Mother-to-child transmission of HIV infection and its associated factors in the district of Bilene, Gaza Province-Mozambique.

BACKGROUND: Mother-to-child transmission of HIV infection is a significant problem in Mozambique. This study aims to determine the risk factors associated with mother-to-child transmission of HIV in rural Mozambique.
METHODS: Retrospective case-control study in a rural area of Bilene District, on the coast of southern Mozambique, performed from January 2017 to June 2018. The analysis considered the clinical data of HIV exposed children with definitive HIV positive results and their respective infected mothers (cases), and the data of HIV exposed children with definitive HIV negative results and their respective infected mothers (controls) registered in At Risk Child Clinics from 1st January 2017 to 30th June 2018 at the Macia and Praia de Bilene health facilities in Bilene district, Gaza province-Mozambique.
RESULTS: Ninety pregnant women with HIV were involved in the study, including 30 who had transmitted the infection to their children and 60 who had not. Statistical analysis, adjusted for maternal age and gestational age at first antenatal care visit, showed that independent risk factors for transmission were gestational age at first visit (adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 1.05-1.36), non-adherence to combination antiretroviral therapy (56.7% vs. 5%; aOR 14.12, 95% CI 3.15-63.41); a viral load of 1000 copies/mL or more (90% vs. 5%; aOR: 156, 95% CI 22.91-1,062) and female sex of the neonate (80% vs. 51.7%; aOR: 4.43, 95% CI 1.33-15.87).
CONCLUSION: A high viral load and non-adherence to antiretroviral therapy are important predictors of mother-to-child HIV transmission.

Introduction

HIV infection remains a major public health problem in the world and particularly in developing countries. The prevalence of human immunodeficiency virus or acquired immunodeficiency syndrome (HIV/AIDS) has increased rapidly since the 1980s in developing countries. As a result, this has led to several demographic, economic and social consequences. More than 2 million children are living with HIV/AIDS worldwide, with more than 80% of them living in sub-Saharan African countries. The worst affected areas in Africa include southern and eastern Africa [1, 2].

Mozambique is one of the southern African countries with a high HIV burden. According to the 2015 survey on Malaria, HIV/AIDS, and Immunization Indicators in Mozambique (IMASIDA), HIV prevalence in this country increased in men and women aged 15–49 years, from 11.5% in 2009 to 13.2% in 2015 [3]. In 2019, the Joint United Nations Programme on HIV and AIDS (UNAIDS) estimated a prevalence of 12.4% in this population group [4].

Mother-to-child transmission of HIV (MTCT) is the main mode of HIV transmission in children under the age of 15 years. This problem is significant in sub-Saharan African countries, where more than 80% of children living with HIV reside. Without combination antiretroviral therapy (cART), the risk of HIV transmission from infected mothers to their children is 25% to 40%, with 10% to 25% of transmission occurring during pregnancy, 35% to 40% during labor, and 35% to 40% during breastfeeding. Effective strategies for the prevention of MTCT (PMTCT) reduce this risk to under 2% [5, 6].

Several factors have been associated with the increased risk of MTCT, including delayed initiation of cART and non-combination therapy, high maternal viral load, genital tract infections during the last trimester of pregnancy, mixed breastfeeding, and extended breastfeeding [5, 7–10].

In sub-Saharan Africa, only half of HIV-positive women receive cART during pregnancy. Despite high use of antenatal care services, unacceptably high drop-offs across the prevention of mother-to-child HIV transmission (PMTCT) cascade contributed to an estimated 126,000 new pediatric HIV infections in sub-Saharan Africa in 2019 [11]. A study by Yaya et al. indicated that the situation in Mozambique was similar, with a reported low use of antenatal care services and HIV testing services [12]. According to a study by Marotta et al. 7.89% of the children who visited the At Risk Child Clinics in Beira (Mozambique) were HIV positive; making HIV exposure the main reason for admission to these clinics [13] and providing further proof of a leaky PMTCT cascade. Given the dramatic impacts that health systems can have on health service delivery, there is an urgent need for interventions that improve the delivery of PMTCT services [11]. Mozambique is prone to natural disasters, such as Cyclone Idai and Kenneth in 2019, and developing disaster preparedness plans that ensure continuity of HIV services is critical as we look to improve health services delivery [14].

This study aimed to describe the main risk factors associated with the high rates of vertical transmission of HIV in children in rural Mozambique. This evidence could inform the design of effective, affordable and scalable strategies to improve PMTCT services delivery.

Material and methods

Study design and setting

This retrospective case-control study took place from January 2017 to June 2018 in the maternal and child health (MCH) services of two health centers (Macia and Praia de Bilene) in Bilene District (located in southern Gaza which has a population 155,526), on the southern coast of Mozambique. Bilene District extends across 3,200 km2 and has a population of 57,319 inhabitants; the capital is the town of Macia [15]. The nine health units comprise the district reference center (Macia health center) and eight peripheral health centers (including Praia de Bilene). All provide cART, maternal and child health services, and vaccinations.

Study population and sampling method

The analysis considered the clinical data of HIV exposed children with definitive HIV positive results and their respective infected mothers (cases), and the data of HIV exposed children with a definitive HIV negative results and their respective infected mothers (controls) registered in At Risk Child Clinics from 1st January 2017 to 30th June 2018 at the Macia and Praia de Bilene health facilities in Bilene district, Gaza province–Mozambique.

The study included all those children with definitive HIV positive result with their mothers (30 cases) and for each of the cases were included 2 controls (60 controls). Due to the lower number of HIV infected children, all those with a definitively positive result (cases) were included; while two controls for each were selected using a systematic random method.

Sample size

The study included 90 pairs of mother-child (30 cases and 60 controls) who met the inclusion criteria and were registered in At Risk Child Clinics from 1st January 2017 to 30th June 2018 in the Macia and Praia de Bilene health facilities.

Inclusion criteria were: 1) children 0–18 months old with definitive HIV positive result and their respective mothers (cases) in the study period in Macia and Praia de Bilene health facilities, 2) children 0–18 months with definitive HIV negative result and their respective mothers (controls) in the study period in Macia and Praia de Bilene health facilities. Exclusion criteria were: 1) incomplete pairs mother-child and 2) children 0–18 months who are lost-to-follow-up without definitive HIV results.

Definitions

The National Program for the Control of HIV in Mozambique defines the following criteria for diagnosing HIV in children aged less than 18 months:

Infants exposed to HIV undergo a virological test (HIV PCR-DNA) at age 1 to 9 months. If the result is positive, the test is repeated to confirm infection. If negative, the infants undergo a rapid test (Determine and Unigold) at 9 to 18 months. The result is considered definitively negative if the child had stopped breastfeeding over two months previously and the rapid test was negative.

All HIV-exposed children aged 9 months or older who did not undergo HIV PCR-DNA testing do the rapid test (Determine and Unigold). If the result is positive or borderline, they take the virological test to confirm the diagnosis. If the rapid test is negative, the result is considered definitive if the child had stopped breastfeeding over two months previously.

Children aged more than 18 months undergo only the rapid test to confirm their HIV status.

The study was based on the analysis of secondary data from the information system (clinical registers, clinical patient files and electronic patient database). Data collected were maternal variables (age, occupational, educational attainment, numbers of deliveries, gestational age at first antenatal care visit, number of antenatal care visits, timing of cART initiation, adherence to cART, World Health Organization (WHO) clinical staging [16], sexually transmitted infections during pregnancy, viral load during pregnancy or lactation CD4 counts, timing of birth, type of delivery, delivery setting, HIV prophylaxis during delivery) and child-related variables (gender assigned at birth, birthweight, type of lactation, months of babywearing, and nutritional status.

Data collection and analysis

Data were collected manually from the children’s and their mothers’ clinical files, clinical registers, and the electronic patient database using a standardized data collection form to ensure reliability. Data processing and analysis was undertaken using Microsoft Excel 2010.

Patients’ epidemiological and clinical characteristics were analyzed using descriptive statistics. Continuous and categorical variables are expressed as medians (interquartile ranges [IQR]). The quantitative or qualitative variables (factors) related to the transmission of HIV from mother to child were dichotomized as follows: age group (by percentile 75), ≤ 32years versus > 32 years; occupation, home versus other occupations, educational attainment, ≤ primary school (Grade 1–7) versus secondary school (Grade 8–12); numbers of deliveries (by percentile 75), 1–2 versus ≥ 3; gestational age group (by percentile 75), < 25 week versus ≥ 25 weeks; number of antenatal care visits (by percentile 75), ≤ 2 versus ≥ 3; timing of cART initiation (by percentile 75), pre pregnancy and 1st trimester versus 2rd trimester or more, postpartum o never; adherence to cART, adherent versus treatment dropout or not adherent; WHO clinical staging, 1 versus 2–4, Nutritional status, normal versus moderate malnutrition; sexually transmitted infections during pregnancy, no versus yes; viral load during pregnancy or lactation (machine cutoff), < 1000 copies versus ≥ 1000 copies; CD4 counts, cells/mm3 (by defining of AIDS), ≥ 200 versus <200; timing of birth, term versus pre-term; type of delivery, vaginal versus cesarean; delivery setting, hospital versus, home, HIV prophylaxis delivery, yes, versus no; gender assigned at birth, male versus female; birthweight (standard cutoff), ≥ 2500 g versus < 2500 g, type of lactation, artificial or mixed versus only maternal; month of baby wearing (by percentile 75), 7 to 9 months versus 10 to 12 months; nutritional status, normal vs moderate or severe malnutrition.

Differences between groups were compared using the Mann-Whitney U test for continuous variables and Pearson’s chi-square test for categorical variables. P values of less than 0.05 were considered statistically significant. Associations were expressed using odds ratios (ORs) and 95% confidence intervals (CIs). An adjusted model was performed with binary logistic regression used to identify independent predictors of MTCT. Statistically significant variables identified in the bivariable analysis (p<0.05) were entered one by one into a logistic regression, adjusted for maternal age and gestational age. The adjusted values were expressed as adjusted odds ratios (aOR) with their 95% CI. The Hosmer-Lemeshow test was used to assess the predictive accuracy (discrimination) of MTCT. Statistical data analysis was performed using IBM SPSS Statistics for Windows, Version 22.0 (Armonk, NY: IBM Corp).

Ethical considerations

The Mozambican National Bioethics Committee for Health approved the study protocol (Ref: 14/CIBS-Gaza/2020). No informed consent was administered; the study is a secondary analysis of existing data that are routinely collected as part of standard medical care. There was no direct interaction with study participants. A waiver of informed consent was granted. While personal or identifying patient information was included in patient files, registers and the electronic database, the extraction of data from these sources was de-identified. Each patient record was assigned a unique study participant ID. A log that links the patient’s name to the unique study participant ID was maintained in password-protected files by the investigation team and access restricted to only members of the investigation team.

Results

Ninety pregnant women with HIV were involved in the study, including 30 who had transmitted the HIV infection to their children and 60 who had not transmitted HIV infection to their children. The mothers’ median age was 27 years. The median gestational age at first antenatal visit was 24 years for cases and 20 years for controls. Most (n = 70; 77.8%) did not work outside the home, and 56 (62.2%) had no formal schooling or only primary school education. For 56.7% (n = 51) of the mothers, the baby included in the study was the first or second delivery. The same proportion (56.7%, n = 51) were had stage 1 HIV, while 32.2% (n = 29) had stage II disease. Only 27.8% (n = 25) were on cART before pregnancy, but 77.8% (n = 70) were adherent to treatment during pregnancy. Most delivered at term (88.9%; n = 80), had a vaginal delivery (n = 89, 98.9%), birthed in hospital (95.6%; n = 86), received infant cART prophylaxis (98.9%, n = 89), and breastfed their infants (90.0%; n = 81).

Positive MTCT was confirmed in the children by PCR at a median age of 12 months (range 1 to 18). Table 1 shows the bivariable analysis of factors related to MTCT. Compared to the women whose babies were not infected, mothers who transmitted HIV to their babies were younger (median 26 years vs. 28 years; p = 0.02), presented to antenatal health services at a more advanced gestational age (24 weeks vs. 20 weeks; p = 0.007), had fewer antenatal visits (p = 0.006), were less likely to be on cART before pregnancy or in the first trimester (60.0% vs. 91.7%; p<0.001), were less adherent to treatment (56.7% vs 5.0%; p<0.01), and were more likely to have viral load of 1000 copies/mL or more (90.0% vs. 5.0%; p<0.001). Associated variables related to the neonate were assignment of female sex at birth (80.0% vs. 51.7%; p = 0.009). No relation was found between WHO HIV clinical staging, CD4 count or infant cART prophylaxis and HIV mother-to-child transmission.

Table 1

Factors related to mother-to-child transmission of HIV.

Variables	Cases n/N (%)	Controls n/N (%)	OR (95% Cis)	P-value
Maternal variables
Health center				0.23
Centro de Saúde da Macia	25/30 (83.3)	41/60 (71.7)	1
Centro de Saúde da Praia de Bilene	5/30 (16.7)	17/60 (28.3)	0.50 (0.16–1.53)
Age in years, median (IQR)	26 (23–32)	28 (24–30)	0.97 (0.90–1.05)	0.498
Age group				0.79
≤ 32years	23/30 (76.7)	48/60 (80)	1
> 32 years	7/30 (23.3)	12/60 (20.3)	1.21 (0.42–3.51)
Occupation				0.88
Other	6/28 (21.4)	12/60 (20.0)	1
Home	22/28 (78.6)	48 / 60 (80.0)	0.92 (0.30–2.78)
Educational attainment,				0.74
≤ Primary school *	19/28 (67.9)	37/60 (61.7)	1
Secondary school **	9/28 (32.1)	23 / 60 (38.3)	0.76 (0.29–1.96)
N deliveries				1
1–2	17/30 (56.7)	34/60 (56.7)	1
≥ 3	13 /30 (43.3)	26 /60 (43.3)	1.00 (0.41–2.42)
Gestational age at first antenatal visit, median weeks (IQR)	24 (20–28)	20 (16.5–24)	1.13 (1.03–1.23)	0.007
Gestational age group				0.026
< 25 weeks	14/24 (58.3)	49/60 (81.7)	1
≥ 25 weeks	10/24 (41.7)	11 /60 (18.3)	3.18 (1.12–9.02)
Number of antenatal care visits				0.006
≥ 3	20/30 (66.7)	54 /560 (90)	1
≤ 2	10/30 (33.3)	6/60 (10.0)	4.55 (1.45–14.08)
Timing of cART initiation				<0.001
Pre pregnancy and 1st trimester	18/30 (60)	55/60 (91.7)	1
2rd trimester or more, postpartum o never	12/30 (40.0)	5/60 (8.3)	7.33 (2.27–23.65)
Adherence to cART				<0.001
Adherent	13/30 (43.3)	57/60 (95.0)	1
Treatment dropout or not adherent	17/30 (56.7)	3/60 (5.0)	24.84 (6.33–97.58)
WHO clinical staging				0.65
1	18/30 (60)	33/60 (55)	1
2–4	12/30 (40)	27/60 (45.0)	0.81 (0.33–1.98)
Nutritional status				0.24
Normal	23/24 (95.8)	60 /60 (100)	NC
Moderate malnutrition	1/24 (34.2)	0 /60 (0)	NC
Sexually transmitted infections during pregnancy				1
No	25/25 (100)	59/60 (98.3)	NC
Yes	0/25 (0.0)	1 /60 (1.7)	NC
Viral load during pregnancy or lactation				<0.001
< 1000 copies	2/20 (10)	57/60 (95)	1
≥ 1000 copies	18/20 (90)	3/60 (5)	171 (26.4–1195)
CD4 counts, cells/mm3				0.18
≥ 200	21/27 (77.8)	54/60 (90)	1
<200	6/27 (22.2)	6/60 (10)	2.56 (0.74–8.87)
Delivery variables
Timing of birth				0.085
Term	25/29 (86.2)	58/60 (96.7)	1
Pre-term	4/29 (13.8)	2/60 (3.3)	4.62 (0.78–26.99)
Type of delivery				1
Vaginal	30/30 (100)	59/60 (98.3)	NC
Cesarean	0/30 (0.0)	1 7 60 81.7)	NC
Delivery setting				0.59
Hospital	28/30 (93.3)	58/60 (96.7)	1
Home	2/30 (6.7)	2/60 (3.3)	2.07 (0.27–15.47)
HIV prophylaxis during delivery				0.33
Yes	29 /30 (96.7)	60/60 (100)	NC
No	1/30 (3.3)	0/60 (0.0)	NC
Child variables
Gender assigned at birth				0.009
Male	6/30 (20.0)	29/60 (48.3)	1
Female	24/30 (80)	31/60 (51.7)	3.85 (1.34–10.42)
Birthweight				0.65
≥ 2500 g	26/28 (92.6)	57/60 (95.0)	1
< 2500 g	2/28 (7.1)	3/60 (5.0)	1.47 (0.23–9.26)
Type of lactation				0.47
Artificial or mixed	4/30 (13.3)	5 /60 (8.3)	1
Only maternal	26/30 (86.7)	55 /60 (91.7)	0.59 80.16–2.389
Month of babywearing				1
7 to 9 months	4/6 (66.7)	34/56 (60.7	1
10 to 12 months	2/6 (33.3)	22/56 (39.3)	0.77 (0.13–4.58)
Nutritional status				0.68
Normal	26/28 (92.9)	57/60 (95.0)	1
Moderate or severe malnutrition	2/28 (7.1)	3 /60 (5.0)	1.46 (0.23–9.289

cART: combination antiretroviral treatment; NC: not calculable.

Data shown as n/N (%) unless specified otherwise. In bold, statistically significant differences.

*Grade 1–7;

**Grade 8–12.

In the bivariable models adjusted for maternal and gestational age, factors associated with MTCT were gestational age at first visit to antenatal care (aOR 1.19, 95% CI 1.05 to 1.36), non-adherence to cART (aOR 14.1, 95% CI 3.1 to 63.4); viral load of 1000 copies/mL or more (aOR: 156 95% CI 22.91 to 1,062 and female sex (aOR: 4.43, 95% CI 1.33 to 15.87) (Table 2).

Table 2

Factors related to mother to child transmission of HIV (bivariable and multivariable analysis).

	Bivariable analysis	Adjusted multivariable analysis
		Model 1	Model 2	Model 3	Model 4	Model 5
Variables	OR (95% CI)	aOR (95% CI)	aOR (95% CI)	aOR (95% CI)	aOR (95% CI)	aOR (95% CI)
Maternal age	0.97 (0.90–1.05)	1.00 (0.91–1.09)	0.98 (0.90–1.07)	0.95 (0.85–1.05)	0.97 (0.23–1.15)	0.98 (0.90–1.07)
Gestational age at first antenatal visit	1.13 (1.03–1.23)	1.19 (1.05–1.36) *	1.11 (1.01–1.23)Φ	1.09 (0.99–1.20)	1.09 (0.92–1.27)	1.14 (1.04–1.24) ρρ
< 3 visits to antenatal care	4.55 (1.45–14.08)	4.16 (0.50–34.0)
Initiation of ART 2rd trimester or later, postpartum or never	7.33 (2.27–32.6)		0.73 (0.15–3.65)
Non-adherence to cART	24.8 (6.33–97.5)			14.12 (3.15–63.41) θ
Viral load ≥ 1000 copies/mL	171 (26.4–1195)				156 (22.91–1062) Ψ
Female sex assigned at birth	3.85 (1.34–10.42)					4.43 (1.33–15.87) ρ
Hosmer and Lemeshow test		0.823	0.52	0.623	0.370	0.777

cART: combination antiretroviral treatment; OR: odds ratio; CI: confidence interval; aOR: adjusted OR.

In bold, statistically significant differences;

* p = 0.005;

Φ p = 0.03;

θ p = 0.001;

Ψp<0.001;

ρ p = 0.015;

ρρ p = 0.015.

Discussion

Our results show that in rural Mozambique, the main predictor of MCTC is a maternal viral load of 1000 copies/mL or more before delivery, as well as fewer than three antenatal care visits. Bivariable analysis also showed that not being on cART by the first trimester and treatment non-adherence were also related to transmission. The relationship between a high maternal viral load and the risk of MTCT has been previously described in a study by Bucagu et al. where they demonstrated a significant association between maternal viral load and child’s HIV status both at 6 weeks of age and 6 months of age [17].

The absence of maternal PMTCT interventions also increases the risk of transmission [11]. A study conducted in Côte d’Ivoire, Kenya, and Mozambique demonstrated the importance of optimizing antenatal care services. So, each additional first antenatal care visit per nurse per month was associated with a 4% decline in the odds that an HIV-positive pregnant woman would receive both HIV testing and cART medications [18]. Mozambique, as many sub-Saharan countries, began implementing task-shifting ART care and treatment from physicians to physician assistants and nurses in 2006, in response to the low ratio of human resources for health in the face of a worsening HIV epidemic [19]. Task-shifting is the skill transfer from a trained health worker to another health worker not previously trained for the task and does not routinely perform that task. The impact of this effort was assessed in the maternal and child services in a study done in Beira (Mozambique), looking specifically at the task shifting from physician assistants to MCH nurses. Although the study had some notable limitations; it did show an overall positive impact on the service delivery (e.g. shorter time to ART initiation, prescription of prophylaxis) in MCH clinics and recommended continued technical support to the MCH nurses [20].

We did not observe an association between mixed or formula feeding and HIV transmission, as reported elsewhere [11]. This is due to a limited study size–only 30 cases and 60 controls. A larger study would be necessary to show this association.

The results of this study support measures to prevent mother-to-child HIV transmission in the Mozambican context, including early initiation of cART in HIV-positive women of childbearing age—before pregnancy or in the first trimester, early antenatal care and monitoring, and HIV viral load suppression in pregnant women on cART. These strategies can reduce MTCT in this population. In Mozambique, several initiatives have shown potential to improve the quantity and quality of maternal and child health services, including performance-based financing for healthcare providers [21]. However, such mechanisms require rigorous planning, and their effect on the quality of service delivery must be carefully monitored [22]. Other initiatives have been designed to address the failure to retain HIV-positive pregnant women in cART, such as a review of retention (timeliness and regularity of antenatal care visits) in pregnant women at antenatal care services [23].

Initiatives aimed at the structural gaps in the health system have also been proposed in various studies to improve maternal and child health services, namely capacity building. In Uganda, an important study by Marotta et al. proposes capacity building at different levels of the health system closing gaps in leadership, human resources, service delivery, service integration and patient perceptions. Such assessments would allow for a holistic approach in designing intervention strategies given the significant existing gaps in the health system [24].

This study has some limitations. First, its retrospective nature led to some incomplete mother-child pairs, due to the absence or disappearance of clinical patient files; poor conservation and inadequate recordkeeping of clinical files, and lack of CD4 and viral load records.

The results of this study are subject to the idiosyncrasies of our working environment. While these can be generalized to other areas of Mozambique, conditions may differ substantially in other parts of Africa. However, our data are amenable to inclusion in systematic reviews, meta-analyses, and other evidence syntheses based on similar studies.

Conclusions

The results of our research show the importance of viral load suppression to prevent mother-to-child transmission of HIV/AIDS, including through measures like early initiation of cART in HIV-positive women of childbearing age, before pregnancy or in the first trimester, as well as early and regular antenatal care visits (coupled with continuous technical support of the nurses). These are the measures that will be implemented in our district.

MTCT study database_english translation.

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23 Feb 2021

PONE-D-21-02247

Mother-to-child transmission of HIV infection and its associated factors on the rural coast of southern Mozambique

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Reviewer #1: I read with great interest the paper. I find it well wrote and with good idea research.

In fact Mozambique has high burden of HIV and burden control is very topic in this country

Only some suggestions

1. Introduction: Add data on global burden of HIV and newly diagnosis wordwide and in low setting. Child with HIV are "child at risl" to poor health adn social outcome (see and cite The At Risk Child Clinic (ARCC): 3 Years of Health Activities in Support of the Most Vulnerable Children in Beira, Mozambique. Int J Environ Res Public Health. 2018 Jun 27;15(7):1350. doi: 10.3390/ijerph15071350). Furthermore, mozabique has also a catastrofic events as Ciclone Idai and Eloise. I think that this is crucial to mantein HIV services expecailly for mother and child during this frequent natural disaster (see and cite HIV continuity of care after Cyclone Idai in Mozambique. Lancet HIV. 2020 Mar;7(3):e159-e160.)

2. Method: are clear

3. ethics Committee: it is ok

3. Result: appear correct statistical analisys

4. Discussion: discuss better two action to improve the services : 1. Improve capacity building (see and cite Capacity assessment for provision of quality sexual reproductive health and HIV-integrated services in Karamoja, Uganda) crucial in Africa and the role of task shiting to improve the service may play a role in the improvement of the global effectiveness of care for HIV infected children if integrated into a wider range of public health measures. (cite Pathways of care for HIV infected children in Beira, Mozambique: pre-post intervention study to assess impact of task shifting. BMC Public Health. 2018 Jun 7;18(1):703. )

5. Conclusion: are coherent with the paper.

Reviewer #2: The title should be as follows: vertical transmission of HIV in the district of Belene, Province of Gaza-Mozambique.

Because the mother's transmission for children can be done using the same sharp objects that is common to the rural population and without education.

it is not clear how the sample was obtained.

I think the 90 sample is not representative for all of Mozambique.

Reviewer #3: Manuscript Number: PONE-D-21-02247

Title: Mother-to-child transmission of HIV infection and its associated factors on the rural

coast of southern Mozambique.

Reviewer’s comments:

Congratulations to the authors for the study. This manuscript reports an interesting analysis with the great impact to the public health, conducted in the rural coast of southern Mozambique, an area with a high prevalence of HIV infection.

My minor comments/suggestions are listed below to improve the manuscript:

1. Abstract

Methods Section:

The study methodology described in the summary does not allow readers to understand how the study was conducted, you just say the type of study it is. Please, the authors should briefly describe how the study was carried out, for example: Who are "the Cases", how were they enrolled, what age were they. Also who were controls and how the contorols were also enrolled to the study, there was some matching between case and controls? Each enrolled “Case” how many “Controls” were considered.

2. The main body of manuscript

a) Results Section:

• The description of the results appears to be confusing. It is not clear how many women were recruited for study. It is understood that the study included 90 pregnant women, 30 women who transmitted HIV infection to their children and 60 women who did not transmitted HIV. Is that what you mean here? Please this is strongly recommended to rewrite the results section to make it clearer. It could be better if the author presents the percentage of women who transmitted HIV to their children and the percentage of women who did not transmitted HIV.

• The authors say that in the adjusted analysis for maternal age and gestational age at the first ante natal consultation shown to be as risk factors of transmission but do not say what was the gestational age of the first antenatal consultation that was associated with HIV transmission from the mother to the child. This is important to guide the staff who dealing with this issue to take into account when they are giving lectures to prevent mother-to-child transmission of HIV infection as you present regarding to the pregnant woman's viral load. It is very clear that viral load of 1000 copies or more is a risk factor for transmission. Authors should present to readers what was the gestational age at the first antenatal consultation that was associated with HIV transmission from mother to child.

• In evaluating factors related to the transmission of HIV from mother to child in the Table 1, it would be good to calculate the Odds ratio of each variable analyzed to see the trends of the associations.

• In the table 2 Please calculate the P-value

b) Discussion section

The discussion seems weak. In this section you have to bring what your results and the results found by other scientists and do not refer readers to the bibliographic references. For example, in the first paragraph of your discussion you say that the factors for mother-to-child transmission of HIV are described in a fair job in Rwanda, but what does the publication of Rwanda's work say? Please rewrite and discussion.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Sozinho Acacio

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28 Feb 2021

PONE-D-21-02247

Mother-to-child transmission of HIV infection and its associated factors on the rural coast of southern Mozambique

PLOS ONE

Dear Editors

We thank you very much for giving us the opportunity to revise our manuscript. We have carefully considered the comments made by the editor and the reviewers and agree with most of them. Each comment has been addressed and we have modified the manuscript accordingly. We sincerely hope that the current version of the manuscript will be acceptable for publication in your journal. All changes are shown in blue so that they may be easily seen.

Regards,

Dr. Isabelle Munyangaju

Response to academic editor:

1.Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

Response: Point addressed as per guidance. Format changed. File names changed.

2.In your Methods section, please provide additional information on how each variable was defined and categorized in your analysis; and on how matching was performed. Moreover, please refer to the specific statistical analyses performed as well as any post-hoc corrections to correct for multiple comparisons. If these were not performed please justify the reasons.

Response: We have included a paragraph variables were dichotomized according to the 75th percentile or according to clinical epidemiological criteria indicating which of the variables were dichotomized.

We have included a paragraph saying � The quantitative or qualitative variables (factors) related to the transmission of HIV from mother to child were dichotomized as follows: age group (by percentile 75), ≤ 32years versus > 32 years; occupation, home versus other occupations, educational attainment, ≤ primary school (Grade 1 – 7) versus secondary school (Grade 8 – 12) ; numbers of deliveries (by percentile 75), 1-2 versus ≥ 3; gestational age group (by percentile 75), < 25 week versus � 25 weeks; number of antenatal care visits (by percentile 75), ≤ 2 versus ≥ 3; timing of cART initiation (by percentile 75), pre pregnancy and 1st trimester versus 2rd trimester or more, postpartum o never; adherence to cART, adherent versus treatment dropout or not adherent; WHO clinical staging, 1 versus 2-4, Nutritional status, normal versus moderate malnutrition; sexually transmitted infections during pregnancy, no versus yes; viral load during pregnancy or lactation (machine cutoff), < 1000 copies versus � 1000 copies; CD4 counts, cells/mm3 (by defining of AIDS) , � 200 versus <200; timing of birth, term versus pre-term; type of delivery, vaginal versus cesarean; delivery setting, hospital versus, home, HIV prophylaxis delivery, yes, versus no; gender assigned at birth, male versus female; birthweight (standard cutoff), � 2500 g versus < 2500 g, type of lactation, artificial or mixed versus only maternal; month of baby wearing (by percentile 75), 7 to 9 months versus 10 to 12 months; nutritional status, normal vs moderate or severe malnutrition.

3.Please provide additional details regarding participant consent.

Response: We have provided further information in the text lines 169 – 176 about consent and confidentiality of study participants.

Response to Reviewers

Reviewer #1:

I read with great interest the paper. I find it well wrote and with good idea research. In fact Mozambique has high burden of HIV and burden control is very topic in this country

Only some suggestions

1. Introduction: Add data on global burden of HIV and newly diagnosis wordwide and in low setting. Child with HIV are "child at risl" to poor health adn social outcome (see and cite The At Risk Child Clinic (ARCC): 3 Years of Health Activities in Support of the Most Vulnerable Children in Beira, Mozambique. Int J Environ Res Public Health. 2018 Jun 27;15(7):1350. doi: 10.3390/ijerph15071350). Furthermore, mozabique has also a catastrofic events as Ciclone Idai and Eloise. I think that this is crucial to mantein HIV services expecailly for mother and child during this frequent natural disaster (see and cite HIV continuity of care after Cyclone Idai in Mozambique. Lancet HIV. 2020 Mar;7(3):e159-e160.)

Response: Thanks for the suggestion. We have included the suggestions of the reviewer. We have added and cited arguments from the suggestions in lines 49 – 54; 75 – 78; 80 – 82 of the introduction.

2. Method: are clear

Response: Thank you

3. Ethics Committee: it is ok

Response: Thank you

3. Result: appear correct statistical analisys

Response: Thank you

4. Discussion: discuss better two action to improve the services : 1. Improve capacity building (see and cite Capacity assessment for provision of quality sexual reproductive health and HIV-integrated services in Karamoja, Uganda) crucial in Africa and the role of task shiting to improve the service may play a role in the improvement of the global effectiveness of care for HIV infected children if integrated into a wider range of public health measures. (cite Pathways of care for HIV infected children in Beira, Mozambique: pre-post intervention study to assess impact of task shifting. BMC Public Health. 2018 Jun 7;18(1):703. )

Response: Thank you for the suggestions. We have included the suggestions in lines 253-262 ; 279 -284 and 299 of the discussion

5. Conclusion: are coherent with the paper.

Response: Thank you for the words of reviewer.

Reviewer #2:

The title should be as follows: vertical transmission of HIV in the district of Belene, Province of Gaza-Mozambique. Because the mother's transmission for children can be done using the same sharp objects that is common to the rural population and without education.

it is not clear how the sample was obtained.

I think the 90 sample is not representative for all of Mozambique.

Response: Thank you for the comment. We have changed the title to “ Mother-to-child transmission of HIV infection and its associated factors in the district of Bilene, Gaza Province – Mozambique”. The sample included all the mother-child pairs that presented at the Macia and Praia de Bilene health facility in the period from 1st Jan 2017 – 30th June 2018 and met the inclusion criteria. Please refer to lines 100 – 122 of the methods section.

Reviewer #3:

Manuscript Number: PONE-D-21-02247

Title: Mother-to-child transmission of HIV infection and its associated factors on the rural coast of southern Mozambique.

Reviewer’s comments:

Congratulations to the authors for the study. This manuscript reports an interesting analysis with the great impact to the public health, conducted in the rural coast of southern Mozambique, an area with a high prevalence of HIV infection.

Response: Thanks for the words of the reviewer

My minor comments/suggestions are listed below to improve the manuscript:

1. Abstract

Methods Section:

The study methodology described in the summary does not allow readers to understand how the study was conducted, you just say the type of study it is. Please, the authors should briefly describe how the study was carried out, for example: Who are "the Cases", how were they enrolled, what age were they. Also who were controls and how the contorols were also enrolled to the study, there was some matching between case and controls? Each enrolled “Case” how many “Controls” were considered.

Response: Thank you for the feedback; we have addressed this by adding sub-sections on “study population and sampling method” and “sample size” in lines 100 – 122.

2. The main body of manuscript

a) Results Section:

• The description of the results appears to be confusing. It is not clear how many women were recruited for study. It is understood that the study included 90 pregnant women, 30 women who transmitted HIV infection to their children and 60 women who did not transmitted HIV. Is that what you mean here? Please this is strongly recommended to rewrite the results section to make it clearer. It could be better if the author presents the percentage of women who transmitted HIV to their children and the percentage of women who did not transmitted HIV.

Response: Thank you for the feedback; in lines 181 – 183 we have addressed this. The cases (30) were recruited as women who transmitted HIV and the controls (60) were recruited as women who did not transmit HIV. We then compared cases and controls to see what factors were associated with HIV transmission. It is a case-control study.

• The authors say that in the adjusted analysis for maternal age and gestational age at the first ante natal consultation shown to be as risk factors of transmission but do not say what was the gestational age of the first antenatal consultation that was associated with HIV transmission from the mother to the child. This is important to guide the staff who dealing with this issue to take into account when they are giving lectures to prevent mother-to-child transmission of HIV infection as you present regarding to the pregnant woman's viral load. It is very clear that viral load of 1000 copies or more is a risk factor for transmission. Authors should present to readers what was the gestational age at the first antenatal consultation that was associated with HIV transmission from mother to child.

Response: Thank you our suggestions. We included the clarification in the result section in line 182 – 183. The median gestational age at first antenatal visit was 24 years for cases and 20 years for controls.

• In evaluating factors related to the transmission of HIV from mother to child in the Table 1, it would be good to calculate the Odds ratio of each variable analyzed to see the trends of the associations.

Response: According the suggestions of the reviewer, we have include de odds ratio of the factors related to transmission of HIV

• In the table 2 Please calculate the P-value

Response: According the suggestions of the reviewer we have include p-value of adjusted multivariable analysis in the footnote

b) Discussion section

The discussion seems weak. In this section you have to bring what your results and the results found by other scientists and do not refer readers to the bibliographic references. For example, in the first paragraph of your discussion you say that the factors for mother-to-child transmission of HIV are described in a fair job in Rwanda, but what does the publication of Rwanda's work say? Please rewrite and discussion.

Response: Thank you for the feedback. We have addressed this and improved the discussion.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

22 Nov 2021

Mother-to-child transmission of HIV infection and its associated factors in the district of Bilene, Gaza Province - Mozambique

PONE-D-21-02247R1

Dear Dr. Isabelle,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Claudia Marotta

Academic Editor

PLOS ONE

Additional Editor Comments:

dear authors congratulations

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors wrote an important paper from interesting setting. Research from low setting are precious and key to global health action

Reviewer #3: Congratulations to the authors for the study. This manuscript reports an interesting analysis with a major impact on public health, carried out on the rural coast of southern Mozambique, an area with a high prevalence of HIV infection. That is why I think it will be of interest to readers of this journal, especially those who work in areas of high HIV prevalence, a fact that will contribute to reducing the transmission of HIV from mother to child. It as original research and well statiscally conducted.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: No

3 Dec 2021

PONE-D-21-02247R1

Mother-to-child transmission of HIV infection and its associated factors in the district of Bilene, Gaza Province - Mozambique

Dear Dr. Munyangaju:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

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on behalf of

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