1 possible
during delivery and breastfeeding? Guest
Editorial AIDS Newsletter 13(2):1-2.)
2. Lately it seems to be generally accepted that
an infant testing negative on PCR at birth and
during the first 4-6 weeks, and testing positive
after this time has been infected during
breastfeeding. But a 2003 paper found that
sensitivity of HIV RNA testing for non-breastfed
infants was only 29% in the first week
postpartum, 79% from 8-28 days and 90% from 29
days onwards. Specificity was 100% in all periods
except at 29-60 days of age when it was
93%. Paired analysis of DNA and RNA
measurements revealed no advantage for either test.
Nesheim S, Palumbo P, Sullivan K, Lee F, Vink P,
Abrams E, Bulterys M. Quantitative RNA testing
for diagnosis of HIV-infected infants. J Acquir
Immune Defic Syndr. 2003;32(2):192-5.
3. Persistently false-negative results for
infected infants have been recorded due to
inability of tests to detect non B sub-type HIV
(ie the most common sub-type found in the US).
Obaro SK, Losikoff P, Harwell J, Pugatch D.
Failure of Serial Human Immunodeficiency Virus
Type 1 DNA Polymerase Chain Reactions to Identify
Human Immunodeficiency Virus Type 1 Clade A/G.
Ped Infect Dis J. 2005:24(2);183-184,
Kline NE, Schwarwald H, Kline MW. False negative
DNA polymerase chain reaction in an infant with
subtype C HIV-1 infection. Pediatr Infect Dis J. 2002;21:885-886,
Lyall EGH, Blott M, de Ruiter A, et al.
Guidelines for the management of HIV infection in
pregnant women and the prevention of
mother-to-child transmission. HIV Med. 2001;2:314-334,
Lyall EGH , Taylor GP, Clarke J, McLure MO.
Polymerase chain reaction diagnosis of human
immunodeficiency virus infection. Pediatr Infect
Dis J. 2003;22(3):295, O'Shea S, Mullen J, Tong
CY. Pediatric diagnosis of human immunodeficiency
virus type 1 infection: the problem of false
negative DNA polymerase chain reaction results.
Pediatr Infect Dis J. 2003;22(5):476-7,
Barlow KL, Tosswill JH, Parry JV, Clewley JP.
Performance of the Amplicor human
immunodeficiency virus type 1 PCR and analysis of
specimens with false-negative results. J Clin
Microbiol. 1997 Nov;35(11):2846-53.
4. A negative infant PCR result before 2 months
may be inconclusive due to maternal/infant zidovudine treatment.
Prasitwattanaseree S, Lallemant M, Costagliola D,
Jourdain G, Mary JY. Influence of mother and
infant zidovudine treatment duration on the age
at which HIV infection can be detected by
polymerase chain reaction in infants. Antivir Ther. 2004;9(2):179-85.
5. Different cut-off points for exclusion of
intra-partum transmission are employed for
breastfed and non-breastfed infants, eg
Non-breastfed in the US require a negative HIV
DNA PCR assay result at birth, at 4–7 weeks of
age, and at 8–16 weeks before in utero or
intrapartum HIV infection can be excluded, but in
Africa transmission may be attributed to
breastfeeding if the first positive PCR is
obtained as early as 28 days after birth.
Centers for Disease Control and Prevention.
Guidelines for national human immunodeficiency
virus case surveillance, including monitoring for
human immunodeficiency virus infection and
acquired immunodeficiency syndrome. MMWR Recomm
Rep. 1999;48(RR-13):1–27, 29–31).
Richardson BA, Mbori-Ngacha D, Lavreys L, et al.
Comparison of human immunodeficiency virus type 1
viral loads in Kenyan women, men, and infants
during primary and early infection. J Virol 2003;77: 7120–23.)
6. One other point is the matter of estimates
and assumptions. In the research setting the
timing of infection is often estimated to be the
midpoint between the last negative and the first
positive PCR result, ie it's an estimate, but you
may have to read the small print to realize
this. In the clinical setting, for reasons of
cost PCR testing is often not available and so a
single ELISA is performed to assess HIV-free
survival at 15-18 months. There may be an
assumption that an HIV-exposed baby died of AIDS,
but unless the child's HIV status is known, this
is only an assumption. He may also fall into the
"loss to follow-up" category, since his mother is
unlikely to return to the PMTCT site if her baby
has died. So one ELISA at 15 months may not
accurately reflect the cause of death for babies
who have not survived to this age - an important
consideration when evaluating whether the
intervention of formula-feeding to replace
breastfeeding is beneficial or harmful - I don't
believe this has been looked at in quite this way, yet, so no refs.
Pamela Morrison IBCLC
Co-coordinator WABA Task Force on HIV and Infant Feeding
<mailto:[log in to unmask]>[log in to unmask]
.
-----------------------------
Date: Wed, 7 Feb 2007 10:10:04 -0800
From: Karen Seroussi <[log in to unmask]>
Subject: HIV and breastfeeding- need references
I am looking for some bfing/HIV literature.
I corrected a Pediatrician speaking to my
Medical School class in regard to HIV and
breastfeeding. He is now after the references.
I recall reading an excellent review of the
flaws in the research that established that HIV
is passed by breastfeeding, including things like
early HIV testing that didn't pick up children
who were HIV positive at birth then later testing
that showed positive the assumption was made that
breastmilk passed HIV. Now I can't find
it. Does anyone recall seeing this and have the link?
Any good references would be very helpful.
Thanks! Karen
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