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PLOS One logoLink to PLOS One
. 2020 May 20;15(5):e0233136. doi: 10.1371/journal.pone.0233136

Factors associated with unmet need for limiting childbirth among women living with HIV in Togo: An averaging approach

Issifou Yaya 1,2, Aboubakari Nambiema 2, Sokhna Dieng 3, Lihanimpo Djalogue 4, Mawuényégan Kouamivi Agboyibor 5, Mathias Kouamé N’Dri 6, Takiyatou Baba-Toherou 2, Akouda Akessiwe Patassi 7, Dadja Essoya Landoh 8, Kanfitine Kolani 9, Abdoul-Samadou Aboubakari 10, Bayaki Saka 11,*
Editor: Kwasi Torpey12
PMCID: PMC7239477  PMID: 32433689

Abstract

Background

Access to antiretroviral treatment has improved the life expectancy of HIV-positive patients, most often associated with a desire to limit childbearing. Women living with HIV (WLHIV) commonly have unmet need for contraception and could be at risk of unintended pregnancy. Preventing unintended pregnancies among women living with HIV are effective strategies to eliminate mother-to-child transmission of HIV.

Objective

The aim of this study was to assess unmet need for limiting childbirth and its associated factors among women living with HIV in Togo.

Methods

This facility based cross-sectional study was conducted, between June and August 2016, among WLHIV in their reproductive age (15–49 years) in HIV-care settings in Centrale and Kara regions Data was collected using a structured and pretested questionnaire. WLHIV who desired to limit childbirth but not using contraception were considered to have unmet need of birth limitations. Univariate and multivariate Poisson regression models with robust variance were performed to identify associated factors with unmet needs. A multi-model averaging approach was used to estimate the degree of the association between these factors and the unmet need of birth limitations.

Results

A total of 443 WLHIV were enrolled, with mean age of 34.5 years (standard deviation [SD] = 7.0). Among them 244 (55.1%) were in couple and 200 (45.1%) had at least the secondary level of education. 39.1% were followed-up in a private healthcare facility. At the time of the survey, 40.0% did not desire childbearing but only 9.0% (95% CI [6.7–12.1]) of them expressed unmet needs for limiting childbirth. In multivariable analysis, associated factors with unmet needs of birth limitations were: being aged 35 years or more (adjusted prevalence ratio (aPR) = 3.11, 95% confidence intervals (95% CI) [1.52–6.38]), living in couple (aPR = 2.32 [1.15–4.65]), living in Kara region (aPR = 0.10 [0.01–0.76]), being followed in a private healthcare facility (aPR = 0.08[0.01–0.53]) and having severe HIV symptoms (aPR = 3.50 [1.31–9.37]).

Conclusion

Even though the unmet need for births limitation was relatively low among WLHIV in Togo, interventions to improve more access to contraceptive methods, and targeting 35 to 49 years old women, those in couple or followed in the public healthcare facilities would contribute to the eradication of mother-to-child transmission of HIV.

Background

Improving the reproductive health of women living with HIV (WLHIV), including access to high-quality services for family planning would help slow the HIV epidemic in low- and middle-income countries [1]. In low-income countries women are disproportionately affected by HIV [2,3]. For every three new HIV infections among young men aged 15–24 years in Western and Central Africa there were five new infections among young women [3,4]. It is estimated that women account for nearly two-thirds of the people living with HIV/AIDS (PLWHA) in this region.

WLHIV of reproductive age might continue to spread the HIV epidemic through the transmission of HIV to their children during pregnancy or breastfeeding. For HIV-positive pregnant women, in the absence of any intervention related to HIV prevention, the risk of HIV transmission from mother to child is estimated at 15%–30% during pregnancy and childbirth, and 10% to 20% during breast-feeding [57]. In 2016, about 87% (140,000 cases) of new HIV infections worldwide among children occurred, the vast majority (over 90%) through mother-to-child transmission (MTCT) during pregnancy, delivery or breast feeding periods [1], in 23 sub-Saharan African countries, where a 48% decline in new child infections since 2010 was reported [8].

Prevention of MTCT of HIV, advocated by WHO as one of the most effective strategies in the fight against HIV/AIDS, is receiving increasing attention at the international, regional and national levels. Access to antiretroviral treatment (ART) and preventing unintended pregnancies among WLHIV are effective strategies to eliminate MTCT [8,9].

In Western and Central Africa, it was estimated 330,000 the number of pregnant women living with HIV in 2017, of whom less than half (42%) received ART to prevent mother-to-child transmission of HIV. Consequently, the rate of mother-to-child transmission (including during the breastfeeding period) was 20.2% [10]. Family planning (FP), by preventing unintended pregnancies and helping to space childbirth for women and couples living with HIV, constitute an important measures to prevent MTCT of HIV [11,12]. Several studies have shown low prevalence of contraceptive use among HIV-positive compared to their HIV-negative counterparts [13,14], and therefore they have higher unmet need for FP and reproductive health services [15,16], and higher level of unplanned pregnancy [17,18]. The unmet need for FP is increasingly a reliable indicator of reproductive health among WLHIV [11,19,20]. The level of unmet need in FP is the result of several factors, including individual, contextual or structural factors. In low-income countries, availability, cost and geographic accessibility are major barriers to contraceptive use in women of reproductive age, including WLHIV. In a DHS-based study addressing unmet need for FP in WLHIV in Lesotho, Adair [21] found that currently HIV-positive married women, or older WLHIV, were more likely to reported unmet need for FP, while WLHIV with higher household wealth reported lower level of unmet need for FP. But what about the prevalence of unmet need for FP in WLHIV in west Africa, particularly in Togo? And how can we explain it among this group? Even if few studies have examined the use of modern contraception in WLHIV, little is known about unmet need for limiting childbirth among WLHIV in Togo.

A previous study among WLHIV of childbearing age in Togo found a prevalence of 73.1% for the use of modern contraceptives (74.7% for condom use alone and 16.9% in combination with hormonal contraceptive) [22]. It was also reported in that study the education level, marital status, WHO clinical stage, follow-up in private care facilities and having a child were associated factors modern contraception use [22].

This study aimed to assess the prevalence and identify associated factors of unmet need for limiting childbirth among WLHIV attending HIV clinics in two regions of Togo.

Methods

Study design

Between May and August 2016, a cross-sectional study was conducted among WLHIV of reproductive age (15–49 years) and sexually active attending HIV clinics in two health regions of Togo including the Centrale and Kara regions.

Setting and study population

More than 30 medical clinics were accredited to deliver HIV-related care in the Centrale and Kara regions, two of the Togo’s six health regions located about 350 km and 420 km from the capital city Lomé, respectively. About 10,361 PLWHA, including 616 children were followed-up in these two health regions [23]. The prevalence of HIV infection in these two regions was 2.2% in the Centrale region and 1.8% in the Kara region in 2013 [24]. The both health regions are characterized by important population mobility seasonally, mainly from the surrounding health regions, and sometimes from outside of the country, occurring during the cultural and traditional events that could increase the risks of HIV transmission.

WLHIV aged 15–49 years who reported a sexual partner in the six months prior the study and who were followed-up at selected study’s sites for HIV care or active ART (for at least 6 months) were included in this study. But women who were pregnant at the moment of the study were excluded.

Sampling

The sampling procedure was described in a previous study [22]. In order to ensure representative HIV clinics with a high number of PLWHA, we performed a random probability sampling proportional to the number of patients in the active file of the 30 HIV clinics in the two regions. We assumed that a sample of 15% of HIV clinics should be representative of all the HIV clinics. This led to the random selection of 5 HIV clinics for the implementation of this study. “Then, a non-probabilistic, convenience sampling was performed” [22]. In the selected HIV clinics, it was proposed to participate to this study, any PLWHA who were admitted in the active file for a follow-up from May to August 2016, who met the inclusion criteria and who signed the consent form to participate in the study. “The prevalence of unmet needs for limiting childbirth among WLHIV was assumed to be 50% with the precision of 5%, 20% refusal or incomplete data and the design effect was estimated at 1. Based on this assumption, the sample size was estimated at 461 WLHIV” [22].

Data collection

Data was collected on a face-to-face basis among participants using a structured and pretested questionnaire in French, explained in the local language for participants if needed. For each participant, the questionnaire was filled by a trained health worker. This questionnaire included socio-demographic information, clinical features, information on ART, sexual activity status and on contraceptives knowledge and its use. Data on HIV status disclosure to the sexual partner was also collected. We defined unmet needs for limiting childbirth as the fecund women who were sexually active and intend to stop childbearing (limiting) but were not using any contraceptive method. We did not included needs for birth spacing.

Data’s statistical analysis

Data entry was performed using Epi Data software version 3.1. Data were then exported for statistical analyses using STATA/SE, version 15.1 (Statacorp LP, College Station, Texas, USA).

In descriptive analysis step, for continuous variables, mean and standard deviation were calculated while for categorical variables we calculated proportions. Our main outcome variable was WLHIV who reported unmet needs for limiting childbirth coded 1 and 0 if else. Pearson chi-square test or Fisher′s exact test were used when appropriate in bivariate analysis All variables significant during bivariate analysis at a p-value <0.10 were included in a multivariate model.

A multivariable Poisson regression analysis was performed to identify independent factors associated with the dichotomous outcome “unmet needs for limiting childbirth or no”. The estimates were presented as prevalence ratio (PR). All these analyses were performed with 95% confident interval (CI).

A multimodal averaging method was therefore performed using both a Poisson regression model (with robust variance) and the Akaike information criterion (AIC) for weighting models, based on the contribution of each covariate in explaining the risk of unmet needs for limiting childbirth. This process helps not only to select a final model (all the possible models) with Poisson regression procedures, but also to rank the covariates according to their relative importance. It compares the likelihood of an empty model with the likelihood of the model with covariates, provides also the proportion of the variation explained by the specified model. This averaging multimodel approach was described elsewhere [25].

In addition, we used relative importance weights (values between 0 and 1) to classify the associated factors according to the weight of the evidence with the following classification [26]: [0–0.5 [=  no evidence; [0.5–0.75 [=  weak evidence; [0.75–0.95 [=  positive evidence; [0.95–0.99 [=  strong evidence; [0.99–1 [=  very strong evidence.

Ethical issues

This study was approved by the National AIDS and STI Program of Togo (Ref N° 098/2016/MS/DSSP/PNLS-IST). We obtained consent from patients that participated in the study. For each respondent, the objectives and benefits of participating in the survey and its conduct were clearly stated, as well as their right to interrupt the interview without justification. An informed consent form signed after the verbal explanation was made by the investigating officer in the language understood by the participant. For participants the aged between 15 and 17, we asked for the consent of the parents or the legal guardian.

Results

Socio-demographic and clinical characteristics

Table 1 shows the socio-demographic and clinical characteristics of the participants. In total 461 WLHIV of reproductive age and sexually active were enrolled into this study, we excluded 18 (3.9%) participants who were pregnant at the time of the survey. Of the 443 participants, 252 (56.9%) were living in the Centrale health region and 191 (43.1%) in the Kara health region. The mean ± (Standard Deviation) age of the participants was 34.5±7.0 years, ranging from 16 to 49 years, and half of them aged 35 years or older. Among participants, 40.9% had primary education level, and 45.1% had secondary or higher education level, 55.1% lived in couple and 62.5% lived in urban area. Of the 443 WLHIV who were interviewed, 403 (91.0%) were on ART and for more than two years for 71.4% of them. The mean duration on ART was 4.1 years ± 2.8 (SD). A quarter (25.7%) of participants had a CD4 cells count < 350 cells/mm3 at the last visit. At the time of the survey, 52.4% of participants reported moderate HIV symptoms, while symptoms were severe in 4.5% of participants. The partner’s HIV status was unknown for 42.4% (188/443) of participants. Most of the patients were followed-up in a public healthcare facility (60.9%), with a psychologist (56.7%). Three hundred and sixty-three participants had at least one child at the time of the survey.

Table 1. Characteristics of the study participants (WLHI, N = 443).

n (%) Unmet needs p-value
No, n (%) Yes, n (%)
Age, (mean±SD) years (443) 34.5±7.0 0.004
< 35 218 (49.2) 207 (95.0) 11 (5.0)
35–49 225 (50.8) 196 (87.1) 29 (12.9)
Education level 0.161
No education 62 (14.0) 58 (93.5) 4 (6.5)
Primary 181 (40.9) 159 (87.9) 22 (12.1)
Secondary and more 200 (45.1) 186 (93.0) 14 (7.0)
Profession of participant 0.187**
Public sector 33 (7.4) 31 (93.9) 2 (6.1)
Private sector 19 (4.3) 18 (94.7) 1 (5.3)
Informal sector 226 (51.0) 199 (88.1) 27 (11.9)
No profession 165 (37.3) 155 (93.9) 10 (6.1)
Marital status 0.020
In couple 244 (55.1) 215 (88.1) 29 (11.9)
Single 199 (44.9) 188 (94.5) 11 (5.5)
Residence of patient 0.735
Urban 277 (62.5) 251 (90.6) 26 (9.4)
Rural 166 (37.5) 152 (91.6) 14 (8.4)
Region 0.015
Centrale 252 (56.9) 222 (88.1) 30 (11.9)
Kara 191 (43.1) 181 (94.8) 10 (5.2)
Religion 0.664**
None 38 (8.6) 36 (94.7) 2 (5.3)
Islam 148 (33.4) 135 (91.2) 13 (8.8)
Christianism 257 (58.0) 232 (90.3) 25 (9.7)
WHO’s clinical stage 0.013
Stage I 243 (55.2) 226 (93.0) 17 (7.0)
Stage II 118 (26.8) 109 (92.4) 9 (7.6)
Stage III & IV 79 (18.0) 65 (82.3) 14 (17.7)
Symptoms’ Intensity 0.018
None 191 (43.1) 170 (89.0) 21 (11.0)
Moderate 232 (52.4) 218 (94.0) 14 (6.0)
Severe 20 (4.5) 15 (75.0) 5 (25.0)
CD4 cell counts 0.789
< 350 114 (25.7) 103 (90.4) 11 (9.7)
≥ 350 329 (74.3) 300 (91.2) 29 (8.8)
ART 0.389
Yes 403 (91.0) 368 (91.3) 35 (8.7)
No 40 (9.0) 35 (87.5) 5 (12.5)
ART’s scheme (n = 403) 0.340*
1rst line 370 (91.8) 336 (90.8) 34 (9.2)
2nd line 33 (8.2) 32 (97.0) 1 (3.0)
ART duration (= 414) 0.669
< 2 years 115 (28.6) 104 (90.4) 11 (9.6)
≥2 years 287 (71.4) 263 (91.6) 24 (8.4)
Partner’s HIV status 0.583
Unknown 188 (42.4) 174 (92.5) 14 (7.5)
HIV-positive 134 (30.3) 121 (90.3) 13 (9.7)
HIV-negative 121 (27.3) 108 (89.3) 13 (10.7)
Type of health center <0.0001
Private 173 (39.1) 168 (97.1) 5 (2.9)
Public 270 (60.9) 235 (87.0) 35 (13.0)
Presence of psychologist in the center 0.004
No 192 (43.3) 166 (86.5) 26 (13.5)
Yes 251 (56.7) 237 (94.4) 14 (5.6)
Number of children 0.037
None 53 (12.7) 51 (96.1) 2 (4.7)
1–3 304 (73.1) 279 (91.8) 25 (8.2)
4–7 59 (14.2) 49 (83.0) 10 (17.0)
Fertility desire <0.0001
No 175 (40.0) 135 (77.1) 40 (22.9)
Yes 263 (60.0) 263 (100.0) 0 (0.0)
Contraceptive methods <0.0001
None 119 (26.9) 80 (67.2) 39 (32.7)
Condom alone 242 (54.6) 241 (99.6) 1 (0.4)
Condom+hormonal contraceptive 55 (12.4) 55 (100.0) 0 (0.0)
Hormonal contraceptive 26 (5.9) 26 (100.0) 0 (0.0)
Intrauterine devices 1 (0.2) 1 (100.0) 0 (0.0)

Unmet needs for limiting childbirth

Based on the conceptual definition in this study, 9.0% (95%CI [6.7–12.1]) of participants expressed unmet needs for limiting childbirth. However, this prevalence varies cross participants characteristics. Indeed, the proportion of participants with unmet needs was significantly lower (p = 0.004) among under 35 women than those aged from 35 years and older (5.0% vs 12.9%). A higher proportion of participants in couple (11.9%, p = 0.020), those having four children or more (17.0%, p = 0.037) and those who reported severe HIV symptoms (25.0%, p = 0.008) expressed also unmet needs for limiting childbirth during this study. However, WLHIV living in the Kara health region (p = 0.015), those followed-up in private healthcare facility (p = 0.001) or those followed-up in a center with a psychologist (p = 0.004) were less susceptible to report unmet needs for limiting childbirth (Table 1).

Factors associated with unmet needs for limiting childbirth

After adjustment for significant covariates (with a p-value <0.10), multivariable analysis revealed a strong association between unmet needs for limiting childbirth, age of patients and the type of healthcare facility, a positive association with marital status and intensity of HIV symptoms and a weak association with the health region. In this study, older participants were more likely to report unmet needs for limiting childbirth than the younger. The prevalence of unmet needs for limiting childbirth was almost three times higher in WLHIV aged 35 or older (aPR = 3.11, 95%CI [1.52–6.38]; p = 0.002) than those aged less than 35 years. Concerning the marital status, the prevalence of unmet needs for limiting childbirth was two times higher among participants living in couple (aPR = 2.32 [1.15–4.65]; p = 0.018) compared to those who were single. Prevalence of unmet needs for limiting childbirth were 90% and 92% lower among patients respectively living in the Kara region (aPR = 0.10 [0.01–0.76]; p = 0.026) and followed in a private healthcare center (aPR = 0.08 [0.01–0.53]; p = 0.009) than respectively those living in the Centrale region and those who were followed in a public settings. Finally, WLHIV who reported severe HIV symptoms were more likely to express unmet needs for limiting childbirth (aPR: 3.50, 95%CI [1.31–9.37]; p = 0.013) than those without HIV symptoms (Table 2).

Table 2. Factors associated with unmet needs for limiting childbirth (multi-model averaging, N  =  443).

Poisson regression models
Univariate Multivariate Akaike weights (level of evidence) Rank
cPR p-value aPR p-value
Age, years
< 35 1 1
35–49 2.55 [1.22–4.28] 0.006 3.46 [1.76–6.82] <0.0001 0.99 (strong) 1
Education level
No education 1
Primary 1.88 [0.67–5.26] 0.227
Secondary and more 1.09 [0.37–3.20] 0.882
Profession of participant
No profession 1
Public sector 1.0 [0.23–4.36] 1.0
Private sector 0.86 [0.12–6.43] 0.890
Informal sector 1.97 [0.98–3.96] 0.057
Marital status
In couple 2.15 [1.10–4.20] 0.025 2.28 [1.23–4.24] 0.009 0.87 (positive) 3
Single 1 1
Residence of patient
Urban 1
Rural 0.90 [0.48–1.67] 0.736
Region
Centrale 1 1
Kara 0.44 [0.22–0.88] 0.020 0.10 [0.01–0.82] 0.032 0.68 (weak) 5
Religion
None 1
Islam 1.67 [0.39–7.09] 0.488
Christianism 1.84 [0.46–7.50] 0.390
Symptoms’ Intensity
None 1 1
Moderate/severe 0.55 [0.29–1.05] 0.070 0.70 [0.37–1.34] 0.286 0.89 (positive) 4
2.27 [0.96–5.38] 0.061 4.39 [1.90–10.14] 0.001
CD4 cell counts
< 350 1
≥ 350 0.91 [0.47–1.77] 0.879
ART
No 1
Yes 0.69 [0.29–1.67] 0.417]
ART’s scheme (n = 415)
1rst line 1
2nd line 0.33 [0.05–2.34] 0.267
ART duration (= 414)
< 2 years 1
≥2 years 0.87 [0.44–1.73 0.699
Knowledge of partner’s 0.284
HIV status
No 1
Yes 1.37 [0.73–2.55] 0.323
Type of health center
Public 1 1
Private 0.22 [0.09–0.56] 0.001 0.07 [0.01–0.48] 0.007 0.98 (strong) 2
Presence of psychologist in the center
No 1 1
Yes 0.41 [0.22–0.77] 0.005 8.51 [0.98–73.85] 0.051 0.59 (weak) 6
Number of children
None 1
1–3 2.18 [0.53–8.95] 0.280 7
4–7 4.49 [1.03–19.61] 0.046

According to the value of the importance weights [26]:

[0–0.5]: no evidence.

[0.5–0.75]: weak evidence.

[0.75–0.90]: positive evidence.

[0.95–0.99]: strong evidence.

[0.99–1]: very strong evidence.

Based on importance weight.

Discussion

This cross-sectional study described an important public health issue in a country where reproductive health and the fight against HIV are the focus of health policy. It is one of the few studies that focused on reproductive health as well as unmet need for limiting childbirth among WLHIV in Togo. Indeed, 40% of participants expressed the desire not to have children any more in the future, but some of them did not use any contraceptive method. In our study, the overall prevalence of unmet need for limiting childbirth was estimated at 9%, which is lower than previously reported in the general population in Togo (12%) [24] as well as that reported in most epidemiological studies of conducted among WLHIV in Sub-Saharan Africa. In a cross-sectional studies among WLHIV, Yotebieng et al in DR Congo and Wanyenze et al in Uganda found respectively that 17.6% and 36.8% of the WLHIV had an unmet need for limiting childbirth [20,27]. However, similar result of 9% was reported in another study among WLHIV attending HIV Care and Treatment Service at Saint Paul’s Hospital Millennium Medical College in Addis Ababa, Ethiopia [28]. Although the prevalence of unmet need for limiting childbirth was low among WLHIV in our study, these results nevertheless suggest that it is very important to implement strategies to address these needs, thereby reducing the risk of MTCT of HIV. To effectively guide the development of these strategies at the level of the study regions, the results of this study among WLHIV allow us to rank the factors associated with unmet need for limiting childbirth according to the importance of weight.

This study found that the age of the participants was the main factor that could influence mostly the prevalence of unmet need for limiting childbirth, with older WLHIV being more likely to have an unmet need to limit childbirth. This is consistent with the findings of a study conducted in HIV clinics at Mulago in Uganda, where WLHIV were about six times more likely to have unmet need for FP [20]. Older WLHIV may probably experience the side effects of contraception use and might be reluctant to use modern contraceptive. In addition, older women may have a lower perception of the risk of pregnancy.

WLHIV attending private HIV clinics were less likely to have unmet needs for limiting childbirth compared to those attending public HIV clinics. Private HIV clinics may provide better reproductive health services, including FP services. They are most often highly motivated to improve client satisfaction by providing integrated reproductive health care, and also work better at retaining patients living with HIV [29]. This result was consistent with that found in a study done in Mexico which reported that women were less likely to have unmet needs for limiting if they had access to private health service [30].

In this study, WLHIV in couple, either married or not, were more likely to report unmet need for limiting childbirth compared to those who were sexually active but not in couple. This result was consistent with studies conducted in Ethiopia [28] which found that WLHIV who were married were higher to report unmet need for limiting childbirth. In addition, similar findings from a study in Zambia and Swaziland [31] reported that WLHIV living in couples were twice as likely to have an unmet need for limiting childbirth. These women may have already the number of children that they wanted and may express their willingness to limit childbearing.

Not surprisingly, WLHIV who have reported moderate or severe symptoms of AIDS are more likely to have an unmet need for limiting childbirth. Indeed, in general, WLHIV who have symptoms of AIDS most often make the priority choice to regain their well-being and relegate to the second plan other health care, including reproductive health care. But WLHIV receiving antiretroviral therapy become more sexually active which could be accompanied by return to fertility [32]. In that context, most of them are reluctant to be pregnant, fearing transmit HIV to their child. In LMIC, where reproductive health services are not often integrated in the basic care in the HIV clinics, WLHIV may have to their demand for reproductive health services not satisfied [33]. However, those with moderate or severe symptoms may need to take additional pills each day for eventually treatment of opportunistic infections or symptomatic relief. Fearing potential drug interactions, clinician delay the use of contraceptive methods, hormonal contraceptives, as much as possible [34].

Finally, it should be noted that there is a disparity of the prevalence of unmet need for limiting childbirth between health regions. We found that WLHIV living in Kara health region were less likely to have unmet need for limiting childbirth compared to those living in Centrale health region. This variability between these two regions could be explained not only by cultural differences but also by the poverty index in these regions. Indeed, the central region is one of the poorest regions of Togo [35] and this could mostly influence the use of modern contraceptive. Similarly, a study conducted in Mexico using national demographic survey found that women living in the poorest region of the country have greater unmet needs for both spacing and limiting than those living in the capital of the country [30].

This study assessed the relative weight of each risk factor on unmet need for limiting childbirth among WLHIV and showed that the women’s age and the type of HIV clinic greatly influenced the prevalence of the unmet need for limiting childbirth. This suggests that, to be effective, interventions to eradicate unmet need for limiting childbirth should target WLHIV aged 35 years and older or those attending public HIV clinics in Togo.

Limitations of study

This study has several limitations. It was conducted in health facilities with a low probability to include WLHIV who were not followed-up or less regularly followed-up in the HIV clinics including in this study. They may have different characteristics. As for with most cross-sectional studies, not only the study sample may not be representative of all the WLHIV residing in Togo, but also it should be noted a possible reverse causality.

Conclusion

This research showed that the prevalence of unmet need for limiting childbirth among WLHIV was relatively low, but heterogeneous across the health regions involved in this study. Older women (aged 35 years and older), those in couple, those attending public HIV clinics, those with moderate or severe symptoms of AIDS, and those residing in the Centrale health region had the highest unmet needs for contraception to limit childbirth. Interventions to improve more access to modern contraception, targeting women aged 35 to 49 years, those in couple or those attending public healthcare facilities would contribute to the eradication of mother-to-child transmission of HIV in Togo.

Supporting information

S1 Data

(PDF)

S2 Data

(PDF)

Acknowledgments

We would like to thank health workers involved in data collection for their contribution. We acknowledge all patients who accepted to participate in this study.

Abbreviations

HIV

Human immunodeficiency virus

AIDS

acquired immunodeficiency syndrome

aPR

adjusted prevalence ratio

ART

Antiretroviral therapy

PLWHA

People Living With HIV and AIDS

WLHIV

women living with HIV

FP

Family planning

MTCT

mother-to-child transmission

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Kwasi Torpey

26 Feb 2020

PONE-D-20-01103

Factors associated with unmet need for limiting childbirth among HIV-positive women in Togo: an averaging approach

PLOS ONE

Dear Dr Saka,

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https://doi.org/10.1136/bmjopen-2017-019006

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Reviewers' comments:

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Reviewer #1: Partly

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

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5. 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: Understanding unmet FP needs of women with HIV+ women is important to understand programmatic gaps, meet women's RH goals, and reduce MTCT. The authors present data from women in Togo on this topic, and identify some gaps. There are some notable methodological issues (namely in the definition of the outcome and in analysis/lack of accounting for clustering) that are important to fully comprehend study results. In addition, the authors could do a better job in the background and discussion describing the rationale for the study (ie many studies have already been conducted, although not in Togo) and synthesize findings in the discussion rather than only repeat findings and compare to the literature.

Abstract and Methods

-Unmet need – did you exclude needs for birth spacing? If so please overtly state in methods. If not, add birth spacing to definition of unmet need.

Background

-The background could be more focused; contraception isn’t mentioned until the 3rd paragraph. Suggest cutting much of 1st 3-4 paragraphs to narrow focus on your topic.

Methods

-The sample was selected at the facility level and then participants within the facility. The authors should account for clustering in all of their analysis.

-Describe the rationale for the AIC/Poisson model; ie how it differs from the multivariate model and why it was done.

-In the analysis of unmet need who is the comparator, women with their FP needs met who desire to not have future children? Or are woman who want to conceive in the comparator? This is an important methodological issue, as if women who want to conceive are in the comparison group than there is a lot of heterogeneity in the comparison group (needs met + desire for future children); these groups are very different.

Results

-Results need more specificity in their description; for example age of patient and type of healthcare facility are associate with unmet need. These are variables but don’t describe the association (ie older age, or younger age?). Suggest cutting these types of statements as later you go on to describe the relationship with age > and < 35.

-“Weak with the health region”unclear sentence.

- Was contraceptive use measured? Among women who had their “needs met” what was the method mix? Women who are not using condoms plus another method (dual method) technically have their FP needs met, with a less effective method. In contrast, women using DMPA have FP needs met but are at risk for HIV transmission and STIs. Would be nice to more comprehensively describe the cohort.

-Did the authors look to see if any of their variables were collinear in the MV model? Ie age and # children?

Discussion

-The authors did not “address” a public health issue as it is just descriptive; suggest rephrasing.

-There are actually several studies on RH and unmet need (the authors cited some in the background but there are many more). Claiming this sis one of a few studies is not accurate.

-The comparison with the Uganda results does not make sense; you are discussing age among HIV+ women whereas the Uganda study was comparing HIV+ to HIV-. This should be removed for comparison or change context to refer to % unmet need among HIV+.

-The marital status findings are mentioned 2X in the discussion, suggest consolidating into one section.

-The interpretation of the women with severe findings is inconsistent with your results. You found women with symptoms were MORE likely to have unmet need, but the following sentence supports these women having LESS unmet need. Please revise accordingly.

Limitations

-You should acknowledge possibility of reverse causality due to the cross-sectional design.

Conclusions

-This seems to repeat the study findings but should describe the “so what” about the research. What are next steps as a result of this research?

Table 1

-Unmet need should be defined, including making it clear who is in the “no” category.

-N for age is not listed

-Can you include partner status, would be helpful to know among those with known partner status if partners are HIV+ vs HIV-

-Why is fertility desire not described for both groups?

-Unmet need should not be in the rows it is the outcome.

The manuscript would benefit from a native English speaker review/copyedit. There are several grammatical errors throughout.

Reviewer #2: Overall comment:

This is an interesting cross-sectional study that examined the prevalence of unmet need for limiting childbirth and associated factors among women living with HIV in Togo. This is an important and timely piece of work conducted at a time when the global community is increasing efforts to close the remaining gaps in prevention of mother-to-child transmission of HIV programs.

While the study is analytically sound and clearly written, there was some lack of detail and consistency regarding the definition of the outcome and some key variables. The authors should expand the Methods section to include details of appropriate definitions of the outcome and key variables, including questions from which these variables were constructed. Also, I would advise the authors to revise extensively for typos to improve readability of the text.

Abstract and Background:

1. The terms ‘in a relationship’, ‘marital status’ ‘in a couple’ mean different things and have been used interchangeably in the abstract (result and conclusion) and also throughout the paper. The definition of relationship status e.g. cohabiting (married or not) should be clarified and consistently used.

2. Depending on editorial preference, consider using women living with HIV rather than HIV-positive women.

3. Page 3: first sentence in last paragraph is unclear. Rephrase sentence.

4. Page 3, second paragraph line 9: uncap the ‘Sub’ in ‘Sub-Saharan’

Methods:

5. Similar to the varying prevalence of unmet need for limiting childbirth across health regions, I wonder if you could add to your predictors some metric (if you have this in your database) for patients’ ease of accessibility to health facility? For instance, distance to the clinic?

6. Page 6: line 1 and 2 implies a contradiction to the earlier definition of your study population. My understanding based on the inclusion criteria on page 5 is that all women included were sexually active. Clarify.

7. Page 7, first paragraph: Clearly define how you categorized ‘moderate vs. severe’ HIV symptoms.

Results:

8. I wonder if some information on type of contraceptive methods used among those without the outcome can be included. It would be useful to better understand possible targeted interventions to improve unmet needs in the region.

9. For the categorical variable that you created for age, is there a reason why this was not a 3-level variable? Considering the age range of 16-49 in your study sample, I imagine that fertility intentions, contraceptive use and health seeking behaviors might be different for 16-25 year old women compared to those 26-35 years of age.

Discussion:

10. I had some concerns about the potential for under representation of unmet needs for limiting childbirth in your sample, due to the fact that you recruited women who were followed at HIV care sites for at least 6 months, but I think you have addressed this adequately in the limitations.

11. Page 11, Line 2 in Conclusion: a word is missing between ‘health’ and ‘involved’

**********

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2020 May 20;15(5):e0233136. doi: 10.1371/journal.pone.0233136.r002

Author response to Decision Letter 0


16 Apr 2020

Authors‘ response

Here is a point-by-point response to the Editor and the reviewers’ comments and concerns.

Editor Comments:

When submitting your revision, we need you to address these additional requirements:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Answer: As suggested the editor, we have formatted our manuscript as required.

2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. If you developed and/or translated a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

Answer: Thank you so much, As suggested the editor, we have included the French version of the questionnaire used in the study. We are still working to translate it in English.

3. We noticed you have some minor occurrence(s) of overlapping text with the following previous publication(s), which needs to be addressed: https://doi.org/10.1136/bmjopen-2017-019006

In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the Methods section. Further consideration is dependent on these concerns being addressed.

Answer: Thank you so much. As suggested the editor, we have cited my previous paper and put overlapping text in quote.

4. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

Answer: Here is my ORCID iD : orcid.org/0000-0002-2554-6515

5. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 2 in your text; if accepted, production will need this reference to link the reader to the Table.

Answer: Thank you for this comment, we included the reference of the table 2 as it is required in the text of our manuscript

Reviewer #1: Understanding unmet FP needs of women with HIV+ women is important to understand programmatic gaps, meet women's RH goals, and reduce MTCT. The authors present data from women in Togo on this topic, and identify some gaps. There are some notable methodological issues (namely in the definition of the outcome and in analysis/lack of accounting for clustering) that are important to fully comprehend study results. In addition, the authors could do a better job in the background and discussion describing the rationale for the study (ie many studies have already been conducted, although not in Togo) and synthesize findings in the discussion rather than only repeat findings and compare to the literature.

We would like to thank the reviewer for careful reading of our manuscript and for the valuable comments, which were of great help in revising in order to improve the quality of this manuscript. Our responses to the reviewer’s comments are given below.

Abstract and Methods

-Unmet need – did you exclude needs for birth spacing? If so please overtly state in methods. If not, add birth spacing to definition of unmet need.

Answer: Thank you for this comment, we did not included needs for birth spacing in the outcome definition (Unmet need for limiting childbirth), so we stated it in the methods, thank you

Background

-The background could be more focused; contraception isn’t mentioned until the 3rd paragraph. Suggest cutting much of 1st 3-4 paragraphs to narrow focus on your topic.

Answer: As suggested the reviewer, we have deleted the first paragraph and we have reorganized the other paragraphs by focusing more on family planning and contraceptive use, thank you

Methods

-The sample was selected at the facility level and then participants within the facility. The authors should account for clustering in all of their analysis.

Answer: Thank you for this comment. In our statistical analysis strategies, we had tried multilevel regression models taking into account the health facilities. However, the variability between health facilities was not significant. So, we had to abandon this analysis strategies.

-Describe the rationale for the AIC/Poisson model; ie how it differs from the multivariate model and why it was done.

Answer: As suggested the reviewer, we describe with more details the rationale in the methods section. So we added in the “Data’s statistical analysis” section the following paragraph: “This process helps not only to select a final model (all the possible models) with Poisson regression procedures, but also to rank the covariates according to their relative importance. It compares the likelihood of an empty model with the likelihood of the model with covariates, provides also the proportion of the variation explained by the specified model. This averaging multimodel approach was described elsewhere [25]”

The multivariable model provided adjusted prevalence ratio, while multimodal averaging helped to rank covariates based on their contribution in explaining the risk of unmet needs for limiting childbirth.

-In the analysis of unmet need who is the comparator, women with their FP needs met who desire to not have future children? Or are woman who want to conceive in the comparator? This is an important methodological issue, as if women who want to conceive are in the comparison group than there is a lot of heterogeneity in the comparison group (needs met + desire for future children); these groups are very different.

Answer: Thank you for this relevant comment. We agree with the reviewer that the comparison group in our study is very heterogeneous.

Results

-Results need more specificity in their description; for example, age of patient and type of healthcare facility are associate with unmet need. These are variables but don’t describe the association (ie older age, or younger age?). Suggest cutting these types of statements as later you go on to describe the relationship with age > and < 35.

-“Weak with the health region”unclear sentence.

Answer: Thank you for this comment. We correct it, thank you

- Was contraceptive use measured? Among women who had their “needs met” what was the method mix? Women who are not using condoms plus another method (dual method) technically have their FP needs met, with a less effective method. In contrast, women using DMPA have FP needs met but are at risk for HIV transmission and STIs. Would be nice to more comprehensively describe the cohort.

Answer: Thank you for pointing this out. We added in the Table 1 the description of type of contraception reported by participants. We agree with your comment, that not all methods protect against STIs. But as you will note, about two thirds of participants used condoms and could therefore avoid STIs.

-Did the authors look to see if any of their variables were collinear in the MV model? Ie age and # children?

Answer: Thank you for this suggestion. We finally excluded the number of children in the MV model, as these variables are collinear.

Discussion

-The authors did not “address” a public health issue as it is just descriptive; suggest rephrasing.

Answer: we correct it, thank you

-There are actually several studies on RH and unmet need (the authors cited some in the background but there are many more). Claiming this sis one of a few studies is not accurate.

Answer: We agree with this comment. We correct it, we specified that is was related to studies conducted in Togo, we omitted to mention it, thank you

-The comparison with the Uganda results does not make sense; you are discussing age among HIV+ women whereas the Uganda study was comparing HIV+ to HIV-. This should be removed for comparison or change context to refer to % unmet need among HIV+.

Answer: As suggested the reviewer, we have removed this reference, thank you

-The marital status findings are mentioned 2X in the discussion, suggest consolidating into one section.

-The interpretation of the women with severe findings is inconsistent with your results. You found women with symptoms were MORE likely to have unmet need, but the following sentence supports these women having LESS unmet need. Please revise accordingly.

Answer: The reviewer has raised an important point here. So, we revised this paragraph in the “Discussion” section as following “Not surprisingly, WLHIV who have reported moderate or severe symptoms of AIDS are more likely to have an unmet need for limiting childbirth. Indeed, in general, WLHIV who have symptoms of AIDS most often make the priority choice to regain their well-being and relegate to the second plan other health care, including reproductive health care. But WLHIV receiving antiretroviral therapy become more sexually active which could be accompanied by return to fertility [32]. In that context, most of them are reluctant to be pregnant, fearing transmit HIV to their child. In LMIC, where reproductive health services are not often integrated in the basic care in the HIV clinics, WLHIV may have to their demand for reproductive health services not satisfied [33]. However, those with moderate or severe symptoms may need to take additional pills each day for eventually treatment of opportunistic infections or symptomatic relief. Fearing potential drug interactions, clinician delay the use of contraceptive methods, hormonal contraceptives, as much as possible [34]”.

Limitations

-You should acknowledge possibility of reverse causality due to the cross-sectional design.

Answer: As suggested the reviewer, we have added a sentence mentioning a possible reverse causality due to the cross-sectional design.

Conclusions

-This seems to repeat the study findings but should describe the “so what” about the research. What are next steps as a result of this research?

Answer: Thank you for this comment. We will disseminate our results to policy decision-makers in order firstly, to convince them to reproduce this study in other regions and secondly translate these results into effective interventions adapted to reduce unmet needs.

Table 1

-Unmet need should be defined, including making it clear who is in the “no” category.

Answer: Thank you for pointing this out. We defined unmet needs for limiting childbirth as the fecund women who were sexually active and intend to stop childbearing (limiting) but were not using any contraceptive method. And furthermore, our main outcome variable was WLHIV who reported unmet needs for limiting childbirth coded 1 (oui) and 0 (non) if else.

-N for age is not listed

Answer: As suggested the reviewer, we included it in the table 1, thank you

-Can you include partner status, would be helpful to know among those with known partner status if partners are HIV+ vs HIV-

Answer: As suggested the reviewer, we included it in the table 1, thank you

-Why is fertility desire not described for both groups?

Answer: the fertility desire is included in the outcome definition, it is why we decided not to include it in the description, thank you

-Unmet need should not be in the rows it is the outcome.

Answer: As suggested the reviewer, we deleted the row containing the outcome, thank you

The manuscript would benefit from a native English speaker review/copyedit. There are several grammatical errors throughout.

Reviewer #2: Overall comment:

This is an interesting cross-sectional study that examined the prevalence of unmet need for limiting childbirth and associated factors among women living with HIV in Togo. This is an important and timely piece of work conducted at a time when the global community is increasing efforts to close the remaining gaps in prevention of mother-to-child transmission of HIV programs.

While the study is analytically sound and clearly written, there was some lack of detail and consistency regarding the definition of the outcome and some key variables. The authors should expand the Methods section to include details of appropriate definitions of the outcome and key variables, including questions from which these variables were constructed. Also, I would advise the authors to revise extensively for typos to improve readability of the text.

Abstract and Background:

1. The terms ‘in a relationship’, ‘marital status’ ‘in a couple’ mean different things and have been used interchangeably in the abstract (result and conclusion) and also throughout the paper. The definition of relationship status e.g. cohabiting (married or not) should be clarified and consistently used.

Answer : Thank you for this comment. In our study, we have chosen to use the term “In couple” which was define as participant cohabiting with his/her sexual partner. We change it through the text of the manuscript.

2. Depending on editorial preference, consider using women living with HIV rather than HIV-positive women.

Answer : As suggested the reviewer, we have changed it through the whole manuscript

3. Page 3: first sentence in last paragraph is unclear. Rephrase sentence.

Answer : Thank you for this suggestion, we have rephrased the sentence.

4. Page 3, second paragraph line 9: uncap the ‘Sub’ in ‘Sub-Saharan’

Answer : As suggested the reviewer, we have corrected it

Methods:

5. Similar to the varying prevalence of unmet need for limiting childbirth across health regions, I wonder if you could add to your predictors some metric (if you have this in your database) for patients’ ease of accessibility to health facility? For instance, distance to the clinic?

Answer: Thank so much for this suggestion, we agree the reviewer, these factors could help to improve the explanation of the outcome, but unfortunately, we did not collect them.

6. Page 6: line 1 and 2 implies a contradiction to the earlier definition of your study population. My understanding based on the inclusion criteria on page 5 is that all women included were sexually active. Clarify.

Answer: We agree with this comment, we have corrected it, thank you

7. Page 7, first paragraph: Clearly define how you categorized ‘moderate vs. severe’ HIV symptoms.

Answer: Thank you for pointing this out. In our study, to provide information on the intensity of the symptoms; participants were asked to describe the symptoms of HIV through the following question: How do you describe your current HIV symptoms? and we proposed a response with 5 modalities :None = 1; medium = 2; moderate = 3; severe = 4; don't want to answer = 99. In the data analysis, we had combined the modalities 2 and 3 which takes the name of "moderate".

Results:

8. I wonder if some information on type of contraceptive methods used among those without the outcome can be included. It would be useful to better understand possible targeted interventions to improve unmet needs in the region.

Answer: As suggested the reviewer, we have added in the Table 1 the description of type of contraception reported by participants. Thank you.

9. For the categorical variable that you created for age, is there a reason why this was not a 3-level variable? Considering the age range of 16-49 in your study sample, I imagine that fertility intentions, contraceptive use and health seeking behaviors might be different for 16-25 years old women compared to those 26-35 years of age.

Answer: We agree with these comments. Initially, we create a variable with 3 levels <25; 26-35 and >35 years. However, in the regression models, we found that PR for 16-25 years old women was not statistically different compared to those 26-35 years of age. So, we decided to combine these two categories. Thank you.

Discussion:

10. I had some concerns about the potential for under representation of unmet needs for limiting childbirth in your sample, due to the fact that you recruited women who were followed at HIV care sites for at least 6 months, but I think you have addressed this adequately in the limitations.

Answer: Thank you for mention this.

11. Page 11, Line 2 in Conclusion: a word is missing between ‘health’ and ‘involved’

Answer: we correct it, thank you

Attachment

Submitted filename: Response_to_reviewers.docx

Decision Letter 1

Kwasi Torpey

24 Apr 2020

PONE-D-20-01103R1

Factors associated with unmet need for limiting childbirth among women living with HIV in Togo: an averaging approach

PLOS ONE

Dear Dr Saka,

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PLOS ONE

Additional Editor Comments (if provided):

Thanks. The revised manuscript has improved. However, there are some comments that were not fully addressed

1. Reviewer 1: The comment below by Reviewer 1 and the corresponding response does not address the issue raised. Kindly ensure it is adequately addressed

-In the analysis of unmet need who is the comparator, women with their FP needs met who desire to not have future children? Or are woman who want to conceive in the comparator? This is an important methodological issue, as if women who want to conceive are in the comparison group than there is a lot of heterogeneity in the comparison group (needs met + desire for future children); these groups are very different.

Answer: Thank you for this relevant comment. We agree with the reviewer that the comparison group in our study is very heterogeneous

2. Copy-editing: The manuscript needs copyediting by native English speaker to address language corrections starting from the abstract then the main paper. See a few a examples (CAPS) in the abstract

Background: With the LARGE access to antiretroviral treatment...….. the subsequent sentence also needs revision

Methods: A cross-sectional study was conducted between June and August 2016, INCLUDING WLHIV of reproductive age (15–49 years), sexually active and followed-up in HIV-care settings in Centrale and Kara regions, in Togo. Data WERE collected on a face-to-face basis - The whole methods section in the abstract needs revision

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PLoS One. 2020 May 20;15(5):e0233136. doi: 10.1371/journal.pone.0233136.r004

Author response to Decision Letter 1


27 Apr 2020

"-In the analysis of unmet need who is the comparator, women with their FP needs met who desire to not have future children? Or are woman who want to conceive in the comparator? This is an important methodological issue, as if women who want to conceive are in the comparison group than there is a lot of heterogeneity in the comparison group (needs met + desire for future children); these groups are very different.

Answer: Thank you for this relevant comment. We agree with the reviewer that the comparison group in our study is very heterogeneous. In the comparator group we have women with their FP needs met who desire to not have future children and those who want to conceive."

Copy-editing: The manuscript needs copyediting by native English speaker to address language corrections starting from the abstract then the main paper. See a few a examples (CAPS) in the abstract

Answer: Done

Background: With the LARGE access to antiretroviral treatment...….. the subsequent sentence also needs revision

Answer: Done

Methods: A cross-sectional study was conducted between June and August 2016, INCLUDING WLHIV of reproductive age (15–49 years), sexually active and followed-up in HIV-care settings in Centrale and Kara regions, in Togo. Data WERE collected on a face-to-face basis - The whole methods section in the abstract needs revision

Answer: Done

Attachment

Submitted filename: Response_to_reviewers.docx

Decision Letter 2

Kwasi Torpey

29 Apr 2020

Factors associated with unmet need for limiting childbirth among women living with HIV in Togo: an averaging approach

PONE-D-20-01103R2

Dear Dr. Saka,

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

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Professor Kwasi Torpey, MD PhD MPH

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Kwasi Torpey

8 May 2020

PONE-D-20-01103R2

Factors associated with unmet need for limiting childbirth among women living with HIV in Togo: an averaging approach

Dear Dr. Saka:

I am 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 notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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.

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With kind regards,

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on behalf of

Professor Kwasi Torpey

Academic Editor

PLOS ONE

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