Clinical-epidemiological characteristics of pregnant women with HIV/syphilis coinfection: an integrative review

Características clínico-epidemiológicas de gestantes com coinfecção HIV/sífilis: revisão integrativa

Características clínico-epidemiológicas de gestantes con coinfección VIH/sífilis: revisión integrativa

Sexually Transmitted Infections (STIs) are considered a public health problem and are part of the most common communicable pathologies, directly influencing the epidemiological scenario due to the negative consequences for individuals’ health and lives o worldwide.¹

Syphilis is an infectious, systemic disease, exclusive to humans, and transmitted mainly through sexual and vertical routes. Its association with the Human Immunodeficiency Virus (HIV) occurs frequently, since both are influenced synergistically: increased HIV transmissibility, transient increase in viral load, decreased number of TCD4+ lymphocytes, or even changes in the natural evolution of treponemal infection, with exacerbation of clinical manifestations, in addition to changes in diagnosis and decreased response to treatment.^2-3 Furthermore, both STIs affect similar vulnerable groups, such as homeless people, low education, multiple sexual partners and the young-adult age group.¹^,2,3

HIV and syphilis are diseases that must be notified to the Epidemiological Surveillance. However, many professionals do not include it in their routines, which can harm the planning of actions to prevent and control these infections and vertical transmission. From this perspective, HIV notification has occurred more effectively than syphilis⁴.

In Brazil, in 2020, 61,441 cases of syphilis in pregnant women were reported in the Notifiable Diseases Information System (SINAN - Sistema de Informação de Agravos de Notificação), with a detection rate of 21.6/1,000 live births. Between 2017 and 2019, there was an increase of 25.7%. In part, this increase can be attributed to the change in the criterion for defining cases for surveillance purposes, which made it more sensitive⁵.

In the period from 2000 to June 2021, 141,025 pregnant women with HIV were reported, with the highest prevalence in the Southeast. The detection rate of HIV infection has shown a slight upward trend in recent years, mainly due to the increase in rapid tests distributed by Stork Network⁶.

Regarding simultaneous HIV/syphilis infection, both are transmitted mainly through unprotected sex and vertically.¹ These are important problems during pregnancy, due to several negative outcomes, such as spontaneous abortion, fetal or neonatal death, prematurity and congenital infections⁷.

There is difficulty for SINAN in crossing information about HIV/syphilis co-infection, making it impossible to know the prevalence of these diseases in an associated way, as there are no co-infection data in the notification and investigation forms⁸. Therefore, to obtain this information, it would be necessary to cross-reference databases relating to each problem, using nominal data.

In this way, in isolation, the clinical-epidemiological characteristics of the diseases⁸ of interest for this work are known. However, identifying scientific evidence that reports pregnant women who acquired HIV/syphilis co-infection is necessary to understand the factors, whether clinical, social and/or epidemiological, that can influence the prevalence of these STIs.

From this perspective, the objective was to synthesize scientific evidence about the clinical-epidemiological characteristics of pregnant women with HIV/syphilis co-infection globally.

This is an integrative review, organized in the following stages: guiding question elaboration, literature search, data collection or extraction, study critical analysis, interpretation and presentation of results⁹.

The research question was prepared using the PICo strategy,¹⁰ in which P (Population): pregnant women, I (Phenomenon of interest): clinical-epidemiological characteristics and Co (Context): HIV/syphilis co-infection, resulting in the following question: What is the scientific evidence related to the clinical-epidemiological characteristics of pregnant women with HIV/syphilis co-infection?

The survey of studies was carried out from June to September 2022 in the U.S. National Library of Medicine (PubMed), Cumulative Index to Nursing and Allied Health Literature (CINAHL Latin American Literature in Health Sciences (LILACS), Medical Literature and Retrieval System Online (MEDLINE) and Nursing Database (BDENF) databases. The controlled terms in Portuguese and their respective English counterparts were used, such as “HIV”, “Syphilis”, “Epidemiology”, “Coinfection” and “Pregnant”, with the help of the Boolean operators “AND” and “OR”.

Full articles on the topic, available online and free of charge, published in Portuguese, English and/or Spanish and published between 2012 and 2022, were included. Duplicate articles and articles that did not answer the guiding question were excluded.

As for the time frame of the study, it is justified by the establishment of Ordinance 77 of January 12, 2012, which provided for rapid tests to be carried out in Primary Care to detect HIV and syphilis.¹¹

To report the process of identification, screening, eligibility and inclusion of studies, the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) was used.¹² Duplication detection and article selection were carried out by two independent reviewers, using the Rayyan Systems Inc and EndNote (TM) platforms.

Data extraction and analysis were carried out using an adapted instrument, but validated by Ursi (2005), using the variables on identification, country and/or institution hosting the study, publication journal and methodological characteristics.¹³ The interpretative analysis of included references was presented and organized in a descriptive way.

The methodological quality of studies was assessed in accordance with a tool modified by Machotka et al., (2009), consisting of 12 criteria that represent key elements to assess the methodological quality of the studies. Each item marked affirmatively was assigned a score=1, with the total score on this scale (maximum 12 points) being converted into a percentage (0-100%). The higher this result, the better the methodological quality of the study, with a score of 8.0 being considered acceptable.¹⁴

As this is an integrative literature review, this work did not require authorization from the Research Ethics Committee, in accordance with Resolutions 466/2012 and 510/2016, which deal with research carried out exclusively with scientific texts to review scientific literature.

Based on the criteria established for the integrative review, 8 studies were selected, published between 2015 and 2020. The results found in the search are displayed in the flowchart (Figure 1) adapted from PRISMA.¹²

The articles were published between 2015 and 2020. The majority were in English, and one of them was in Portuguese. The methodological quality assessment scale¹⁴ found that the majority of studies (87.5%) reached an acceptable score.

In Chart 1, the studies, authors and year of publication, country of publication, study design and a summary of the content of studies are presented, focusing on the main results, clinical-epidemiological characteristics and conclusions.

Regarding study setting, it was observed that the studies were carried out in America, Asia and Africa. Regarding the research design, there was a predominance of cross-sectional studies, and two used secondary analysis of data from randomized clinical trials (Chart 1).

Figure 1
Study selection flowchart adapted from the PRISMA methodology (2021).

Chart 1
General characterization of included studies, authors and year, countries, study design, in addition to a summary of the content of studies focusing on the main results, clinical-epidemiological characteristics and conclusions of selected studies

The pregnant women who were part of the study sample had similar sociodemographic characteristics that place them in a situation of greater vulnerability to contracting STIs, such as age range between 20 and 49 years old, black race/color, single, low level of education, housewives and early late prenatal care.

The diversity in the epidemiological scenario of HIV/syphilis co-infection indicated prevalence rates that varied from 0.05% to 10.2%.^15-17 The different prevalence shows the heterogeneous distribution of syphilis, and may also be related to the diagnostic criteria adopted by services. ^17,18

Other factors attributed to variation in prevalence may be related to the laboratory diagnosis method used, sociocultural diversity, socioeconomic status, prevention and control strategies, social risk factors, level of knowledge about prevention and, finally, access to health units to carry out prenatal care.¹⁹

In general, younger women are at greater risk of acquiring an STI.^20-21 However, in the case of pregnant women with HIV/syphilis co-infection, the prevalence was higher among those aged 25 or older, increasing with each change in age group, a finding also observed among the selected studies.^16-18,23-24 The finding may be attributed to the increased risk of exposure to STIs over time, making women more vulnerable to engaging in sexual activities without using barrier methods.²⁵

Regarding the race/color variable, co-infection was more common in non-white women, and they are twice as affected as white women.^15,17,24 However, two studies, one in the city of Salvador (BA) and another carried out in 17 locations in Brazil, South Africa, Argentina and the USA, found different results, in which 89% of pregnant women with HIV/syphilis co-infection were white.^24,26

Regarding marital status, four studies considered this variable.^16,23,27-28 Studies on HIV infection have shown that married pregnant women are the most exposed to the HIV virus, with a 3.29 greater chance of being infected with HIV when compared to single women, especially when partners have multiple partnerships.^{17,20,23,29-30}

Considering that pregnant women and partners who participated in the studies had fewer years of study, it is possible to infer that formal education can be decisive in accessing health information and, consequently, in understanding the importance of prenatal care and adherence to treatment.^17,27-30

The occurrence of STIs may be associated with income, as the most economically disadvantaged social stratum results in less access to preventive information and health care, greater use of sex for economic purposes and as a psychosocial coping mechanism, and housing in rural areas, characterized by compromised socioeconomic indicators, which impose difficulties in accessing specialized care.^15-18

Two of the studies reported a higher prevalence of HIV/syphilis coinfection in pregnant women living in urban areas. Possible reasons are the presence of sex workers and the high prevalence of HIV in the urbanized population.^23,28

It is also important to highlight the vulnerable situation in which these pregnant women find themselves, as most of them were housewives, financially dependent on their partners, financially fragile and unable to negotiate the use of condoms.^{17, 23,28}

Pregnant women with HIV are more susceptible to developing other STIs, and syphilis is one of the most common co-infections.²¹ When they occur in association, one can affect the natural evolution of the other.^2,3 Syphilis can increase HIV viral load and decrease CD4 T lymphocyte cells.²¹ HIV, on the other hand, influences the worsening of syphilis symptoms.^2,3 Furthermore, ulcerative genital lesions caused by syphilis have been associated with increased HIV acquisition and transmission.^24,27

In this context, studies show that the prevalence of vertical transmission of HIV is substantially higher among pregnant women with co-infection,^17,24,27 presenting odds that vary from two to 3.71 times,^17,24 being explained by placental inflammation caused by T. pallidum, which compromises the structural and functional integrity of cells.^18,27

It was found that pregnant women with HIV/syphilis co-infection do not adequately adhere to the recommended treatment.^17,24,27 At the same time, a reduced percentage of partners is treated, which contributes to maintaining prevalence and vertical transmission rates, due to ineffectiveness of treatment and, in the case of syphilis, reinfection.^17,24,27,32

Regarding perinatal outcomes, syphilis causes high rates of negative pregnancy outcomes, especially among pregnant women who are not adequately treated.¹⁷ Abortions and perinatal or neonatal deaths occur in 40% of children infected by untreated mothers or those who started prenatal care late, making timely treatment impossible.^1,15

Another variable associated with HIV/syphilis co-infection was the consumption of alcohol and illicit drugs during pregnancy.^17,24 This association occurred with greater prevalence in single pregnant women and is linked to other risk factors, such as low education, low socioeconomic level, unwanted pregnancy, adoption of risky sexual behaviors, in addition to inadequate adherence to prenatal care and treatment.^32-34

The fragility of the care provided was pointed out, as the lack of focus on prevention increases the risk of mother-to-child transmission of HIV by up to 30%, and non-adherence to antiretroviral therapy (ART) during pregnancy increases this risk.³¹

Based on the principle of equity of the Brazilian Health System (SUS - Sistema Único de Saúde), pregnant women with HIV/syphilis co-infection should be a priority in health care, however indicators of prenatal care quality indicate otherwise.¹⁷

In this sense, the importance of Primary Health Care and its integration with Specialized Care Services (SCS), maternity hospitals and Epidemiological Surveillance stands out, aimed at improving pregnant women’s adherence to prenatal care, considering that this is an opportune moment for STI diagnosis, in order to reduce the risk of intrauterine infection.¹⁷ Another issue would be to strengthen the actions that permeate the notification and monitoring system for mothers and newborns so that, like other countries, syphilis notification is based on data relating to the stage of the disease and monitoring of the main exposures and of HIV co-infection.^17,31,35-37

Furthermore, the adoption of records in pregnant women’s booklet about the actions adopted and referral to reference services are of great value. In regions that are difficult to access, there is a need to implement an outpatient clinic to monitor infectious diseases instead of adopting separate and disjointed services, especially in areas where the prevalence of diseases remains high. This location will support comprehensive health care, which includes health care, human rights and social participation. It will develop promotion, prevention, diagnosis, treatment and guarantee of clinical and laboratory follow-up of STIs¹.

As limitations of this integrative review, the possibility of underreporting of cases of HIV/syphilis co-infection is cited, as most studies used secondary data, and, in the case of studies carried out in Brazil, notification forms do not have a field to fill in a form. comorbidities. It is also worth highlighting the difficulty in accessing some restricted publications, with only free access texts being included in the study, made available in full.

It was found that HIV/syphilis co-infection is more prevalent in pregnant women in the young-adult age group, of non-white race/color, married, with a low level of education, housewives as their occupation, residents of urban areas and belonging to classes most economically disadvantaged social groups.

Additionally, an association was observed between syphilis and the late start of prenatal care with an increased rate of unfavorable pregnancy outcomes, such as miscarriage, stillbirth and prematurity. It has been shown that the natural evolution of diseases can be affected when diseases are associated.

The studies analyzed showed the need to improve prenatal care, in order to ensure assistance, especially in medication administration and diagnostic test provision, with the aim of reducing the risks of vertical transmission by monitoring pregnant women with co-infection, partners and newborns.

Studies of this nature are important so that more effective strategies can be redirected in the implementation of public policies aimed at clinical management of pregnant women with HIV/syphilis co-infection, allocation of resources and development of specific intervention protocols.

To the Coordination for the Improvement of Higher Education Personnel (CAPES), the Research Support Foundation, the Scientific and Technological Development of Maranhão (FAPEMA - Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão) and the Brazilian National Center for Scientific and Technological Development (CNPq - Centro Nacional de Desenvolvimento Científico e Tecnológico).