Factors Associated With Loss To Follow Up Among Hiv Exposed 17ut3gh1
Factors Associated With Loss To Follow Up Among Hiv Exposed 17ut3gh1
Factors Associated With Loss To Follow Up Among Hiv Exposed 17ut3gh1
Abstract
Background: There are many inequalities in terms of prevention and treatment for pregnant women with HIV and
exposed children in low and middle-income countries. The Brazilian protocol for prenatal care includes rapid diagnos-
tic testing for HIV, compulsory notification, and monitoring by the epidemiological surveillance of children exposed
to HIV until 18 months after delivery. The case is closed after HIV serology results are obtained. Lost to follow-up is
defined as a child who was not located at the end of the case, and, therefore, did not have a laboratory diagnosis. Lost
to follow-up is a current problem and has been documented in other countries. This study analyzed factors associated
with loss to follow-up among HIV-exposed children, including sociodemographic, behavioral, and health variables of
mothers of children lost to follow-up.
Methods: This historical cohort study included information on mothers of children exposed to HIV, born in Porto
Alegre, from 2000 to 2017. The research outcome was the classification at the end of the child’s follow-up (lost to
follow-up or not). Factors associated with loss to follow-up were investigated using the Poisson regression model. Rel-
ative Risk calculations were performed. The significance level of 5% was adopted for variables in the adjusted model.
Results: Of 6,836 children exposed to HIV, 1,763 (25.8%) were classified as lost to follow-up. The factors associated
were: maternal age of up to 22 years (aRR 1.25, 95% CI: 1.09–1.43), the mother’s self-declared race/color being black
or mixed (aRR 1.13, 95% CI: 1.03–1.25), up to three years of schooling (aRR 1.45, 95% CI: 1.26–1.67), between four and
seven years of schooling (aRR 1.14, 95% CI: 1.02–1.28), intravenous drug use (aRR 1.29, 95% CI: 1.12–1.50), and HIV
diagnosis during prenatal care or at delivery (aRR 1.37, 95% CI: 1.24–1.52).
Conclusion: Variables related to individual vulnerability, such as race, age, schooling, and variables related to social
and programmatic vulnerability, remain central to reducing loss to follow-up among HIV-exposed children.
Keywords: HIV/AIDS, Children exposed to HIV, Lost to follow-up, Mother-to-child transmission of HIV
Background
*Correspondence: [email protected]
Vertical HIV transmission in children can be avoided
1
through prevention and treatment for pregnant women
Graduate Studies Program in Public Health, Federal University of Rio Grande
Do Sul, Porto Alegre, RS 90620‑110, Brazil
with HIV and exposed children [1, 2]. In 2020 85%
Full list of author information is available at the end of the article [63%–98%] of pregnant women living with HIV had
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da Silva Calvo et al. BMC Public Health (2022) 22:1422 Page 2 of 8
access to antiretroviral drugs to prevent transmission of In the city of Porto Alegre, approximately 400 children
HIV to their children [3]. This percentage, however, var- exposed to HIV are monitored annually. Case closure as
ies according to the weaknesses related to prenatal and lost to follow-up is not uncommon. Ignoring the HIV
postnatal care of health systems, especially in developing status of exposed children makes it impossible to start
countries [4–6]. early interventions, contributing to infant morbidity
In Brazil, from 2000 to June 2020, 134,328 HIV-infected and mortality [1, 27–29]. This study analyzed the factors
pregnant women were notified [7]. As for the rate of HIV associated with the children exposed to HIV being lost to
detection in pregnant women, there was an increase of follow-up (sociodemographic, behavioral, and health var-
21.7% over ten years: in 2009, 2.3 cases/thousand live iables of mothers lost to follow). All sociodemographic
births were registered, and, in 2019, this rate increased to and behavioral variables available in the National Surveil-
2.8 cases/thousand live births. Compared to other Brazil- lance System related to pregnant women living with HIV
ian state capitals, Porto Alegre, the location of this study, were investigated.
is the capital with the highest detection rate, with 17.6 We believe that this analysis can contribute to develop-
cases/thousand live births recorded in 2019, a rate six ing more systematic monitoring strategies, strengthening
times higher than the national rate. The AIDS detection epidemiological surveillance in Porto Alegre, the Brazil-
rate in children under five years of age has been used as ian state capital with the highest rate of HIV detection in
a proxy indicator for monitoring vertical HIV transmis- pregnant women.
sion. In 2019, this rate in Brazil was 1.9 cases/100,000
inhabitants. Porto Alegre is the fourth capital with the Methodology
highest rate, with 7.2 cases/100,000 inhabitants [7]. A historical cohort study was conducted in 2021. We
Reducing the number of children infected with HIV extracted data from a national registry system from 2000
and offering 95% treatment coverage is among the 95–95- to 2017, characterizing the follow-up period.
95 goals that aim to prevent 5.9 million infections in chil-
dren up to 15 years of age by 2030 [8]. Over the years, Population
many actions have been documented in this area, espe- The study uses a national database with information on
cially in prenatal care, among which are the intensifica- pregnant women living with HIV and children exposed
tion of educational activities, the provision of rapid tests, to HIV who were born in Porto Alegre. In the study sce-
the supply of antiretroviral therapy, and supplies of sub- nario, the investigation of the child’s exposure to HIV
stitute inputs for breastfeeding [9–12]. Despite this, early ends up to 24 months after birth. This historical cohort
diagnosis remains one of the main challenges [13–15]. study included information on pregnant women living
The absence of a confirmatory test in children precludes with HIV and the outcome of the child’s exposure to HIV.
the timely start of ART [16–18]. For diagnosis in children under 18 months of age, the fol-
There are many inequalities prevention and treatment lowing tests are available: molecular test to quantify HIV-
for pregnant women with HIV and exposed children in RNA/HIV viral load (CV-HIV) and detect HIV proviral
low and middle-income countries [6, 18–21]. In Brazil, DNA. The first CV-HIV collection must be performed
ART is universally distributed by the public health sys- immediately after birth. Any test whose result shows
tem. Therefore, an epidemiological surveillance system detectable CV-HIV, regardless of the viremia value, will
with complete information on children exposed to HIV require an immediate CV-HIV collection. The second
would significantly increase the ability to target services test, if the first CV-HIV is undetectable, will be collected
to those that need them. at 14 days of age. Unconfirmed cases should continue
The Brazilian protocol for prenatal care includes rapid under investigation, with CV-HIV collections at two and
diagnostic testing for HIV in the prenatal period with eight weeks after the end of antiretroviral prophylaxis.
compulsory notification. Compulsory notification is a An anti-HIV test should be performed at 12 months and,
standardized document filled out during the pregnant if positive, repeated at 18 months. In children with CV-
woman’s visit when the HIV test result is positive. In the HIV below 5,000 copies/mL or discordant results, pro-
postnatal period, children exposed to HIV are moni- viral DNA, which has high specificity, should be used.
tored by epidemiological surveillance until 18 months The child will be considered HIV-infected if there are
after delivery [22]. The case is closed after HIV serology two detectable CV-HIV results above 5,000 copies/mL or
results are obtained. All this data is stored in a single positive proviral DNA [30].
database. Lost to follow-up is defined as a child who was In Porto Alegre, the deadline for closing the case runs
not located at the end of the case and, therefore, did not from 18 to 24 months. The child is considered lost to
have a laboratory diagnosis. Lost to follow-up is a current follow-up at 24 months of follow-up without the comple-
problem documented in other countries [18, 23–26]. tion of the laboratory diagnosis when the case is closed
da Silva Calvo et al. BMC Public Health (2022) 22:1422 Page 3 of 8
Table 1 Demographic, behavioral, and health profile of mothers of HIV-exposed children who were lost to follow-up notified to
SINAN, in Porto Alegre, according to the outcome lost to follow-up, 2000 – 2017
Lost to follow-up
Characteristics Total (%) a
Yes (%)a No (%)a p valueb
Table 2 presents the results of the non-adjusted models surveillance system in Porto Alegre is unaware of the
and adjusted models age, race/Color, schooling, intrave- diagnosis of about a quarter of the children exposed
nous drug use, and time of HIV diagnosis. The follow- to HIV. The absence of data also implies possible dis-
ing socioeconomic, behavioral, and health factors of the tortions in the rate of mother-to-child transmission of
studied mothers were associated with lost to follow-up HIV, as many children considered to have been lost to
in the final model: being up to 22 years of age (aRR 1.25; follow-up may have had a positive result.
95% CI 1.09–1.43); being self-declared as black or mixed This is a problem that affects not only Brazil but also
(aRR 1.13; 95% CI 1.03–1.25); up to three years of study other countries that often have higher rates of loss to fol-
(aRR 1.45; 95% CI 1.26–1.67); from four to seven years of low-up of children exposed to HIV [14, 21, 34, 35]. In a
study (aRR 1.14; 95% CI 1.02–1.28); intravenous drug use systematic review with meta-analysis [36], the estimated
(aRR 1.29; 95% CI 1.12–1.50); and HIV diagnosis during loss of follow-up of children exposed to HIV in 11 Sub-
prenatal care (aRR 1.37; 95% CI 1.24–1.52). Saharan African countries was 33.9% (95% CI 27.6%-
41.5%) in the three-month postpartum period. This study
Discussion showed that there was little research in Sub-Saharan
This study demonstrates the importance of a public Africa that included a longer follow-up period. Two of
database to improve the monitoring of exposed chil- them followed children for 12 months, with lost to fol-
dren in a public policy to prevent HIV. The lack of low-up of 50.2% [37] and 85.1% [38]. Other surveillance
information on the serology status of exposed children services that investigated children exposed to HIV for
within the health care system can impact the plan- 18 months showed that the loss to follow-up ranged from
ning and implementation of HIV prevention and care 20.8 [39] to 66.1% [40]. In a recent study that analyzed
[18, 32, 33]. Our data indicate that the epidemiological the follow-up of children exposed to HIV at a referral
da Silva Calvo et al. BMC Public Health (2022) 22:1422 Page 5 of 8
Table 2 Factors associated with lost to follow-up of children exposed to HIV in Porto Alegre, 2000—2017
Unadjusted RR CI 95% p Adjusted RRb CI 95% p
RRa
hospital in Uganda, the percentage of lost to follow-up socioeconomic status, lower education, and knowledge
was 48% in 18 months [4]. about HIV [50]. Regarding race/color, black or mixed
Our data indicate that the loss to follow-up of children women had a relative risk 13% higher to have children
exposed to HIV is associated with the different dimen- lost to follow-up. These data can be contextualized from
sions of the vulnerability of pregnant women with HIV the perspective of institutional racism [51, 52], which
[41]. In the individual dimension, there is intravenous accentuates the inequality of access to health which has
drug use; in the social dimension, being under 26 years of already been observed in the issue of race/color in Brazil
age, being black or mixed and having up to seven years of in relation to HIV [7]. Regarding schooling, women with
study; and in the programmatic dimension, the diagnosis up to three years of schooling had a 45% excess risk of
of HIV during prenatal care or at delivery. This last result having children lost to follow-up. In the discussion on
indicates that women with HIV enter the health service social vulnerability, education is an important element,
later [42, 43]. as it represents possibilities for entering the labor market
In the individual dimension, drug use appears to be and has also been interpreted as an income proxy [53]. In
associated with lower adherence to care for the pre- a recent study in Mozambique, higher levels of schooling
vention and treatment of HIV [44, 45]. In addition to showed greater chances of having an early start of prena-
the effects of the substances used, marginalization and tal care [54]. This study was carried out in a scenario with
stigma related to drug use and HIV itself are factors that cultural issues intertwined with the definition of roles
interfere with access to and adherence to treatment [46]. associated with gender. We understand that younger
In this sense, we emphasize that harm reduction strate- women with less schooling may be financially depend-
gies [47] could improve care, avoiding loss of follow-up. ent on their sexual partners, which would make the child
Care and social support interventions for drug users have more vulnerable to being lost to follow-up.
shown better standards of care and adherence to drugs In the programmatic dimension, women diagnosed
[48, 49]. with HIV during the prenatal period or at delivery had an
In the social dimension, children whose mothers excess risk of 37% to have a child classified as lost to fol-
were up to 22 years old were at an excess risk of 25%, low-up. In our study, the percentage of pregnant women
when compared to children of mothers over 32. Age who received the diagnosis in prenatal care or at deliv-
may be interconnected with other factors, such as low ery was high and was even greater in the loss to follow-up
da Silva Calvo et al. BMC Public Health (2022) 22:1422 Page 6 of 8
group (34.7% versus 24%). Barriers to HIV testing in pri- team. In addition, the information was complemented
mary care have been documented [55–57], so the possi- by access to other health information systems. Therefore,
bility of HIV testing during prenatal care appears to be an we believe that this limitation has been reduced. Another
opportunity to improve care. limitation of the data already mentioned is the lack of
This would be an alert for health professionals. The HIV diagnosis during prenatal care or delivery, which
creation of a bond with pregnant women could prevent prevented us from identifying the percentage of women
adverse health outcomes for the child. In fact, in a study diagnosed at each of these care moments.
carried out in Kenya, knowledge of the diagnosis before
prenatal care proved to be a protective factor against Conclusion
loss to follow-up (OR 0.23; 95% CI 0.05–0.71) [18]. A When considering the sociodemographic, behavioral,
study conducted in the United States found that women and health characteristics of the mothers, we found that
diagnosed with HIV during pregnancy are less likely to the factors associated with loss to follow-up in Porto
receive ART adequately during pregnancy and to obtain Alegre are age, race/color, schooling, intravenous drug
viral suppression after pregnancy [58]. use, and time of HIV diagnosis. We recommend investing
In our study, the variable moment of diagnosis was in integrated health information systems so that children
divided into two strata: diagnosis during prenatal care or exposed to HIV can be located within the health care
at delivery and diagnosis before prenatal care. Therefore, system, thus reducing the number of losses to follow-up.
because the women who may have been diagnosed dur- We also recommend a particular focus on women using
ing prenatal care were grouped with those diagnosed at intravenous drugs, and the adoption of harm reduction
delivery, we do not know the actual number of women actions, in order to avoid the loss to follow-up of exposed
who were diagnosed at childbirth. This is a limitation of children.
our study and is a critical issue to be discussed. Diagnosis
at delivery may express the total absence of connection
Abbreviations
with primary care services or even the failure to perform ART: Antiretroviral therapy; SINAN: Notifiable Diseases Information System;
an HIV test during prenatal care, a recommendation in SISCEL: Laboratory Examination Control System; SICLOM: Logistic Control
force in a national protocol. A recent study discussed this System for Medicines; E-SUS: Electronic medical record of the primary care
user; CADSUS: SUS User Registration System.
issue in Brazil, showing that almost 20% of women in the
state of Amazonas reached childbirth without knowing Acknowledgements
their HIV status, complementing another Brazilian study, This research was supported by a Grant from Programa Pesquisa para o SUS—
PPSUS/FAPERGS/MS/CNPq/SESRS n. 03/2017.
in which 29% of women were not tested during prenatal
care [59]. Authors’ contributions
From a Brazilian public policy perspective, these LBT and DRK conceptualized the idea. All authors contributed to the study
study’s conception and design. Material preparation, data collection, and
results indicate primary care services’ difficulty in iden- analysis were performed by LBT and KSC. The first draft of the manuscript was
tifying, linking, and retaining care for children exposed written by KSC, LBT, BH, and DRK. All authors commented on previous versions
to HIV, problems also seen in other studies [10, 23, 26, of the manuscript. All authors read and approved the final manuscript.
35, 36, 60–63]. In Brazil, primary care services monitor Funding
all newborns within their geographic areas of coverage Partial financial support was received from “Programa Pesquisa para o SUS
[64]. In a review of access to services to prevent mother- (PPSUS/FAPERGS/MS/CNPq/SESRS n. 03/2017)”.
to-child transmission of HIV, Hiarlaithe et al. (2014) Availability of data and materials
identified the following access barriers: cost of traveling The datasets used and/or analyzed during the current study is available from
to the health service, secrecy in relation to diagnosis, the the corresponding author upon reasonable request.
stigma surrounding HIV, and relationship with the part-
ner [65]. In a study conducted in Ethiopia, it was found Declarations
that the proportion of pregnant women who have com- Ethics approval and consent to participate
prehensive knowledge about preventing mother-to-child This study complied with the guidelines of Resolution 466/2012 of the
transmission of HIV was low [47]. The difficulty of access Brazilian National Health Council. The Ethics and Research Committee of the
Federal University of Rio Grande do Sul (UFRGS) and the Ethics Committee of
and level of knowledge was not investigated in this study, the Municipal Government of Porto Alegre approved the study, and waived
however, these issues may be related to loss to follow-up. the informed consent, due to the relevance of the study whose methodology
Like all scientific research, our study is not without lim- used of a municipal secondary database with a large sample.
itations. The main one is that our study uses secondary Consent for publication
databases, with the researcher having no control over the Not applicable.
quality of data collected. However, we emphasize that we
Competing interests
have used a greatly valued database by the surveillance All authors declare that they have no competing interests.
da Silva Calvo et al. BMC Public Health (2022) 22:1422 Page 7 of 8
Author details 19. Frey MT, Meaney-Delman D, Bowen V, et al. Surveillance for Emerg-
1
Graduate Studies Program in Public Health, Federal University of Rio Grande ing Threats to Pregnant Women and Infants. J Womens Health.
Do Sul, Porto Alegre, RS 90620‑110, Brazil. 2 Department of Social Medicine, 2009;28(8):1031–6.
Federal University of Rio Grande Do Sul, Porto Alegre, RS, Brazil. 3 Graduate 20. Melo GC de, Oliveira ECA de, Leal IB, et al. Spatial and temporal analysis
Studies Program in Epidemiology, Federal University of Rio Grande Do Sul, of the Human Immunodeficiency Virus (HIV) in an area of social vulner-
Porto Alegre, RS, Brazil. 4 Graduate Studies Program in Public Policy, Federal ability in Northeast Brazil. Geospat Health. 2020;15(2). https://doi.org/
University of Rio Grande Do Sul, Porto Alegre, RS, Brazil. 5 Professional Master’s 10.4081/gh.2020.863.
in Family Health, Federal University of Rio Grande Do Sul, Porto Alegre, RS, Bra- 21. Mofenson LM, Cohn J, Sacks E. Challenges in the Early Infant HIV Diag-
zil. 6 School of Nursing, Federal University of Rio Grande Do Sul, Porto Alegre, nosis and Treatment Cascade. JAIDS. 2020;84(1):S1-4.
RS, Brazil. 7 General Directorate of Health Surveillance, Porto Alegre, RS, Brazil. 22. BRASIL. Ministério da Saúde. SVS. Coordenação Geral de Desenvolvi-
8
Department of Public Health, Federal University of Rio Grande Do Sul, Porto mento da Epidemiologia em Serviços. Guia de Vigilância em Saúde.
Alegre, RS, Brazil. Brasília: Ministério da Saúde, 2021. p. 126.
23. Mpinganjira S, Tchereni T, Gunda A, Mwapasa V. Factors associated with
Received: 30 July 2021 Accepted: 5 April 2022 loss-to-follow-up of HIV-positive mothers and their infants enrolled in
HIV care clinic: A qualitative study. BMC Public Health. 2020;20(1):298.
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