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1PhD in Health Sciences - University of Brasília - UnB, Brazil; PhD in Science - University of Havana (Cuba); Post-Doctor in Health
Sciences - UnB and Degli Studi D'Aquila University - IT. Professor at the Federal University of Maranhão, Brazil.
2PhD in Information Engineering. Universidade de Nagoya – Japan; Post-Doctor. The Institute of Physics and Chemistry (RIKEN), Japan.
6PhD in Physics (UFC), with post-doctorate in Scientific Regional Development (DCR/CNPq). Researcher of the Doctoral and Master
Program in Regional Development and Environment (PGDRA/UNIR) ― Federal University of Rondonia, Brazil.
7PhD in Information Engineering. Federal University of Maranhão, Brazil. Researcher at the Federal University of Maranhão, Brazil.
8PhD in Electrica Engineering. Federal University of Maranhão, Brazil. Professor at the Federal University of Maranhão, Brazil.
9PhD and researcher linked to the graduate program in administration and the academic Department of Social and Environmental Sciences
Abstract— Objective: to analyze HIV during pregnancy and develop a protocol for diagnosis and treatment
of HIV during pregnancy to be used at the Hospital de Base Ary Pinheiro in the State of Rondônia, Western
Amazon. Methods: bibliographic review from the database of virtual Scielo and Bireme. The following
descriptors for research in the Portuguese language were combined: “HIV infections”; “Vertical
transmission of infectious disease”; “Highly active antiretroviral therapy”; “Adverse effects” and
“pregnancy”. Results: as a result of the research, a protocol was developed to be followed by the
professionals of the Obstetric Center of the Hospital de Base Dr. Ary Pinheiro (HBAP) in the management
of HIV-positive patients during pregnancy. Final considerations: the most effective measure to avoid
vertical transmission is the use of antiretrovirals and the use of combined antiretrovirals, in general, from
the 14th week of gestation and the use of intravenous AZT at delivery. Adequate care for infected pregnant
women involves, in addition to treatment with antiretrovirals capable of making and / or maintaining the
viral load undetectable, general measures in prenatal care (such as care for the pregnant flora of the
pregnant woman, vaccines), care during work delivery and suspension of breastfeeding. Thus, the expansion
of the offer of antenatal care and the improvement of its quality are essential conditions for the reduction of
vertical transmission to effectively occur.
Keywords— HIV. Gestation. Protocol. Diagnosis and Treatment. Hospital.
by vertical transmission in the Southeast region of Brazil and epidemiology, clinical manifestations, vertical
today is 4%). transmission, use of illicit drugs, unprotected sexual
Pregnancy is a very favorable moment for the diagnosis of practices, maternal factors, obstetric factors, prolonged
the disease, due to the countless exams requested to labor, fetal factors, attached factors, viral factors,
pregnant women during prenatal care. Most infected serological screening and diagnosis, concern and
pregnant women will be in the asymptomatic stage of the precaution of the medical team, treatment, adverse effects
disease. Proper screening for HIV infection is of utmost of antiretrovirals during pregnancy, general adverse
importance, so that prophylactic measures are taken in effects, among other variables.
time to obtain the best possible results. Two different The protocol for the diagnosis and management of HIV
types of HIV are known: 1 and 2. What predominates in patients during pregnancy for the Obstetric Center of
the Americas is HIV-1, subtype B. Hospital de Base Dr. Ary Pinheiro is based on the
The Ministry of Health of Brazil made the notification of literature review and medical experiences and is
HIV-positive pregnant women and their children structured in the sequence of the description of the
compulsory. The use of antiretrovirals is undoubtedly the infection with the indicative conditions of
attitude with the greatest impact in reducing vertical immunodeficiency, prenatal serological diagnosis,
transmission. Studies are evolving, combined prenatal exams, prenatal and postpartum care, drug
antiretroviral regimens are being recommended and more treatment during pregnancy, prophylactic regimen using
and more interventions are being proposed to reduce AZT at the time of delivery, care and assistance during
vertical transmission. delivery.
This research is a literature review on the diagnosis and To carry out the protocol, the researchers asked the Ethics
treatment of HIV during pregnancy. We seek to have Committee for Research in Human Beings - CEP of the
enough information to be able to diagnose and treat HIV Hospital de Base Ary Pinheiro, waiving the Informed
in pregnancy, having the necessary theoretical Consent Term because the study did not require
foundations, to know the importance of HIV in pregnancy intervention in the patient or collection of biological
as obstetric morbidity, to identify risk factors for the material, and no possibility of embarrassment to the
development of the disease (mode of transmission, patient and family.
epidemiology, groups risk, therapy for the prevention of
vertical transmission), make an early diagnosis, III. LITERATURE REVIEW
developing and indicating more appropriate measures to
Infection with the acquired immunodeficiency virus (HIV)
deal with HIV during pregnancy and, finally, as a general
is a worldwide pandemic, affecting almost 40 million
objective, develop a protocol for the diagnosis and
people worldwide and more than 700.000 in Brazil,
conduct of HIV during pregnancy to be used at the
considering that these numbers may be underestimated by
Hospital de Base Ary Pinheiro in the State of Rondônia,
more than 20%. At the beginning of the epidemic, in the
Western Amazon.
1980s, most new cases of infection occurred in men with
homosexual behavior. The epidemic evolved and took on
II. METHODS a characteristic of feminization and, in the group of
The methodological design followed a descriptive adolescents, there is already a trend towards a greater
bibliographic review study, based on structured literature, number of infected girls than infected boys. It is estimated
obtained from books and scientific articles from that more than 200.000 women in Brazil have the human
conventional and virtual libraries. After defining the immunodeficiency virus, with a prevalence of pregnant
theme, a search for bibliographic review was carried out women affected around 0.4% [1].
in the virtual databases of Scielo and Bireme. The Mother-to-child transmission (vertical transmission) is the
following descriptors for research in the Portuguese main means by which children acquire HIV infection
language were combined: “HIV infections”; “Vertical worldwide [2].
transmission of infectious disease”; “Highly active According to Freitas et al [3]:
antiretroviral therapy”; “Adverse effects” and
It is known that approximately 68% of
“pregnancy”.
HIV-positive women are of reproductive
The bibliographical discussion focused on cross-cutting age, and more than 90% of children
themes such as the conceptual basis of HIV, types of HIV infected with HIV have been infected due
to vertical transmission. Most women section and suspension of breastfeeding corroborate the
become infected through heterosexual decrease in these rates.
transmission. The transmission of the virus through breastfeeding
Santos et al [4] claim that: reaches 42%, as observed in African countries, where the
The AIDS epidemic in the world has been few resources do not allow the reduction of vertical
the subject of numerous studies and transmission to desirable levels [5].
research that seek not only to reduce The period corresponding to five years showed a tenfold
transmission and mortality, but also to increase in coverage of antiretroviral treatment in the
improve the quality of life of individuals world, reaching almost three million people. Antiretroviral
living with HIV. coverage in HIV-positive pregnant women, for the
According to Zugaib [5]: prevention of vertical HIV transmission, increased from
9% to 33%. The rapid expansion of treatment has
The importance of studying HIV in
guaranteed a decline in the annual number of AIDS deaths
pregnancy lies in the effort to reduce the
since 2005 (2.3 million), including deaths of individuals
rates of vertical transmission of the disease.
under the age of 15. It should be noted that children
The incidence of human immunodeficiency
infected by vertical transmission without treatment will
syndrome acquired in children has been
die in about 2 years [1].
decreasing and a series of studies in the
medical literature worldwide shows a According to the Febrasgo High Risk Gestation Manual
significant reduction in vertical [1]:
transmission rates. Studies carried out in several countries
show that the rate of vertical transmission
ranged from 5 to 35%, with the highest
In the absence of intervention, vertical transmission of
rates in developing countries. However,
HIV is around 25%. It is estimated that in symptomatic
there has been a significant decline in this
pregnant women with a clinical picture of AIDS, these
rate over time, as a result of the
rates are around 50%. The reduction to levels between
introduction and expansion of specific
zero and 2% is already a reality in developed countries. In
therapeutic approaches for HIV-positive
the Southeast region of Brazil, the number of infected
pregnant women in different areas of the
children is currently below 4% [5].
world. In developed countries,
Intrauterine transmission is less frequent in the first interventions such as the use of
trimester. Most cases of vertical transmission happen near antiretroviral therapy, elective cesarean
or during delivery. Breastfeeding represents an additional section and artificial breastfeeding resulted
risk of transmission that can vary from 7% to 22%. This in a reduction in the TV rate from 15.5%
risk increases to approximately 30% when the mother's before 1994 to 5.1%, between 1997 and
infection occurs during the breastfeeding period [3]. 1998, and to 0.99%, between 2001 and
For Zugaib [5], the control of vertical transmission is 2002, when potent antiretroviral therapy
related to the quality of prenatal care, peripartum (ART) became widely used.
antiretroviral prophylaxis and the suspension of According to the Treatment Guide - Recommendations for
breastfeeding. Prophylaxis of Vertical HIV Transmission and
In prenatal care, it is extremely important to adequately Antiretroviral Therapy in Pregnant Women of the
screen for HIV infection, so that prophylactic measures Ministry of Health [6]:
are taken in time to obtain the best possible results. The In a national, multicentre study, a reduction
use of combined antiretroviral therapy in HIV-positive in the vertical transmission rate from 8.6%
pregnant women and the maintenance of viral load below to 3.7%, over a 3-year period in the
1.000 copies \ ml not only prevent vertical transmission, Southeast region of Brazil, was
but also prevent the appearance of opportunistic demonstrated.
infections, which can lead to obstetric complications, such
An important marker for the adequate application of HIV
as prematurity. The administration of zidovudine (AZT) in
TV prophylaxis actions is the use of injectable AZT in
the peripartum period is the attitude of greatest impact in
parturient women. This indicator has remained stable over
reducing vertical transmission of HIV. Elective cesarean
the past 3 years - around 57%. Such data seems to point to opportunistic infections, associated with
the need to expand the use of rapid tests in maternity important immunity impairment.
hospitals and during prenatal care, primarily in situations Two different types of HIV are known: 1 and 2. HIV-2 is
where the diagnosis of HIV infection cannot be made in a found predominantly in West Africa, can be transmitted
timely manner for the adoption of measures that aim to the from mother to child, but has a slower and less severe
reduction of HIV TV [6]. clinical course of infection. For HIV-1, numerous
This suggests that the main factors that hinder the subtypes are recognized. Subtype B predominates in the
decrease in national rates of vertical transmission of HIV Americas (including Brazil) and Europe; types A, C and D
are the late diagnosis of HIV infection during pregnancy, in Africa and E is found in Asia. Subtype C seems to be
the low adherence to technical recommendations by health related to higher plasma viral load (CV) and vaginal
services (such as those that do not offer serology) for HIV elimination, when compared to subtypes A and D [1]. The
during prenatal care at recommended times) and the etiologic agents of the immunodeficiency syndrome are
quality of care, especially in regions with less service human immunodeficiency viruses. HIV - 1 and HIV - 2.
coverage and less access to the health network. Most cases in the world are caused by HIV - 1; HIV - 2
Freitas et al [3] claim that: infection is endemic in West Africa.
The World Health Organization proposes Differences in vertical transmission (VT) are also
four strategic points to try to reduce the associated with specific viral subtype behaviors, in
number of HIV-infected children: primary addition to immune responses and the ability to recognize
HIV prevention in women of reproductive viral antigens by the host and the effect of preventive
age; guidance on contraceptive methods for interventions [1].
HIV-positive women; prevention of vertical Konopka et al [7] analyzed the clinical and
transmission; and treatment for women and epidemiological profile of HIV-infected pregnant women
their families. attended in the prenatal care at the Hospital Universitário
de Santa Maria (RS) and concluded:
membrane to form its "envelope" - the lipoprotein per genome per duplication cycle, it is concluded that the
envelope of the virus. When it replicates on a large scale, mutability rate is quite high [1].
it harms cell physiology, culminating in its death [8]. At least a decade ago, it was believed that the relative
After infection, over time the number of T cells decreases immunodeficiency of pregnancy contributed to the
insidiously and progressively, ultimately resulting in progression of the disease. Currently, it is known that
profound immunosuppression. Thus, the common changes in CD4 and CD8 lymphocyte counts and
denominator of AIDS is profound immunosuppression, proportions occur during pregnancy with a physiological
mainly of cellular immunity, which causes several and adaptive character of the pregnant woman's body,
opportunistic infections and neoplasms. Infected with no significant differences between HIV-positive and
monocytes, and infection of microglia brain cells can HIV-negative pregnant women [5].
cause neuropsychiatric abnormalities. HIV-infected In HIV infection in non-pregnant adults, indications for
people also have a higher incidence of cancer, notably antiretroviral therapy follow well-established standards,
kaposi sarcoma, B-cell and non-Hogdkin lymphomas, as which are not compatible for use in pregnant women. The
well as some carcinomas. indication for antiretroviral therapy in pregnant women is
It is speculated that whatever the antiretroviral drug, the much broader, focusing on the prophylaxis of vertical
phenomenon of emergence of resistant viral “quasi- transmission of the disease. For this reason, the more
species” is intrinsic and inevitable in the medium or long widespread use of antiretrovirals raises concerns about the
term, depending on three main factors: mutation rate risk of virus resistance and disease rebound. Recent
(lower in DNA viruses and higher in the case of RNA), studies note that, despite the increase in viral load in the
replication rate and selective pressure exerted by the drug puerperal period, there was no evidence of increased rates
(function, basically, of its potency, concentration and of infection progression to AIDS, showing a fundamental
duration of exposure). In the case of HIV, the viral role of the adaptive immunological mechanisms of
turnover is in the range of 1,010 viral particles per day, pregnancy [5].
meaning that 99% of the virions produced at each instant What is known about clinical manifestations. The exact
are from infected cells in the last 2 weeks; thus, knowing incubation period from infection to clinical disease is
that reverse transcriptase makes an average of one error unknown, however, it is usually 2 to 3 months.
HIV-1 infection runs with a wide spectrum of clinical syndrome (AIDS) . In untreated individuals, the average
presentations, from the acute phase (which can be time between infection and the onset of the disease is
asymptomatic or manifest as an acute retroviral estimated at 10 years [1].
syndrome) to the advanced stage of the disease, with the Acute retroviral syndrome resembles infectious
defining manifestations of acquired immunodeficiency mononucleosis and is associated with elevated plasma
viremia and a transient but significant drop in CD4 placental vascular damage, increasing the permeability of
lymphocyte count. Symptoms include high fever, the placenta, and, consequently, the risk of passing HIV
sweating, transient lymphadenomegaly, with symmetrical, and intrauterine transmission. In pregnant women who use
mobile and painless nodules, mainly affecting the anterior illicit drugs, antiretroviral therapy, even if prophylactic,
and posterior cervical, submandibular, occipital and should be started as early as possible [4]. Unprotected
axillary chains, with progressive decrease in the first sexual practice increases the risk of reinfection by HIV
weeks. Splenomegaly, fatigue, loss of appetite, itself (causing an increase in viral load), in addition to
depression, oral and genital ulcers can also occur, exposure to resistant variants of the virus and the
sometimes reaching up to the esophagus. Some patients acquisition of other STDs [6] and the multiplicity of
may develop a rash after the onset of fever. The clinical partners [4]. Important maternal factors are the high
diagnosis, in this phase, usually goes unnoticed by the maternal viral load (CV): from a practical point of view,
transitory character of the symptoms [1]. vertical transmission occurs in pregnant women with a
With the exception of lymphadenopathy, in the clinical CV> 1,000 copies \ ml (transmission with a CV below this
latency phase there are no changes on physical number is considered a rare event). Low T-CD4
examination. Laboratory changes may occur, with mild lymphocyte count: in general, the reduction in T-CD4
thrombocytopenia being the most frequent. Some lymphocytes is related to high viral load. Reduction of
individuals may have mild anemia and leukopenia. neutralizing antibodies. Acute infection during pregnancy:
Nonspecific skin lesions can also occur as seborrheic in this situation, transmission occurs more than 50% of the
dermatitis, folliculitis and molluscum. As long as the CD4 time. Associated infections: genital and systemic
lymphocyte level is above 350, the most frequent infections increase vertical transmission. Smoking:
infectious episodes will be bacterial. As the disease Cigarette causes placental lesions that allow the virus to
progresses, atypical presentations of infections, late pass through this organ. Non-use (prophylactic or
response to antibiotic therapy and / or reactivation of old therapeutic) of antiretrovirals (ARV). The use of
infections such as tuberculosis and neurotoxoplasmosis antiretroviral therapy (ART) is one of the most effective
begin to be observed [1]. The appearance of opportunistic actions for reducing VT, which has been demonstrated in
infections and neoplasms is defining AIDS. AIDS- several studies (level of evidence 1a, degree of
indicating diseases include multiple opportunistic recommendation A) [4].
infections, such as esophageal or pulmonary candidiasis, Obstetric factors are the prolonged rupture of the
herpes simplex and persistent, tuberculosis, membranes [4]. According to the Ministry of Health
cytomegalovirus, Pneumocystis, toxoplasmosis, cervical Manual [6], the longer the rupture time, the greater the
cancer and others. risk of HIV transmission, particularly when longer than 4
Most HIV-infected pregnant women present in the hours.
asymptomatic stage of the infection, so the clinical Regarding prolonged labor, it is important to observe the
examination adds little in this regard. In the acute phase of exposure to maternal blood: decreasing the newborn's
the infection, or when the pregnant woman shows signs of contact with maternal blood reduces the chance of VT
immunodeficiency, the diagnosis can be made; however, (episiotomy should be avoided, rapid clamping of the
confirmed only with serological tests [4]. umbilical cord, newborn as soon as possible); Invasive
Recently, a CD4 + count below 200 / ul is also considered fetal propaedeutics: invasive procedures increase the risk
definitive for the diagnosis of AIDS in HIV positive of VT (cordocentesis, amniocentesis, among others) [4].
individuals. The AIDS mortality rate is extremely high, According to the Ministry of Health Manual [6] this is due
with many patients dying within 2 years. to placental injury. Observe the type of delivery. Several
studies show that elective cesarean section reduces the
It is important that health professionals should ensure that
chances of HIV VT in women with CV> 1,000 copies \ ml
all pregnant women are advised and encouraged to be
(there is no evidence of benefits of elective cesarean
tested for HIV infection in order to allow women to know
section in women with CV below this level). Vaginal
their infection status both for their own health and to
delivery (especially with episiotomy or using forceps)
reduce the risk of perinatal transmission of HIV. There
presents a higher risk of VT even when compared to
are a number of factors that increase the risk of mother-to-
emergency cesarean sections in women with CV> 1,000
child transmission of HIV, which is why they need early
copies \ ml (level of evidence 1st degree of
identification, which allows for appropriate intervention,
recommendation A) [4].
whenever possible [4]. The use of illicit drugs causes
The Ministry of Health Manual [6] explains:
The presence of uterine contractility can reduce the risk of VT of the virus in question. For the
triggers placental microtransfusions, diagnosis of fetal anemia in Rh isoimmunization,
leading to greater contact of the fetus with amniocentesis can be replaced by assessing the systolic
maternal blood. peak velocity of the fetal middle cerebral artery
Regarding gestational age, the Ministry of Health Manual (doplervelocimetry). It is clear, however, that these
[6] clarifies that the TV rate is inversely proportional to behaviors must be thoroughly discussed with family
gestational age, that is, every effort must be made to members [9]. It is known that the umbilical cord blood
ensure a good quality of prenatal care, in order to avoid test is not suitable for diagnosing intrauterine HIV-1
preterm labor [4]. The transmission of HIV through the infection, and does not offer the necessary sensitivity or
uterus is greater in the third trimester of pregnancy, which specificity for this diagnosis. Due to all these difficulties
justifies that all pregnant women are under treatment and limitations, the diagnosis of fetal HIV-1 infection,
during this period. without risks to the fetus, is not yet possible [9].
Fetal, adnexal and viral factors must be observed in detail. Serological screening and diagnosis of HIV infection.
In fetal factors, genetic susceptibility: fetuses and Knowledge of the serological status of HIV infection and
newborns that express secondary HIV receptors the early diagnosis make it possible to adopt measures that
(especially CCR-5, CXCR-4); Reduced function of fetal substantially reduce the risk of vertical HIV transmission
cytotoxic lymphocytes; Failure in the integrity of the skin [6].
and mucous membranes; Prematurity and low birth Testing and counseling are essential and are part of
weight. In the adnexal factors. Expression of HIV prenatal care, as recommended by the Ministry of Health,
receptors in the placenta: the expression of CD4, CXCR-4 which recommends testing in the first trimester or the first
and CCR-5 receptors in the placenta increases the risk of prenatal consultation, repeating it in the third trimester.
infection of this tissue and, consequently, vertical The physician must perform pre- and post-test counseling
transmission; Impairment of the integrity of the placenta: and request an anti-HIV test during prenatal care,
adnexal infections (placenta and membranes), trauma and safeguarding confidentiality and recording in the medical
solutions of continuity of the placental surface resulting record that such measures were adopted, as well as the
from infections and smoking [4]. Viral factors. Viral consent or refusal of the pregnant woman to perform the
genotype and phenotype: subtypes D and E of HIV 1 are exam [6]. It is important to emphasize that the test must be
more virulent and more transmissible than the others; offered and its performance is voluntary, confidential and
Resistance to ARVs; Greater macrophage tropism; confidential, for the pregnant woman and her partner (s).
Postnatal factors; Breastfeeding (there is an additional risk Curitiba, capital of the State of Paraná, was the first
with each feeding, which varies from 7 to 22%) [4]. In among Brazilian capitals to implement decentralized HIV
cases of acute maternal infection, breastfeeding increases serological testing for all pregnant women monitored by
HIV VT to 29% [6]. It has been proven that mother-to- SUS [10].
child transmission is responsible for most human HIV
When a seropositive pregnant woman is discovered, it is
infections among children.
imperative that the serological examination of her sexual
The Febrasgo High Risk Pregnancy Manual, reports a partner be performed, which makes pregnancy a window
study by Magder and colleagues in 2005, which showed of opportunity for the diagnosis of the couple's viral
that low birth weight was strongly associated with infection.
intrauterine TV, while gestational age at birth, CD4 before
According to studies carried out by Feldmann et al [11],
delivery, year and weight at birth and duration of
following articles and resolutions of the Code of Medical
membrane rupture greater than 4 hours were associated
Ethics, on HIV positive pregnant women who omit their
with intrapartum VT. This study reiterated that there was
sexual partner from being a carrier of the virus, the best
greater control of peripartum risk factors and consequent
approach adopted is as follows:
deviation to increase intrauterine transmission in the
absence of antiretroviral therapy. The doctor must convince the pregnant
woman to reveal her condition of being
The Ministry of Health [6] considers that high viral load is
HIV positive to her sexual partner. If the
the main risk factor associated with vertical transmission
patient is resistant to unveiling the status,
of HIV. If there is an imperative need for single invasion,
the doctor has the duty to intervene and
such as drainage of polyhydramnios, the use of 2 mg / kg
inform the partner, for his protection.
of maternal weight of intravenous AZT before puncture
Breach of confidentiality, in this case, is
done for just cause, which exempts the If still in the first sample, after positive step I, the test in
doctor from problems or legal implications. step II is negative or indeterminate, the second sample
Screening for HIV infection during pregnancy should be should not be taken immediately, but after a period of 30
performed using a test capable of detecting anti-HIV 1 days, to avoid repeating the exam in the period of the so-
and anti-HIV 2 antibodies. This first serological screening called “window immunological ”. In this situation, the
step, called step I, when it results in a non-reactive test, second sample is submitted to both stage I and stage II [5].
determines in blood sample as a negative HIV sample. In According to the Ministry of Health Manual [6], the
these cases, post-test counseling is advised, warning the methods used in the step II test are as follows: indirect
pregnant woman about risk situations [5]. immunofluorescence - IFI; Immunoblot - IB;
Commercial kits for detecting HIV infection have Immunoblotrápido - IBR; Western Blot - WB; Other
undergone considerable changes, allowing to reduce the methodologies registered with ANVISA and validated by
period of immunological window and increasing the the Department of Surveillance, Prevention and Control of
capacity to detect HIV-1 and HIV-2, in addition to several Sexually Transmitted Diseases and Acquired
subtypes [6]. According to the Ministry of Health [6], the Immunodeficiency Syndrome.
use of the following laboratory methods in the test of step For the interpretation of the results and release of the
I is allowed: Immunoenzymatic assay - ELISA; report, the results obtained in the tests of Steps I and II are
Immunoenzymatic assay of microparticles - MEIA; analyzed together.
Immunological assay with chemiluminescent staining and When the step I test of the first sample is inconclusive,
derivations - EQL; Enzyme-linked fluorescent step II is not performed on this blood sample. In this case,
immunological assay - ELFA; Magnetic the second sample is taken immediately and step I is
chemiluminescent immunological assay - CMIA; Rapid repeated. Resulting negative, the patient receives the final
tests: immunochromatography, agglutination of particles definitive diagnosis of a negative sample for HIV. As a
in latex or immunoconcentration; New methodologies result of the test of step I of this second sample, again
registered with ANVISA and validated by the Department inconclusive, the final result will be of an undetermined
of Surveillance, Prevention and Control of Sexually sample for HIV, and the patient must repeat the serology
Transmitted Diseases and Acquired Immunodeficiency after 30 days, to rule out that the inconclusiveness is due
Syndrome. to the “immunological window”. Finally, if in the second
Once the test shows a positive result, another test must be sample the triaging test of step I is positive, then the
performed on the same sample. This second stage, called confirmatory test of step II will be carried out on that
stage II or of serological confirmation, presupposes the sample, and only through positive results in both steps
use of another type of test, whose methodological does the patient receive the definitive diagnosis of a
principle or investigated antigens must be different. If the positive HIV sample [5 ].
step II test is positive, the patient's first blood sample is Faced with an indeterminate result, the risk-benefit ratio
considered to be positive for HIV, and another sample of indicating the procedures to reduce vertical
should be collected immediately and repeat step I in this transmission of HIV should be considered, together with
new sample. The finding, in the second sample, only of the pregnant woman [6].
the positive step I already allows to issue a final definitive
Eventually, false-positive results may occur. False
report that the blood sample is positive for the HIV virus
positivity in testing is more frequent in pregnancy than in
[5].
children, non-pregnant men and women and can occur in
Santos et al [4] propose another way to conduct positive some clinical situations, such as in the case of
tests in step I: autoimmune diseases. To exclude the diagnosis of HIV
If the result is positive, the serology must infection in cases of suspected false-positive results,
be repeated in a second collection. testing should be repeated on a new sample [6].
Continuing the ELISA positivity, it is
necessary to carry out a confirmatory test,
which has greater specificity (indirect
immunoflorescence or Western-blot).
The rapid HIV test has high sensitivity and specificity and, Samples with reagent results in TR1 and TR2 will have
therefore, high rates of false positives in low-prevalence their result defined as: “Sample Reagent for HIV” without
populations, such as pregnant women. It is reserved for the need for any additional tests [6].
cases in which the pregnant woman did not collect HIV Samples with discordant results between TR1 and TR2 will
serology during the prenatal period, in situations in which not have their result defined. In this case, the report will not
there is no access to the test result or when the patient is at be released and a new sample must be collected by
risk of constant exposure and has not repeated the serology venipuncture and submitted to the flow chart. If the
at the end of pregnancy. The patient's verbal consent for the definitive diagnosis is not established, the doctor and the
examination is mandatory [5]. The following rapid tests pregnant woman must jointly define the conduct,
have been validated: Rapid Check HIV 1 & 2TM; Rapid considering the risk-benefit relationship and including the
HIV Test 1 / 2TM - Biomanguinhos; Determine HIV 1 / use of other diagnostic methods [6].
2TM; Unigold HIV TM; BD Check HIV Multi-test; HIV
What concerns should the medical team take?. All
1/2 Colloidal Gold.
members of the medical team participating in invasive
The sample with a non-reactive result in the rapid test 1 procedures, including surgical or obstetric procedures, must
(TR1) will be defined as “Non-Reagent Sample for HIV”. use appropriate barrier precautions to avoid contact with
In this case, the diagnosis of the infection is completed, and the skin and mucosa with the blood and other body fluids
there is no need to perform any additional tests [6]. of all patients. Gloves, surgical masks and goggles should
Samples with reagent results in TR1 should be subjected to be used in all invasive procedures that commonly result in
rapid test 2 (TR2). When available at the health service, the the generation of droplets, blood and other body fluids, or
rapid immunoblot can also be used as TR2 [6]. bone fragments. Liquid-resistant cloaks or aprons that
provide an effective barrier should be used.
In the event that any member of the team is exposed or from HIV-associated immunodeficiency, regardless of CD4
punctured with a needle, prophylactic treatment must be count and plasma viral load and T-CD4 lymphocyte count
initiated. As an important addendum to the safety of <200 / mm3 [1].
medical staff, unfortunately, if guidance on these The goal of prophylactic ART in pregnant women is to
precautions is reserved for women who are known to be achieve undetectable CV, thus reducing the risk of VT. The
HIV positive, a large number of women with incubated or scheme with the best results in reducing viral load should
asymptomatic infections, who are not diagnosed, will pose be offered, which unleashes the least potential for maternal
a greater threat to medical team. and fetal toxicities and has the least risk of inducing viral
How to proceed with treatment. The two main categories of resistance [1].
antiretrovirals (ARV) are: those that inhibit the viral The first clinical study that used antiretroviral therapy in
enzyme reverse transcriptase and those that inhibit the order to reduce rates of vertical HIV transmission was
enzyme viral protease. Reverse transcriptase inhibitors may Protocol 076, from the Pediatrics Aids Clinical Trial Group
be non-nucleoside (NRTI), such as zidovudine (AZT) and (PACTG 076). This was a randomized, placebo-controlled
lamivudine, or nucleoside (NRTI), such as nevirapine. study that used a protocol consisting of oral zidovudine
They block the HIV replication cycle in RNA-dependent (AZT) from the 14th week, intravenous AZT (EV) 4 hours
DNA synthesis (reverse transcription). Inhibitors of the before delivery and AZT oral solution for the newborn, for
viral protease enzyme prevent virions, formed within the 6 weeks [ 6].
infected cell, from being released to infect new cells. An
This intervention reduced the rate of vertical HIV
example of ARVs in this group is ritonavir [12].
transmission by 67.5%. Vertical transmission rates were
Current recommendations for the use of antiretroviral 25% in the placebo group and 8.3% in the group that
therapy (ART) in pregnancy are quite aggressive and use received the AZT intervention. In PACTG 076, the
broader criteria for indication than for adults in general. development of viral resistance to zidovudine monotherapy
This is due to the objective of achieving undetectable viral was observed in approximately 2.7% of patients [6].
load at the end of pregnancy and the consequent benefit of
The effect of AZT on HIV viral load is not the only factor
non-vertical transmission. However, it is questioned
responsible for reducing vertical transmission. Studies of
whether the “prophylactic” use of antiretrovirals would not
placental perfusion have shown that AZT is metabolized to
harm the future treatment schemes for this patient, outside
active triphosphate within the placenta, which could be
the gestational period. On the other hand, it is known that,
responsible for additional protection against intrauterine
after delivery of women without ART or using AZT, there
transmission.
is a rebound effect with an increase in viral load that
reaches levels higher than those observed pre-treatment. In comparison with other antiretrovirals, resistance to
Stopping or continuing ART in the puerperium, an increase zidovudine develops slowly, especially when associated
in viral load is observed in the period, suggesting that the with high viral load. Resistance has not been found in
physiological changes in pregnancy are responsible for this women who have used shortened regimens of these drugs
increase in viral load (CV). Women who received ART to prevent vertical HIV transmission [6].
during pregnancy have a lower risk of developing AIDS in The use of regimens combined with two antiretrovirals
the postpartum period, regardless of therapy [1]. (dual therapy) showed a five-fold reduction in the rate of
It is necessary to be clear the difference between the vertical transmission compared to the results of AZT
institution of antiretrovirals in pregnant women with the monotherapy. Dual therapy consisted of the association
aim of preventing vertical transmission - prophylactic between zidovudine and lamivudine.
TARV - and the institution of this therapy because there is In the Ministry of Health Manual [6], a study published in
an indication for the compromised clinical and / or 2002, evaluating 1,442 pregnant women, showed the
immunological status of the woman - ART treatment. following vertical transmission rates: 20% in the absence of
Women on antiretrovirals, under ART prophylaxis, may ART, 10.4% with AZT monotherapy, 3.8 % in dual therapy
have this therapy suspended at the end of pregnancy. This and 1.2% in highly active regimens (combination of three
assessment should be carried out, preferably, in the first 2 ARVs or HAART - high potency antiretroviral therapy).
weeks postpartum, in a specialized service [1]. Other studies have confirmed this hypothesis.
The indications for starting ART treatment in pregnant The HIV-NET 012 randomized clinical trial, which
women follow the same principles as for non-pregnant compared nevirapine versus oral zidovudine administered
patients: clinical manifestations or complications resulting at the beginning of labor and in newborns, showed that
perinatal HIV transmission rates were lower in the group pregnant women; adequate prenatal care; and elective
receiving nevirapine (13.1% vs 21.5%; p <0.001), RR 0.58 cesarean section when the viral load was high.
(95% CI 0.40-0.83). However, nevirapine resistance can be The prohibition of breastfeeding, with the provision of milk
induced by a single genotypic mutation, detected in 15% of formula for the newborn, is also an important measure of
women in six weeks postpartum, making it impossible to reducing vertical transmission of HIV [13].
use this drug or any other protease inhibitor later, and for
In children fed with breast milk, the effectiveness of
this reason, it should be used only if there is no other
antiretroviral has been reduced to about 30%. There is no
alternative (evaluate risk-benefit).
doubt that the use of ARVs during pregnancy has been the
The goal of reducing vertical transmission means that every factor with the greatest impact in reducing the rate of
HIV-infected pregnant woman is treated with potent vertical transmission in recent years (Brocklehurst). There
antiretroviral therapy, regardless of her immunological or are, however, some studies that show the possible side
virological status. The prophylactic use of ARVs should be effects in pregnant women and newborns (NB) who are
started from the 14th week of pregnancy; the start of ARVs submitted to this practice [13].
is not an emergency, and clinical and laboratory
In addition to antiviral treatment to prevent vertical
evaluations must be carried out prior to the start of ART,
transmission, prenatal care should include counseling and
except in pregnant women who start care in advanced
aspects of contraception to avoid future pregnancy.
pregnancies (more than 28 weeks) or in those who use
recreational drugs or co-infections that can disturb the However, in the guidance on contraception we must
placental barrier and increase the risk of VT. In these remember:
situations, the initiation of ART should be carried out even Although HIV infection is sexually
before obtaining the results of the pre-treatment tests, transmitted, and vertical transmission of the
which should ideally be collected before the initiation of virus may also occur, infected women have
ART [1]. the same reproductive rights as all others,
Women who have already received ARV prior to recognized by foreign and national
pregnancy should be informed about the potential risks / legislation. These recommendations
benefits of maintaining, modifying or suspending establish the right of every couple to decide
treatment, with regard to the evolution of their own disease. freely and responsibly about their
In addition, the potential adverse effects of ARV therapy reproduction, and to have access to
on the child should be considered. The conduct should be information on ways to do so and how to
decided, case by case, by the obstetrician and clinician / have a healthy and safe sex life, free from
infectologist, together with the pregnant woman. In discrimination or violence [14].
general, it is recommended that if the woman is not using Regarding the adverse effects of antiretrovirals during
therapy known to be associated with teratogenicity to the pregnancy, the Ministry of Health Manual [6] states that:
fetus (mainly efavirenz), the need to maintain ART to
The adverse effects rarely determine the
benefit the pregnant woman and, indirectly, maintain
suspension of the use of ARVs, since the
virological control and TV reduction [1].
effectiveness of these drugs in preventing
The Ministry of Health Manual [6] recommends: vertical transmission of HIV, clearly
Due to its potential to inhibit viral outweighs the risks of adverse reactions to
replication, lower risk of viral resistance in them.
the short term and greater safety of The physiological changes that occur during pregnancy can
antiretrovirals, ART should be administered affect the kinetics of drug absorption, distribution,
to all HIV-infected pregnant women, with biotransformation and elimination, potentially changing the
the association of three antiretrovirals, pregnant woman's susceptibility to toxicity to different
regardless of virological, clinical or drugs [6].
immunological.
Among the antiretrovirals available, zidovudine (AZT) and
In addition to the appropriate antiretroviral treatment, other the one that most presents data related to pregnancy safety;
measures were necessary and contributed to the great information about other antiretrovirals is limited [6].
decrease in the vertical transmission rate in recent years:
With the use of AZT we can observe spinal toxicity,
anti-HIV examination during pregnancy and counseling for
macrocytic anemia (severe when Hb <8 g / dl) and
neutropenia (severe when leukocytes <1.000 cells / mm3) consequences and exclusively related to the use of ARVs
[4]. during pregnancy [13].
The use of ARVs during pregnancy can cause side effects Table 1 lists in which category ARVs are classified by the
similar to those seen in any patient, such as mitochondrial Food and Drug Administration (FDA) and whether or not
toxicity, hypersensitivity reaction and lipodystrophy. In there is a transplacental passage.
addition to these effects, there are other possible
Table 1 - Antiretrovirals, FDA pregnancy categories and transplacental passage.
Antiretroviral FDA (Food and Drug Passage through the
Administration) Gestation placenta
Categories
Fusion Inhibitors
Enfuvirtide Ignored
Integrase Inhibitors
Raltegravir B Yes (rats, rabbits)
Source: Adapted From Recomendations for use Of Antiretroviral Drugs In Pregnant Hiv Infected Women For Maternal Helth
And Interventios To Reduce Perinatal Hiv Transmission In The United States (2008).
In a study carried out by Alcântara et al [15] on situations Women reported difficulties in accepting
that make it difficult for pregnant women to adhere to the diagnosis of HIV, especially when it
treatment, it was shown: occurred during pregnancy, a situation that
Barros et al [13] recognize ARV and pre-eclampsia as We prospectively evaluated 109 HIV-
adverse effects related to pregnancy. Preeclampsia positive pregnant women using
complicates about 3% of pregnancies, and is one of the antiretrovirals and 200 control pregnant
major causes of maternal and perinatal morbidity and women, with monthly obstetric ultrasound
mortality, especially in developing countries. Some monitoring and fetal and postnatal
studies have tried to demonstrate the association between echocardiography performed with the
the onset of pre-eclampsia and the use of ARV for assessment of amniotic fluid volume,
prophylaxis of vertical HIV transmission. Despite very weight adequacy. the presence of fetal
controversial findings in different studies, there seems to structural changes and perinatal results. As
be no strong association between the use of ARV and relevant results, a higher prevalence of fetal
preeclampsia during pregnancy. Some studies suggest that heart disease and changes in the amount of
HIV infection may decrease the prevalence of amniotic fluid were observed in the studied
preeclampsia due to incompetence of the immune system. group compared to the control group. Fetal
With the use of ARVs, the prevalence is equivalent to that and perinatal echocardiographic evaluations
found in uninfected patients, considering that the showed four cases (3.7%) of heart disease
competence of the immune system is restored [13]. in the study group and none in the control
Barros et al [13] report the adverse effect of group. Thus, although there were no
Teratogenicity related to the use of ARV. The treatment of differences for malformations as a whole,
HIV infection with ARV during pregnancy has been a when we considered only heart diseases,
very common and effective practice, used in recent there was a significant difference.
decades to reduce vertical transmission of the virus. This Considering their findings, Lopes et al [17] suggest:
practice has led to the current concern with the possibility Thus, it should be noted that routine fetal
of a teratogenic effect due to the use of these medications, echocardiography is indicated in HIV
prophylactically, during pregnancy. Efavirenz has been seropositive patients on ART.
associated with neural tube malformations in baby
There is still an adverse effect of hepatotoxicity related to
monkeys exposed to medication for some years, but most
the use of ARV during pregnancy. A randomized clinical
studies in humans are inconclusive [13]. Most studies
trial, comparing nelfinavir and ne¬virapine, showed
have shown no association between the use of ARV and
severe hepatic adverse effects in pregnant women with a
fetal malformations. The use of AZT in the first trimester
CD4 + T-cell count greater than 250 cells / mm3, using
was associated with an increased risk of hypospadias in
nevirapine [13]. According to Barros et al [13], in a
male fetuses. It should be noted, however, that in the last
retrospective study published in 2005, there was a
decades there has been an increase in the incidence of
significant association between the use of nevirapine and
hypospadias, and this association may be just a
the increase in liver enzymes during pregnancy. Such an
correspondence to the world trend.
association was not significant in non-pregnant women. In
Santos et al [4] contraindicate the use of some ARVS and another Brazilian, he showed liver toxicity in 5.6% of the
affirm its deleterious effects: patients using nevirapine, with a case of Steven Jonhson's
Efavirenz: anencephaly, anophthalmia, Syndrome [13].
microphthalmia, cleft palate, About ARV, prematurity and low birth weight, Barros et
myelomeningocele. Amprenavir: fetal al [13], explain that perinatal adverse events related to the
alcohol syndrome. Tenofovir: osteomalacia use of ARV have been questioned by several authors.
(study in animals). Indinavir: associated
A possible association between ARV use and prematurity
with hyperbilirubinemia and
was initially detected in 1998, when the observation of the
nephrolithiasis.
occurrence of ten preterm infants in 30 women using
In a study by Lopes et al [17] comparing fetal structural ARV therapy was published in a Swiss study. A combined
and / or functional changes to ultrasound and analysis of the European and Swiss study confirmed the
echocardiography and perinatal results in pregnant women increased risk of early delivery in the group of women
seropositive for the human immunodeficiency virus (HIV) using combined ARV therapy, compared to women
in relation to a control group of patients attended by low- without treatment. There was also an association with a
risk prenatal care, he discussed his findings: higher occurrence of prematurity in patients using
HAART therapy compared to those using therapy with regimen, regardless of her immunological or virological
only one or two ARVs [13]. status. Currently, the use of AZT monotherapy is no
Barros et al [13], complement that several studies have longer recommended, as this regimen does not offer good
been done in this sense, however, the association between control of maternal viremia, which is the factor most
prematurity and low weight with the use of ARVs during strongly associated with VT. Following data from ART
pregnancy remains controversial. On the other hand, it recommendations in adults, the AZT / 3TC association
appears that the birth of low birth weight neonates, in was maintained as the pair of nucleoside analogs of first
pregnant women who have been treated with HAART choice to compose the initial ARV scheme. In cases of
therapy, is more frequent. However, there is no doubt AZT intolerance, enteric didanosine (DDI EC) or
about the great benefit of combined ARV therapy in tenofovir remain as substitution alternatives, always
reducing vertical transmission, which should continue to associated with 3TC [1].
be used, taking into account the neonatal risks and future Due to the adverse effects of efavirenz, mainly due to its
benefits for these children. Pregnant women must have teratogenicity, it is no longer the third preferred drug in
careful postnatal care, since prematurity and low weight the regimen for pregnant women. Since nevirapine has
are factors that significantly increase perinatal morbidity been associated with serious side effects, mainly allergy
and mortality. and hepatotoxicity in women with a high CD4 level
Figueiro, Coelho, Tamura [16] agree (greater than 250), it was preferred to use protease
inhibitors as the third preferred drug in the regimen,
In a study evaluating the effect of
according to the Febrasgo High Risk Gestation Manual
antiretroviral drugs and their association
[1].
with changes in the anthropometric
parameters of neonates of pregnant women Thus, the preferred regimen of prophylactic ART during
with HIV-1, it was observed that there was pregnancy or the first therapeutic regimen will be the use
no difference between the Control Group of AZT + 3TC + lopinavir / ritonavir, based on experience
compared to the group using zidovudine of use, in the largest number of clinical studies with this
and the group who used the combination of protease inhibitor and in high potency and durability of
zidovudine with lamivudine and nelfinavir that ARV scheme. In the event of intolerance to lopinavir,
with regard to the duration of pregnancy, atazanavir is a safe and effective alternative, always
Apgar score and neonatal anthropometric associated with ritonavir [1].
classification. There was also no increase in For Bassichetto et al [18] PIs should always be
the incidence of preterm births in pregnant combined with ritonavir as a pharmacological adjuvant,
women who received the combination of which has the advantage of providing higher and more
antiretroviral drugs containing a protease stable IP blood levels for a longer time, which determines
inhibitor. a low risk of mutations that confer resistance viral.
The Febrasgo High Risk Pregnancy Manual [1] clarifies In practical terms, after the 14th week of gestation, the use
about antiretrovirals in prenatal care. Every HIV-infected of prophylactic ARVs to reduce HIV-1 VT is indicated,
pregnant woman should receive ART during pregnancy. It and should be instituted as soon as the laboratory tests of
is necessary to detect the difficulties of understanding on liver function show that its use can be started. If the
the part of the patient in relation to the use of medications, patient is being treated for HIV-1 infection, it is not
as well as other possible obstacles to her adherence to the advisable to stop the treatment because of the pregnancy,
treatment, guaranteeing her access to clear information just adjust it. If zidovudine is not part of the scheme used,
about the objectives of the treatment; the meanings of it is suggested to introduce it [9].
viral load tests and CD4 + T lymphocyte count; the need According to Duarte et al [9]:
to adhere to the proposed therapeutic regime; the potential
The combination of two reverse
adverse effects for the mother and fetus; the drugs that
transcriptase inhibitors (zidovudine and
make up the scheme and its mechanisms of action; the
lamivudine) is marketed in the Brazilian
importance of avoiding the use of alcoholic beverages and
market in a single product (zidovudine 300
recreational drugs; the importance of the systematic use of
mg tablet + 150 mg lamivudine),
condoms and the need for periodic consultations and
administered orally, twice daily. The
exams in the segment [1]. Every pregnant woman should
protease inhibitors recommended for
use potent ART as a prophylactic or initial therapy
preferential use in pregnant women are a
combination of two drugs in this group genotyping prior to switching to a new ART scheme. It is
(200 mg lopinavir tablets + 50 mg ritonavir argued that all pregnant women should be genotyped
tablets) and two tablets are administered before the introduction of the first ARV regimen, aiming
orally twice daily. This guideline has also mainly to avoid the onset of an inadequate or flawed
been adopted by the Brazilian Ministry of regimen and that increase the risk of virological non-
Health's National STD / AIDS Program. suppression and the possibility of fetal / newborn resistant
According to the Frebasco “High Risk Pregnancy strain TV. This is still a consideration not fully supported
Guidance Manual - Human Immunodeficiency Virus by the Brazilian Ministry of Health, due to the low
Infection in Pregnancy” [1] in the event of a non- occurrence of primarily resistant strains in our population.
virological response after the introduction of ART, the Table 2 summarizes the antiretroviral therapy
patient should follow ART recommendations in adults and recommendations during prenatal care, following the
whenever possible, these cases should be conducted after guidelines of the Ministry of Health [6].
Table 2 - Recommendations for prophylaxis of vertical HIV transmission and antiretroviral therapy in pregnant women.
Gestational Age Pregnant Woman's Clinical and
Medical Conduct
Laboratory Status
Between 14 and 28 symptomatic, with LT-CD4 + count
weeks of gestation ≥ 350 Combined ART prophylaxis (combination of three
ARVs)
After 28 weeks of Asymptomatic, no LT-CD4 + count Collect blood for LT-CD4 + and CV counts, immediately
gestation available start prophylaxis with combined ART (association of
three ARVs) regardless of LT-CD4 + and CV results
<14 weeks and LT-
CD4 + count close to Asymptomatic, with LT-CD4 +
350 cells / mm³ count between 200 and 350 cells / Entering ART after 14 weeks of gestation
mm³
Brazil in the “Treatment Guide - Recommendations for amniotic membranes. Remember that pregnant women
Prophylaxis of Vertical HIV Transmission and with HIV can go into labor one to two weeks before the
Antiretroviral Therapy in Pregnant Women” [6] on expected date. Therefore, it is prudent to discuss this
childbirth care for HIV-infected pregnant women shows possibility with all pregnant women in the same situation,
that several studies published before the introduction of instructing them to seek maternity as soon as possible if
highly active antiretroviral regimens demonstrated the they go into labor or if the amniotic membranes rupture.
benefit of elective cesarean section in reducing vertical In the event that the pregnant woman goes into labor
transmission (VT) of HIV compared to other types of before the scheduled date for the elective cesarean, as long
delivery. However, at the time these studies were carried as the cervical dilation is less than 3 cm and the amniotic
out, the current combined regimens of three antiretrovirals membranes are intact, the cesarean can be performed [6].
(highly active regimens) were not yet used and the Duarte et al [9] agree:
measurement of viral load levels was unknown. The
It is believed that cesarean sections
Cochrane Group carried out a systematic review,
performed at the beginning of labor still
published in 2005, to assess the effectiveness and safety of
bring some benefit for the reduction of
elective cesarean sections in preventing vertical
HIV-1 VT. In view of this practical
transmission. It was concluded that elective cesarean
assertion, it is tolerable that the item "out of
section was an effective intervention for the prevention of
labor" is not completely observed,
vertical transmission of HIV, in women who did not use
accepting "labor still in its initial phase (2
ARV during pregnancy and in those who used only AZT.
to 3 cm of cervical dilation) does not
The studies conducted so far have not shown differences contraindicate cesarean section as
in vertical transmission rates when comparing elective prophylactic measure of HIV-1 TV ”.
cesarean section and vaginal delivery in preventing HIV
The definition of the mode of delivery should be based on
transmission, when the viral load is less than 1,000 copies
the result of the maternal viral load, carried out after the
/ ml in pregnant women who are using a combined
34th week, in association with the obstetric evaluation [6].
antiretroviral regimen. The elective cesarean section is the
In women with a viral load below 1,000 copies / ml, this
one performed before the beginning of labor, with the
definition can be discussed between the pregnant woman
integral amniotic membranes. It is indicated for HIV
and her obstetrician, due to the observation that the type
seropositive pregnant women, when they have viral load
of delivery in these conditions, whether normal or
≥1.000 copies / ml or unknown, after 34 weeks of
operative, does not change the risk of vertical
gestation.
transmission of the baby. HIV, safeguarding the
Duarte et al [9] remember about the causes of placental recommendations regarding the management of childbirth
lesions and amniorrexis in choosing the mode of delivery: [6].
In choosing the mode of delivery, it should Elective cesarean section, in order to reduce vertical
be remembered that placental lesions and transmission of HIV, is indicated for pregnant women
rupture of amniotic membranes are the who, at the end of pregnancy (after 33-34 weeks), have an
main anexial factors that potentially unknown viral load or greater than 1.000 copies / ml.
increase HIV-1 VT, since they facilitate the When the viral load is less than 1.000 copies / ml, the
virus's access to the fetus. In order to avoid mode of delivery will be defined by exclusively obstetric
these changes, it is important to note that criteria.
smoking and the use of illegal recreational
Therefore, elective cesarean section should be indicated
drugs cause placental microinfarctions.
for HIV + pregnant women who did not undergo
Additionally, all clinical situations related
combined antiretroviral prophylaxis during pregnancy,
to premature rupture of the amniotic
who used only AZT monotherapy or who have their viral
membranes must be remembered. Among
load, at 34 weeks or more of gestation, unknown or
these situations, the most frequent are
greater than 1,000 copies / ml [6].
genital and systemic infections and preterm
labor. For pregnant women who arrive at the maternity hospital
in labor and who have not taken antiretroviral prophylaxis
The elective cesarean section should be scheduled
during pregnancy, the indication of the mode of delivery
for the 38th week of pregnancy, avoiding that the pregnant
should take into account the stage of labor in which the
woman goes into labor and premature rupture of the
mother is and the prognosis of the time of evolution for
delivery, as well as the likelihood of complications during will have amniorrhexis whose labor
delivery. When labor is in rapid evolution, with a rapid exceeds this time, some services adopt such
birth prognosis, vaginal delivery should be indicated, conduct, instituting the washing of the
using all precautions to reduce the risk of HIV vaginal canal shortly after establishing the
transmission. If the labor is in its initial phase, with 3-4 diagnosis of labor in the woman infected
cm of dilation of the uterine cervix and the amniotic with HIV-1, in order to remove all vaginal
pouch is complete or with a rupture of less than 2 hours, content. The substance used can be
the cesarean section should be indicated immediately, to polyvinylpyrrolidone-iodine, chlorhexidine
reduce the risk of VT during labor [6]. or benzalkonium chloride.
Brazil in the “Treatment Guide - Recommendations for Every HIV-positive pregnant woman should receive an
Prophylaxis of Vertical HIV Transmission and intravenous infusion of AZT at the beginning of labor
Antiretroviral Therapy in Pregnant Women” [6] until the birth of the newborn, regardless of the
recommends the following general care in labor and antiretroviral regimen used in prenatal care, and the level
delivery: 1. Administer intravenous AZT from the of viral load [6]. Antiretrovirals in use during prenatal
beginning of labor until birth and clamping of the care should be continued during the period of
umbilical cord. All pregnant women in labor should hospitalization for delivery, following the original medical
receive AZT, including those who did not use it during prescription regardless of the prescribed fasting period
pregnancy and those who presented toxicity to it orally; and the use of injectable AZT, to maximize the protective
pregnant women hospitalized for sedation of preterm effect of vertical transmission and to reduce the risk of
labor must receive AZT EV while they are experiencing developing resistance to antiretrovirals. If it is possible to
uterine contractions; 2. Clamp the umbilical cord stop taking medications after delivery (ARV for
immediately after birth, without performing milking; 3. prophylactic purposes), all drugs should be suspended
Avoid invasive procedures during pregnancy, labor and together, except for regimens containing nevirapine,
delivery, such as cordocentesis, amniocentesis, which should be phased out: initially, remove nevirapine,
amniotomy, the use of forceps and vacuum extractor; 4. In maintaining AZT and 3TC for a period of one to two
vaginal delivery, avoid episiotomy whenever possible; 5. weeks, according to the “Recommendations for
Monitor labor, using the partogram, avoiding repeated antiretroviral therapy in HIV-infected adults - 2008”. If
touches; 6. In case of early rupture of the amniotic the pregnant woman is using stavudine, this medication
membranes during labor, assess the prognosis of evolution should be discontinued before the administration of
and use oxytocin, if necessary, to avoid prolonged labor intravenous AZT [6].
with an increased risk of vertical transmission. If oxytocin For pregnant women with indication for elective cesarean
is contraindicated and prolonged labor is foreseen, section, the AZT infusion should start 3 hours before
caesarean section may be indicated (1, A); 7. After birth, surgery and be maintained until the time of birth.
the woman and the newborn, being in good health, can be
HIV positive patients who arrive at the maternity hospital
referred to joint accommodation.
in labor, and who have not taken ARV prophylaxis during
For Duarte et al [9], patients who evolve to normal pregnancy, will immediately start using intravenous AZT
delivery, it is necessary to wash the vaginal canal, right and the newborn will receive AZT orally, starting within 2
after the diagnosis of labor is confirmed: hours. after birth.
Defining that the mode of delivery will be Duarte et al [9] explain the intravenous AZT dosage in the
vaginal, when the patient goes into labor, a peri-delivery period:
series of small interventions must be
In cases where the mode of delivery will
carried out. Despite divergent opinions
depend only on obstetric criteria, as soon as
regarding the effect of washing the birth
the pregnant woman enters labor,
canal on the effective reduction of HIV-
zidovudine should be administered
1,8,12 VT, it is known that it reduces this
intravenously at a dose of 2 mg / kg of
complication in cases of amniorrexis with
weight, followed by continuous infusion at
more than four hours of evolution. For
a dose of 1 mg / kg body weight / hour until
other authors, washing the vaginal canal
delivery, regardless of having used ARV
with 0.4% chlorhexidine is associated with
during prenatal care. In cases of elective
reduced perinatal transmission of this virus.
cesarean section, it is advisable to start the
As it is not possible to predict which patient
AZT infusion three hours before beginning The Febrasgo High Risk Gestation Manual [1]
the surgery, with hourly peaks of 1 mg / kg recommends the same dosing schedule as PACTG 076,
of weight. thus disagreeing with Duarte et al [9] with regard to the
attack dose in elective cesareans, as it deems it necessary.
Table 5 - Dilution of zidovudine considering the loading dose and maintenance doses, according to the weight of the
pregnant woman and the desired concentration. In the example in this table, 100 ml of 5% glucose serum will be used,
remembering that each ml of the zidovudine ampoule has 10 mg of the drug.
Pregnant weight
Dose Variables 40 kg 50 kg 60 kg 70 kg 80 kg 90 kg
The first consultation is extremely important, as in it the 1. CBC: monitoring the toxicity of antiretrovirals (mainly
doctor must collect all the data necessary to understand AZT);
the patient, in addition to guiding the possible risks that 2 CD4 cells: assessment and staging of the disease;
she runs, as well as the fetus.
3. Liver and kidney function: monitoring the toxicity of
Laboratory tests include basic prenatal examinations, plus antiretrovirals;
the necessary tests to assess the progression of the disease,
4. VDRL: HIV / Syphilis co-infection;
possible changes caused by antiretrovirals and serologies
and tests for opportunistic infections. Possible adverse 5. Hepatitis B and C: hepatitis C / HIV co-infection and
factors should be identified, such as smoking, use of hepatitis B vaccination;
intravenous drugs and alcoholism. 6. Toxoplasmosis: Risk of reactivation, especially if the
The initial physical examination should be as detailed as CD4 cells are below 100 / mm³;
possible, with special attention to the systems most 6. Rubella, urine culture, ABO blood group, RH factor,
affected by HIV and the possible signs of blood glucose: basic tests;
immunodeficiency that they may show. The table below
7. Cytomegalovirus (CMV): risk of reactivation;
shows the main ones.
8. PPD: positive test (> 5mm): perform tuberculosis
prophylaxis;
Table 7 - Signs of immunodeficiency.
9. Culture and / or PCR for chlamydia and gonococci: Not
Signs of Immunodeficiency mandatory;
- Repeated vaginal candidiasis; 10. Cervico-vaginal oncotic cytology: screening for
- Oral and esophageal cadidiasis; cervical intraepithelial neoplasia and cervical cancer.
- Atypical pneumonia; The administration of vaccines with live attenuated
viruses in pregnant women and / or patients with
- Recurrent herpes zoster;
immunodeficiency is subject to individual risk-benefit
- Extragenital contagious mollusk; analysis and should not be performed in case of severe
- Recurrent cervical intraepithelial neoplasia (CIN); immunodepression. In addition to the aspects that concern
- Recurrent and atypical genital herpes. pregnancy, it is necessary to consider the immunological
conditions of the pregnant woman. In HIV infection, as
immunodepression increases, the possibility of a
Among the routine exams, the first consultation of the consistent immune response is reduced. The table below
HIV positive pregnant woman should also contain: shows recommendations on vaccination for HIV-positive
pregnant women.
Hepatitis B vaccine Recommended for susceptible pregnant women (anti-HBs negative), at risk. The dose
should be twice that recommended by the manufacturer: time 0, 1, 2 and 6 or 12 months.
Human immunoglobulin Recommended for susceptible pregnant women (anti-HBs negative), drug users who share
for hepatitis B virus syringes and needles, those who have unprotected sexual contact with HBsAg positive
(HBIG) people or in the case of victims of sexual violence. It must be started within the first 14 days
of exposure.
Hepatitis A vaccine Recommended for susceptible pregnant women (anti-HAV negative) co-infected with
hepatitis B or C. Perform two doses with an interval of 06 months.
Influenza Recommended annually for those infected with HIV before the influenza period. Trivalent
inactivated vaccine, one annual dose, can be given during pregnancy.
Immunoglobulin for Recommended for susceptible pregnant women (negative anti-VZV) after exposure to the
varicella zoster virus home, hospital or close neighbors.
(VZV)
Source: Brasil [6].
woman using the specific forms - Notification and 5. Human immunoglobulin for hepatitis B virus
investigation form for HIV + pregnant women and (recommended for susceptible pregnant women who have
exposed children. had unprotected sexual contact or drug users who have
1. Routine prenatal examinations at the first consultation shared syringes and drugs with HBsAG positive people or
of the HIV-positive pregnant woman: in the case of victims of sexual violence. Must be started
within the first 14 days exposure);
• CBC, liver and kidney function (monitoring of ARV
toxicity) 6. Immunoglobulin for varicella zoster virus
(recommended for susceptible pregnant women, after
• VDRL, hepatitis B and C (HIV / Syphilis co-infection,
exposure to the home, hospital or close neighbors);
hepatitis C / HIV;
7. Prophylaxis for Pneumocystis carinii pneumonia (PCP)
• Toxoplasmosis and Cytomegalovirus (risk of
is indicated in pregnant women with previous pneumonia,
reactivation, especially if CD4 cells are below 100 /
by CD4 below 200 and unexplained fever:
mm3);
Sulfametoxazol-Trimetropina (400mg / 80mg) 2 tablets a
• Basic exams (Rubella, urine culture, ABO blood group, day 3 times a week, after the 1 trimester, stopping at 36
RH factor, blood glucose); weeks;
• PPD (Perform tuberculosis prophylaxis); 8. Guide patients not to breastfeed.
• Cervical-vaginal cytology. Other Recommendations: Follow-up by a
2. Others that are necessary according to the associated multidisciplinary team, in which the infectious disease
pathologies. specialist plays an important role in guiding antiretroviral
medication, as well as in guiding prophylaxis and treating
3. Count of CD4 lymphocytes every quarter.
opportunistic infections (such as those caused by
4. Quantification of viral load every quarter. Pneumocystis and Toxoplasma gondi); Avoid invasive
Pre-Christmas and Puerperium: procedures, such as amniocentesis and cordocentesis; At
each prenatal visit, pay attention to the presence of
1. Early supplementation of iron and folic acid;
intercurrent gynecological infections, including HPV;
2. Guide the use of condoms in all intercourse during Virological and immunological assessment tests should be
pregnancy; performed periodically (viral load, CD4 and CD8), as well
3. Guide to quit smoking and illicit drugs; as blood count, kidney and liver function; Serologies
4. Routine vaccination against tetanus and diphtheria (dT) indicating susceptibility should be repeated every quarter;
(Booster indicated if the last dose has been administered If the pregnant woman already uses antiretroviral therapy,
more than 5 years ago. If the pregnant woman is not it should be maintained until the infectologist evaluates;
vaccinated or the vaccination status is unknown, indicate drugs contraindicated in pregnancy should be replaced.
three doses), hepatitis B ( Recommended for susceptible Drug Treatment in Pregnancy: Aiming only at
pregnant women, the dose should be twice that prophylaxis of vertical transmission, treatment should be
recommended by the manufacturer: time 0, 1, 2 and 6 or started from the 14th week of pregnancy. The
12 months), H1N1 (Recommended annually for those recommended first choice regimen is Biovir® (AZT 300
infected with HIV before the influenza period. Trivalent mg + Lamivudine 150 mg) - 1 tablet orally every 12 hours
inactivated vaccine. DO NOT PERFORM DOSING CD4 combined with Kaletra® (Lopinavir 200 mg + Ritonovir
AND CV UP TO 4 WEEKS AFTER VACCINATION) 50 mg) - 2 tablets orally every 12 hours hours.
and Hepatitis A vaccine (recommended for susceptible The following table summarizes the recommendations for
pregnant women co-infected with hepatitis B or C. ART during prenatal care.
Perform two doses at an interval of 06 months);
Table 10 - Recommendations for prophylaxis of vertical HIV transmission and antiretroviral therapy in pregnant women.
Prophylactic schedule using AZT at the time of Table 12 - Maintenance (1mg / Kg / hour) - in continuous
Childbirth: All pregnant women who enter the Hospital de infusion - Preparation in 100 ml of SG5%.
Base Dr Ary Pinheiro should be asked for an HIV Qty of Number
serological test. Patient
Zidovudine in (drops /
Weight in Kg
In labor: Indicated for all patients, regardless of ART ml minute)
(Antiretroviral Therapy) used in pregnancy. Its presentation
40 4 35
is a 20 ml vial with 200 mg (10 mg / ml) of AZT. Attack
dose: 2 mg / Kg IV in the first hour (diluted in 100 ml of 50 5 35
5% SG) Maintenance dose: 1mg / Kg / hour IV until the 60 6 35
umbilical cord is clamped In elective cesareans, start AZT
70 7 36
at least 3 hours before withdrawal of the fetus. Do not
exceed a concentration of 4 mg / ml. 80 8 36
3. The elective cesarean section should be scheduled for the In cases of elective cesarean sections, use AZT
38th week of pregnancy, preventing the pregnant woman for 4 hours before the procedure.
from going into labor and premature rupture of the Childbirth care - general rules
amniotic membranes.
In cesarean section, perform a technique with
4. Regardless of viral load: advise cesarean in cases of rigorous hemostasis of all planes, including the
premature labor THAT DOES NOT RESPOND TO lower segment, with removal of impelled fetus (if
INHIBITION, giving AZT IV for at least 1 ½ hours, possible).
reassessing cervical dilation.
• Immediate clamping of the umbilical cord
Care in elective cesarean section
• Immediate removal of blood and secretions in
1. Administer AZT at least 3 hours before; contact with the newborn's skin and mucous
2. Maintain the ARVs taken by the pregnant membranes
woman while waiting for delivery, at the usual • Avoid prolonged labor
time, regardless of fasting (except stavudine - d4T
• Avoid amniotomy and prevent more than 4 hours
- which must be suspended 12 hours before);
of broken bag
3. Follow cesarean technique with emphasis on
• Do not perform forceps or episiotomy
removal of the fetus with intact membranes
(impelled), if possible; • Remove AZT intravenously after clamping the
cord
4. Clamp the cord immediately without milking;
• Maintain the antiretroviral regimen in the
5. Remove the maternal AZT IV; puerperium, when indicated (if it is therapeutic,
6. Use antibiotic prophylaxis routinely. and not only prophylactic for vertical
Comments transmission).
In cases of delivery with very rapid evolution, Maternal, obstetric, fetal, attachment, viral and postnatal
the loading dose of AZT should be administered factors increase HIV VT. Table 13 summarizes the factors
in 30 minutes. that increase Vertical HIV Transmission.