Final Program and Oral Abstracts [International Conference on AIDS (8th: 1992: Amsterdam, Netherlands)]

WeC 1057-WeC 1062

TRACK C: EPIDEMIOLOGY

WeC 1057 LACK OF INCREASED RISK OF HIV PERINATAL TRANSMISSION TO
SUBSEQUENT SIBLINGS BORN TO AN HIV-INFECTED MOTHER.
Perinatal AIDS Collaborative Transmission Studies Group
Centers for Disease Control, Atlanta, GA; NYC Perinatal HIV Transmission Collaborative Study,
NY, NY; UMDNJ/Newark Perinatal Study, Newark, NJ; Montefiore Perinatal Study, NY, NY;
Emory/Grady Perinatal Study, Atlanta; U Maryland Perinatal Study, Baltimore, MD; USA.
Objective: To evaluate whether the second of 2 children born to a mother with known HIV infection
is more likely to be HIV-infected (inf) than the first exposed sibling (sib).
Methods: Sibs born to HIV-inf mothers and followed in 5 prospective HIV perinatal transmission
studies in the U.S. were analyzed according to the HIV infection status of the sib relationship.
Results: Of 107 sibships identified in these 5 studies, 69 (64%) of sib pairs thus far have a known
infection outcome for both infants. The sibships' infection status is (status of first sib, followed by
status of second sib, represented as one pair):
inf-- > uninf inf-- > in uninf-- > inf uninf-- > uninf
15 (22%) 7 (10%) 14 (20%) 33 (48%)
Overall, 22/69 (32%) of first sibs and 21/69 (30%) of second sibs were infected, both consistent
with the background transmission rates in these studies. The rate of infection among second-born
sibs was 32% (7/22) when the first sib was infected, compared with 29% (14/47) when the first sib
was uninfected. These findings will be further evaluated in relation to the mother's clinical and
immunologic status, obstetrical outcome, and spacing between the sibs.
Conclusion: Contrary to our expectations, we did not find an increased risk of infection in the
second-born exposed infant, regardless of whether the first-born was infected or uninfected.
Oxtoby, Margaret J, Centers for Disease Control, MS E-45, Atlanta, GA,
30333, USA, Telephone: [phone], FAX: [phone]
WeC 1059 MATERNAL PREDICTORS OF PERINATAL HIV
TRANSMISSION. Thomas, Pauline; Heedon, Jeremy; and the New
York City Perinatal HIV Transmission Collaborative Study Group.
OBJECTIVE. To identify characteristics in pregnant HIV+ women that
predict transmission of HIV-1 to the infant.
METHODS. Data including demographics, illicit drug use, STD history, clinical HIV
illness, and CD4, immunoglobulin, and hemoglobin levels were collected on
pregnant women at risk for HIV. Babies were followed to detect HIV infection
using a modified CDC classification. Transmission rates for women with selected
characteristics were calculated on the cohort who gave birth >18 months ago.
RESULTS. Of 324 HIV+ women enrolled, 129 had babies >18 months ago with defined
outcomes: 41 infected, 88 uninfected [Transmission rate (TR)=32%]. TR for women
with (TR1) and without (TR2) selected characteristics during pregnancy are shown:
Characteristic TRI (N with) TR2 (N w/o) Dp_(Fishers exact)
CDC class B or C HIV illness 39% (33) 28% (72) 0.263
CD4<200 361 (14) 32% (86) 0.767
CD4<500 42% (53) 23% (47) 0.060
IgG>1710 (90Xile HIV- controls) 43% (56) 15% (39) 0.007
HIV ill, CD4<200, or IgG<1710 42% (69) 14% (28) 0.010
Hospitalized for pneumonia
_3 years prior to delivery 73% (15) 26% (112) 0.0005
Genital vesicles during pregnancy 75% ( 8) 28% (65) 0.013
Race, age, gravidity, prior STD history, injection and crack drug use, anemia
(Hgb<10) and detectable P24 antigen were not associated with transmission.
CONCLUSIONS. No single characteristic evaluated here predicts transmission for
all HIV+ women. Women with clinical or immunologic evidence of HIV illness
(including pneumonia) should be counseled that transmission may be increased. The
association with parturient genital vesicles warrants further investigation.
Pauline Thomas, NYC Dept. Health, Box 44, NY, NY, 10013. Tel
212-566-7723; FAX [phone].
WeC 1 061 HOMOLOGOUS AND HETEROLOGOUS NEUTRALIZATION ACTIVITY IN SERA OF
HIV-1 INFECTED MOTHERS: CORRELATION TO TRANSMISSION.
Scarlatti. Gabriella*; Albert, J.**; Rossi, P.*; Biraghi, P.***; Massironi,
E.****; FenyS, E.M.*.*Karolinska Institute, **National Bacteriological
Laboratory, Stockholm, Sweden; ***USSL75/1, ****L.Sacco Hospital,
Milan, Italy.
Objectives: The factors that protect the child from infection from their mother are still
unknown. Many attemptes have been done to find maternal markers prognostic for
transmission. We have attempted to study maternal immunological response to the virus by
neutralization assay against homologous as well as against heterologous viral isolates.
Methods: The serum of 16 mothers taken during pregnancy, at delivery or shortly after
delivery was tested against their own isolate (homologous) taken in paralell, and against the
isolate of the other mothers (heterologous). The mothers were divided into transmitting
(n=7) and non-transmitting (n=9) according to the infectious state of their child as
determined by polymerase chain reaction and virus isolation. Furthermore, the serum of 5
transmitting mothers was tested against the first virus isolated from the corresponding
child (between 0 and 3 months of age). Clinical stage, HIV-antigenemia and CD4+
lymphocyte count of the mothers were known at the time of sampling.
Results: Neutralizing titers against the homologous isolate were found in the serum of 1
transmitting and 5 non-transmitting mothers (p=0.12). Seven out of 8 non-transmitting
mothers and 1 out of 3 transmitting mothers showed titers of neutralizing activity when
tested against the heterologous isolates (p=0.14). Altogether, only 2 out of 7 transmitting-and
8 out of 9 non-transmitting mothers had neutralizing antibodies (p=0.03). None of the
mothers presented neutralizing antibodies against the isolate of their own child. In the 3
children from which follow-up sera were available no neutralizing response appeared
during a period of 3 to 6 months.
Conclusions: The presence of neutralizing antibodies in the serum of HIV infected mothers
appears to correlate with delivery of uninfected children. Our results indicate that humoral
immunity of the mother, among other factors, may play a role in preventing virus
transmission.
Scarlatti Gabriella, Department of Virology, c/o SBL,
105 21 Stockholm, Sweden.
phone: -46-8-7351000
fax: -46-8-7304407

WeC 1058 NATURAL HISTORY OF HIV INFECTION IN UGANDAN INFANTS. Hom, David*;
Guay L*; Kenya-Mugisha N**; Ball P*; Olness K*; Ndugwa C**;
Kataaha P**; Goldfarb J*. *Case Western Reserve University,
Cleveland, OH, USA. **Makerere University, Kampala, Uganda.
Obiectives: Determine the natural history and vertical transmission of HIV infection
in infants born to HIV infected women in Kampala, Uganda.
Methods: Infants of selected HIV positive and negative women were prospectively
followed in a study of HIV infection. History and physical exam were done at
regularly scheduled clinic visits where investigators were blind to HIV status.
Infant HIV serology was determined at 12 and 18 mos. with western blot confirmation.
Results: Of 565 infants actively followed, 470 would now be 18 mos. old, with 335
born to positive and 130 to negative mothers. Of 73 deaths, 68 were infants born
to positive (20.2%), and 5 to negative mothers (3.8%, p<.0001). Mean age at death
was 7.8~4.8 mos. for both groups. Of 68 infant deaths to positive mothers, twothirds had either AIDS by WHO or CDC criteria (25%), or symptoms suggestive of HIV
infection (43%) at death. Six infants (9%) died with no symptoms of HIV infection.
Failure to thrive (58% vs. 12%), generalized lymphadenopathy (58% vs. 26%) and
splenomegaly (35% vs. 13%) were the best (p<.0001) predictors for mortality among
infants born to HIV positive mothers. Of the remaining 267 infants born to positive
mothers alive at 18 months, 37 were HIV infected (13.8%, 95%CI: 9.7-17.9%). This
rate is higher when adjusted for deaths (47) attributed to or suggestive of HIV
infection (26.7%, 95%CI: 21.8-31.6%). Several major factors were significantly
associated with HIV infection. These included prolonged diarrhea, hepatomegaly,
developmental delay, parotitis, skin infections, generalized lymphadenopathy and
failure to thrive. By 18 mos., 53% had AIDS, 37% had symptoms of HIV infection,
and 10% had no symptoms. No factors differentiated the 230 uninfected infants born
to infected mothers from the 130 infants born to uninfected mothers.
conclusions: Vertical transmission in this breastfed cohort ranges from 14 to 27
percent. Uninfected infants born to HIV positive mothers could not be distinguished
clinically from the uninfected infants born to HIV negative mothers. Ninety percent
of HIV infected infants were symptomatic by age 18 months.
Hom, David, Epidemiology, School of Medicine, Case Western
Reserve University. 10900 Euclid Ave., Cleveland, OH, 44106,USA.
[phone]; FAX: [phone].
WeC 1060 PERINATAL TRANSMISSION OF HIV-1: LACK OF
DETECTABLE VIRUS IN PERIPHERAL BLOOD CELLS AT BIRTH,AND PROGNOSTIC
VALUES OF POLYMERASE CHAIN REACTION RESULTS IN INFANTS.De Rossi A.,
Ometto L.,Mammano F.,Zanotto C.,Giaquinto C.*,Chieco-Bianchi L.
Inst of Oncology,*Dept of Pediatrics,University of Padova,Italy
Objective. To assess early diagnosis of perinatal HIV-1 infection, and define
prognostic markers for AIDS onset.
Methods. Virus culture was performed by culturing patient peripheral blood
mononuclear cells (PBMC) with normal PHA-stimulated PBMC. HIV-1 copy number was
determined by direct Polymerase chain reaction (PCR) in lysed patient cells using
env and LTR HIV-1 specific primers. Amplified products were quantified by
densitometer analysis, and copy number was estimated on a reference curve obtained
with 8E51 cells containing 1 provirus/cell.
Results. 46 children born to HIV-1 seropositive mothers were studied since birth;
none was breast-fed. Only 1 out of 24 newborns tested within 48 hours of delivery
(group A) and 2 out of 22 infants tested from 3-15 days of life (group B) were
found to be HIV-1 positive in both PCR and virus culture. Re-testing at 1 month of
age identified additional 8 infected children (6 and 2 in group A and B,
respectively). Quantitative PCR analysis in 1-3 month old infected infants showed
that HIV-1 proviral copy number ranged from 10 ->750/105 PBMC; high number of
HIV-1 copies correlated with onset of AIDS within first year of life.
Conclusions. HIV-1 diagnosis cannot be achieved at birth in most infected
children, which suggests that mother-to-child transmission occurs late in
pregnancy and/or during delivery. Quantitative PCR results in 1-3 month old
infants may be useful to identify the early progressors to AIDS.
De Rossi Anita. Institute of Oncology - Via Gattamelata, 64 - 35128
Padova, Italy (Tel.: [phone]) (FAX: [phone])
WeC 1062 High risk of HIV-1 infection for first-born twin: the role of intra-partum
transmission
Anne Marie Duliege. MD*, S. Felton" and J.J. Goedert, MD***; and the
International Registry of HIV-exposed twins Genentech, So. San Francisco, CA;
** RTI, Washington DC; "* Viral Epidemiology Section NCI, Rockville, MD
Objectives: To update our previous report on twins (Lancet 1991;338:1471), with
emphasis on genetic and intrapartum factors.
Method: 50 investigators in 11 countries contributed demographic, clinical and epidemiological
retrospective data on 147 sets of twins and 2 sets of triplets. Data were analyzed by McNemar's test
for the match twin pairs, Kaplan-Meier survival curves, and Logrank test.
Results: In the 92 sets that could be assessed for HIV-infection, neither twin was infected in 49
(53%) sets, both were infected in 13 (14%), only the 1st-born in 23 (25%), and only the 2ndborn in 7 (8%). By mode of delivery:
I Vaginal delivery C-section Total
1st-born twin 20/46 (43%) 13/37 (35%) 36/92 (39%) p=.006
16/19 (84%) of the monozygotic sets were concordant for HIV status, as compared to 40/64 (62%)
of the dizygotic sets. When both twins were infected, CDC stage was discordant in only 2/13 sets, both
of which were dizygotic. AIDS-free survival rates were similar for the 36 1st-born twins (45%~
10%) and for the 20 2nd-born twins (35% ~ 13%); so was their median age at onset of AIDS: 43
months and 34 months respectively, p=.97.
Conclusion: 1) Twins Registry data continue to show lower concordance for HIV status among dizygotic
than monozygotic twins, and a higher risk of HIV-infection for 1st-born than for 2nd-born twins,
apparently by proximity to the birth canal. Possibly beneficial non-invasive procedures ("cleansing
the birth canal", suctioning the mouth and the nose) should be evaluated. 2) The progression of HIV
disease is similar in 1st-born and 2nd-born twins.
Anne-Marie Duliege, M.D., 460 Pt. San Bruno Blvd.,
So. San Francisco, CA 94080, 415-266-1367, 415-266-3957 (FAX)

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