Determinants and trends in perinatal human immunodeficiency virus type 1 (HIV-1) transmission in the metropolitan area of Belo Horizonte, Brazil: 1998 - 2005.
ABSTRACT Significant decrease in human immunodeficiency virus type 1 (HIV-1) vertical transmission has been observed worldwide in centers where interventions such as antiretroviral therapy (ART), elective cesarean section, and avoidance of breastfeeding have been implemented. This prospective cohort study aimed to assess the determinants of and the temporal trends in HIV-1 vertical transmission in the metropolitan area of Belo Horizonte, Brazil from January 1998 to December 2005. The rate of HIV-1 vertical transmission decreased from 20% in 1998 to 3% in 2005. This decline was associated with increased use of more complex ART regimens during pregnancy. Multivariate analysis restricted to clinical variables demonstrated that non ART, neonatal respiratory distress/sepsis and breastfeeding were independently associated with HIV-1 vertical transmission. When laboratory parameters were included in the model, high maternal viral load and non maternal ART were associated with HIV-1 vertical transmission. The results from this study confirm the impact of ART in the reduction of HIV-1 vertical transmission and indicate the need for improvement in the care and monitoring of mother and infant pairs affected by HIV-1.
- [Show abstract] [Hide abstract]
ABSTRACT: OBJECTIVE: To identify risk factors associated with mother-to-child transmission of HIV in the Brazilian state of Pernambuco. METHODS: Retrospective cohort study with 1200 HIV-exposed children born in Pernambuco, registered up to the age of 2 months in a public programme to prevent vertical transmission. Univariate and multivariate logistic regression analyses were conducted for maternal and peripartum characteristics and prophylactic interventions, to identify risk factors for mother-to-child transmission of HIV. RESULTS: The transmission rate was 9.16% (95% CI: 7.4-10.9). The following risk factors were independently associated with transmission: non-use of antiretroviral during pregnancy (OR: 7.8; 95% CI: 4.1-15); vaginal delivery (OR: 2.02; 95% CI: 1.2-3.4); prematurity (OR: 2.5; 95% CI: 1.3-4.7); and breastfeeding (OR: 2.6; 95% CI: 1.4-4.6). CONCLUSIONS: This mother-to-child transmission rate is unacceptably high, as prophylactic interventions such as antiretroviral therapy and infant feeding formula are free of charge. Absence of antiretroviral therapy during pregnancy was the main risk factor. Therefore, early identification of exposed mothers and initiating prophylactic interventions are the main challenges for controlling transmission.Tropical Medicine & International Health 12/2012; · 2.30 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Background: HIV infection in children is an important public health problem in the world, mainly in poorer countries. If all recommendations are followed, the elimination of HIV vertical transmission is a concrete possibility. This study aims to estimate vertical transmission rates of HIV in São Paulo State, Brazil, based on pregnant women diagnosed and reported in 2006, identifying potentially associated factors. Methods: This study involves a retrospective cross-sectional analysis of information systems and records of infected pregnant women and children exposed to HIV. The rate of vertical transmission was estimated and variables associated with the antenatal, delivery, and postnatal periods were analyzed by the chi-square test, and Fisher exact test was used for variables with an expected frequency <5. The relative risks were calculated with 95% confidence intervals. Results: The rate of vertical transmission in São Paulo state was 2.7% (95% confidence interval: 1.86 to 3.94) in 2006, decreasing 83.1% in comparison with 1988-1993. The main associated variables were lack of prenatal visits or <6 visits, no antiretroviral prophylaxis during labor or neonatal use for <6 weeks, and maternal breastfeeding. Conclusions: There is a decreasing trend of HIV vertical transmission in São Paulo with levels approaching elimination, which seems to be associated with antiretroviral policy and interruption of breastfeeding. Although there are serious operational issues, conditions exist to respond effectively. São Paulo state demonstrates that it is possible to achieve advanced levels of control for this mode of HIV transmission.JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2011; 57(Suppl 3):S164-S170. · 4.39 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To describe the access to the interventions for the prevention of HIV mother to child transmission and mother to child transmission rates in the outskirts of Rio de Janeiro, from 1999 to 2009. This is a retrospective cohort study. Prevention of HIV mother to child transmission interventions were accessed and mother to child transmission rates were calculated. The study population is young (median: 26 years; interquartile range: 22.0-31.0), with low monthly family income (40.4% up to one Brazilian minimum wage) and schooling (62.1% less than 8 years). Only 47.1% (n=469) knew the HIV status of their partner; of these women, 39.9% had an HIV-seronegative partner. Among the 1259 newborns evaluated, access to the antenatal, intrapartum and postpartum prevention of HIV mother to child transmission components occurred in 59.2%, 74.2%, and 97.5% respectively; 91.0% of the newborns were not breastfed. Overall 52.7% of the newborns have benefited from all the recommended interventions. In subsequent pregnancies (n=289), 67.8% of the newborns received the full package of interventions. The overall rate of HIV vertical transmission was 4.7% and the highest annual rate occurred in 2005 (7.4%), with no definite trend in the period. Access to the full package of interventions for the prevention of HIV vertical transmission was low, with no significant trend of improvement over the years. The vertical transmission rates observed were higher than those found in reference services in the municipality of Rio de Janeiro and in the richest regions of the country.The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases 01/2014; · 1.04 Impact Factor
Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 103(4): 351-357, June 2008
online | memorias.ioc.fiocruz.br
Determinants and trends in perinatal human immunodeficiency virus
type 1 (HIV-1) transmission in the metropolitan area of
Belo Horizonte, Brazil: 1998 - 2005
Fabiana Maria Kakehasi, Jorge A Pinto/1/+, Roberta Maia de Castro Romanelli,
Mariângela Carneiro/2, Carolina Silva Cardoso, Maria do Carmo Teatini Tavares/3,
Victor Hugo Melo/4, Regina Amélia Lopes Pessoa de Aguiar/4
Grupo de Aids Materno-Infantil 1Departamento de Pediatria 4Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina,
2Epidemiologia de Doenças Infecciosas e Parasitárias, Departamento de Parasitologia, Instituto de Ciências Biológicas Universidade
Federal de Minas Gerais, Av. Alfredo Balena 190, s/ 161, 30130-100 Belo Horizonte, MG, Brasil 3Centro de Treinamento e Referência em
Doenças Infecciosas e Parasitárias Orestes Diniz, Secretaria de Saúde da Prefeitura Municipal de Belo Horizonte, MG Brasil
Significant decrease in human immunodeficiency virus type 1 (HIV-1) vertical transmission has been observed
worldwide in centers where interventions such as antiretroviral therapy (ART), elective cesarean section, and avoid-
ance of breastfeeding have been implemented. This prospective cohort study aimed to assess the determinants of and
the temporal trends in HIV-1 vertical transmission in the metropolitan area of Belo Horizonte, Brazil from January
1998 to December 2005. The rate of HIV-1 vertical transmission decreased from 20% in 1998 to 3% in 2005. This
decline was associated with increased use of more complex ART regimens during pregnancy. Multivariate analysis
restricted to clinical variables demonstrated that non ART, neonatal respiratory distress/sepsis and breastfeeding
were independently associated with HIV-1 vertical transmission. When laboratory parameters were included in the
model, high maternal viral load and non maternal ART were associated with HIV-1 vertical transmission. The re-
sults from this study confirm the impact of ART in the reduction of HIV-1 vertical transmission and indicate the need
for improvement in the care and monitoring of mother and infant pairs affected by HIV-1.
Key words: HIV-1 - vertical transmission - pregnant women - antiretroviral therapy
By the end of 2006, it was estimated that almost 39.5
(CI95%: 34.1-47.1) million adults and children were in-
fected with the human immunodeficiency virus (HIV-1)
worldwide, with 1.7 million (CI95%: 1.3-2.5) HIV-1-
positive individuals living in Latin America (UNAIDS
2007). The vertical transmission of HIV-1 is the major
route for HIV-1 acquisition in children, and 13,012 cases
of pediatric acquired immunodeficiency syndrome
(AIDS) cases have been reported in Brazil (MS 2007a).
In the absence of interventions, the reported HIV-1 ver-
tical transmission rate varies from 15 to 25% in Europe
and the USA and extending to 40% in under-developed
countries (WGMCT 1995). In Brazil, initial studies
demonstrated a transmission rate of 16% (CI 95%: 13-20)
(Tess et al. 1998), but a significant decrease has been ob-
served in recent years; a nation-wide study reported a
transmission rate of 7.1% in 2001, but centers in Rio de
Janeiro and São Paulo have described lower rates (3.57%
between 1996 to 2001 and 2.4% in 2002, for each city
respectively) (João et al. 2003, Matida et al. 2005, Succi
2007). Brazilian data reflect the progress achieved in
the reduction of HIV-1 vertical transmission reported
worldwide in centers where maternal antiretroviral ther-
apy (ART) and breast milk replacement are available
Financial Support: CNPq
+ Corresponding author: firstname.lastname@example.org
Received: 30 January 2008
Accepted: 5 June 2008
(Dorenbaum et al. 2002, Wade et al. 2004, Magder et al.
2005, Newell et al. 2007).
The Pediatric AIDS Clinical Trials Group Protocol
076, a multicenter study published in 1994 (Connor et
al. 1994) demonstrated a decrease of 67.5% in the HIV-1
vertical transmission rate when zidovudine (ZDV) was
offered prophylactically to HIV-1 pregnant women and
to their newborns. Following this landmark study, differ-
ent ART regimens have demonstrated variable impact in
the reduction of HIV-1 vertical transmission rates (Dabis
et al. 1999, Guay et al. 1999, Shaffer et al. 1999, Wiktor
et al. 1999, PST 2002, Lallemant et al. 2004, Read et
al. 2007). In addition to ART, other interventions have
contributed to the reduction of HIV-1 vertical trans-
mission, such as elective cesarean section (C-section)
(IPHIVG 1999, EMDC 1999), vaginal cleaning during
the intrapartum period (Taha et al. 1997), vitamin A
supplementation (Semba 1997), and avoidance of breast-
feeding (Nduati et al. 2001, RoUsseau et al. 2004).
The objective of this prospective study was to evaluate
the determinants associated with HIV-1 transmission and
to describe the temporal trends in HIV-1 vertical trans-
mission rates in the metropolitan area of Belo Horizonte
(BH), Brazil, from January 1998 to December 2005.
PATIENTS, MATERIALS AND METHODS
Population - This prospective observational study
was carried out at the main referral center for HIV-1/
AIDS care and treatment in BH (Centro de Referência
em Doenças Infecciosas e Parasitárias Orestes Diniz –
UFMG/PBH). Eligible cases included HIV-1 infected
Determinats of perinatal HIV-1 transmission • Fabiana M Kakehasi et al.
pregnant women and/or mothers and their exposed ba-
bies who were admitted before three months of age to
the outpatient clinic. The participants were enrolled
from January 1998 to December 2005.
Data collection - Clinical and laboratory data were
collected using standardized forms. Maternal data in-
cluded HIV-1 route of acquisition, date of diagnosis,
pregnancy and delivery history, ART during pregnancy,
and disease classification (revised by CDC 1992). Re-
sults from maternal CD4+ lymphocyte count and viral
load closest to delivery were also collected for analysis.
Results from tests performed between three months pri-
or to to three months post delivery date were considered.
Infants were evaluated monthly for the first six months
of life and every three months thereafter until defini-
tion of HIV-1 status was determined. CD4+ lymphocyte
count and plasma viral load were performed in infected
infants every three months.
Definitions - Mode of delivery was categorized as
elective C-section or other. ART regimens were de-
scribed as ZDV monotherapy, dual nucleoside reverse
transcriptase inhibitor therapy (NRTI; ZDV plus an-
other NRTI), highly active ART therapy (HAART; 2
NRTIs plus 1 protease inhibitor or 1 non-NNRTI), or no
therapy at any stage of gestation. Duration of ruptured
membranes was considered prolonged if it occurred pri-
or to 4 h of delivery.
Infants were classified as low birth weight if they
weighed less than 2.500 g and classified as premature if
they were born at less than 37 weeks of gestational age as-
sessed by Capurro et al. (1978) method. HIV-1 infection
was defined in infants who presented: (i) a plasma viral
load greater than 10,000 copies per ml in two samples
collected after four weeks of life; (ii) any class C diagno-
sis according to CDC (1994) pediatric HIV-1/AIDS case
definition; or (iii) a persistent positive HIV-1 antibody
exam (enzyme-linked immunoassay and western blot)
after 18 months of age. Uninfected infants were defined as
those who presented with two negative plasma viral load
exams after four weeks of life or those who seroreverted
(a negative serologic test performed after 12 months of
age). All mothers were counseled to not breastfeed.
Statistical analysis - The relationships between ma-
ternal factors and HIV-1 status of the infants were first
analyzed by univariate analysis using the chi-square
test, Fisher’s exact test, chi square for trend test, Mann-
Whitney test, estimative of odds ratio (OR), and 95% CI.
Following univariate analysis, the independent contribu-
tion from risk factors was assessed using stepwise logistic
regression. The initial model included all variables with
p-values less than 0.25 or those variables known to have
biological plausibility for perinatal HIV-1 transmission.
New models were built using a backward process with
statistical significance determined by the likelihood ratio
test (Hosmer & Hjort 2002). Interactions between vari-
ables selected for the final multivariate model were also
considered if they remained significantly associated with
the transmission risk. Statistical analyses were performed
using SPSS version 12.0 (SPSS Inc. Chicago IL USA).
The study was approved by the Ethical Comitee from
Universidade Federal de Minas Gerais (ETIC 008/97) and
all participants provided writen informed consent.
During the period from January 1998 to December
2005, 939 mother-infant pairs were evaluated. Analyses
were performed with 900 pairs; data from 39 (4.2%) pairs
were either lost to follow-up or reported no infection
status at time of analysis. HIV-1 vertical transmission
occurred in 56 infants, with an overall rate of transmis-
sion of 6.2% (95% CI: 4.8-8.1). A significant decrease in
transmission was observed throughout the study period
(Fig. 1) (p < 0.05). The relative reduction in HIV-1 verti-
cal transmission rate from 1998 to 2005 was 85%.
Maternal characteristics - No maternal demographic
characteristics were associated with HIV-1 vertical
transmission: Overall, 46.6% of mothers had mixed eth-
nic origin (“mulata”), 63.8% had a stable marital status,
and 62.8% had less than eight years of formal education.
Transmitting and non-transmitting mothers had simi-
lar median ages (26.0 and 27.9 years, respectively; p =
0.30). Illicit drug use was not associated with transmis-
sion (OR 1.0, 95% CI: 0.4-2.5). Information on route of
HIV-1 acquisition was available for 93.1% of the women
and sexual contact with HIV-1-positive partner was re-
ported by 96.9% of the women. The majority of mothers
were asymptomatic or had mild manifestations (CDC
1992, class A = 60%). CD4+ lymphocyte counts and
plasma viral load were available for 49.4% and 55.4%,
respectively, of the HIV-1-infected mothers (Table I).
Median time of these blood tests from delivery (pre to
post) was 6.4 weeks for CD4+ count (interquartile range:
IQR25%-75%: 2.0-6.4) and six weeks for viral load as-
sessment (IQR25%-75%: 2.1-13.7). Transmitting mothers
were significantly more immunossupressed and demon-
strated higher plasma viremia than non-transmitting
Fig. 1: HIV vertical transmission rate among HIV-infected women
per study year, from 1998 to 2005.
Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 103(4), June 2008
mothers. Maternal viral load greater than 1,000 copies/ml
was significantly associated with vertical transmission
(OR 13.0, 95%CI: 2.9-80.6); however, we were not able
to establish a plasma viral load threshold that predicted
Obstetric history - Neither rupture of membranes
prior to 4 h of delivery, complications during pregnancy,
nor maternal death were associated with an increased
risk of HIV-1 vertical transmission. Rates for mode of
delivery varied throughout the study period: Elective C-
section rates rose until 2001 and then declined; rates for
vaginal deliveries increased since 2001 (Fig. 2). Rates of
non-elective C-section deliveries remained stable during
the study years, accounting for less than 7% of deliver-
ies. Vaginal deliveries were associated with increased
risk of transmission (OR 3.33, 95% CI: 1.82-5.88).
In this cohort, ART during pregnancy has shown to
increase from 66.7% in 1998 to 89.9% in 2005 (p = NS).
In the first three years of this study, ZDV monotherapy
and dual therapy (2 NRTI drugs, including ZDV) were
the most common ART regimens used by pregnant
women (Fig. 3). HAART increased from 11.1% in 1998
to 76.1% in 2005 (chi-square for trend = 134.67, p < 0.05)
and it was inversely correlated with HIV-1 vertical trans-
Infant follow-up - Mean birth weights for infected
and uninfected infants was 2,890 g and 2,910 g, respec-
tively (p = 0.25). Numbers of low birth weight (infected:
25.5% vs. uninfected: 20.5%, p = 0.39) and premature
(infected: 20% vs. uninfected: 11.7%, p = 0.07) infants
Characteristics of women and infants in the study population, according to HIV vertical transmission (n = 900)
Characteristics HIV Transmission: Yes (n = 56) HIV Transmission: No (n = 844) Statistic
Median age (years)
None (%) 34/48 (70.8%)
ZDV monotherapy (%) 7/48 (14.6%)
Dual therapy (%) 4/48 (8.3%)
HAART (%) 3/48 (6.3%)
Prolonged rupture of membranes (%)b
Mode of delivery (%)b
Elective C-section 21/56 (37.5%)
Emergence C-section 02/56 (3.6%)
Vaginal delivery 33/56 (58.9%)
Median CD4 count (cells/mm3)
Median Plasma Viral Load (log)
Viral load > 1,000 copies/ml (%) 23/25 (92%)
26.0 27.9 0.30a
Birth Weight (grams)
(IQR 25%-75%) (2,875-3,443)
Low birth weight (%)b
Neonatal Morbidity (%)b
Median CD4 count (cells/mm3)
(IQR 25%-75%) (1,040-2,325)
2,890 2,910 0.25a
a: Mann Whitney Test; b: Qui –square; c: Odds ratio (CI 95%); IQR: interquartile range.
Fig. 2: rate of elective C-section and vaginal deliveries among HIV
infected pregnant women, from 1998 to 2005.
Determinats of perinatal HIV-1 transmission • Fabiana M Kakehasi et al.
occurred equally between infected and uninfected.
Breastfeeding was significantly higher among infected
compared to uninfected infants (infected: 4.3% vs. un-
infected: 33.9%) and represented an important risk fac-
tor for HIV-1 vertical transmission (OR = 11.5, 95% CI:
7.8-23.1, p < 0.05) as shown in Table II. Neonatal mor-
bidities due to sepsis and respiratory discomfort were
associated with HIV-1 vertical transmission (OR 3.6,
95%CI: 2.0-6.3). Although still in the normal range, in-
fected presented decreased CD4+ lymphocyte counts in
the first trimester of life when compared with uninfected
(median values: infected: 1,792 cells/ml vs. uninfected:
2.555, p < 0.05, median age of collection = 1.9 months).
Multivariate analysis - Two models were analyzed
in this cohort: one model included only clinical data
(Model 1) and a second model included both clinical and
laboratory data (CD4+ lymphocyte count and viral load;
Model 2). Among the available 900 mother-infant pairs,
the clinical-only model included 748 (83.1%) pairs and
the clinical and laboratory model comprised 339 (37.7%)
pairs. The initial step in both models included the logis-
tic modeling of all variables that demonstrated known
biological plausibility for HIV-1 vertical transmission
or demonstrated statistical importance in the initial uni-
variate analysis (Table II). Model 1 included delivery
type (elective C-section vs other), timing of amniotic
membrane rupture (< or > 4 h prior to delivery), ART
use (ZDV, ZDV + NRTI, HAART, or no therapy), pre-
maturity (< 37 weeks gestational age), birth weight (g),
neonatal disease and breastfeeding as variables. Model
2 included all clinical variables listed above and added
absolute CD4+ lymphocyte count and plasma viral load
in log scale (Table II). Absence of maternal ART was
the major independent risk factor associated with an
increased risk in both models. Despite that prematurity
was not a significant independent risk factor in the clini-
cal model, neonatal disease was associated with HIV-1
vertical transmission. Multiplicative interactions between
breast feeding or prematurity and neonatal disease were
not statistically significant (p = 0.08 and p = 0.918, re-
spectively). In Model 2, higher maternal viral load was as-
sociated with a two-fold increased risk of HIV-1 vertical
transmission. There was no interaction between maternal
viral load and ART during pregnancy (p = 0.49)
The rate of HIV-1 vertical transmission declined from
20% to 3% during the seven-year period (1998-2005)
of this prospective observational study carried out at a
HIV-1/AIDS referral center in BH: The relative reduc-
tion was 85%. This decline is similar to what has been
reported in other studies both in-country and internation-
ally (João et al. 2003, Wade et al. 2004, Matida et al. 2005,
Succi 2007), demonstrating the effectiveness of strategies
aimed at reducing mother to child transmission. Results
from a multicenter observational study conducted in
Latin America and Caribbean countries that included 770
mother-infant exposed to different ART regimens (Read
et al. 2007) also demonstrated a low (0.91%, 95%CI: 0.37
- 1.86) HIV-1 mother to child transmission rate. The Na-
tional AIDS Brazilian Program (NAP) has been provid-
ing routine HIV-1 testing for all pregnant women during
prenatal care and for all HIV-1 exposed babies at birth.
In addition NAP has been providing infant formula,
ART drugs, and laboratory monitoring universally and
free of charge. The NAP strategy focuses on all steps to
block HIV-1 vertical transmission (MS 2007b).
The conclusions drawn from our study could have
been affected by selection bias or our studied cohort
might not be representative of all HIV-1-infected preg-
nant women from metropolitan BH. However, this po-
Multivariate analyses of factors associated with HIV vertical
transmission performed in two models
Models and variables Adjusted OR 95% CI p-value
Model 1: clinical dataa
Absence of maternal ART use
Model 2: clinical and laboratory datab
Maternal viral load by log
Absence of maternal ART use
a: variables included in a full model were time of membrane
rupture, prematurity, birth weight, breastfeeding, maternal
antiretroviral use, neonatal diseases and C-section (n = 748);
b: variables included in a full model were membrane rupture,
prematurity, birth weight, breastfeeding, neonatal diseases, an-
tiretroviral use, C-section, maternal viral load by log and mater-
nal absolute CD4 count (n = 339).
Fig. 3: antiretroviral schema used among HIV-infected pregnant
women, from 1998 to 2005.
Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 103(4), June 2008
tential bias is attenuated by the fact that we are the only
referral center for the care of HIV-1 exposed and infected
children in the area.
In this observational study there were no differences
in the transmission rates between mothers who had pro-
longed rupture of membranes (> 4 h prior to delivery) or
any reported complication during pregnancy. In a meta-
analysis conducted by the IPHIVG (2001) the probability
of HIV-1 vertical transmission rate increased from 8%
(for rupture 2 h prior to delivery) to 32% (for rupture
24 h prior to delivery) among HIV-1-infected women.
Other studies have also described associations between
premature labor, intrapartum transmission, and timing
of rupture of membranes among HIV-1-infected women
(Magder et al. 2005). However, the contribution of com-
plex ART regimens was not addressed in this study, in
which the majority of women were exposed to ZDV
monotherapy or less complex regimens.
The C-section pattern described in this current study
is similar to the increasing proportion of C-section rates
among HIV-1-infected women performed in the US.
Dominguez et al. (2003) observed that the proportion of
deliveries conducted by C-section increased from 24%
before June 1998 to 58% after June 1998. Similarly, an in-
crease in C-section rates was detected by the ECS (2005)
from 1985 to 2004. It was recommended that all HIV-1-
infected pregnant women be offered elective C-sections
to reduce HIV-1 vertical transmission, including women
receiving ART (ECS 2005). A recent publication com-
paring characteristics of HIV-1-infected pregnant wom-
en from Europe and the USA demonstrated a greater
elective C-section delivery rate in Europe (61% vs 22%,
Europe vs. USA, respectively), but an earlier initiation
of ART and HAART in the USA (Newell et al. 2007). It
is likely that the release of the results from EMDC study
(1999) was an important determinant for the increment in
C-section rates, especially in Brazil and European coun-
tries. It is important to emphasize that the HIV-1 vertical
transmission rates continued to decline, even when the
elective C-section rates reached a plateau around 2002.
This trend was probably associated with the increased use
of HAART regimens as depicted in Fig. 3.
The importance of maternal viremia was confirmed
in the second model of the multivariate analysis. This
factor was associated with an increased risk of HIV-1
vertical transmission (OR 2.3, 95% CI: 1.2-4.4) consis-
tent with results from international studies including
the women infant transmission study (WITS) (OR 2.4,
95% CI: 1.69-2.34), an African study (OR 2.66, 95% CI:
1.95-3.63), and the NICHD International Site Develop-
ment Initiative study (OR3.3, 95% CI: 2.0-5.4) (Cooper
et al. 2002, Taha et al. 2004, Read et al. 2007). However,
the quality of prenatal care remains a key issue: The
large numbers of mothers without assessment of CD4+
lymphocyte count and viral load are an indirect marker
of missed opportunities in prenatal care. Additionally,
the extended interval between laboratory assessment
and delivery time is a limitation that may potentially
compromise our findings and conclusions. Despite
the significant difference between mean viral load in
mother to child transmission and non- mother to child
transmission, a threshold for predicting mother to child
transmission was not established, similar to other stud-
ies (Mayaux et al. 1997, Garcia et al. 1999, ECS 2005,
Read et al 2007).
The maternal use of combined ART regimens has in-
creased significantly throughout the study period. This
finding is consistent to what has been reported in a large
American cohort of HIV-1 infected women (Tuomala
et al. 2002) that demonstrated a significant increase in
HAART use with and without protease inhibitor from
the early 90s to 1998. In the WITS study, HIV-1 verti-
cal transmission rate was 20% for women not receiving
prenatal ART 10.4% for those receiving ZDV monother-
apy, 3.8% for multi-ART, and 1.2% for HAART (Cooper
et al. 2002). Unfortunately, our study did not measure
the duration of therapy during pregnancy or assess the
suppression of viral replication. The benefit of ART was
confirmed and this was independently associated with a
reduction in the HIV-1 vertical transmission in both sce-
narios described in the multivariate analyses as is histori-
cally demonstrated in maternal-to-child transmission.
In our study, low birth weight and prematurity were ob-
served equally among infected and exposed/uninfected.
However, other studies have reported low birth weight
(LBW) and prematurity to be associated with mother
to child transmission, and a possible explanation for the
discrepancy could be the higher frequency of LBW and
prematurity described in other populations (Nogueira et
al. 2001, João et al. 2003, Magder et al. 2005, Szyld et al.
2006). However, neonatal diseases such as respiratory
distress syndrome, sepsis, and neonatal jaundice were
associated with HIV-1 vertical transmission indicating
that others factors are associated with the newborn in-
fection. In addition, the administration of ART to moth-
ers and ZDV to infants that is associated with elective
C-section could also have contributed to the prevention
of mother to child transmission of HIV-1 in most of our
preterm and LBW infants. Also, the current study did
not demonstrate a demographic difference among in-
fected and non-infected newborns; it was not possible to
demonstrate the timing of HIV-1 infection, whether in-
tra or peripartum (Bryson et al. 1992, Kalish et al. 1997).
A significant issue to be addressed is the high frequency
of breastfeeding in a country where formula is available.
This statistic could reflect a subgroup of HIV-1 infected
women that had not been diagnosed during pregnancy or
at labor. Unfortunately, time of maternal diagnosis was
not addressed in our study. The opportunity to advise
against breastfeeding was missed in this subpopulation
and thus, a number of HIV-1 transmissions were not
avoided. Neonatal disease can predict if an exposed baby
is HIV-1-infected, but prematurity does not influence
this factor. A lower CD4+ lymphocyte count was present
in HIV-1 infected children. However this finding is nor-
mal for children of this age, and thus additional studies
must be done to establish the value of this measure for
predicting risk of infection and disease.
This current study reports a decrease in HIV-1 verti-
cal transmission rates for metropolitan BH and also re-
ports the impact of ART on the reduction of infection
rates in this population. The real scenario in impover-
Determinats of perinatal HIV-1 transmission • Fabiana M Kakehasi et al.
ished communities is as is expressed in Model 1, where
only clinical data are available to predict the risk of
HIV-1 vertical transmission. It has clearly been observed
that two interventions must be implemented: avoidance of
breastfeeding, and maternal/neonatal ART. The effective-
ness of high quality, multidisciplinary prenatal care can
improve the maternal-infant follow-up and outcomes.
Bryson YJ, Luzuriaga K, Sullivan JL, Wara DW 1992. Proposed defini-
tions for in utero versus intrapartum transmission of HIV-1. N Engl
J Med 327: 1246-1247.
Capurro H, Korichzky S, Fonseca O, Caldeiro-Barcia R 1978. A sim-
plified method for diagnosis of gestational age in the newborn
enfant. J Pediatr 93:120-122.
CDC - Centers for Disease Control and Prevention 1992.Revised clas-
sification system for HIV infection and expanded surveillance
case definition for AIDS among adolescents and adults. MMWR
Recomm Rep 41: 1-19.
CDC - Centers for Disease Control and Prevention 1994. Revised
classification system for human immunodeficiency virus (HIV)
infection in children under 13 years of age. MMWR Morb Mortal
Wkly Rep 43: 1-10.
Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O’Sullivan
MJ, VanDyke R, Bey M, Shearer W, Jacobson RL, Jimenez R,
O’Neill E, Bazin B, Delfraissy JF, Culnane M, Coombs R, Elkins
M, Moye J, Stratton P, Balsley J, for The Pediatric AIDS Clini-
cal Trials Group Protocol 076 Study Group 1994. Reduction of
maternal-infant transmission of human immunodeficiency virus
type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials
Group Protocol 076 Study Group. N Engl J Med 331: 1173-1180.
Cooper ER, Charurat M, Mofenson L, Hanson IC, Pitt J, Diaz C,
Hayani K, Handelsman E, Smeriglio V, Hof R, Blattner W,
Women and Infnats Transmission Study Group 2002. Combina-
tion antiretroviral strategies for the treatment of pregnant HIV-1-
infected women and prevention of perinatal HIV-1 transmission.
J Acquir Immune Defic Syndr 29: 484-494.
Dabis F, Msellati P, Meda N, Welfens-Ekra C, You B, Manigart O,
Leroy V, Simonon A, Cartoux M, Combe P, Ouangré A, Ramon
R, Ky-Zerbo O, Montcho C, Salamon R, Rouzioux C, Van de
Perre P, Mandelbrot L 1999. Six-month efficacy, tolerance, and
acceptability of a short regimen of oral zidovudine to reduce ver-
tical transmission of HIV in breastfed children in Côte d’Ivoire
and Burkina Faso: a double-blind placebo-controlled multicentre
trial. DITRAME Study Group. Diminution de la Transmission
Mère-Enfant. Lancet 353: 786-792.
Dominguez KL, Lindegren ML, D’Almada PJ, Peters VB, Frederick
T, Rakusan TA, Ortiz IR, Hsu HW, Melville SK, Sadek R, Fowl-
er MG, Pediatric Spedtrum of HIV Disease Consortium 2003.
Increasing trend of cesarean deliveries in HIV-infected women
in the United States from 1994 to 2000. J Acquir Immune Defic
Syndr 33: 232-238.
Dorenbaum A, Cunningham CK, Gelber RD, Culnane M, Mofen-
son L, Britto P, Rekacewicz C, Newell ML, Delfraissy JF, Cun-
ningham-Shrader B, Mirochnick M, Sulivan JL, International
PACTG316 Team 2002. Two-dose intrapartum/newborn nevirap-
ine and standard antiretroviral therapy to reduce perinatal HIV
transmission: a randomized trial. JAMA 288: 189-198.
ECS - European Collaborative Study 2005. Mother-to-child transmis-
sion of HIV infection in the era of highly active antiretroviral
therapy. Clin Infect Dis 40: 458-465.
EMDC - The European Mode of Delivery Collaboration 1999. Elec-
tive caesarean-section versus vaginal delivery in prevention of
vertical HIV-1 transmission: a randomised clinical trial. The Eu-
ropean Mode of Delivery Collaboration. Lancet 353: 1035-1039.
Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burhett SK,
Kornegav J, Jackson B, Moye J, Hanson C, Zorilla C, Lew JF
1999. Maternal levels of plasma human immunodeficiency virus
type 1 RNA and the risk of perinatal transmission. Women and
Infants Transmission Study Group. N Engl J Med 341: 394-402.
Guay LA, Musoke P, Fleming T, Bagenda D, Allen M, Nakabiito C,
Sherman J, Bakaki P, Ducar C, Deseyve M, Emel L, Mirochnick
M, Fowler MG, Mofenson L, Miotti P, Dransfield K, Bray D,
Mmiro F, Jackson JB 1999. Intrapartum and neonatal single-dose
nevirapine compared with zidovudine for prevention of mother-
to-child transmission of HIV-1 in Kampala, Uganda: HIVNET
012 randomised trial. Lancet 354: 795-802.
Hosmer DW, Hjort NL 2002. Goodness-of-fit processes for logistic
regression: simulation results. Stat Med 21: 2723-2738.
IPHIVG - The International Perinatal HIV Group 1999. The mode
of delivery and the risk of vertical transmission of human im-
munodeficiency virus type 1- a meta-analysis of 15 prospective
cohort studies. The International Perinatal HIV Group. N Engl J
Med 340: 977-987.
João EC, Cruz ML, Menezes JA, Matos HJ, Calvet GA, d’Ippolito MM,
Salgado LT, Silva SS, Bazin GR, Braga RC 2003. Vertical trans-
mission of HIV in Rio de Janeiro, Brazil. AIDS 17: 1853-1855.
Kalish LA, Pitt J, Lew J, LandesmanS, Diaz C, Hershow R, Hollinger
FB, Pagano M, Smerigli V, Moye J 1997. Defining the time of fetal
or perinatal acquisition of human immunodeficiency virus type 1
infection on the basis of age at first positive culture. Women and
Infants Transmission Study (WITS). J Infect Dis 175: 712-715.
Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Houng N,
Koetsawang S, Kanshana S, McIntosh K, Thaineua V, Perinatal
HIV Prevention Trial Investigators 2004. Single-dose perinatal
nevirapine plus standard zidovudine to prevent mother-to-child
transmission of HIV-1 in Thailand. N Engl J Med 351: 217-228.
Magder LS, Mofenson L, Paul ME, Zorilla CD, Blattner WA, Tuomo-
la RE, LaRussa P, Landesman S, Rich KC 2005. Risk factors for
in utero and intrapartum transmission of HIV. J Acquir Immune
Defic Syndr 38: 87-95.
Matida LH, da Silva MH, Tayra A, Succi RC, Gianna MC, Gonçalves
A, de Carvalho HB, Hearst N 2005. Prevention of mother-to-
child transmission of HIV in São Paulo State, Brazil: an update.
AIDS 19 (Suppl 4): S37-41.
Mayaux MJ, Dussaix E, Isopet J, Rekacewicz C, Mandelbrot L,
Ciraru-Vigneron N, Allemon MC, Chambrin V, Katlama C, Del-
fraissy JF, Puel J 1997. Maternal virus load during pregnancy and
mother-to-child transmission of human immunodeficiency virus
type 1: the French perinatal cohort studies. SEROGEST Cohort
Group. J Infect Dis 175: 172-175.
MS - Ministério da Saúde 2007a. Programa Nacional de DST e AIDS,
MS-PNDST/AIDS, Boletim Epidemiológico [serial on the Inter-
net]; 4(1) [cited 2007 Jan]. Available from:http://www.aids.gov.br/
MS - Ministério da Saúde 2007b. Recomendações para Profilaxia da Trans-
missão Vertical do HIV e Terapia Anti-Retroviral em Gestantes – 2006.
Secretaria de Vigilância em Saúde [cited 2007 Jan]. Available from: http://
Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 103(4), June 2008
Nduati R, Richardson BA, John G, Mbori-Ngacha D, Mwatha A,
Ndinya-Achola J, Bwayo J, Onyango FE, Kreiss J 2001. Effect
of breastfeeding on mortality among HIV-1 infected women: a
randomised trial. Lancet 357: 1651-1655.
Newell ML, Huang S, Fiore S, Thorne C, Mandelbrot L, Sullivan JL,
Maupin R, Delke I, Watts DH, Gelber RD, Cunningham CK,
PACTG 316 Study Team 2007. Characteristics and management
of HIV-1-infected pregnant women enrolled in a randomised trial:
differences between Europe and the USA. BMC Infect Dis 7: 60.
Nogueira SA, Abreu T, Oliveira R, Araújo L, Costa T, Andrade M,
Garcia MF, Rodrigues K, Mercadante R, Fernandes I, Sapia MC,
Lambert JS 2001. Successful prevention of HIV transmission
from mother to infant in Brazil using a multidisciplinary team
approach. Braz J Infect Dis 5: 78-86.
PST - Petra Study Team 2002. Efficacy of three short-course regi-
mens 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 359: 1178-1186.
Read JS, Cahn P, Losso M, Pinto J, Joao E, Duarte G, Cardoso E,
Freimanis-hance L, Stoszek SK; NISDI Perinatal Study Group
2007. Management of human immunodeficiency virus-infected
pregnant women at Latin American and Caribbean sites. Obstet
Gynecol 109: 1358-1367.
Rousseau CM, Nduati RW, Richardson BA, John-Stewart GC, Mbori-
Ngacha DA, Kreiss JK, Overbauh J 2004. Association of levels
of HIV-1-infected breast milk cells and risk of mother-to-child
transmission. J Infect Dis 190: 1880-1888.
Semba RL 1997 Overview of the potential role of vitamin A in
mother-to-child transmission of HIV-1. Acta Paediatr 421
Shaffer N, Chuachoowong R, Mock PA, Bhadrakom C, Siriwasin W,
Young NL, Chotpitayasunondh T, Chearsdkul S, Roongpisuthip-
ong A, Chinayon P, KaronJ, Mastro TD, Simonds RJ 1999. Short-
course zidovudine for perinatal HIV-1 transmission in Bangkok,
Thailand: a randomised controlled trial. Bangkok Collaborative
Perinatal HIV Transmission Study Group. Lancet 353: 773-780.
Succi RCM 2007. Mother-to-child transmission of HIV in Brazil dur-
ing the years 2000 and 2001: results of a multi-centric study. Cad
Saúde Pública 23 (Suppl. 3): S379-S389.
Szyld EG, Warley EM, Freimanis L, Gonin R, Cahn PE, Calvet GA,
Duarte G, Melo VH, Read JS, NISDI Periantal Study Group
2006. Maternal antiretroviral drugs during pregnancy and infant
low birth weight and preterm birth. AIDS 20: 2345-2353.
Taha TE, Biggar RJ, Broadhead RL, Mtimavalve LA, Justesen AB, Li-
omba GN, Chiphanqwi JD, Miotti PG 1997. Effect of cleansing the
birth canal with antiseptic solution on maternal and newborn mor-
bidity and mortality in Malawi: clinical trial. BMJ 315: 216-219.
Taha TE, Kumwenda NI, Hoover DR, Fiscus SA, Kafulafula G,
Nkhoma C, Nour S, Chen S, Liomba G, Miotti PG, Broadhead
RL 2004. Nevirapine and zidovudine at birth to reduce perinatal
transmission of HIV in an African setting: a randomized con-
trolled trial. JAMA 292: 202-209.
Tess BH, Rodrigues LC, Newell ML, Dunn DT, Lago TD 1998. Infant
feeding and risk of mother-to-child transmission of HIV-1 in São
Paulo State, Brazil. São Paulo Collaborative Study for Vertical
Transmission of HIV-1. J Acquir Immune Defic Syndr Hum Ret-
rovirol 19: 189-194.
UNAIDS - Joint United Nations Programme on HIV/AIDS (UN-
AIDS) and World Health Organization 2007. AIDS epidemic up-
date. [cited 2007 Jan]. Available from: http://www.unaids.org/en/
Tuomala RE, Shapiro DE, Mofenson LM, Bryson Y, Culnane M,
Hughes MD, O’Sullivan MJ, Scott G, Stek AM, Wara D, Bulterys
M 2002. Antiretroviral therapy during pregnancy and the risk of
an adverse outcome. N Engl J Med. Jun 346: 1863-1870.
Wade NA, Zielinski MA, Butsashvili M, McNutt LA, Warren BL, Gla-
ros R, Cheku B, Pulver W, Pass K, Fox K, Novello AC, Birkhead
GS 2004. Decline in perinatal HIV transmission in New York
State (1997-2000). J Acquir Immune Defic Syndr 36: 1075-1082.
Wiktor SZ, Ekpini E, Karon JM, Nkengasong J, Maurice C, Severin
ST, Roels TH, Kouassi MK, Lackritz EM, Coulibaly IM, Green-
berg AE 1999. Short-course oral zidovudine for prevention of
mother-to-child transmission of HIV-1 in Abidjan, Côte d’Ivoire:
a randomised trial. Lancet 353: 781-785.
WGMTCT - The Working Group on Mother-To-Child Transmission
of HIV 1995. Rates of mother-to-child transmission of HIV-1 in
Africa, America, and Europe: results from 13 perinatal studies. J
Acquir Immune Defic Syndr Hum Retrovirol 8: 506-510.