Group Title: BMC Infectious Diseases
Title: Characteristics and management of HIV-1-infected pregnant women enrolled in a randomised trial: differences between Europe and the USA
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Title: Characteristics and management of HIV-1-infected pregnant women enrolled in a randomised trial: differences between Europe and the USA
Physical Description: Book
Language: English
Creator: Newell, Marie-Louise
Huang, Sharon
Fiore, Simona
Thorne, Claire
Mandelbrot, Laurent
Sullivan, John
Maupin, Robert
Delke, Isaac
Watts, D. H.
Gelber, Richard
Cunningham, Coleen
PACTG 316 Study Team
Publisher: BMC Infectious Diseases
Publication Date: 2007
 Notes
Abstract: BACKGROUND:Rates of mother-to-child transmission of HIV-1 (MTCT) have historically been lower in European than in American cohort studies, possibly due to differences in population characteristics. The Pediatric AIDS Clinical Trials Group Protocol (PACTG) 316 trial evaluated the effectiveness of the addition of intrapartum/neonatal nevirapine in reducing MTCT in women already receiving antiretroviral prophylaxis. Participation of large numbers of pregnant HIV-infected women from the US and Western Europe enrolling in the same clinical trial provided the opportunity to identify and explore differences in their characteristics and in the use of non-study interventions to reduce MTCT.METHODS:In this secondary analysis, 1350 women were categorized according to enrollment in centres in the USA (n = 978) or in Europe (n = 372). Factors associated with receipt of highly active antiretroviral therapy and with elective caesarean delivery were identified with logistic regression.RESULTS:In Europe, women enrolled were more likely to be white and those of black race were mainly born in Sub-Saharan Africa. Women in the US were younger and more likely to have previous pregnancies and miscarriages and a history of sexually transmitted infections.More than 90% of women did not report symptoms of their HIV infection; however, more women from the US had symptoms (8%), compared to women from Europe (4%). Women in the US were less likely to have HIV RNA levels <400 copies/ml at delivery than women enrolling in Europe, and more likely to receive highly active antiretroviral therapy, and to start therapy earlier in pregnancy. The elective caesarean delivery rate in Europe was 61%, significantly higher than that in the US (22%). Overall, 1.48% of infants were infected and there was no significant difference in the rate of transmission between Europe and the US despite the different approaches to treatment and delivery.CONCLUSION:These findings confirm that there are important historical differences between the HIV-infected pregnant populations in Western Europe and the USA, both in terms of the characteristics of the women and their obstetric and therapeutic management. Although highly active antiretroviral therapy predominates in pregnancy in both settings now, population differences are likely to remain.TRIAL REGISTRATION:NCT00000869
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Research article

Characteristics and management of HIV- I-infected pregnant
women enrolled in a randomised trial: differences between Europe
and the USA
Marie-Louise Newell* 1, Sharon Huang2, Simona Fiore', Claire Thorne1,
Laurent Mandelbrot3, John L Sullivan4, Robert Maupin5, Isaac Delke6, D
Heather Watts7, Richard D Gelber2, Coleen K Cunningham8 for the PACTG
316 Study Team


Address: 'Centre of Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, UK, 2Centre for Biostatistics
in AIDS Research, Harvard School of Public Health, Boston, USA, 3Service de Gynecologie-Obstetrique, APHP Hopital Louis Mourier, F-75701
Colombes, Universite Diderot, Paris 7, and Inserm, U822, IFR69, F-94276, France, 4Department of Pediatrics and Molecular Medicine, University
of Massachusetts Medical School, Worcester, USA, 5Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center,
New Orleans, USA, 6Department of Obstetrics and Gynecology, University of Florida College of Medicine, Jacksonville, USA, 7Pediatric,
Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, Bethesda, USA and SDepartment of
Pediatrics, Duke University Medical Center, Durham, USA
Email: Marie-Louise Newell* m.newell@ich.ucl.ac.uk; Sharon Huang sharon@sdac.harvard.edu; Simona Fiore s.fiore@ich.ucl.ac.uk;
Claire Thorne c.thome@ich.ucl.ac.uk; Laurent Mandelbrot laurent.mandelbrot@lmr.aphp.fr;
John L Sullivan john.sullivan@umassmed.edu; Robert Maupin rmaupi@lsuhsc.edu; Isaac Delke isaac.delke@jax.ufl.edu; D
Heather Watts wattsh@exchange.nih.gov; Richard D Gelber gelber@jimmy.harvard.edu;
Coleen K Cunningham coleen.cunningham@duke.edu
* Corresponding author


Published: 20 June 2007
BMC Infectious Diseases 2007, 7:60 doi:10.1 186/1471-2334-7-60


Received: 18 July 2006
Accepted: 20 June 2007


This article is available from: http://www.biomedcentral.com/1471-2334/7/60
2007 Newell et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Abstract
Background: Rates of mother-to-child transmission of HIV-1 (MTCT) have historically been
lower in European than in American cohort studies, possibly due to differences in population
characteristics. The Pediatric AIDS Clinical Trials Group Protocol (PACTG) 316 trial evaluated the
effectiveness of the addition of intrapartum/neonatal nevirapine in reducing MTCT in women
already receiving antiretroviral prophylaxis. Participation of large numbers of pregnant HIV-infected
women from the US and Western Europe enrolling in the same clinical trial provided the
opportunity to identify and explore differences in their characteristics and in the use of non-study
interventions to reduce MTCT.
Methods: In this secondary analysis, 1350 women were categorized according to enrollment in
centres in the USA (n = 978) or in Europe (n = 372). Factors associated with receipt of highly active
antiretroviral therapy and with elective caesarean delivery were identified with logistic regression.
Results: In Europe, women enrolled were more likely to be white and those of black race were
mainly born in Sub-Saharan Africa. Women in the US were younger and more likely to have
previous pregnancies and miscarriages and a history of sexually transmitted infections.
More than 90% of women did not report symptoms of their HIV infection; however, more women
from the US had symptoms (8%), compared to women from Europe (4%). Women in the US were


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less likely to have HIV RNA levels <400 copies/ml at delivery than women enrolling in Europe, and
more likely to receive highly active antiretroviral therapy, and to start therapy earlier in pregnancy.
The elective caesarean delivery rate in Europe was 61%, significantly higher than that in the US
(22%). Overall, 1.48% of infants were infected and there was no significant difference in the rate of
transmission between Europe and the US despite the different approaches to treatment and
delivery.
Conclusion: These findings confirm that there are important historical differences between the
HIV-infected pregnant populations in Western Europe and the USA, both in terms of the
characteristics of the women and their obstetric and therapeutic management. Although highly
active antiretroviral therapy predominates in pregnancy in both settings now, population
differences are likely to remain.
Trial registration: NCT00000869


Background
Rates of mother-to-child transmission of HIV-1 (MTCT)
have historically been lower in European than in Ameri-
can cohort studies [1-8]. It has been suggested that this
was likely to be related to differences in population char-
acteristics [9,10]. Although in the 1980s and early 1990s
the HIV epidemic among pregnant women in Europe was
mainly associated with injecting drug use (IDU) [11,12],
since the mid-1990s there has been a shift towards heter-
osexually-acquired HIV, largely in women of sub-Saharan
origin [12,13]. Generally, health care services and in par-
ticular antenatal care is readily available to these popula-
tions in Western Europe. In the USA, there has been a
similar trend, with heterosexual acquisition overtaking
IDU as the main transmission category among women
with AIDS in 1995 [14]; in 2004, 78% of HIV infections
among women were due to heterosexual contact, 20% to
IDU and 2% to other routes [14]. Differences in health
care provision and standards of care may have led to dif-
ferences between these two geographical regions in the
availability and uptake of various interventions available
for HIV infected pregnant women [15-19].

The PACTG 316 trial was a placebo-controlled ran-
domised trial to evaluate the additional value of single
dose nevirapine (sdNVP) at delivery in reducing MTCT in
women already receiving antiretroviral prophylaxis [20].
The trial was initiated in the USA in 1997 and extended
through collaboration with two large ongoing European
perinatal cohort studies, the French Perinatal Cohort
Study (ANRS 083) and the European Collaborative Study
[21]. The trial was stopped prematurely in June 2000 after
the results of a planned interim analysis indicated a lower
than anticipated overall MTCT rate (1.5%), without a sig-
nificant difference between the sdNVP and the placebo
arms [20].

We here take the opportunity to identify and explore dif-
ferences in the characteristics of HIV infected pregnant


women enrolling in the trial, and in the use of interven-
tions to reduce MTCT between Europe and USA, in partic-
ular, the use of highly active antiretroviral therapy
(HAART) and elective caesarean delivery.

Methods
The PACTG 316 trial was initiated in the United States
(including Puerto Rico) in May, 1997. Between May 1997
and June 2000, centres collaborating in France, Italy,
Spain, Sweden, UK, Belgium, Germany, Switzerland, Hol-
land, Denmark, Bahamas and Brazil were invited to join
the PACTG 316 trial. The methods of this randomized,
blinded trial have been fully described elsewhere [20]. In
brief, HIV-infected pregnant women were initially
enrolled in the trial after 28 weeks of gestation (later
reduced to 20 weeks), with written informed consent.
They were randomised to receive either oral nevirapine
(200 mg at onset of labour) or placebo; their infants
received the same study drug (infant 2 mg/kg oral nevirap-
ine or placebo) 48-72 hours after birth. All clinicians were
encouraged to offer all HIV-infected pregnant women at
least a regimen of prophylactic zidovudine monotherapy
in line with the ACTG 076 protocol [22]. Women were
allowed to receive any combination of licensed antiretro-
viral drugs in pregnancy as prescribed by their clinician,
with the exception of non-nucleoside reverse transcriptase
inhibitors.

In all participating centres, HIV-infected women were sys-
tematically identified during pregnancy, according to
local practice. At enrolment, baseline information includ-
ing socio-demographic characteristics, obstetric history,
history of and current use of antiretroviral therapy (ART),
results from screening for sexually transmitted infections
(STI) (gonorrhea, chlamydia, human papilloma virus,
herpes simplex, syphilis and trichomonas vaginalis) and
clinical history were collected using standardized forms.
Clinical and laboratory evaluations, including CD4 lym-
phocyte count and HIV RNA quantification were carried


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out at enrolment, delivery and post-partum. CD4 counts
and viral load measurements were carried out locally in
laboratories which were certified by ACTG or other
regional quality assurance programme. Infants had clini-
cal and laboratory information collected at birth, and sub-
sequently according to the protocol.

Definitions
In this analysis, we compared all mother-child pairs
enrolled in the European centres participating in the trial
with those enrolled in the sites in the USA and Puerto
Rico. Mode of acquisition of HIV infection was assessed
on the basis of self-report; no illicit drug screening was
carried out. Gestational age was estimated with ultra-
sound performed at less than 20 weeks gestation or use of
date of last menstrual period that corresponded with uter-
ine size. Caesarean deliveries taking place before the onset
of labour and before rupture of membranes were classi-
fied as elective caesarean deliveries, with all other caesar-
ean deliveries classified as emergency procedures
regardless of indication. Low birth weight was defined as
birth weight <2500 g. Classification of type of antenatal
ART was on the basis of the most potent therapy received.
ART was classified as monotherapy if a single nucleoside
was administered at a time, as dual therapy if any two
nucleosides were administered and as HAART if a protease
inhibitor plus two other drugs (excluding NNRTIs as this
was an exclusion criteria for the trial) were administered.
Undetectable viral load was defined as having HIV RNA
levels below 400 copies/ml. Symptomatic HIV disease was
defined as being in the Centers for Disease Control (CDC)
disease category B and C.

Statistical analysis
For univariate comparisons among women between
Europe and USA, two-sided tests were performed using Z2
test or Fisher exact tests for discrete outcomes, and Wil-
coxon test for continuous outcomes. For the multivariate
comparisons, logistic regression analysis was used to
obtain odds ratios (OR), adjusted odds ratios (AOR) and
95% confidence intervals (95% CI). Statistical software
SAS (SAS Institute, Cary, North Carolina, USA) was used
for the statistical analysis.

Results
A total of 1350 women enrolled in the trial had delivered
by the time the trial was stopped, 978 (72%) from the
USA and 372 (28%) from Europe. Table 1 presents socio-
demographic and most likely mode of acquisition of HIV
infection by continent. There was a significantly higher
proportion of white women in the European centres than
in the USA. Nearly half of the women from European cen-
tres were black; most had been born in sub-Saharan
Africa. As Table 1 shows, there were significant differences
between the two populations with regard to history of


reproductive health, with women in the USA having a
higher prevalence of previous miscarriages (28% versus
13%) and higher parity compared to those in Europe,
who had a higher prevalence of history of pregnancy ter-
mination (48% versus 27% in the USA). Substantially and
significantly fewer women enrolling in Europe had a his-
tory of STI compared with those in the USA.

In terms of HIV-related characteristics, although there
were no significant differences between continents with
regard to immunological status at study entry and at deliv-
ery, women from the USA were more likely to have symp-
tomatic HIV disease (Table 2). Very similar proportions in
the two settings had HIV RNA levels below 400 copies/ml
at study entry; however, by the time of delivery there was
a significant difference between geographic areas, with
fewer women in the US having HIV RNA below 400 cop-
ies/ml and an overall higher median in the US versus
Europe. In a sub-analysis of the 259 women from Euro-
pean and the 539 women from USA sites who had been
diagnosed with HIV infection prior to their current preg-
nancy, almost identical proportions (182/259, 70% and
357/539, 66%) were already receiving ART at enrolment.
Among the 606 women in the USA who started ART in
pregnancy, the median gestational age at initiation was 18
weeks (range, 14-25 weeks), substantially earlier than the
median of 27 weeks (range 18-32) among the 190
women in Europe starting therapy antenatally.

Median gestational age at delivery was 38.4 weeks (37.3-
39.6) and 38.1 weeks (37.1-39.0), and median birth
weight was 3077 g and 3020 g in the USA and Europe,
respectively. The prevalence of low birth weight was simi-
lar in both continents, at 12% in the US (n = 122) and
14% in Europe (n = 54). Mode of delivery varied signifi-
cantly by geographic area (p < 0.0001). In the USA, the
elective caesarean delivery rate was 22% (n = 212), the
emergency caesarean delivery rate was 17% (n = 169) and
the vaginal delivery rate was 61% (n = 597); respective
rates in Europe were 61% (n = 228), 18% (n = 65) and
21% (n= 79).

Subsequent analyses focused on geographic differences in
the use of HAART in pregnancy and of elective caesarean
delivery. Table 3 presents the results of univariable and
multivariable logistic regression analyses to identify fac-
tors associated with likelihood of receiving HAART in
pregnancy. Univariably, geographic area, low CD4 count
and undetectable viral load at entry and at delivery were
associated with receipt of HAART. In analyses adjusting
for ethnicity, mode of delivery and immunological and
virological status, women from the USA were nearly twice
as likely to receive HAART as women from Europe, whilst
those with CD4 counts > 400 cells/ml and detectable viral
load at trial entry were significantly less likely to receive


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Table I: Characteristics of HIV-infected pregnant women in PACTG 316, USA versus Europe


Characteristics


Total mothers delivered
Median age: entry (IQR)
Ethnicity
White
Black
Hispanic
Other
Parity
0-1
2-3
4-5
>6
Previous miscarriages
0
1-2
3-6
Previous terminations
0
1-2
3-4
5-12
Timing of HIV diagnosis
Pre-pregnancy
Antenatal
Mode of acquisition#
Sexual with HIV at risk
Sexual with HIV positive
Sexual with HIV unknown
Current IDU
Previous IDU
Blood transfusion
Occupational risk
Other risk factor
Unknown risk factor
STD history
Yes
No
Unknown


# Some women reported multiple risk factors
* for the difference USA versus Europe


HAART in pregnancy. Stratified analyses for the two geo-
graphic areas identified the same risk factors, with odds
ratios of similar magnitudes.

In addition to use of antiretroviral drugs in pregnancy and
avoidance of breastfeeding, elective caesarean delivery is
the other key PMTCT intervention. Further logistic regres-
sions were therefore carried out for likelihood of having
an elective caesarean versus other delivery modes (emer-
gency caesarean or vaginal delivery) (Table 4). Delivery in
centres in the USA was associated with an adjusted 82%
reduced odds of elective caesarean delivery compared
with delivery in Europe. Black women were 33% less
likely to deliver by elective caesarean than white women,


and those receiving two or more antiretroviral drugs ante-
natally were less likely to have an elective caesarean deliv-
ery compared with women receiving monotherapy or no
ART (Table 4). As there were distinct differences between
the continents regarding many of these explanatory varia-
bles (Tables 1 and 2), stratified analyses were carried out
for each geographic area separately. Among the women
from the USA, none of the explanatory variables in Table
3 were associated with elective caesarean delivery univari-
ably [data not shown]. In Europe, black versus white eth-
nicity was associated with a reduced likelihood of elective
caesarean, with borderline significance (AOR 0.65, 95%
CI 0.42-0.99, p = 0.048), and dual therapy and HAART
with around a two-thirds reduced likelihood of elective



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USA


978
27.2 (22.9-31.8)

119 (12%)
621 (64%)
223 (23%)
15 (1.5%)

161 (17%)
399 (41%)
267 (27%)
151 (15%)

707 (72%)
247 (25%)
24 (2.5%)

710 (73%)
220 (22%)
41 (4%)
7(1%)

539 (55%)
439 (45%)

336 (34%)
214 (22%)
716 (73%)
12 (1%)
68 (7%)
20 (2%)
22 (2%)
44 (4%)
47 (5%)

280 (29%)
450 (46%)
248 (25%)


Europe


372
30 (26.9-34)

190 (51%)
172 (46%)
8 (2%)
2 (0.5%)

80 (22%)
168 (45%)
97 (26%)
27 (7%)

325 (87%)
44 (12%)
3 (1%)

192 (52%)
149 (40%)
28 (7%)
3 (1%)

259 (70%)
1 12(30%)

44(12%)
105 (28%)
162 (44%)
11 (3%)
35 (9%)
7 (2%)
3 (1%)
8 (2%)
46(12%)

19(5%)
353 (95%)
0 (0)


Total


1350
28.1 (23.9-32.4)

309 (23%)
793 (59%)
231 (17%)
17(1%)

241 (18%)
567 (42%)
364 (27%)
178 (13%)

1032 (76%)
291 (22%)
27 (2%)

902 (67%)
369 (27%)
69 (5%)
10 (1%)

798 (59%)
551 (41%)

380 (28%)
319 (24%)
878 (65%)
23 (2%)
103 (8%)
27 (2%)
25 (2%)
52 (4%)
93 (7%)

299 (22%)
803 (60%)
248 (18%)


p-value*


<0.000 I
<0.000 I





0.0001





<0.0001



<0.0001





<0.0001



<0.0001
0.0623
<0.0001
0.0331
0.1340
0.9999
0.1108
<0.000 I1
0.0401
<0.0001


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Table 2: Characteristics of HIV infected pregnant women, USA versus Europe: disease progression and treatment


Characteristic


Median CD4 count: entry (IQR)
<200 cells per ml
200-499
>500
Median HIV RNA: entry (IQR)
<400 copies/ml
400-2,499
2,500-10,000
> 10,000
Median CD4 count: delivery (IQR)
<200 cells/ml
200-499
>500
Median HIV RNA: delivery (IQR)
<400 copies/ml
400-2,499
2,500-10,000
> 10,000
Maternal ARV use
HAART
Dual therapy
Monotherapy
No ARV
Timing of ARV initiation
Pre-pregnancy
During pregnancy
Symptomatic HIV disease at entry
Yes
No


caesarean versus no therapy or monotherapy (AORs 0.35
[0.21-0.60] p < 0.0001; 0.41 [0.24-0.72] p = 0.0015
respectively).

The primary outcome measure of the PACTG 316 trial was
detection of HIV infection in the infants. Overall there was
avery low rate of MTCT at 1.48% [95% CI 0.91-2.28] (20
vertical transmissions; USA 1.64% [95% CI 0.94-2.64]
and Europe 1.08% [0.29-2.73]).

Discussion
There were distinct differences between the HIV-infected
pregnant women enrolling in the PACTG 316 trial in the
USA (accounting for nearly three-quarters of the total
mother-child pairs in the trial) compared with the Euro-
pean centres. Black women of African-American ethnicity
predominated in the US setting, with a further quarter of
the women enrolling of Hispanic ethnicity, and only 12%0
being non-Hispanic white. Those recruited in Europe were
almost equally divided between white European and non-
white women, the vast majority of whom were of African
origin who had arrived in Europe as asylum-seekers, refu-
gees or migrants. These ethnic patterns are consistent with
what is known about the epidemiology of HIV infection
in pregnancy in the USA and in Europe [13,16,231.


Substantially more women from the European sites had
been diagnosed with HIV prior to their current pregnancy
than in the USA. Today, most identified HIV-infected
women of child-bearing age are most likely diagnosed
either as a result of antenatal testing or through more tar-
geted testing of specific risk groups, such as injecting drug
users or attenders of STD clinics. Parity was somewhat
higher among the US women. Although there was a signif-
icantly higher prevalence of active IDU in Europe, this was
only 3% in this setting. On the basis of these findings, the
lower ascertainment of infection status among the US
women before entry may reflect poorer access to or uptake
of antenatal HIV testing in prior pregnancies or of HIV
testing outside antenatal care, or alternatively, the possi-
bility that the women from the USA acquired their HIV
infection more recently (i.e. since a previous pregnancy),
which is consistent with their younger age compared with
the women from European sites, and their somewhat
higher CD4 count at entry.

In terms of reproductive health, the HIV-infected women
in the USA had a significantly higher prevalence of previ-
ous miscarriages than in Europe, double that in Europe,
which may reflect a variety of factors including possible
geographic/cultural differences with regard to reporting

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USA


437 (293-600)
124 (13%)
294 (30%)
560 (57%)
581 (274-3635)
424 (43%)
252 (26%)
143 (15%)
138 (14%)
480 (308-658)
103 (12%)
233 (27%)
531 (61%)
405 (237-2638)
450 (50%)
220 (24%)
115 (13%)
116(13%)

448 (46%)
342 (35%)
182 (19%)
6 (0.6%)

357 (37%)
606 (63%)

74 (8%)
904 (92%)


Europe


420 (299-568)
37(10%)
132 (35%)
203 (55%)
700 (200-4740)
142 (38%)
92 (24%)
62(17%)
57(15%)
444 (320-632)
26 (8%)
109 (34%)
187(58%)
200 (68-1300)
176 (64%)
49(18%)
36(14%)
16(6%)

119(32%)
132 (35%)
119(32%)
2 (0.5%)

182 (49%)
190 (51%)

15 (4%)
357 (96%)


Overall


430 (294-592)
161 (12%)
426 (32%)
763 (57%)
594 (243-3845)
566 (42%)
344 (25%)
205 (15%)
195 (14%)
469 (310-653)
129 (I 1%)
342 (29%)
718 (60%)
400 (200-2300)
626 (53%)
269 (23%)
151 (13%)
132 (11%)

567 (42%)
474 (35%)
301 (22%)
8 (0.6%)

539 (40%)
796 (60%)


P-value

0.6958



0.1225




0.6849



0.0001




<0.000 I




0.0001


0.0194


89 (7%)
1261 (93%)


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Table 3: Factors associated with antenatal HAART use


N (%)


Ethnicity
White
Black
Other
Geographic area
Europe
USA
Mode of delivery
Vaginal delivery or non-elective caesarean
Elective caesarean
CD4 count (entry)
< 400 cells per ml
>400 cells per ml
CD4 count (delivery)
< 400 cells per ml
>400 cells per ml
Viral load (entry)
Undetectable
Detectable
Viral load (delivery)
Undetectable
Detectable


309 (23)
793 (59)
248 (18)

372 (28)
978 (72)

910 (67)
440 (33)

586 (43)
764 (57)

543 (40)
807 (60)

570 (44)
740 (56)

626 (53)
555 (47)


OR (95% Cl)



1.0
1.06 (0.82, 1.39)
1.15 (0.82, 1.62)

1.0
1.79 (1.39, 2.30)

1.0
0.80 (0.64, 1.01)

1.0
0.43 (0.35, 0.54)

1.0
0.49 (0.40, 0.62)

1.00
0.58 (0.46, 0.72)

1.0
0.79 (0.62, 0.99)


AOR (95% Cl)



1.0
0.84 (0.62, 1.13)
0.96 (0.66, 1.39)

1.0
1.82 (1.40, 2.38)

1.0
0.99 (0.76, 1.28)

1.0
0.36 (0.28, 0.46)

1.0
0.76 (0.56, 1.03)

1.0
0.48 (0.38, 0.61)

1.0
0.97 (0.71, 1.31)


p-value




0.2470
0.8374


<0.000 I1


0.9366


<0.000 I


0.0757


<0.000 I


0.8197


Table 4: Factors associated with likelihood of delivery by elective caesarean


N (%)


Ethnicity
White
Black
Other
Geographic area
Europe
USA
Antenatal ART
None/monotherapy
Dual therapy
HAART
CD4 count (entry)
< 400 cells per ml
>400 cells per ml
CD4 count (delivery)
< 400 cells per ml
>400 cells per ml
Viral load (entry)
Undetectable
Detectable
Viral load (delivery)
Undetectable
Detectable


309 (23)
793 (59)
248 (18)

372 (28)
978 (72)

309 (23)
474 (35)
567 (42)

586 (43)
764 (57)

543 (40)
807 (60)

570 (44)
740 (56)

626 (53)
555 (47)


OR (95% Cl)



1.0
0.41 (0.31, 0.53)
0.40 (0.28, 0.57)

1.0
0.18 (0.14, 0.23)

1.0
0.51 (0.38, 0.69)
0.54 (0.41, 0.72)

1.0
1.06 (0.84, 1.33)

1.0
1.04 (0.83, 1.31)

1.00
0.97 (0.77, 1.23)

1.0
0.82 (0.64, 1.05)


AOR (95% Cl)



1.0
0.67 (0.49, 0.91)
0.89 (0.60, 1.32)

1.0
0.18 (0.14, 0.24)

1.0
0.57 (0.41, 0.78)
0.70 (0.52, 0.96)

1.0
1.08 (0.84, 1.39)

1.0
1.10 (0.86, 1.42)

1.0
0.83 (0.65, 1.07)

1.0
0.90 (0.69, 1.17)


p-value




0.0107
0.5490


0.0001


0.0006
0.0263


0.5371


0.4486


0.1571


0.4308


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prior miscarriage as this was a self-reported variable.
Although the women recruited in the US were younger
than those enrolled in Europe, they had a higher parity
than their European counterparts, whilst women from
Europe had a significantly higher pregnancy termination
rate; these findings may not only reflect cultural differ-
ences, but also access to reproductive care services [24].

The PACTG 316 trial spanned an important and dynamic
era with regard to use of ART in pregnancy, both for
maternal health and for preventing MTCT. Our findings
reflect regional differences in use of combination ART,
with more rapid uptake in the USA than in Europe
[19,25,26]. In the Women and Infants Transmission
Study, based in the USA and Puerto Rico, half of the preg-
nant women enrolled by 1998 were receiving HAART,
increasing to more than 60% in 1999-2000 [27]. In
Europe, although there was a steadily increasing uptake of
combination therapy in pregnancy, in the absence of a
randomised trial to show the efficacy of HAART in preven-
tion of MTCT, some clinicians showed caution regarding
prescribing HAART for women without symptomatic HIV
disease, preferring to continue using the combination of
zidovudine monotherapy according to the 076 regimen,
elective caesarean delivery and avoidance of breastfeeding
[28-311.

These parallel situations are apparent in the geographic
differences seen here, with significantly more HAART use
in the USA versus more monotherapy use in Europe.
However, these differences are largely historical, and
HAART now predominates in the treatment of pregnant
women in Europe [32,33]. A fifth of women in Europe
received the dual combination of zidovudine and lamivu-
dine in pregnancy (data not shown); this partly reflects
ongoing research in France at the time [34]. Furthermore,
the lower prevalence of HAART use in European women
may also reflect the non-eligibility of those women on
HAART due to prior or current use of NVP-containing
HAART, which was a popular regimen in Europe at the
time [28]. Although the enrolled women from the US and
Europe had similar CD4 counts and viral loads at entry,
the US women had double the prevalence of symptomatic
disease at entry (although this was low overall in both
areas) and were less likely to have been diagnosed with
HIV infection before the current pregnancy or to already
be on ART at the time they became pregnant. Overall,
60% of women started ART for the first time in pregnancy
and antenatal ART initiation was significantly earlier in
the US than in Europe (18 weeks versus 27 weeks), prob-
ably reflecting timing of HIV diagnosis and/or manage-
ment differences. By the time of delivery, although the
two geographic groups remained immunologically simi-
lar, women from the USA were significantly less likely to
have undetectable viral loads at delivery compared with


women delivering in Europe, despite more women from
the US receiving earlier and/or more potent ART. How-
ever, MTCT rates were similar between continents. In a
previous analysis focused on women in the US sites of the
PACTG 316 trial, black women (accounting for nearly
two-thirds of the women enrolled) were significantly less
likely to achieve undetectable viral loads by delivery than
white women [35].

There was a considerably lower elective caesarean rate
among the women delivering in the USA than in Europe,
at 22% versus 61%. None of the explanatory variables
(ethnicity, ART, maternal CD4 count or viral load) pre-
dicted likelihood of elective caesarean delivery among
women from the USA. This is consistent with an individ-
ualised approach to elective caesarean delivery in this set-
ting among HIV-infected women, with those with
obstetric indications for elective caesarean most likely to
constitute the majority of the elective caesarean group
[36,371.

In Europe, guidelines current during the trial recom-
mended universal offer of elective caesarean delivery to
prevent MTCT [38-40]. However, as indicated by the sub-
analysis of European women, receipt of HAART was asso-
ciated with a significantly lower likelihood of having an
elective caesarean delivery. This reflects the growing
uncertainty from this time of the added benefit of elective
caesarean delivery for women with undetectable plasma
HIV RNA loads, and specifically concerns that the poten-
tial benefits in terms of reduced MTCT risk may be out-
weighed by the costs, such as the increased risk of post-
partum complications and greater burden on health care
services associated with elective caesarean delivery. This
lack of consensus has continued in the absence of a defin-
itive answer, with current policy and practice regarding
mode of delivery varying considerably across Europe,
although an increasing number of policies now recom-
mend offering a vaginal delivery to women on successful
HAART with undetectable viral load [41].

Concerns exist regarding the generalizability of results
from HIV clinical trials, particularly those with stringent
inclusion and exclusion criteria [42-44]. The PACTG 316
trial was designed with broad inclusion criteria, although
the exclusion criteria of previous NNRTI-use may limit the
generalizability of specific results here, as discussed above.

Conclusion
These findings confirm that there are important historical
differences between the HIV-infected pregnant popula-
tions in Western Europe and the USA, both in terms of the
characteristics of the women and their obstetric and ther-
apeutic management. Although the therapeutic manage-
ment of pregnant HIV-infected women is now more


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uniform between the continents, with the predominance
of HAART initiated from before or during pregnancy, sig-
nificant population differences are likely to remain. This
is of importance in interpreting results from previous
research and in the design of future studies.

Abbreviations
ART Antiretroviral therapy

HAART Highly active antiretroviral therapy

HIV Human immunodeficiency virus

IDU Injecting drug user

MTCT Mother-to-child transmission

PMTCT Prevention of mother-to-child transmission

RNA Ribonucleic acid

sdNVP Single dose nevirapine

Competing interests
The authors) declare that they have no competing inter-
ests.

Authors' contributions
CKC, RDG, JS and MLN contributed to study concept and
design. CKC, RDG, MLN, SF, LM, JS, RM, ID, DHW were
involved in the acquisition of data. MLN, SF and CT
drafted the manuscript. SH performed the statistical anal-
yses. All authors critically revised the manuscript for
important intellectual content. All authors read and
approved the final manuscript.

Acknowledgements
Sources of support

Supported by the Pediatric AIDS Clinical Trials Group of the National Insti-
tute of Allergy and Infectious Diseases and the Pediatric/Perinatal AIDS
Clinical Trials Group of the National Institute of Child Health and Human
Development, National Institutes of Health, the Agence Nationale de
Recherches sur le SIDA (ANRS 083) and Boehringer Ingelheim (France);
and the European Commission (QLRT-1999-30002) and the Medical
Research Council (UK). This analysis was supported by the Statistical and
Data Analysis Centerofthe AIDS Clinical Trials Group, under the National
Institute of Allergy and Infectious Diseases cooperative agreement No. UO I
A141I 110.

The PACTG 316 Study Team includes Alejandro Dorenbaum, MD, (Uni-
versity of California, San Francisco, Ca), Lynne Mofenson MD (National
Institute of Child Health and Human Development, Bethesda, Md), Mary
Culnane, MS, CRNP, (National Institute of Allergy and Infectious Disease,
Rockville, Md), Brigitte Bazin, MD (ANRS, Villejuif, France), Paula Britto, MS
and Rajalakshm Balasubramanian Sc.D (Statistical and Data Analysis Center,
Harvard School of Public Health, Boston, Mass), Yvonne Bryson, MD
(UCLA School of Medicine, Los Angeles, Calif),, Bethann Cunningham-


Schrader, MS and Kathleen A. Kaiser, AAS, COTA (Frontier Science and
Technology Research Foundation, Buffalo, NY), Scharla Estep, MS, RPh
(NIAID, Bethesda, Md), Maria Gigliotti, MS (Boehringer Ingelheim), Adolfo
Gonzalez-Garcia, MD (University of Miami), Mark Mirochnick, MD (Boston
University, Boston, Mass), Claire Rekacewicz, MD and Jean Francois Delf-
raissy, MD (ARNS, Villejuif, France), Maureen Shannon, MS, FNP (San Fran-
cisco General Hospital, San Francisco, Calif), Savita Pahwa (University of
Miami) and John L. Sullivan, MD (University of Massachusetts, Worcester,
Mass). The European Collaborative Study (ECS) includes investigators and
study sites throughout Europe (listed below). Collaborating investigators
include PACTG: Dr Beverly E. Sha and Ruth M. Davis, RN (Rush-Presbyte-
rian/St Lukes, Chicago, III), Dr Arlene D. Bardeguez and Jocelyn Grand-
champ, RN (University of Medicine and Dentistry of NJ), Lisa Melton and
Audra Deveikis (Long Beach Memorial), Dr William T. Shearer and Dr
Hunter A. Hammill (Baylor College of Medicine), Dr Ram Yogev and Donna
Stanislawski (Children's Memorial and Prentice Women's Hospital), Dr
Charles D. Mitchell and Patricia Bryan, RN (University of Miami), Dr Wil-
liam Borkowsky and Maryann Minter, RN (Bellevue Hospital), Dr Diane
Wara and Maureen Shannon, RN, MS FNP, CNM (UCSF Moffitt Hospital),
Dr Diane Wara and Dr Karen Beckerman (San Francisco General), Dr Ana
Puga and Dr Winston Bliss (Children's Diagnostic and Treatment Center),
Dr Jane Pitt and Dr Gina Brown (Columbia University), Dr Gary Kaufman
and Laureen Katz, RN (Boston Medical Center), Andrew D. Hull and
Stephen A. Spector (UCSD Medical Center), Dr Elizabeth Livingston and
Lori Ferguson, RN (Duke University), Dr Mobeen Rathore and Dr Isaac
Delke (University of Florida Health Sciences Center), Dr Wilma Lim and
Betsy Pitkin, RN (University of North Carolina at Chapel Hill), Dr Jorge
Gandia and Dr Eleanor Jimenez (San Juan City Hospital), Dr Sohail Rana and
Marilyn Dennis (Howard University Hospital), Dr Alice Stek and Dr Andrea
Kovacs (University of Southern California), Dr Elizabeth J. McFarland and
Carol Salbenblatt, RN (Children's Hospital), Dr Myron J. Levin and Dr Adri-
ana Weinberg (Denver Medical Center), Susan Laverty, RN, and Dr Geof-
frey A. Weinberg (University of Rochester), Dr Hannah Gay and Netta
Boudreaux, RN (University of Mississippi Medical Center), Dr Susanne R.
Lavoie and Tima Y. Smith, RN (Medical College of Virginia), Dr Edwin
Thorpe and Ms Nina Sublette (Regional Medical Center), Dr Dan Lancaster
and Dr Debra Terry (Methodist Hospital Central), Dr Gregory J. Wilson
and Peggy Bender, FNP (Vanderbilt University Medical Center), I. Heyer,
RN, BSN, and Dr L. Lugo (University of Puerto Rico), Harold W. Lischner,
MSN, and Kelly R. Hassey, MSN, CRNP (St Christopher's Hospital for Chil-
dren), Deb Goldman, ARNP, and Dr Jane Hitti (Children's Hospital and
Medical Center), Dr Robert Maupin and Dr Thomas Alchediak (Tulane Uni-
versity Hospital), Dr Katherine Luzuriaga and Sheila Noone, RN, PhD (Uni-
versity of Massachusetts Medical School), Dr Winston Campbell
(University of Connecticut), Gail Karas, RN, and Dr Juan C. Salazar (Con-
necticut Children's Medical Center), Dr George Wendel and Dr Janet
Squires (Children's Medical Center), Dr Theodore Jones and Dr Ellen
Moore (Children's Hospital of Michigan), Dr Jaime Deville and Maryanne
Dillon, BSN (University of California Medical Center), Dr Ruth Tuomala
(Brigham and Women's Hospital), Dr Sandra Burchett (Children's Hospi-
tal), Dr John Farley and Barbara Davis, RN, MEd (University of Maryland),
Dr Kenneth Rich and Dr Mark Vajaranant (University of Illinois), Dr Indu
Pathak and Dr Hamida Khakoo (Metropolitan Hospital Center), Dr Nancy
Wade and Dr Renee Samelson (Children's Hospital at Albany Medical
Center), Emily Barr and Dr John Nosovitch (State University of New York
Upstate Medical University), Pam Daniel and Patty Kohler, RN (University
of Cincinnati), Dr Margaret Keller and Marie Beall (Harbor University of
California Medical Center), Angela Ranzini and Marian Lake (St Peter's
Medical Center), Dr Robert Pass and Dr Marilyn Crain (University of Ala-
bama), Dr Valerie Whiteman and Dr Ellen Tidaldi (Temple University
School of Medicine), Carla Duff, RN and Dr John Sleasman (University of
Florida, Gainesville), Dr Hector Cintron and Wanda Figueroa (Ramon


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Ruiz), Dr George Johnson and Moya Clarken, RN (Medical University of
South Carolina), Dr Savita Pahwa (North Shore LIJ Research Institute), Dr
Sunanda Gaur and Patricia Whitley Williams (Robert Wood Johnson AIDS
Program), Dr Michael Hughes and Dr David Shapiro (Statistical and Data
Analysis Center, Harvard School of Public Health). European Collabora-
tive Study: Dr I. Grosch-Worner (Charite Virchow-Klinikum, Berlin, Ger-
many), Dr J. Jimenez (Hospital 12 De Octubre, Madrid, Spain); Dr A.B.
Bohlin, Dr S. Lindgren, (Huddinge and Karolinska Hospitals, Sweden), DrA.
Mur, Dr A. Paya, (Hospital del Mar, Barcelona, Spain), Dr 0. Coll, Dr C.
Fortuny (Hospital Clinic, Barcelona, Spain), Dr M. Casellas Caro (Hospital
Vail D'Hebron, Barcelona, Spain), Dr M. Leyes, Dr L. Ciria (Hospital Son
Dureta, Mallorca), Prof P. Martinelli, Dr W. Buffolano, DrM. Sansone (11
Policlinico, Naples, Italy), Dr C. Tibaldi, Dr N. Ziarati (S Anna Hospital,
Torino, Italy), Dr S. Alberico, Dr C. Salvatore (Burlo Garofolo Hospital,
Trieste, Italy), Prof M. Temmerman (University of Ghent), Dr I. Hoesli, Dr
C. Rudin (University of Basel), Dr X. Carnet, DrJ. Pich (Clinical Pharmacol-
ogy Unit, University of Barcelona), Dr M. Ravizza, Prof G. Pardi, Dr L.
Mangiarotti (San Paolo Hospital, Milan, Italy), DrV. Savasi, Dr A.E. Semprini,
Prof E. Ferrazzi (Sacco Hospital, Milan, Italy), Dr M. Sharland, Ms T. Ches-
ter, (St George's Hospital, London, UK), Dr A. Fakoya (Newham General
Hospital, London, UK), Dr G. Scaravelli (PUI, Rome, Italy), Dr W. Coro-
leou, Dr Cavalle Gelabret (H Germans Trials Ipujol, Badalona, Spain), Prof
C. Loveday (University College London, UK); France (ANRS 083 Trial
group): Scientific Committee: Annie Metro (ANRS), Marie-Jeanne Mayaux,
Stephane Blanche, Christine Rouzioux, Marc Tardieu (Enquete Pediatrique
Francaise (EPF)); Jean-Pierre Aboulker (Service Commun 10, INSERM);
Bertrand Baumelo (Boehringer Ingelheim, France); Clinicians: Veronique
Chambrin, Hassina Razafimahefa (Hopital Antoine Beclere, Clamart), Lau-
rent Mandelbrot, Guislaine Firtion (Hopital Cochin-Port Royal, Paris),
Nicole Ciraru-Vigneron, Claudine Bruner (Hopital Lariboisiere, Paris),
Alain Berrebi, Joelle Tricoire (Hopital Purpan, Toulouse), Claude Hocke,
Daniele Douard (Hopital Pellegrin, Bordeaux), Catherine Crenn-Hebert,
Corinne Floch-Tulal (Hopital Louis-Mourier, Colombes), Etienne Wilmer,
Annick Ottenvalter (Hopital Robert Debre, Paris), Marie-Aude Khuong,
Jean-Marc Retbi (Hopital Delafontaine, Saint-Denis), Vincent Jeantils, Eric
Lachassine (Hopital Jean-Verdier, Bondy), Sophie Matheron, Jean-Louis
Benifla (Hopital Bichat-Claude-Bernard, Paris), Cristianne Huraux-Rendu,
Joelle Teboul (Hopital Henri-Mondor, Creteil), Deborah Fried, Brigitte
Heller-Roussin (Hopital Intercommunal Montreuil), Brigitte Clavier, Vero-
nique Brossard (Hopital Charles Nicolle, Rouen), Andre Bongain, Fabrice
Monpoux (Hopital de I'Archet, Nice), Michel Levardon, Fabienne Mazy
(Hopital Beaujon, Clichy), Veronique Cayol, Catherine Dolfus (Hopital
Saint-Antoine-Trousseau, Paris), Paul Benos,Joelle Nicolas (Hopital Arnaud
De Villeneuve, Montpellier), Daniel Raudrant, Laurent Cotte (Hopital de
I'Hotel Dieu, Lyon), Cecile Francois, Francoise Mechinaud (Hopital de
I'Hotel-Dieu, Nantes), Rose Nguyen, Adrien May (Hopital Louise Michel,
Evry), Benedicte Mougeon, Alain Devidas (Hopital Gilles de Corbeil, Cor-
beil).

References
I. European Collaborative Study: Risk factors for mother-to-child
transmission of HIV-1. Lancet 1992, vol. 339:1007-1012.
2. Blanche S, Rouzioux C, Moscato ML, Veber F, Mayaux MJ,Jacomet C,
Tricoire J, Deville A, Vial M, Firtion G: A prospective study of
infants born to women seropositive for human immunodefi-
ciency virus type I. HIV Infection in Newborns French Col-
laborative Study Group. N EnglJ Med 1989, 320:1643-1648.
3. Landesman SH, Kalish LA, Minkoff HL, Fox HE, Zorrilla C, Garcia PM,
Fowler MG, Mofenson LM, Tuomala RE, The Women and Infants
Transmission Study: Obstetrical factors and the transmission of
human immunodeficiency virus type I from mother-to-
child. N EngJ Med 1996, 334:1617-1623.
4. Dabis F, Msellati P, Dunn DT, Lepage P, Newell ML, Perre P, Working
Group on Mother-to-Child Transmission of HIV: Estimating the
rate of mother-to-child transmission of HIV. Report of a


workshop on methodological issues, Ghent (Belgium), 1 7-20
February 1992. AIDS 1993, 7:1139-1148.
5. Nair P, Alger L, Hines S, Seiden S, Hebel R, JohnsonJP: Maternal and
neonatal characteristics associated with HIV infection in
infants of seropositive women. J Acquir Immune Defic Syndr 1993,
6:298-302.
6. Kind C, Brandle B, Wyler CA, Calame A, Rudin C, Schaad UB, Schup-
bach J, Senn HP, Perrin L, Matter L, The Swiss Neonatal HIV Study
Group: Epidemiology of vertically transmitted HIV-1 infec-
tion in Switzerland: results of a nationwide prospective
study. EurJ Pediatr 1992, 151:442-448.
7. Abrams EJ, Matheson PB, Thomas PA, Thea DM, Krasinski K, Lambert
G, Shaffer N, Bamji M, Hutson DG, Grimm K, Kaur A, Rogers MF,
New York City Perinatal HIV Transmission Collaborative Study
Group: Neonatal predictors of infection status and early
death among 332 infants at risk of HIV- I infection monitored
prospectively from birth. Pediatrics 1995, 96:451-458.
8. European Collaborative Study: The mother-to-child HIV trans-
mission epidemic in Europe: evolving in the East and estab-
lished in the West. AIDS 2006, 20:1419-1427.
9. Ryder RW, Behets F: Reasons for the wide variation in reported
rates of mother-to-child transmission of HIV-1. AIDS 1994,
8:1495-1497.
10. Cohen MH, Cook JA, Grey D, Young M, Hanau LH, Tien P, Levine
AM, Wilson TE: Medically eligible women who do not use
HAART: the importance of abuse, drug use, and race. Am J
Public Health 2004, 94:1 147-1151.
I I. Hamers FF, Batter V, Downs AM, Alix J, Cazein F, Brunet JB: The
HIV epidemic associated with injecting drug use in Europe:
geographic and time trends. AIDS 1997, 11:1365-1374.
12. European Collaborative Study: Vertical transmission of HIV-I:
maternal immune status and obstetric factors. AIDS 1996,
10:1675-1681.
13. Hamers FF, Downs AM: The changing face of the HIV epidemic
in western Europe: what are the implications for public
health policies? The Lancet 2004, 364:83-94.
14. Centers For Disease Control and Prevention: HIV/AIDS Surveil-
lance in Women. Slide Series www cdc govlhivlgraphics/women htm
2004, L264:.
15. Dominguez KL, Lindegren ML, D'Almada PJ, Peters VB, Frederick T,
Rakusan TA, Ortiz IR, Hsu HW, Melville SK, Sadek R, Fowler MG:
Increasing Trend of Cesarean Deliveries in HIV-Infected
Women in the United States From 1994 to 2000. J Acquir
Immune Defic Syndr 2003, 33:232-238.
16. Centers For Disease Control and Prevention: Enhanced Perinatal Sur-
veillance United States, 1999-2001 4th edition. Atlanta, US Depart-
ment of Health and Human Sciences; 2004:1-22.
17. Gebo KA, Fleishman JA, Conviser R, Reilly ED, Korthuis PT, Moore
RD, Hellinger J, Keiser P, Rubin HR, Crane L, Hellinger FJ, Mathews
WC, Network HIVR: Racial and gender disparities in receipt of
highly active antiretroviral therapy persist in multstate sam-
ple of HIV patients in 2001. J Acquir Immune Defic Syndr 2005,
38:96-103.
18. Palacio H, Kahn JG, Richards TA, Morin SF: Effect of race and/or
ethnicity in use of antiretrovirals and prophylaxis for oppor-
tunistic infection: a review of the literature. Public Health Rep
2002, 117:233-251.
19. European Collaborative Study: Therapeutic and other interven-
tions to reduce the risk of mother-to-child transmission of
HIV-I in Europe. BrJ Obstet Gynaecol 1998, 105:704-709.
20. Dorenbaum A, Cunningham CK, Gelber RD, Culnane M, Mofenson
LM, Britto P, Rekacewicz C, Newell ML, Delfraissy JF, Cunningham-
Schrader B, Mirochnick M, Sullivan JL, Team IPACTG: Two-dose
intrapartum/newborn nevirapine and standard antiretrovi-
ral therapy to reduce perinatal HIV transmission. A ran-
domised trial. JAMA 2002, 288:189-198.
21. Fiore S, Thorne C, Newell ML: European involvement in an
international perinatal trial. Developmental Period Medicine 2003,
7:449-458.
22. Connor EM, Sperling RS, Gelber RD, Kiselev P, Scott GB, O'Sullivan
MJ, Van Dyke R, Bey M, Shearer WT, Jacobson RL, Jimenez E, O'Neill
E, Bazin B, DelfraissyJF, Culnane M, Coombs RW, Elkins MM, Moye
JJ, Stratton P, Balsey J: Reduction of maternal-infant transmis-
sion of human immunodeficiency virus type I with zidovu-
dine treatment. N EngJ Med 1994, 331:1173-1180.




Page 9 of 10
(page number not for citation purposes)


BMC Infectious Diseases 2007, 7:60








http://www.biomedcentral.com/1471-2334/7/60


23. Hamers FF, Infuso A, Alix J, Downs AM: Current situation and
regional perspective on HIV/AIDS surveillance in Europe. j
Acquir Immune Defic Syndr 2003, 32:S39-S48.
24. Mosher WD, Bachrach CA: Understanding U.S. fertility: conti-
nuity and change in the National Survey of Family Growth,
1988-1995. Fam Plann Perspect 1996, 28:4-12.
25. The CAESAR Coordinating Committee: Randomised trial of addi-
tion of lamivudine or lamivudine plus loviride to zidovudine-
containing regimens for patients with HIV-1 infection: the
CAESAR trial. Lancet 1997, 349:1413-1421.
26. Carpenter CCJ, Fischl MA, Hammer SM, Hirsch MS, Jacobsen DM,
Katzenstein DA, MontanerJSG, Richman DD, Saag MS, Schooley RT,
Thompson MA, Vella S, Volberding PA: Antiretroviral therapy for
HIV infection in 1997: updated recommendations of the
International AIDS Society-USA panel. JAMA 1997,
277:1962-1969.
27. Cooper ER, Charurat M, Mofenson LM, Hanson IC, Pitt J, Diaz C,
Hayani K, Handelsman E, Smeriglio V, Hoff R, Blattner WA: Combi-
nation antiretroviral strategies for the treatment of preg-
nant HIV-1-infected women and prevention of perinatal
HIV-1 transmission. j Acquir Immune Defic Syndr 2002, 29:484-494.
28. European Collaborative Study: HIV-infected pregnant women
and vertical transmission in Europe since 1986. AIDS 2001,
15:761-770.
29. Mandelbrot L, Le Chenadec J, Berrebi A, Bongain A, Benifla JL, Delf-
raissyJF, Blanche S, Mayaux MJ, Cohort FP: Perinatal HIV-1 Trans-
mission Interaction Between Zidovudine Prophylaxis and
Mode of Delivery in the French Perinatal Cohort. JAMA 1998,
280:55-60.
30. European Collaborative Study: Pregnancy-related changes in the
longer-term management of HIV infected women in Europe.
Eurj Obstet Gynecol Reprod Biol 2003, I I 1:3-8.
31. The Italian Register for HIV Infection in Children: Determinants of
mother-to-infant human immunodeficiency virus I trans-
mission before and after the introduction of zidovudine
prophylaxis. Arch Pediatr Adolesc Med 2002, 156:915-921.
32. European Collaborative Study: Mother-to-child transmission of
HIV Infection in the era of highly active antiretroviral ther-
apy. Clin Infect Dis 2005, 40:458-465.
33. Warszawski J, Tubiana R, Le Chenadec J, Blanche S, Teglas JP, al : Is
intrapartum intravenous zidovudine still beneficial to pre-
vent mother-to-child HIV-1 transmission? 12th Conference on
Retroviruses and Opportunistic Infections, 22-25 February 2005, Boston,
USA 2005, Abstract:78 1.
34. Mandelbrot L, Landreau A, Rekacewicz C, Berrebi A, Benifla JL, Bur-
gard M, Lachassine E, Chaix ML, Bongain A, Ciraru-Vigneron N,
Crenn-Herbert C, Delfraissy JF, Rouzioux C, Mayaux MJ, Blanche S,
the Agence Nationale de Recherches sur le SIDA ANRSG: Lamivu-
dine-Zidovudine Combination for Prevention of Maternal-
Infant Transmission of HIV-1. JAMA 2001, 285:2083-2093.
35. Cunningham CK, Balasubramanian R, Delke I, Maupin R, Mofenson L,
Dorenbaum A, Sullivan JL, Gonzalez-Garcia A, Thorpe E, Rathore M,
Gelber RD: The impact of race/ethnicity on mother-to-child
HIV transmission in the United States in Pediatric AIDS
Clinical Trials Group Protocol 316. j Acquir Immune Defic Syndr
2004, 36:800-807.
36. Fiscus SA, Adimora AA, Funk ML, Schoenbach VJ, Tristram D, Lim W,
McKinney RE, Rupar D, Woods C, Wilfert C: Trends in interven-
tions to reduce perinatal human immunodeficiency virus
type I transmission in North Carolina. Pediatr Infect Dis] 2002,
21:664-668.
37. Stringer JSA, Rouse DJ, Goldenberg RL: Prophylactic cesarean
delivery for the prevention of perinatal human immunodefi-
ciency virus transmission. The case for restraint. JAMA 1999,
281:1946-1949.
38. Brockmeyer N: German-Austrian Guidelines for HIV-therapy
during pregnancy--status: May/June I 998--common state-
ment of the Deutsche AIDS-Gesellschaft (DAIG) and the
Osterreichische AIDS-Gesellschaft (OAG). Eurj Med Res 1999,
4:35-42.
39. Taylor GP, Lyall EGH, Mercey D, Smith JR, Chester T, Newell ML,
Tudor-Williams G: British HIV Association guidelines for pre-
scribing antiretroviral therapy in pregnancy (1998). Sexually
Transmitted Infections 1999, 75:90-97.
40. Newell ML, Rogers MF: Pregnancy and HIV infection: a Euro-
pean Consensus on management. AIDS 2002, 16:S I-S18.


41. British HIV Association: Guidelines for the management of HIV infection
in pregnant women and the prevention of mother-to-child transmission of
HIV London, British HIV Association; 2005:www.bhiva.org.
42. Hankins C, Lapointe N, Walmsley S: Participation in clinical trials
among women living with HIV in Canada. Canadian
Women's HIV Study Group. CMAj 1998, 159:1359-1365.
43. Gandhi M, Ameli N, Bacchetti P, Sharp GB, French AL, Young M,
Gange SJ, Anastos K, Holman S, Levine A, Greenblatt RM: Eligibility
criteria for HIV clinical trials and generalizability of results:
the gap between published reports and study protocols. AIDS
2005, 19:1885-1896.
44. Moore DAJ, Goodall RL, Ives NJ, Hooker M, Gazzard BG, Easter-
brook PJ: How generalizable are the results of large rand-
omized controlled trials of antiretroviral therapy? HIV
Medicine 2000, 1:149-154.

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