Valdiléa G Veloso Hiv Rapid Testing as a Key Strategy for Prevention of Mother-to-child Transmission in Brazil

Teste rápido para o HIV como estratégia de prevenção da transmissão vertical no Brasil ABSTRACT OBJECTIVE: To assess the feasibility of HIV rapid testing for pregnant women at maternity hospital admission and of subsequent interventions to reduce perinatal HIV transmission. METHODS: Study based on a convenience sample of women unaware of their HIV serostatus when they were admitted to delivery in public maternity hospitals in Rio de Janeiro and Porto Alegre, Brazil, between March 2000 and April 2002. Women were counseled and tested using the Determine HIV1/2 Rapid Test. HIV infection was confi rmed using the Brazilian algorithm for HIV infection diagnosis. In utero transmission of HIV was determined using HIV-DNA-PCR. There were performed descriptive analyses of sociodemographic data, number of previous pregnancies and abortions, number of prenatal care visits, timing of HIV testing, HIV rapid test result, neonatal and mother-to-child transmission interventions, by city studied. In Porto Alegre most of women were tested during labor (88.7%), while in Rio de Janeiro most were tested in the postpartum (67.5%). One hundred and forty-four infants were born to 143 HIV-infected women. All newborns but one in each city received at least prophylaxis with oral zidovudine. It was possible to completely avoid newborn exposure to breast milk in 96.8% and 51.1% of the cases in Porto Alegre and Rio de Janeiro, respectively. Injectable intravenous zidovudine was administered during labor to 68.8% and 27.7% newborns in Porto Alegre and Rio de Janeiro, respectively. Among those from whom blood samples were collected within 48 hours of birth, in utero transmission of HIV was confi rmed in 4 cases in Rio de Janeiro (4/47) and 6 cases in Porto Alegre (6/79). CONCLUSIONS: The strategy proved feasible in maternity hospitals in Rio de Janeiro and Porto Alegre. Efforts must be taken to maximize HIV testing during labor. There is a need of strong social support to provide this population access to health care services after hospital discharge. 804 HIV perinatal intervention in Brazil Veloso VG et al The prevention of mother-to-child transmission (PMTCT) has been a major successful public health effort to prevent HIV infection in developed countries. The use of highly active antiretroviral therapy (HAART) regimens during pregnancy for PMTCT, along with scheduled cesarean delivery and breas-tfeeding avoidance, have reduced HIV transmission rates to under 2%. 4 In developing countries, where the HIV impact is greatest, success has been limited not only by the cost …

The prevention of mother-to-child transmission (PMTCT) has been a major successful public health effort to prevent HIV infection in developed countries.The use of highly active antiretroviral therapy (HAART) regimens during pregnancy for PMTCT, along with scheduled cesarean delivery and breastfeeding avoidance, have reduced HIV transmission rates to under 2%. 4 developing countries, where the HIV impact is greatest, success has been limited not only by the cost involved on universal implementation of these interventions, but also by the weakness of health systems. 6SUMO OBJETIVO: Analisar a viabilidade da testagem rápida para o HIV entre gestantes na admissão à maternidade e de intervenções para reduzir a transmissão perinatal do HIV.MÉTODOS: Amostra de conveniência de mulheres que desconheciam sua situação sorológica para o HIV quando admitidas para o parto em maternidades públicas do Rio de Janeiro, RJ, e de Porto Alegre, RS, entre março de 2000 e abril de 2002.As mulheres foram aconselhadas e testadas com teste rápido Determine HIV1/2 na maternidade.Infecção pelo HIV foi confi rmada pelo algoritmo brasileiro para o diagnóstico da infecção pelo HIV.A transmissão intra-útero foi determinada pelo PCR-DNA-HIV.Foram realizadas análises descritivas dos dados sociodemográfi cos, número de gestações e de abortos prévios, número de visitas de pré-natal, momento da testagem para o HIV, resultado do teste rápido para o HIV, intervenções recebidas pelos recém-natos e de transmissão vertical do HIV, de acordo com cada cidade.

INTRODUCTION
Brazil was the fi rst developing country to implement a countrywide program to prevent HIV vertical transmission.HIV counseling and testing, HAART and infant formula are provided free of charge to patients. 21lthough signifi cant progress in reducing HIV motherto-child transmission (MTCT) has been seen in Brazil, 7 a signifi cant number of new HIV cases among infants continue to occur yearly.Women are either not tested during pregnancy or results are not available by the time of delivery. 20Rapid assays emerged to meet the demand where HIV testing is the main barrier to PMTCT.In Brazil, over 95% of women give birth in hospitals, a creating a key opportunity for systematic offering of HIV rapid testing, and other PMTCT interventions.The objective of the present study was to assess the feasibility of HIV rapid testing for pregnant women at maternity hospital admission and of interventions to reduce perinatal HIV transmission.

METHODS
We conducted a cross-sectional study.The study population was a convenience sample of women with unknown HIV serostatus, admitted for delivery in middle-and high-complexity maternity departments of charity or state-run hospitals in the metropolitan areas of Rio de Janeiro (RJ) and Porto Alegre (POA), Southeastern and Southern Brazil, respectively.The study was conducted between March 2000 and April 2002.The study sites in the city of POA started the study on May 2001.
The inclusion criteria included: unknown HIV serostatus (not tested in the current pregnancy or tested but women were not aware of the test result) by the time of admission for delivery; and signed informed consent.Women younger than 18 years old, not married or living with a partner or whose parents could not provide an informed consent for their participation were excluded as well as those with any clinical condition that could prevent them from being interviewed.Liveborn infants delivered by women found to be HIV infected were enrolled.
Women admitted were approached before delivery or in the postpartum.The underlying reasons for ineligibility or for refusing to participate were recorded in a contact form.
Women were informed that, although a positive result in the rapid testing would not be a fi nal diagnosis, PMTCT intervention (intravenous AZT, oral AZT and infant formula feeding) would be provided following the Brazilian Ministry of Health guidelines.b Women were counseled and tested on-site using the Determine HIV 1/2 Rapid Test (Abbott, Chicago, IL, USA) on whole blood.All positive results were confi rmed by local laboratories following the Brazilian Ministry of Health algorithm for HIV diagnosis (HIV-1 EIA followed by HIV indirect immunofl uorescence or HIV Western blot assay).Women with positive test results were seen once by a study team member in the postpartum and referred to HIV/AIDS specialized care in reference centers.At discharge, study outpatient visits were scheduled at one, three and six months for infants born to these women.For infant's HIV diagnosis, blood samples were collected within 48 hours of birth and during study visits.HIV-1 infection in infants was defi ned as the detection of HIV DNA by polymerase chain reaction (PCR) on two peripheral blood samples collected in different visits or the development of AIDS or death from an HIV-1-related cause.A child was classifi ed as HIV-1 uninfected if he or she was PCR negative on at least two occasions (with the second sample being obtained at three months of age or later).Infants with a positive DNA PCR in the blood sample collected within 48 hours of birth were defi ned as in utero-infected. 2For children who missed study visits, serology data were retrospectively collected and persistence or absence of antibody to HIV-1 beyond 18 months was considered for the determination of HIV infection status.Sociodemographic, reproductive and prenatal care data were collected by trained interviewers through of a structured questionnaire.All forms were piloted in the fi eld by at least one member of local study teams.Complementary clinical and laboratory data were obtained from women's and infant's charts.Ethnicity/skin color was classifi ed by the interviewers.The EpiInfo software 6.04 version was used to create study forms, enter data and minimize errors in data entry process.Data analysis was performed using the Statistical Package for Social Sciences (SPSS), version 7.0 for Windows.
Descriptive statistics were generated for all variables: age, schooling, skin color/ethnicity, family income, number of prenatal care visits, number of previous pregnancies and abortions, timing of HIV testing, HIV rapid test results, PMTCT intervention (intravenous AZT, oral AZT and infant formula feeding) and HIV MTCT.Mean (standard deviation, SD) and median (interquartile interval, IQI) were used to describe continuous variables.Contingency table statistics were used to verify non-homogeneity of proportions to compare women's sociodemographic, reproductive characteristics and prenatal care use in RJ and POA.
In RJ and POA, 23,360 women were contacted; of them, 73.5% and 74.1%, respectively, were tested during the current pregnancy and were unaware of their HIV serostatus.Among pregnant women with unknown HIV serostatus at delivery, 3.3% in RJ (4,347) and 0.3% in POA (1,794) refused to participate in this study.Other reasons for exclusion are presented in the Figure .The study protocol was approved by Institutional Review Boards of each maternity hospital and by the National Research Ethics Committee (CONEP) (Process Nr. 25000.002537/99-67;Approval date 02/26/1999).

RESULTS
Table 1 shows sociodemographic, reproductive and prenatal characteristics of pregnant women studied.Mean age was 24.6 (SD=6.5)and median age was 23 (IQI: 12;47).Overall, 82.6% of the women had eight or less years of schooling.About 60.0% of women were white in POA, and 70.0% were black or mixed ethnicity in RJ (p=0.000).Mean and median family income in Brazilian monthly minimum wages (BMMWs) in the last month was 2.5 (SD=2.3)and 2.0 (IQI: 0;60) in RJ and 2.6 (SD= 2.4) and 2.0 (IQI: 0;40) in POA.Family income up to one BMMW in the last month was reported by 30.3% of the women.
The proportion of women who did not attend prenatal care visits was higher in POA than in RJ.In RJ, women attended a higher number of prenatal visits compared to those in POA.Mean and median number of prenatal visits in RJ was 3.8 (SD=3.0)and 4.0 (IQI= 0;22) and in POA 2.9 (SD=3.1)and 2.0 (IQI: 0;23).
The proportion of women who reported at least one abortion was 23.6% in RJ and 18% in POA (p=0.001).
In RJ, 67.5% of women were tested in the postpartum period, while in POA, 88.7% were tested during labor (p=0.000).HIV infection was diagnosed in 6.5% and 1.3% of women in POA and in RJ, respectively (p=0.000).One hundred and forty-two singletons and a pair of twins were born to 143 HIV-infected women.One stillbirth and one newborn died within a few minutes after birth and were not considered for the description of PMTCT interventions in RJ.All but one newborn in each city received oral zidovudine.Among the newborns, 27.7% and 68.8% in RJ and POA, respectively, were benefi ted from in utero ZDV exposure.Complete avoidance of newborn exposure to breast milk was possible in 96.8% of the cases in POA and 51.1% in RJ while they were in the maternity hospital (Table 2).
About 75% of the newborns from those women tested during labor received pre-and post-exposure ZDV and were not breastfeed during their stay in the maternity hospital.One newborn in RJ did not receive any of the three recommended PMTCT interventions.
Among the newborns whose mothers were tested in the postpartum, 100% in RJ and POA received post-exposure prophylaxis with ZDV.In RJ, 33.3% of newborns from women tested in the postpartum period were not breastfeed while in the maternity hospital.In POA, none of the newborns were breastfeed (Table 2).
Perinatal HIV transmission was confi rmed in 14.6% and 11.7% of the newborns in RJ and POA, respectively.Blood samples collected within 48 hours from birth for DNA PCR were obtained for 126 newborns and in utero transmission of HIV was confi rmed in ten newborns, of which four (4/47) in RJ and six (6/79) in POA.Two newborns had a positive HIV DNA PCR result in the sample collected within 48 hours of birth, but their diagnosis could not be confi rmed due to the lack of a subsequent sample.Three infants in RJ had an undetermined DNA PCR within 48 hours from birth, with no subsequent sample for confi rmation.HIV infection status could not be determined in 44.4% of the infants because they were lost to follow-up early during the study.

DISCUSSION
We found a high level of acceptance of HIV rapid testing among women admitted for delivery in RJ and POA.Similar acceptance rates (98%) were reported in RJ 14 and India. 16Lower rates were reported in the United States by the Miriad study (84.0%) 3 and in Russia (89.2%). 12nsidering the wide availability of PMTCT interventions in Brazil, the proportion of women contacted during this study who reported unknown HIV serostatus is unacceptably high (26.3%).Ideally, all women should be screened for HIV during an initial prenatal visit.Among those enrolled in our study, the overwhelming majority had access to prenatal both in RJ and POA, with roughly 50% having had four or more visits.In spite of this, they were not tested or were unaware of their HIV test results.
In the study, 26.6% of women reported no prenatal care.For these women, HIV testing during delivery is the last opportunity for infants born to them.Although not as effective as when started earlier during pregnancy, a PREP ZDV: Pre-exposure prophylaxis with intravenous zidovudine.b NAM: No breastfeeding while in the maternity hospital.c PEP ZDV: Post-exposure prophylaxis with oral zidovudine.d Information regarding PREP ZDV and PEP ZDV were not available for one newborn in Porto Alegre (mother tested during labor).This newborn was not included in the table as we could not determine which set of interventions he received (missing data).e Information about breastfeeding while in the maternity hospitals was not available for one newborn in Rio de Janeiro.This newborn received PEP AZT (mother tested in the postpartum period).This newborn was not included in the table as we could not determine which set of interventions he received (missing data).
f One stillbirth and one newborn who died within a few minutes after birth both in Rio de Janeiro were not included in the table.
clinical trials and observational studies have demonstrated that short-course interventions administered late in pregnancy can reduce MTCT, 5,9 even when initiated within 48 hours after birth. 22ring labor and delivery, intravenous or oral AZT is administered as pre-and post-exposure prophylaxis for the newborn.Overall, 48% of women in our study were tested during labor and 51.8% in the postpartum period.
A striking difference can be noted between RJ and POA.While in POA the majority was tested during labor, in RJ most of them were tested in the postpartum.The reasons why health teams in POA were most often able to test women before delivery than in RJ are out of the scope of the present study and we could not identify an objective reason for this difference.It should be noted that POA sites started the study almost a year later than RJ sites when HIV rapid testing was already available for regular care in maternity hospitals.
One important aspect in the assessment of the use of HIV rapid testing in the delivery setting is to examine how feasible the implementation of other PMTCT interventions is when a test result is positive.In our study, intravenous AZT was administered to 73.1% of women tested before delivery.Except for one infant for whom this information was missing, all liveborn infants of women with a positive test result received oral AZT.Regimens that include only intrapartum and postpartum drug administration have been shown to be effective in reducing perinatal transmission of HIV. 13,17owever, intrapartum pre-exposure prophylaxis alone with nucleoside reverse transcriptase inhibitor (NRTIs), with no prolonged post-exposure prophylaxis of the infant is not effective. 17owledge of the mother's HIV status provides opportunities for other effective interventions such as formula feeding.In our study, 18.3% of infants born to HIV-infected women were breastfeed at least for one day, in most cases because the mother's HIV serostatus was only determined in the postpartum.This delay in HIV diagnosis unnecessarily exposed these infants to the risk of HIV infection.Incremental risk of HIV transmission through breastfeeding has been estimated to be 14% among chronically infected women. 8Dose-response effect of breastfeeding has been demonstrated.In a study carried out by the Italian Register for HIV Infection 11 in children, the adjusted infection odds ratio for one day of breastfeeding versus exclusive formula feeding was 1.19. 11The probability of HIV-1 infection per liter of breast milk ingested by an infant is 0.00064, comparable to the risk of transmission through one unprotected act of intercourse with an HIV-1-positive individual. 18ailable data indicate that without intervention 25% to 30% of perinatal HIV infection occur in utero. 19In our study, ten infants were confi rmed to have been infected in utero and two others had a positive HIV DNA PCR result in the 48-hour sample, but there was no subsequent sample to confi rm this diagnosis.Unfortunately, for infants infected in utero, interventions provided during labor and delivery are not effective. 2e high proportion of infants lost to follow-up early in the study is a matter of concern.The fact that mothers and infants were not necessarily followed up in the same care service may have contributed to this high rate of lost to follow-up.We do not know whether these mothers and infants got the care they needed.It points out to the need to develop a better referral system for this population with tailored outreach strategies.
We found a higher prevalence of HIV infection among women enrolled in POA when compared to those in RJ.This refl ects the differences on the scope, severity and dynamics of the HIV epidemic in south and southeast Brazil.A study applying spatial analysis techniques using information from AIDS case reporting database and liveborn registers found an HIV prevalence of up to 8% in some impoverished areas of POA. 1 According to the Brazilian Ministry of Health data, by the end of 2002, in RJ and POA regions, 52% and 35% of HIV-infected women, respectively, were not identifi ed during pregnancy due to a variety of factors.The population of women who were not identifi ed with HIV during pregnancy, in POA, may comprise a higher proportion of marginalized women with lower or no access to prenatal services and highly vulnerable to HIV infection when compared to women enrolled in RJ sites.The differences found regarding social demographic data and prenatal care use seen in the study population in POA compared to those of the general female population supports this hypothesis.
One of the main strengths of our study is its large sample size that favors its comprehensiveness, in spite of being a convenience sample.The high level of HIV rapid testing acceptance among the population studied reinforces the generalization of our results on the feasibility of other PMTCT interventions in the context of HIV diagnosis made during labor and delivery.To the best of our knowledge, our study is the largest assessment conducted during labor and delivery in Brazil and, so far, the only one that assessed the feasibility of other PMTCT interventions following a positive HIV rapid test result.
Some limitations of the study should be also considered.
Our fi ndings about acceptance rates may not directly refl ect other contexts, such as non-research settings.
Because patient records from prenatal care are not available at maternity hospitals and HIV test results are not always recorded on prenatal cards women bring to maternity hospitals, we relied on self-reports that are potentially subject to response bias and not subject to independent verifi cation.We also relied on Gestantes.Cuidado Pré-Natal.Aleitamento Materno.Sorodiagnóstico da AIDS.Infecções por HIV, diagnóstico.Transmissão Vertical de Doença Infecciosa.Síndrome de Imunodefi ciência Adquirida, prevenção & controle.

Figure .
Figure.Study population for HIV rapid testing and perinatal intervention in Brazil.Cities of Rio de Janeiro and Porto Alegre, Southeastern and Southern Brazil, 2000-2002. 15

Table 1 .
Sociodemographic, reproductive and prenatal care characteristics of the study participants.Cities of Rio de Janeiro and Porto Alegre, Southeastern and Southern Brazil, 2000-2002.

Table 2 .
Prevention of mother-to-child transmission interventions provided to women and their newborns.Cities of Rio de Janeiro and Porto Alegre, Southeastern and Southern Brazil, 2000-2002.