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. 2021 Jul 30;16(7):e0255330. doi: 10.1371/journal.pone.0255330

Couple oriented counselling improves male partner involvement in sexual and reproductive health of a couple: Evidence from the ANRS PRENAHTEST randomized trial

Cyprien Kengne-Nde 1,2,3,¤a,*, Mathurin Cyrille Tejiokem 1,4, Joanna Orne-Gliemann 5, Bernard Melingui 6, Paul Koki Ndombo 7, Ngo A Essounga 8, Anne Cécile Bissek 9, Simon Cauchemez 3,4, Patrice T Tchendjou 1,4,¤b,*
Editor: Catherine E Oldenburg10
PMCID: PMC8323939  PMID: 34329355

Abstract

Background

Male partner involvement (MPI) has been recognized as a priority area to be strengthened in Prevention of Mother to Child Transmission (PMTCT) of HIV. We explored the impact of Couple Oriented Counselling (COC) in MPI in sexual and reproductive health and associated factors.

Method

From February 2009 to October 2011, pregnant women were enrolled at their first antenatal care visit (ANC-1) and followed up until 6 months after delivery in the Mother and Child Center of the Chantal Biya Foundation within the randomized prenahtest multicentric trial. The MPI index was defined using sexual and reproductive health behaviour variables by using multiple correspondence analysis followed by mixed classification. Men were considered as highly involved if they had shared their HIV test results with their partner, had discussed on HIV or condom used, had contributed financially to ANC, had accompanied their wife to ANC or had practiced safe sex. Factors associated to MPI were investigated by the logistic model with GEE estimation approach.

Results

A total of 484 pregnant women were enrolled. The median age of the women was 27 years (IQR: 23–31) and 55.23% had a gestational age greater than 16 weeks at ANC-1. Among them, HIV prevalence was 11.9% (95% CI: 9.0–15.4). The median duration of the women’s relationship with their partner was 84 months (IQR: 48–120). MPI index at 6 months after delivery was significantly greater in the COC group than the classical counselling group (14.8% vs 8,82%; p = 0,043; Fig 1). The partners of the women who participated in the COC were more likely to be involved during follow up than others (aOR = 1.45; 95% CI = 1.00–2.10). Partners with no incoming activity (aOR = 2.90; 95% CI = 1.96–4.29), who did not used violence within the couple (aOR = 1.70; 95% CI = 1.07–2.68), and whose partner came early for ANC-1 (aOR = 1.37; 95% CI = 1.00–1.89) were more likely to be involved than others.

Conclusion

MPI remains low in stable couples and COC improves partner involvement. Our findings also support the need of strengthening outreach towards "stable" couples and addressing barriers. This could go a long way to improve PMTCT outcomes in Cameroon.

Trial registration

PRENAHTEST, NCT01494961. Registered 15 December 2011—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01494961.

Introduction

HIV / AIDS infection remains a public health problem worldwide. In 2019, 1.7 million people were newly infected with HIV, including 150 000 children under the age of 15 [1]. In sub-Saharan Africa, five in six new infections among adolescents aged 15–19 years were girls [1]. Young women aged 15–24 years are twice likely to be living with HIV than men [1]. In Cameroon, 17 000 people were newly infected with HIV in 2019. Seventy-three per cent of pregnant women living with HIV accessed antiretroviral drugs to prevent transmission of the virus to their baby, preventing 3200 new HIV infections among newborns. Early infant diagnosis stood at 64% [2]. The recent Population-based HIV Impact Assessment (CAMPHIA) conducted in 2017 reported an HIV prevalence of 3.7% in the population aged 15–64 years [3]. The national prevalence was 5.70% (95% CI: 4.93–6.40) among pregnant women with a high incidence of cases among people who live in a stable relationship and who have already used the health care system at least once [4].

Many interventions to reduce new HIV infections have been described. These studied focused on HIV counselling and testing, antiretroviral therapy access, medical circumcision, promotion of safer sex and all strategies facilitating involvement of male partner in the couple’s sexual and reproductive life which improves sexual and reproductive health outcomes [5, 6].

The definition of Male Partner Involvement (MPI) in the sexual and reproductive health of the couple varies from one study to another depending on the socio-cultural context. For Rutenberg et al., Male partner involvement (MPI) was defined as accompanying their partner to the hospital, or participating in a counselling session and being tested for HIV. MPI was also defined as providing financial support or supporting their wives to cope with HIV infection and to benefit from Prevention of Mother-To-Child Transmission (PMTCT) programs [7].

MPI has been recognized as a priority for PMTCT programs of HIV / AIDS [8]. MPI play an important role in the risk of contracting HIV virus in women [5], the use of condoms in couples in order to prevent infection [9, 10], the use of PMTCT services by women [10, 11], women’s decisions regarding treatment [9, 12, 13], and the follow-up infant feeding [9, 13, 14].

In addition, when men are counselled and tested for HIV during prenatal consultations, previous studies found an increase of intake of ARV treatment or prophylaxis [13] and a decline in the MTCT rate and infant mortality [15]).

Behavioural studies suggested an improvement in the context of counselling for HIV testing and an approach favouring greater MPI. It is in this perspective that the ANRS 12127-Prenahtest project was set up in 2009. We therefore sought to explore the impact of Couple Oriented Counselling (COC) on sexual and reproductive health and analysed associated factors.

Methods

ANRS 12127 Prenahtest trial, study site and data collection

The Prenatal HIV Testing (Prenahtest) trial is a multi-country randomized trial aimed to assess the impact of prenatal COC on the incidence of partner HIV testing. It also aimed to assess the impact ofcouple HIV counselling, on sexual, reproductive and HIV prevention behaviours [1619]. The Prenahtest trial was held in four countries with different sociocultural phases (Cameroon, Dominican Republic, Georgia and India). COC is a clinic-based behavioural intervention aiming to replace standard post-test HIV counselling delivered to pregnant women. This individual discussion with the pregnant woman took place during prenatal care, instead of the standard post-test counselling. The couple-oriented post-test HIV counselling session comprised of the standard post-test counselling components and couple-oriented components. It aims at providing the woman with information, building-up their negotiation skills and confidence, and giving them the tools and strategies to actively involve their partner in the prenatal HIV counselling and testing process. The end goal of COC is to facilitate the management of the HIV test results in couples.The framework of COC is based on available reference counselling module, and partly inspired by the Health Belief Model [19, 20].

In Cameroon, Prenahtest took place at Centre Mere Enfant (CME), an urban healthcare structure in care of pregnant women, located in the capital region, Yaounde. CME is a reference healthcare centre, and is accessible to woman of all social classes living in Yaounde. The services offered to mothers included gynaecological consultations, antenatal clinics with a sophisticated component of prevention of mother to child transmission of HIV.

Between February and October 2009, pregnant women who consulted for ANC-1 visit were enrolled and randomized equally into two groups of counselling (COC or CC). Interventions and data collection were conducted by trained healthcare professionals. Enrolment occurred before HIV testing. Free HIV testing using a rapid tests algorithm [Determine (1st) and Immunocomb (2nd)] was carried out on the same day of recruitment. HIV test results were given to the pregnant women during the second scheduled ANC-1 visit, planned to coincide with the appointment for other medical examinations prescribed during ANC-1. Three structured face-to-face quantitative questionnaires were administered to trial participants: at baseline prior to prenatal HIV testing (T0), 2–8 weeks after the HIV post-test counselling (T1), and 6 months post-partum (T2). The questionnaire administered at T0 documented socio-demographic characteristics, couple relationship, women violence experiences, women attitudes and practices concerning sexual behaviours before pregnancy, HIV prevention, family planning as well as history of HIV testing. At T1 and T2, the questionnaire administered documented the occurrence of their male partners’ HIV testing, circumstances when it occurred, evolution of communication in their relationships, women violence experienced during or after pregnancy. Women were assigned identification numbers and all the questionnaires, process forms and laboratory samples were labelled with matching numbers to maintain confidentiality. Women received support (transport, condoms, family planning visits, selected contraceptive methods, screening of selected Sexual Transmitted Infections (STIs), and reference to appropriate specialized services) to facilitate access to care and treatment programs. A second HIV test was offered to all HIV-negative women at T2.

Sample size and eligible criteria

Sample size have been estimated in order to rise the number of men partner tested of 10% within women who followed COC (target:15%) compare to women who followed Classical Counselling (CC target: less than 5%), with an alpha type I error of 5% (two-sided test) and a beta type II risk of 10% (power of 90%). Considered a proportion of 15% of lost to followed-up and inconsistent data, each study site might recruit a minimum of 238 women per group, so 476 women per site [21].

The inclusion criteria consist of the following: (a) to be at least 15 years old, (b) to visit the study site for the first Antenatal Care (ANC-1), (c) have nevered been tested for HIV concerning the current pregnancy, and (d) have a stable partner.

The non-inclusion criteria were: (a) to have a mental deficit at inclusion time, (b) to have a partner absent for more than 6 months in a year, and (c) to be already tested for the current pregnancy.

Enrolment and randomization

Eligible women and men agreeing to participate had attended a recruitment interview. They were explained the project in more details and were asked to sign the informed consent form.

Women enrolled were randomised to the SC group (no intervention, standard post-test HIV counselling) or the COC group (intervention, couple-oriented post-test HIV counselling). All enrolled women were been given a study card (with project ID number, study group, stages of the study completed) including a ticket for free HIV testing for their partners (funded by the Prenahtest project). Enrolled partners were also been given a project ID number [21].

During the recruitment visit with women, the recruiter had:

  • Confirmed the inclusion criteria for women accepting participation to the project and completed the inclusion form

  • Contact the local coordinator who had accessed the randomisation list (computerised) and affected the woman to the SC or COC group and affected a study number

  • Written the group and study number on the inclusion form and on the woman’s study card

  • Referred the woman to the interviewer for the T0 inclusion questionnaire. The randomisation list was computer generated.

Measure of MPI in sexual and reproductive health of the couple

The MPI in sexual and reproductive health of the couple was measured by a composite index variable, built from several variables collected during the study [20, 22, 23]. The variables used to build the MPI index variable were chosen following a literature review. We used the following criteria to define MPI: “A male partner is involved in the sexual and reproductive health of the couple if he is interested in the different aspects of the preventive and reproductive sexual life of the couple and if he proposes attitudes (communications) and adopt practices which ensure and guarantee the couple’s sexual and reproductive health.” The variables selected to build MPI composite index variable were mainly focused on the attitudes and practices in terms of partner behaviour with regard to the couple’s sexual and reproductive health as detailed bellow:

Attitude / ability

  • Risk of HIV infection from male partner

  • Partner’s risk of HIV infection

  • Discussion about contraceptive methods initiated by male partner

  • Communication around the condom in couple

  • Discussion about HIV in the couple initiated by male partner

  • Attendance and discussion about Couple Oriented Counselling (COC)

Practice

  • Male Partner support (consultation, family planning, vaccination)

  • Safe sexual intercourse

  • Testing of HIV,

  • Withdrawal of HIV test results

  • Disclosure of the HIV test result with partner

Statistical analysis

Data entry was done using the EPIINFOS software. Continuous variables were reported by median with Interquartile interval range (25th and 75th percentiles) and by mean and standard deviation, while categorical variables were described as frequencies and percentages. To measure the MPI, we carried out a Multiple Correspondence Analysis (MCA) followed by a mixed classification to affect each participant in a given class according to his behaviour in the different outcomes of the couple’s sexual and reproductive health. To study the factors associated with the MPI, we used a logistic regression model for longitudinal data with a GEE approach. We used this method because the outcome was measured at three different time-points coming from the same women so values were correlated and GEE approach was appropriate to get correct standard errors.

The model estimated is given by the equation bellow:

log(P(MPIij=high)1P(MPIij=high))=β0+β1Group+β2Visit+β3Group*Visit+k=1lγkVarijk+k=1lθkVarik+Visit+k=1lδkVarik

Where:

log represent the link function;

i = 1,…‥,478 represent the pregnant women enrolled;

j = 1,2,3 represent the Visit time attempted by the participant;

p(MPIij = high) represent the probability for Male Partner’s Involvement to be high;

Group represent the trial intervention;

Visit represent the variable which specify the time of interview during follow-up;

Varijk represent the explanatory variable number k collected during follow-up (As explanatory variable we can cite Male partner income activity, gestational age, violence, HIV Status, duration of relationship, religious affiliation, etc.);

Varijk represent the explanatory variable number k collected only at enrollment; β0β3,γk, θk, δk are the parameters of the model to be estimated.

According to information criterion (QICu), we chose an exchangeable correlation matrix. We carried out a univariate analysis to select the explanatory variables to be introduced in the initial model of the multivariable analysis in addition to the main exposure factor (post-test counselling group) and potential confounders. The significance threshold considered at this stage was 20%. We used a manual backward stepwise selection method to obtain the final model. To have our final model, we started with the non-significant interaction terms at the 5% threshold (from the least significant) and then with the main terms while controlling for the confounding biases and looking at the information criterion (QICu). The analysis of the quality fitting of the final model retained was also assessed.

We used R 3.2.3, SAS 9.4 and SPAD 5.5 to carry out our analyses. The association tests (Fisher’s exact test) were carried out with R software version 3.2.3.

The MCA and the mixed classification were implemented by SPAD version 5.5 software.

The regression model was estimated by SAS software version 9.4 and the main procedures used to conduct these analyses were as followed:

  1. PROC GENMOD with REPEATED option in all the adjustment stages for the logistic regression model with the GEE approach;

  2. The option OBSTATS in the specification of the model of the GENMOD procedure allows us to obtain the statistics necessary for the diagnosis of influential and outliers;

The significance threshold considered in our analyses is 5%.

Ethics statement

The Prenahtest study protocol version 4 of the 18th December 2006 received ethical clearance from the National Ethics Committee of Cameroon (Authorization N° FWA IRB 00001954) and was registered on Clinical Trials.gov as NCT01494961 [19]. This trial was not registered before the beginning of enrolment because neither the principal investigators, nor the piloting committee thought it was necessary in the context of an intervention trial (not drug). However, this was an oversight on our part and we quickly registered the trial as soon as we realized it. The authors confirm that all ongoing and related trials for this drug/intervention are registered. The privacy of consenting pregnant women and data confidentiality were ensured by the use of ID codes. All participants had signed informed consent without any incentive. HIV tests were offered for free and all women tested positive were placed on ART according to the national guidelines.

Results

Characteristics of our study population

A total of 484 pregnant women were screened and 478 were finally enrolled and randomized either to follow CC or COC at ANC-1 (Fig 1). Among them, 73.22% (350/478) had less than 30 years (Table 1). Almost 68% (321/478) of them had a high school level and 64.64% (309/478) were catholic or orthodox christians. In addition, more than half did not have an income activity (55.65%) or did not come to their ANC-1 early (55.23% had a gestational age ≥ 16 weeks) and less than one third of women were married (27.82%). Furthermore, about two fifths of them were in a fairly long-term relationship (38.49% had spent more than 5 years with their partner), and 21.55% did not knew the level of education of their partner. Their partners were young adults (75.1% were under 40 years) and were catholic or orthodox christiants (60.67%). In addition, very few of them had no income activity (9%) and around one third had a university level of education (32.22%).

Fig 1. Flowchart of enrolment and follow-up within the cohort of pregnant women in Cameroon, ANRS 12127-12236/Prenahtest trial (2009–2011).

Fig 1

Table 1. Socio-demographics characteristics of couples at inclusion according to the counselling group within the ANRS 12127–12236 trial cohort Prenahtest, Cameroon, 2009–2011; (N = 478).

Variables Overall n (%) CC* n (%) COC* n (%)
Male partner age group (in year)
≤ 30 147 (30.75) 77 (32.22) 70 (29.29)
31–39 212 (44.35) 101 (42.26) 111 (46.44)
≥ 40 78 (16.32) 43 (17.99) 35 (14.64)
Don’t know 41 (8.58) 18 (7.53) 23 (9.62)
Women age group (in year)
≤ 20 59 (12.34) 35 (14.64) 24 (10.04)
21–30 291 (60.88) 140 (58.58) 151 (63.18)
≥ 31 128 (26.78) 64 (26.78) 64 (26.78)
Duration of relationship (in months)
≤ 24 143 (29.92) 73 (30.54) 70 (29.29)
25–60 151 (31.59) 76 (31.80) 75 (31.38)
> 60 184 (38.49) 90 (37.66) 94 (39.33)
Gestational age (in weeks)
< 16 208 (43.51) 103 (43.10) 105 (43.93)
≥ 16 264 (55.23) 132 (55.23) 132 (55.23)
Don’t know 6 (1.26) 4 (1.67) 2 (0.84)
Marital status
Single / Widowed / Divorced 195 (40.79) 93 (38.91) 102 (42.68)
Married 133 (27.82) 68 (28.45) 65 (27.20)
Free union 150 (31.38) 78 (32.64) 72 (30.13)
Male partner income activity
Yes 435 (91.00) 218 (91.21) 217 (90.79)
No 43 (9.00) 21 (8.79) 22 (9.21)
Women income activity
Yes 212 (44.35) 102 (42.68) 110 (46.03)
No 266 (55.65) 137 (57.32) 129 (53.97)
Male partner education level
No level or Primary 24 (5.02) 13 (5.44) 11 (4.60)
high school 197 (41.21) 102 (42.68) 95 (39.75)
University 154 (32.22) 75 (31.38) 79 (33.05)
Don’t know 103 (21.55) 49 (20.50) 54 (22.59)
Women education level
No level or Primary 55 (11.50) 25 (10.46) 30 (12.55)
high school 321 (67.15) 156 (65.27) 165 (69.04)
University 102 (21.34) 58 (24.27) 44 (18.41)
Male partner religious affiliation
Catholic / Orthodox Christianity 290 (60.67) 145 (60.67) 145 (60.67)
Other Christianity 119 (24.90) 59 (24.69) 60 (25.10)
Islam 26 (5.44) 15 (6.28) 11 (4.60)
Other 29 (6.07) 15 (6.28) 14 (5.86)
Don’t know 14 (2.93) 5 (2.09) 9 (3.77)
Women religious affiliation
Catholic / Orthodox Christianity 309 (64.64) 142 (59.41) 167 (69.87)
Other Christianity 143 (29.92) 84 (35.15) 59 (24.69)
Islam 19 (3.97) 10 (4.18) 9 (3.77)
Other 7 (1.46) 3 (1.26) 4 (1.67)

* CC: Classical Counselling; COC: Couple Oriented Counselling.

The distribution of these characteristics according to CC or COC group allowed us to conclude that the randomization was well done as the two groups were very similar on most of these characteristics (Table 1).

The prevalence of HIV within the cohort estimated at the visit during pregnancy was 11.93% (95% Exact confidence interval from Binomial distribution: 9.0% - 15.4%).

MPI in the sexual and reproductive health of the couple

The result of the MCA followed by mixed classification gave for each time of the study 2 groups of MPI (S1 Table). Overall, for each time, we had a group where the partners did not take an HIV test, did not shared the results of the HIV test with partner, did not initiated discussion about HIV or communication about the condom use in the couple. In addition, in this group, they had not accompanied their partner in prenatal consultation, or did not practiced safe intercourse sex (using a condom when you did not know the status of your partner). This group was characterized as low MPI. The other group in which the partners rather displayed behaviours opposite to the first one was characterized as high MPI. The highly MPI group significantly increased during pregnancy (19.76% vs 11.72%; p-value:0.0005) and then decreased after delivery (19.76% vs 11.85%; p-value:0.0016) (S2 Table).

Furthermore, by looking at the evolution of the high MPI by counselling group (Fig 2), we observed the same trend as in the overall study population: the high involvement increased during pregnancy and then decreased 6 months after delivery in the two post-test counselling groups. However, the decrease seemed to be huge in the CC group (Fig 2). After analysing the influence of lost to follow-up in the evolution of the high MPI (S1 Fig and S1 Result) we concluded that the new biomedical intervention (COC counselling) would seemed to be more effective in the medium or long term than the standard counselling (intention-to-treat analysis: 6 months after pregnancy 14.77% vs 8.82%; p-value:0.0435; during pregnancy 18.54% vs 20.95%; p-value: 0.2683).

Fig 2. Evolution of the proportion (%) of high involvement of male partner in sexual and reproductive health of the couple by counselling group among pregnant women cohort, in Yaounde, Cameroon, ANRS 12127-12236/Prenahtest trial (2009–2011).

Fig 2

Factors associated to IPV

In multivariable analysis, the post-test counselling group was significantly associated with the evolution of the MPI. On average, after adjusting for other covariates, partners of women who followed COC were more likely to be highly involved (aOR: 1.45; 95% CI: 1.00–2.10) (Table 2). However, the probability of being highly involved decreased over time (aOR: 0.77; 95% CI: 0.59–1.00). In addition, partners of women who did not had an income activity or who did not exercised physical or verbal violence in the couple during the follow-up were more likely to be highly involved in sexual and reproductive health of the couple (aOR: 2.90; 95% CI: 1.96–4.29 and aOR: 1.70; 95% CI: 1.07–2.68 respectively). Moreover, the partners of women who came to their ANC-1 at ≤ 16 weeks of pregnancy were 1.4 times more likely to be highly involved than the partners of women who came to their ANC 1 at 16 weeks of pregnancy or more (aOR: 1.37; 95% CI: 1.00–1.89).

Table 2. Factors associated with the evolution of high MPI in the couple’s sexual and reproductive health, ANRS trial 12127–12236 Prenahtest, Cameroon, 2009–2011.

Variables n* % HMPI** Univariable analysis OR (CI at 95%) Multivariable analysis# aOR (CI at 95%)
Post-test Counselling Group
CC 239 13.39 1 1
COC 239 10.04 0.49 (0.23–1.04) 0.46 (0.21–1.03)
Visit 0.87 (0.66–1.15) 0.77 (0.59–1.00)
Post-test Counselling Group*Visit
CC 1 1
COC 1.43 (1.00–2.99) 1.45 (1.00–2.10)
Male partner income activity
No 43 25.58 2.71 (1.85–3.97) 2.90 (1.96–4.29)
yes 435 10.34 1 1
Male partner had exercised a type of violence (verbal or physical)
No 223 13.9 1.57 (1.04–2.38) 1.70 (1.07–2.68)
Yes 255 9.8 1 1
Gestational age (in weeks)
<16 208 15.87 2.17 (1.01–4.66) 1.37 (1.00–1.89)
≥ 16 264 8.71 1 1

*: Number at inclusion;

** HMPI: Percentage of High MPI at inclusion;

#: Multivariable model included also primiparous and duration of the relationship variables.

Discussion

The estimated HIV prevalence during pregnancy in our study population was 11.93% (95% Exact confidence interval from Binomial distribution: 9.00% - 15.40%): It was greater than the national HIV prevalence among pregnant women which was estimated at 7.8% during 2009 National sentinel survey [3], which was already high. Other recent studies have estimated that more than 50% of new infections occur within “stable couples (married or cohabiting)” [24, 25].

Our results showed that the new biomedical intervention Couple-Oriented Counselling (COC) improved the high MPI of the partner in the sexual and reproductive health of the couple during follow-up. This interesting result is added to other positive results on the effectiveness of this intervention on other outcomes of sexual and reproductive health such as partner testing or conjugal communication in the couple [26, 27].

In addition, either before or during pregnancy or even after delivery, the proportion of high MPI remains low (less than 20%). This result has already been described in the literature, where there are proportions of high MPI around 33% [28], around 26% [2931] or even around 13% [13]. However, our results show that the MPI is higher during pregnancy than before pregnancy or after delivery. This corroborates with the sociocultural context in Cameroon where pregnancy is a period in the couple during which male partner is more involved and woman receives more attention from him especially for young couples (married or in free union) since in most cases they are waiting their first child.

The multivariable analysis modelling revealed that a pregnant woman who had her ANC-1 before the 16th week of pregnancy was associated with the high MPI in the sexual and reproductive health of the couple. This seems entirely plausible because an involved partner should care about the health of his pregnant wife through regular and fairly early monitoring of the pregnancy by health personnel. Similarly, partners with no income activity seemed more highly involved than those who have an income activity and this could be explained by the fact that partners with income activity do not always have the time to discuss properly with their wife about all the outcomes of sexual and reproductive health of the couple or even to be tested for HIV and are generally limited to support financially the needs of his pregnant partner. Moreover, Men’s roles are sometimes perceived to be limited to provision of appropriate food and supplies, physical and emotional support. Generally, ANC attendance is considered a woman’s private activity because even health care providers are mostly female in many facility as already described [31].

Our results also showed that partners who did not use verbal or physical violence in their relationship were more highly involved in the sexual and reproductive health of the couple during the follow-up, firstly because this created a favourable environment to discussion and communicate on the outcomes of sexual and reproductive health of the couple and secondly demonstrated some kind of attention from the male partner. Some studies published corroborated these results in the literature [32, 33].

In our study we used MCA followed by mixed classification to build MPI. Compared to the manual scoring approach used by some authors to build MPI [29, 30], this technique has the advantage of taking into account the homogeneity of the participants group and the weighting of the different variables used.

The population included in our study lived in urban areas and had an HIV prevalence higher than the national average prevalence. It is therefore difficult to conclude that the COC intervention is effective and integrated into the national health system because we do not know how it would work in rural area or in regions of the country with a low prevalence of HIV. However, the effectiveness of this intervention has already been demonstrated on partner testing in countries with low HIV prevalence such as India and Georgia in the Prenahtest trial [17].

We reported a lost-to-follow-up rate around 25% at the end of the follow-up 6 months after delivery. This may have somehow affected the power of our study. It should be noted, however, that there was no difference between the rates of loss of follow-up in the two post-test counselling groups and that the socio-demographic characteristics of those lost to follow-up were not different.

Moreover, dropping out for a reason which is correlated with MPI in any intervention group could have introduced potential bias into the analysis. In our work we did not assessed the impact of potential bias due to informative censoring.

The fact of having used the data from the Prenahtest project which was not designed with aim of responding primary to our study objective also limited the choice of some explanatory variables, in particular on the financial support of the partner.

Conclusion

Our study found that the proportion of high MPI in the couple’s sexual and reproductive health remains low. It varied between 10% and 20%. After being effective on partner testing and marital communication, our results also shown that COC is efficient in improving the MPI in the couple’s sexual and reproductive health. This allows us to consider the proposal of COC as a strategy or tool with the potential to strengthen prevention among "stable" couples in the fight against the HIV/AIDS epidemic. Barriers to high MPI identified in this study should support the improvement of sensitization messages to "stable" couples specifically.

Supporting information

S1 Fig. Evolution of the proportion (%) of high involvement of male partner in sexual and reproductive health of the couple by counselling group among pregnant women of the cohort who attempted all visit, in Yaounde, Cameroon, ANRS 12127-12236/Prenahtest trial (2009–2011).

(TIF)

S2 Fig. Evolution of the proportion (%) of high involvement of male partner in sexual and reproductive health of the couple by counselling group among pregnant women of the cohort who attempted all visit and the male partner was not involved at ANC-1, in Yaounde, Cameroon, ANRS 12127-12236/Prenahtest trial (2009–2011).

(TIF)

S1 Table. Description of the MPI clusters before pregnancy, during pregnancy and six months after delievery obtained from mixed classification, Prenahtest ANRS 12127–12236 Prenahtest, Cameroon, 2009–2011.

(PDF)

S2 Table. Description of the MPI clusters from mixed classification during follow-up, Prenahtest ANRS 12127–12236 Prenahtest, Cameroon, 2009–2011.

(PDF)

S1 Result. Sensitive analysis of the influence of lost to follow-up in the evolution of the high MPI, Prenahtest ANRS 12127–12236 Prenahtest, Cameroon, 2009–2011.

(PDF)

S1 Checklist. CONSORT 2010 checklist of information to include when reporting a randomised trial*.

(PDF)

Acknowledgments

Prenahtest trial was sponsored by the French Agency ANRS and by EGPAF. The authors thank all pregnant women who accepted to participate in this study; they also thank the Centre Mere-Enfant. The contributions of Tatiana Mossus, Denise Amassana and other members of the Prenahtest team in Yaounde are highly appreciated. The authors also acknowledge the entire Prenahtest team: Marija Miric and Eddy Perez-Then from CENISMI (Santo Domingo, Dominican Republic); Maia utsashvili, Maia Kajaia, George Kamkamidze from Maternal Child Care Union (Tbilisi, Georgia); Shrinivas Darak and Sanjeevani Kulkarni from Prayas Health Group (Pune, India); Fred Eboko from UMR912 INSERM-IRD(Marseille, France); Annabel Desgrees du Lou from UMR 196 CEPED (Paris, France).

Thank you to Brigitte Bazin, Claire Rekacewiz, Laurence Quinty (ANRS) and Catherine Wilfert (EGPAF) for encouraging the study team through the trial.

Special Thanks to Bernard Chawo Silenou (Helmholtz Centre for Infection Research, Department of Epidemiology, Braunschweig, Germany) for edited our article for language.

Abbreviations

AIDS

Acquired Immuno Deficiency Syndrome

ANC-1

First Antenatal care

ANRS

Agence Nationale de Recherches sur le SIDA et les hépatites virales

aOR

Adjusted Odds Ratio

ART

Antiretroviral treatment

ARV

Antiretroviral Therapy

CC

Classical Counselling

CI

Confidence Interval

COC

Couple-Oriented post-test HIV Counselling

GEE

Generalized Estimating Equation

HIV

Human Immuno Deficiency Virus

MCA

Multiple Correspondence Analysis

MPI

Male Partner Involvement

OR

Crude Odds-Ratio

PMTCT

Prevention of Mother to Child Transmission

SC

Standard post-test HIV Counselling

Data Availability

Data supporting the conclusions of this article cannot be made publicly available due to ethical restrictions. These data are available from the Centre Pasteur of Cameroon, Epidemiology and Public Health Service, Yaounde, Cameroon, at P.O BOX: 1274 Yaoundé, 451, Rue 2005, Yaoundé 2 - Cameroun Phone: (237) 222 23 10 15 / 222 23 18 03 - 691 819 685 Email: cpc@pasteur-yaounde.org.

Funding Statement

This study was supported by the Agence Nationale de Recherches sur le SIDA et les hépatites virales (French National Agency on AIDS Research) (grant ANRS 12127). Complementary funding was provided by the Elizabeth Glaser Pediatric AIDS Foundation (Sub-agreement 354–07). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Danielle Poole

29 Mar 2021

PONE-D-20-32163

Couple Oriented Counselling improves male partner involvement in sexual and reproductive health of the couple: evidence from the ANRS 12127/12236 PRENAHTEST Cohort in Cameroon.

PLOS ONE

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Reviewer #1: This is a dated, although interesting, report of the ANRS 12127-Prenahtest trial conducted to evaluate the impact of Couple Oriented Counseling (COC) for increasing the prevalence of male partner involvement (MPI) in women attending antenatal clinics in Cameroon. There are several aspects of the study design and of the statistical analysis that need to be clarified or improved.

1. Randomisation. There is no description of how the randomisation schedule was produced. I assume standard randomisation was employed but needs to be described (random numbers, computer generated etc).

2. Concealment of allocation. Similarly it is not stated whether the randomisation schedule was concealed to the trial staff who recruited the women in the trial.

3. Outcome. The trial was powered in order to detect a 10% increase in the rate of HIV testing in the partners of women receiving COC vs. CC. However, the intervention was then evaluated using a completely different outcome. Why was this? Are results confirmed using the primary outcome used for the power calculations? Also what was the expected underlying prevalence of testing in the CC group? That would have affected the power calculations.

4. Analysis1. The results of the unsupervised analysis should be shown in graphical way to illustrate the clustering of the questions with regards of the classification into low and high MPI. This could go as a single Supplementary Figure showing the first two principal components (replacing Tables S3-S5 which are difficult to follow).

5. Analysis 2. It is a randomised trial and Table 1 shows that randomisation has worked well. The description of the logistic model in confusing. For the evaluation of the effect of the intervention (COC vs CC) there is no need to control for confounding variables as confounding bias is minimised by design. Because there was a marked proportion of women who have been lost to follow-up, one thing that could be done was an adjustment for potential informative censoring using inverse probability of censoring weights. Regarding the association between other factors and the risk of high level MPI the GEE logistic regression is reasonable. However, authors should clarify that this was done because the outcome was measured at 3 different time-points coming from the same women so values are correlated and GEE are needed to get correct standard errors. In contrast, the key exposures of interest (e.g. MP participation at early weeks of pregnancy and income level of the partner) appear to be variables that are unlikely to vary over the study period so very little is added by using repeated measurements of these factors. Because women were not randomised to levels of these factors makes sense to be concerned about confounding in this case. Nevertheless, the construction of the model was derived using an automatic stepwise procedure which should be avoided outside of the context of prediction. Suggest that the analysis is restricted to three GEE logistic regression models: 1) effect of intervention (COC vs CC), only univariable, report OR with 95% CI as Table 2, not in supplementary tables; 2) effect of MP participation at early weeks of pregnancy measured at T0, univariable model and model adjusted for key confounders for this specific association. This should be decided on the basis of previous literature or axiomatic knowledge; 3) effect of partner income level measured at T0, univariable model and model adjusted for key confounders for this specific association. This also should be decided on the basis of previous literature or axiomatic knowledge (of note they might be different factors compared to model 2). Results of analyses 2) and 3) should be shown in a separate Table 3, not Supplementary.

6. Analysis 3. There appears to be interaction between intervention and time (effect larger during pregnancy compared to at the beginning of gestational period or after delivery). This is shown in a number of Figures but need to be formally tested using an interaction test in the GEE model.

Other points

Some sentences are unclear and there are several typos and word spelling (e.g. analyzes?) than need to be corrected. Please see the list below

Abstract conclusions. Our results also confirm that strengthening outreach towards "stable" couples and address barriers could go a long way to improve PMTCT outcomes in Cameroon. Meaning of the sentence unclear

Page 4. Behavioral studies suggest an improvement in the content of counseling for HIV testing and an approach favoring greater MPI. Content or context?

Page 5. For women with personalized information, it provides as well as tools and strategies to actively involve her partner within the prenatal HIV counseling and testing process. Meaning of the sentence is unclear

A few lines below, typo conducted, not conducetc

Page 6. The MPI in sexual and reproductive health of the couple was measure by a composite index variable. Typo was measured, not measure

Page 7. The description of the model using the mathematical formula is too technical for the journal. I would move it to the Appendix

represent the post-test counseling group (Couple Oriented Counseling or Classical Counseling); Assume the author refers to post HIV testing. This is confusing I would say Group represents the trial intervention

Page 9. In addition, very few of them had no income activity (9%) and around one third had a higher level of education (32.22%). Higher than what?

Page 10. On average, adjusted to other covariates... Replace with ‘On average, after adjusting for other covariates…’

Page 11. This corroborates with the sociocultural context in Cameroon where pregnancy is a period in the couple during which male partner is more involve. Typo involved, not involve

Reviewer #2: The paper is interesting even if the data are old.

Some suggestions

Methods:

1) Please specify the references related to the counseling modeling and to the Health Belief Model (pag 5)

2) I don't understand as the enrolment occured before HIV testing: please specify

3) Please specify the literature used to define the MPI index

Discussion:

It would be interesting to deepen the aspects related to the sociocultural context in Cameroon concerning the pregnancy period.

Reviewer #3: Thank you for this manuscript which adds valuable information to the literature available.

Introduction

noted that authors used 2018 statistics on HIV and AIDS and I suggest that they update that information

The sentence about EID seems to be a statement that is not supported.

Add brief literature on Couple Oriented Counselling in the introduction

Methods

Add in the reference regarding COC

Write the sample size section in tense

Results

The last sentence under the MPI in the sexual and reproductive health of the couple is more a premature discussion of the results.

Discussion

The first paragraph should summarise the key findings while answeing the objectives of the study. Then state the key findings so that a reader is aware of the results that will be discussed.

then present the finding then support it with evidence with literature that is similar to the findings , or different and if different provide the evidence that explains the alternative views.

The 4th and 5th paragraphs have not been situated in literature so revise those

the 6th paragraph is more appropriate for the methods section

The article should be edited for language

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Alinane Linda Nyondo-Mipando

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PLoS One. 2021 Jul 30;16(7):e0255330. doi: 10.1371/journal.pone.0255330.r002

Author response to Decision Letter 0


31 May 2021

Editor

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Authors: We had copyedited our revised manuscript by one of our native English speaker. Find below his information.

Name: Bernard Chawo Silenou

Institute: Helmholtz Centre for Infection Research, Department of Epidemiology, Braunschweig, Germany)

Address: Inhoffenstraße 7 | 38124 Braunschweig |

Mail: Bernard.Silenou@helmholtz-hzi.de

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Authors: The current version of our manuscript has the reasons for delay in registering our study in the “Ethics Statement section” as well as the statement “The authors confirm that all ongoing and related trials for this drug/intervention are registered”. Thank you.

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Authors: We removed any funding-related text from the manuscript. We would like our Funding Statement reads as follows:

“This study was supported by the Agence Nationale de Recherches sur le SIDA et les hépatites virales (French National Agency on AIDS Research) (grant ANRS 12127). Complementary funding was provided by the Elizabeth Glaser Pediatric AIDS Foundation (Sub-agreement 354–07). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript”.

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Authors: We have included captions for our Supporting Information files at the end of the manuscript and updated any in-text citations to match accordingly. Thank you.

Reviewer #1:

This is a dated, although interesting, report of the ANRS 12127-Prenahtest trial conducted to evaluate the impact of Couple Oriented Counseling (COC) for increasing the prevalence of male partner involvement (MPI) in women attending antenatal clinics in Cameroon. There are several aspects of the study design and of the statistical analysis that need to be clarified or improved.

Authors: We thank the Reviewer 1 for this summary.

1. Randomisation. There is no description of how the randomisation schedule was produced. I assume standard randomisation was employed but needs to be described (random numbers, computer generated etc).

Authors: Thank you for your comment which gives us the opportunity to provide more details on enrolment and randomization. Effectively the randomisation list had be computer generated. Indeed, we have created a section title "Enrolment and randomization" at page 6. Thank you.

2. Concealment of allocation. Similarly, it is not stated whether the randomisation schedule was concealed to the trial staff who recruited the women in the trial.

Authors: The randomisation schedule was concealed to the trial staff who recruited the women in the trial. Indeed, after confirmed inclusion criteria, when women accepted to participate, the recruiter had to contact the local coordinator who had to access the randomisation list (computerised) and affected the woman to the SC or COC group and affected a study number. These details have been added under "Enrolment and randomization" sub-section at page 6 Thank you.

3. Outcome. The trial was powered in order to detect a 10% increase in the rate of HIV testing in the partners of women receiving COC vs. CC. However, the intervention was then evaluated using a completely different outcome. Why was this? Are results confirmed using the primary outcome used for the power calculations? Also, what was the expected underlying prevalence of testing in the CC group? That would have affected the power calculations.

Authors: The intervention was already evaluated using the primary outcome which to increase at least 10% the rate of HIV testing in the partner of women receiving COC. This was already published. Please find below the published paper on this and the link [1]. Our study evaluated this intervention on a secondary outcome. The underlying prevalence of testing in the CC group expected was less than 5%. We add these details in the current version of the paper under “Sample size and Eligible criteria” sub-section at page 6.

[1] J. Orne-Gliemann et al., « Increasing HIV testing among male partners », AIDS, vol. 27, no 7, Art. no 7, avr. 2013, doi: 10.1097/QAD.0b013e32835f1d8c.

Thank you.

4. Analysis1. The results of the unsupervised analysis should be shown in graphical way to illustrate the clustering of the questions with regards of the classification into low and high MPI. This could go as a single Supplementary Figure showing the first two principal components (replacing Tables S3-S5 which are difficult to follow).

Authors: Thank you to the reviewer 1 for this suggestion. Indeed, as the representation of the first two factorial axes explains only a part of the total inertia, we preferred to keep the results of the mixed classification which was carried out on the total initial at each time point. The tables S3-S5 were condensed in one table to allow a good readability. Thank you.

5. Analysis 2. It is a randomised trial and Table 1 shows that randomisation has worked well. The description of the logistic model in confusing. For the evaluation of the effect of the intervention (COC vs CC) there is no need to control for confounding variables as confounding bias is minimised by design. Because there was a marked proportion of women who have been lost to follow-up, one thing that could be done was an adjustment for potential informative censoring using inverse probability of censoring weights. Regarding the association between other factors and the risk of high level MPI the GEE logistic regression is reasonable. However, authors should clarify that this was done because the outcome was measured at 3 different time-points coming from the same women so values are correlated and GEE are needed to get correct standard errors. In contrast, the key exposures of interest (e.g. MP participation at early weeks of pregnancy and income level of the partner) appear to be variables that are unlikely to vary over the study period so very little is added by using repeated measurements of these factors. Because women were not randomised to levels of these factors makes sense to be concerned about confounding in this case. Nevertheless, the construction of the model was derived using an automatic stepwise procedure which should be avoided outside of the context of prediction. Suggest that the analysis is restricted to three GEE logistic regression models: 1) effect of intervention (COC vs CC), only univariable, report OR with 95% CI as Table 2, not in supplementary tables; 2) effect of MP participation at early weeks of pregnancy measured at T0, univariable model and model adjusted for key confounders for this specific association. This should be decided on the basis of previous literature or axiomatic knowledge; 3) effect of partner income level measured at T0, univariable model and model adjusted for key confounders for this specific association. This also should be decided on the basis of previous literature or axiomatic knowledge (of note they might be different factors compared to model 2). Results of analyses 2) and 3) should be shown in a separate Table 3, not Supplementary.

Authors: Thank you to reviewer 1 for this consistent comment on the methodology used in our paper. As you noted we had a marked proportion of women who have been lost to follow-up. We think that the suggestion for an adjustment for potential informative censoring using inverse probability of censoring weights would not be really necessary since in our design the sample size had taken into consideration a proportion of lost to follow-up. And moreover, there was no difference between the rates of loss of follow-up in the two intervention groups and the socio-demographic characteristics of those lost to follow-up were not different to the participant who participated up to the end of the study. We have adjusted the sub-section "Statistical analysis" to explain the reason for our choice of the logistic regression model with the GEE approach on page 8. Thanks to the reviewer for this observation. Indeed, we used a manual backward stepwise selection approach and not an automatic one, and this was not well specified before. This has been adjusted in the current version of the manuscript. For the model suggestions proposed by reviewer 1, we believe that these elements have already been taken into account in some way. Indeed, for the proposed GEE 1) model, the "Univariable analysis" part of Table 2 is already reporting this information. For the proposed models 2) and 3) the model presented in the current version have used the previous literature or axiomatic knowledge to adjust the model for key confounders. In addition, the current model uses variables such as "partner income level" measured at the three time points to avoid any possible bias in the estimation of the association with MPI even if this would be marginal. We therefore think that it could be more valuable to keep the estimated model reported in table 2. We would like to thank once more the reviewer 1 for these remarks.

Thank you.

6. Analysis 3. There appears to be interaction between intervention and time (effect larger during pregnancy compared to at the beginning of gestational period or after delivery). This is shown in a number of Figures but need to be formally tested using an interaction test in the GEE model.

Authors: the interaction between intervention and time was tested in the GEE model (Variable “Post-test Counseling Group*Visit”) and was significant. Indeed, partners of women who followed COC were more likely to be highly involved as time increased. Thank you.

Other points

Some sentences are unclear and there are several typos and word spelling (e.g. analyzes?) than need to be corrected. Please see the list below

Authors: We have corrected these typos. Thank you.

Abstract conclusions. Our results also confirm that strengthening outreach towards "stable" couples and address barriers could go a long way to improve PMTCT outcomes in Cameroon. Meaning of the sentence unclear

Authors: We divided this sentence in two sentences to make it clearer. Thank you.

Page 4. Behavioral studies suggest an improvement in the content of counseling for HIV testing and an approach favoring greater MPI. Content or context?

Authors: It is context instead of content. We have corrected this in the current version of the manuscript. Thank you.

Page 5. For women with personalized information, it provides as well as tools and strategies to actively involve her partner within the prenatal HIV counseling and testing process. Meaning of the sentence is unclear A few lines below, typo conducted, not conducetc

Authors: We have cancelled this sentence and replace with others sentences to make this clearer? We have also corrected the typo conducted instead of conductec . Thank you.

Page 6. The MPI in sexual and reproductive health of the couple was measure by a composite index variable. Typo was measured, not measure

Authors: We have corrected the typo measure by measured . Thank you.

Page 7. The description of the model using the mathematical formula is too technical for the journal. I would move it to the Appendix

represent the post-test counseling group (Couple Oriented Counseling or Classical Counseling); Assume the author refers to post HIV testing. This is confusing I would say Group represents the trial intervention

Authors: Thank you to reviewer 1 for this suggestion. We think it is important to keep the description of the model in this sub-section for a good understanding of the steps of the analysis strategy described below. Moreover, readers with a background in biostatics could easily appropriate the static model for its eventual reproduction in other study.

We have replaced Group definition as suggested by the reviewer.

Thank you.

Page 9. In addition, very few of them had no income activity (9%) and around one third had a higher level of education (32.22%). Higher than what?

Authors: We meant university level of education. This have been corrected in the current version of the manuscript. Thank you.

Page 10. On average, adjusted to other covariates... Replace with ‘On average, after adjusting for other covariates…’

Authors: We have adjusted this sentence as suggested by the reviewer. Thank you.

Page 11. This corroborates with the sociocultural context in Cameroon where pregnancy is a period in the couple during which male partner is more involve. Typo involved, not involve

Authors: We have corrected as suggested by the reviewer. Thank you.

Reviewer #2:

The paper is interesting even if the data are old.

Authors: We thank the Reviewer 2 for this appreciation.

Some suggestions

Methods:

1) Please specify the references related to the counseling modeling and to the Health Belief Model (page 5)

Authors: The references related to the counseling modeling and to the Health Belief Model have been specified at page 5. Thank you.

2) I don't understand as the enrolment occurred before HIV testing: please specify

Authors: Eligible women and men agreeing to participate had attended a recruitment interview. They were explained the project in more details and were asked to sign the informed consent form. Women enrolled were randomised to the SC group (no intervention, standard post-test HIV counselling) or the COC group (intervention, couple-oriented post-test HIV counselling). All enrolled women were been given a study card (with project ID number, study group, stages of the study completed) including a ticket for free HIV testing for their partners (funded by the Prenahtest project). Enrolled partners were also been given a project ID number. We have specified these details under subsection “Enrolment and randomization” added in the current version of the manuscript. Thank You.

3) Please specify the literature used to define the MPI index

Authors: We have specified the literature used to define the MPI index at page 6. Thank you

Discussion:

It would be interesting to deepen the aspects related to the sociocultural context in Cameroon concerning the pregnancy period.

Authors: We tried to deepen this aspect related to the sociocultural context in Cameroon concerning the pregnancy period. Thank you.

Reviewer #3:

Thank you for this manuscript which adds valuable information to the literature available.

Authors: We thank the Reviewer 3 for this appreciation.

Introduction

noted that authors used 2018 statistics on HIV and AIDS and I suggest that they update that information

Authors: We have updated with 2019 statistics on HIV and AIDS available at the Unaids website. Thank you.

The sentence about EID seems to be a statement that is not supported.

Authors: the sentence about EID is supported with the Camerron’s Statistic on HIV[2]. Please find below the link to access directly to the unaids webside.

2. Cameroon [Internet]. [cité 29 mai 2021]. Available on:https://www.unaids.org/en/regionscountries/countries/cameroon

Thank you..

Add brief literature on Couple Oriented Counselling in the introduction

Authors: To the best of our knowledge the Couple Oriented Counselling post-test as implemented in our project had not been described before the implementation of our project in the literature. However, we describe it under methods section under “ANRS 12127 - Prenahtest Trial, study site and data collection sub-section”. And moreover the 3rd 4th 5th paragraphs give a brief literature on male participation its benefits on PMTCT services packages. Thank you.

Methods

Add in the reference regarding COC

Authors: We have added reference regarding COC (reference N°20 and N°21). Thank you

Write the sample size section in tense

Authors: We do not understand the suggestion of the reviewer. Please could you specify the tense you are referring to. Thank you.

Results

The last sentence under the MPI in the sexual and reproductive health of the couple is more a premature discussion of the results.

Authors: Thank you to reviewer 3 for this opinion. We think it would be better for the readers' understanding to keep this sentence here as it explains an analysis done on the influence of lost to follow up participants on the evolution of high male partner involvement and COC efficiency. In addition, there are results (figures to be presented and interpreted).

Discussion

The first paragraph should summarise the key findings while answeing the objectives of the study. Then state the key findings so that a reader is aware of the results that will be discussed. then present the finding then support it with evidence with literature that is similar to the findings, or different and if different provide the evidence that explains the alternative views.,The 4th and 5th paragraphs have not been situated in literature so revise those

Authors: We have situated The 4th and 5th paragraphs in literature, Thank you.

the 6th paragraph is more appropriate for the methods section

Authors: Thanks to the reviewer 3 for this opinion. We already had described these methods in the methods section. Here we have compared them to other methods used for the same purposes and show the advantages of the ones we used. Thank you

The article should be edited for language

Authors: Thank you to the reviewer 3 for this suggestion. The article has been edited for language.

Decision Letter 1

Catherine E Oldenburg

22 Jun 2021

PONE-D-20-32163R1

Couple oriented counselling improves male partner involvement in sexual and reproductive health of a couple: Evidence from the ANRS PRENAHTEST randomized trial.

PLOS ONE

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PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Please carefully consider Reviewer 1's comment about analyses for selection bias and consider including a sensitivity analysis using methods are Reviewer 1 notes that would assume data are missing at random as a robustness check for potential selection bias due to the high loss to follow-up.

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Reviewer #1: The authors did a good job at addressing most of my earlier concerns. However, with regards to my original point #5, I still think that the authors' response is not satisfactory.

R: Using inverse probability of censoring weights would not be really necessary since in our design the sample size had taken into consideration a proportion of lost to follow-up.

*The fact that sample size was adjusted because loss to follow-up was expected guarantees that the power of the study was retained but it does not eliminate the fact that dropping out for a reason which is correlated with the outcome could have introduced bias into the analysis

R: And moreover, there was no difference between the rates of loss of follow-up in the two intervention groups and the socio-demographic characteristics of those lost to follow-up were not different to the participant who participated up to the end of the study.

*Similarly here, even with the same exact incidence of drop out by the intervention group, bias could be introduced if the reason for dropping out was different by group (i.e. correlated with MPI in one group but not in the other, for example if women dropped out from CoC because the partner interfered with that decision)

If authors are reluctant to properly look into the impact of potential bias due to informative censoring they should at least add a limitation in the Discussion

Please also note some suboptimal English in some of the revised parts

"Enrolment and randomization" sub-section at page 6

The randomisation list had be computer generated - The randomisation list WAS computer generated?

page 13. waiting most of the case their first child - in most cases they are waiting....

Reviewer #2: (No Response)

**********

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PLoS One. 2021 Jul 30;16(7):e0255330. doi: 10.1371/journal.pone.0255330.r004

Author response to Decision Letter 1


27 Jun 2021

Editor

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Authors: Thank you to Editor for your comment. As requested by reviewer 3, we have just updated reference 1 which referenced the UNAIDS statistics below:

Global HIV & AIDS statistics — 2020 fact sheet [Internet]. [cité 29 mai 2021]. Disponible sur: https://www.unaids.org/en/resources/fact-sheet

The previous one was dated March 2020 and this one is dated May 2021. We forgot to remove the previous one. It has been removed in the current version of the manuscript and the entire bibliography has been updated. Thank you

Additional Editor Comments (if provided):

Please carefully consider Reviewer 1's comment about analyses for selection bias and consider including a sensitivity analysis using methods are Reviewer 1 notes that would assume data are missing at random as a robustness check for potential selection bias due to the high loss to follow-up.

Authors: Thanks to the editor for this comment. We have considered the comments of reviewer 1 and have opted for his proposal to include in the limitation of our work (page 13) that we did not evaluated the impact of potential bias due to informative censoring. Thank you.

Reviewer #1:

The authors did a good job at addressing most of my earlier concerns.

Authors: We thank the Reviewer 1 for this summary.

However, with regards to my original point #5, I still think that the authors' response is not satisfactory.

R: Using inverse probability of censoring weights would not be really necessary since in our design the sample size had taken into consideration a proportion of lost to follow-up.

*The fact that sample size was adjusted because loss to follow-up was expected guarantees that the power of the study was retained but it does not eliminate the fact that dropping out for a reason which is correlated with the outcome could have introduced bias into the analysis

R: And moreover, there was no difference between the rates of loss of follow-up in the two intervention groups and the socio-demographic characteristics of those lost to follow-up were not different to the participant who participated up to the end of the study.

*Similarly here, even with the same exact incidence of drop out by the intervention group, bias could be introduced if the reason for dropping out was different by group (i.e. correlated with MPI in one group but not in the other, for example if women dropped out from CoC because the partner interfered with that decision) If authors are reluctant to properly look into the impact of potential bias due to informative censoring they should at least add a limitation in the Discussion

Authors: We thank reviewer 1 for this additional explanation which helps us to understand his point of view. We have added this limitation in the discussion (second last paragraph of the discussion, page 13). Thank You

Please also note some suboptimal English in some of the revised parts

"Enrolment and randomization" sub-section at page 6

The randomisation list had be computer generated - The randomisation list WAS computer generated?

Authors: We have corrected this in the current version of the manuscript. Thank you.

page 13. waiting most of the case their first child - in most cases they are waiting....

Authors: We have corrected this in the current version of the manuscript. Thank you.

Decision Letter 2

Catherine E Oldenburg

15 Jul 2021

Couple oriented counselling improves male partner involvement in sexual and reproductive health of a couple: Evidence from the ANRS PRENAHTEST randomized trial.

PONE-D-20-32163R2

Dear Dr. Kengne-Nde,

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.

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Catherine E Oldenburg

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Catherine E Oldenburg

21 Jul 2021

PONE-D-20-32163R2

Couple oriented counselling improves male partner involvement in sexual and reproductive health of a couple: Evidence from the ANRS PRENAHTEST randomized trial.

Dear Dr. Kengne-nde:

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Fig. Evolution of the proportion (%) of high involvement of male partner in sexual and reproductive health of the couple by counselling group among pregnant women of the cohort who attempted all visit, in Yaounde, Cameroon, ANRS 12127-12236/Prenahtest trial (2009–2011).

    (TIF)

    S2 Fig. Evolution of the proportion (%) of high involvement of male partner in sexual and reproductive health of the couple by counselling group among pregnant women of the cohort who attempted all visit and the male partner was not involved at ANC-1, in Yaounde, Cameroon, ANRS 12127-12236/Prenahtest trial (2009–2011).

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    S1 Table. Description of the MPI clusters before pregnancy, during pregnancy and six months after delievery obtained from mixed classification, Prenahtest ANRS 12127–12236 Prenahtest, Cameroon, 2009–2011.

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    S2 Table. Description of the MPI clusters from mixed classification during follow-up, Prenahtest ANRS 12127–12236 Prenahtest, Cameroon, 2009–2011.

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    S1 Result. Sensitive analysis of the influence of lost to follow-up in the evolution of the high MPI, Prenahtest ANRS 12127–12236 Prenahtest, Cameroon, 2009–2011.

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    S1 Checklist. CONSORT 2010 checklist of information to include when reporting a randomised trial*.

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    Data Availability Statement

    Data supporting the conclusions of this article cannot be made publicly available due to ethical restrictions. These data are available from the Centre Pasteur of Cameroon, Epidemiology and Public Health Service, Yaounde, Cameroon, at P.O BOX: 1274 Yaoundé, 451, Rue 2005, Yaoundé 2 - Cameroun Phone: (237) 222 23 10 15 / 222 23 18 03 - 691 819 685 Email: cpc@pasteur-yaounde.org.


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