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. 2020 Feb 27;15(2):e0229592. doi: 10.1371/journal.pone.0229592

Level and determinants of postpartum adherence to antiretroviral therapy in the Eastern Cape, South Africa

Oladele Vincent Adeniyi 1, Anthony Idowu Ajayi 2,*
Editor: Tanya Doherty3
PMCID: PMC7046212  PMID: 32106255

Abstract

Background

Adherence to antiretroviral therapy (ART), especially during the postpartum period, remains a major challenge in the efforts towards eliminating mother-to-child transmission of HIV. This study examined the levels and determinants of postpartum adherence to ART among mothers with HIV in the Eastern Cape, South Africa.

Methods

In this cross-sectional analytical study, we interviewed 495 postpartum women with HIV between January and May 2018. We measured postpartum adherence using six questions probing participants’ adherence behaviours since child birth. We categorised the adherence behaviours into complete adherence (mothers who reported no missed episode(s) of ART since child birth) and suboptimal adherence (mothers with any missed episode(s) of ART). Adjusted and unadjusted logistic regression models were used to examine the determinants of postpartum adherence to ART.

Results

Overall, 63.9% reported complete adherence during the postpartum period but the rates varied by socio-demographic and behavioural characteristics. The adjusted logistic regression analysis showed that younger mothers were 70% less likely to report complete adherence to ART compared to mothers aged 40 and above. Likewise, mothers who currently use alcohol were 53% less likely to report complete postpartum adherence to ART compared to those who did not use alcohol. However, mothers who knew their partner’s status were twice more likely to report complete postpartum adherence compared to those who did not. There was no statistically significant relationship between ART adherence and breastfeeding durations.

Conclusion

Postpartum adherence to ART is suboptimal in the study setting, and younger mothers and those who use alcohol have a lower odds of complete adherence. Knowing a partner’s status improves adherence, but infant feeding practices did not influence postpartum adherence behaviours. It is critical to design and strengthen interventions which target young mothers and alcohol users. Also, HIV sero-status disclosure should be encouraged among mothers to facilitate partner support.

Introduction

The introduction of antiretroviral therapy (ART) has led to a significant reduction in new HIV infections and AIDS-related deaths globally [1]. AIDs-related deaths have declined by 52% since 2004, and the new HIV infection had fallen from a peak of 3.4 million in 1996 to 1.8 million in 2017 [2]. What is more, over 1.4 million new HIV infections have been averted among children since 2010 [2, 3]. Despite this progress, the reported number of people, particularly children, newly infected is still too high and clearly indicates that the war against HIV has not been won. ART has reduced in-utero transmission to less than 1%, but many babies are still getting infected during the postpartum period. Optimal and sustained (complete) adherence to ART is required for virological suppression, elimination of mother-to-child transmission of HIV, averting new horizontal HIV transmission, and preventing drug resistance and AIDS-related deaths [4, 5].

In 2016, the world health organization (WHO) recommended that mothers with HIV in developing countries should breastfeed exclusively for six months, introduce appropriate complementary feeding and continue to breastfeed for up to two years of the babies life [6]. However, the risk of mother to child transmission of HIV is 28% during the postnatal period but could reduce to 0.2% with the use of antiretroviral therapy (ART) [7]. Complete adherence to ART is required to achieve undetectable levels of breastmilk RNA, a condition necessary for the prevention of mother-to-child transmission (PMTCT) of HIV [4, 8]. Detectable breastmilk RNA is associated with elevated risk of breastmilk transmission [4]. However, complete postpartum adherence to ART is associated with a 52% reduction in the level of breast milk HIV transmission[8]. Even though sustaining viral suppression is crucial for PMTCT of HIV during the postnatal period, a study has shown that only half of women maintain viral suppression through 12 months postpartum in sub-Saharan Africa (SSA), a region with the highest number of people living HIV [5].

It appears that pregnancy motivates women to adhere to ART. Existing evidence suggests that adherence rate decline during the postnatal period after peaking during pregnancy [911]. Also, studies conducted in Uganda and Zambia suggest that adherence rate is higher among pregnant women compared to breastfeeding women [1214]. Younger age, alcohol and tobacco use, higher parity, and postpartum depression are among the main factors associated with non-adherence to ART [15, 16], while disclosure and partner support facilitate adherence [17, 18]. With most mothers with HIV in SSA choosing to breastfeed [19], addressing postpartum non-adherence to ART is vital for realising the full potential of antiretroviral interventions to prevent mother-to-child transmission of HIV.

South Africa has the highest HIV epidemic in the world, with 19% of the global number of people with HIV, 15% of the new infection, and 11% of AIDS-related deaths [20]. Also, the country has the largest treatment programme accounting for 20% of all people on ART [20]. An estimated 13,000 children were newly infected due to MTCT in 2017, and many of these occur during the postpartum period [20]. Adherence to ART remains a major challenge in eliminating mother-to-child transmission of HIV in the country despite the enormous government investment in ART [17]. Given that the risk of MTCT of HIV extends beyond pregnancy period and with breastfeeding mothers with poor adherence at risk of transmitting the virus to their suckling babies, it is crucial to examine adherence to ART beyond the pregnancy period. It is evident that advancing effective strategies to tackle non-adherence to ART is required to eliminate new HIV infection, especially mother-to-child transmission of HIV in South Africa

Most studies on adherence to ART in sub-Saharan Africa tend to focus on pregnant women. Also, existing studies have shown that adherence to ART is higher among pregnant women compared to postpartum mothers. While we know that adherence to ART declines during the postpartum period, it remains unclear how infant feeding practices influence adherence to ART. Based on a previous study that shows that women with older children, most of whom stopped breastfeeding by 13–18 months, reported more barriers and missed doses than women with younger children [21], we assumed in this study that breastfeeding duration may influence adherence to ART. Also, knowing partner’s status could create an enabling environment that increases support for adherence; however, the relationship between knowing a partner’s status and postpartum adherence has not been explored in the Eastern Cape, South Africa, a resource-constrained province in South Africa with the third largest HIV prevalence in the country. In this study, we examine the level of postpartum adherence to ART. Also, we examined the influence of infant feeding practices, younger age, knowing partner’s status and alcohol use on postpartum adherence to ART.

Methods

Study design and settings

To understand the level of postpartum adherence, we conducted a cross-sectional survey of parturient women with HIV enrolled in the electronic database of the East London Prospective Cohort Study after 18–24 months post-delivery. This electronic database was created specifically for research purposes to track the PMTCT outcomes of parturient women with HIV who delivered at the three largest maternity facilities between September 2015 and May 2016 in the Buffalo City and Amathole districts of the East Cape province of South Africa. These maternity centres serve approximately 1.7 million people from rural, peri-urban and urban communities of the selected districts in the central region of the Eastern Cape. The detailed methodology of the East London Prospective Cohort Study has been published elsewhere [22].

Participants and procedure

Postpartum women enrolled in the East London Prospective Cohort Study database were contacted telephonically to participate in the exit survey between January to May 2018. Participants were given options to either complete interviewer-guided interview in person in one of the three hospitals used for the baseline study or on the phone. The research team reimbursed the respondents for the cost of transportation to the hospital. Those who were unable to come to the hospital agreed to complete the survey questions via telephone interview at their most convenient time. We recruited research assistants who understood the IsiXhosa language (local language) and trained them specifically for this study. The research assistants administered the study questionnaires. We successfully contacted 509 participants. Some of the eligible participants could not be reached through their mobile phones or on any of the three contactable numbers obtained at the baseline. We estimated, using the Cochrane formula for estimating sample size for categorical data, a sample size of 485 at a confidence level of 95%, a precision level of +/−4% and 10% possible attrition.

Measures

The questionnaire consisted of relevant items on socio-demographic factors, adherence to current ART and behavioural lifestyles. The main outcome of interest in this study is postpartum adherence to ART medications. We measured postpartum adherence using six questions, probing participants’ adherence behaviours since child birth. The measure of adherence in this study is focused on complete daily episodes of consistent use of ART and not on hourly variations in the use of ART. These questions have a “yes” or “no” response. The six items yielded a reliability score (Cronbach’s Alpha coefficient) of 0.69, which indicate high internal consistency. Our measure of adherence, based on self reporting, has been demonstrated to be robust and predictive of virological suppression [14, 23] and has been previous validated [24]. A response of yes was coded as “1” and no as “0”. A final score between 1–6 was considered to be suboptimal adherence, while a score of 0 indicates complete adherence. A score of zero means participants affirmed to have regularly used their medication since the birth of their child irrespective of all scenarios indicated in our six questions. A score between one and six means that there are instances when respondents have not used their medications.

The main covariates included in this study were demographic and behavioural factors. Age of the respondents was obtained and coded as a continuous variable. Employment and marital status, as well as the level of education, were also obtained. The behavioural factors include smoking and alcohol use, which were categorical variables with “yes” or “no” responses. Further, participants were asked whether they had disclosed their status to their partner and if they knew their partner’s HIV serostatus. Answers to these questions were binary (yes/no). Infant feeding practice was obtained, including formula feeding, duration of breastfeeding, and breastfeeding cessation.

Ethical approval and consent to participate

The Walter Sisulu University Ethical Review Committee granted approval for the study protocol (Reference: 085/2017). Also, permission to conduct the study was obtained from the Eastern Cape Department of Health and the management of the Cecilia Makiwane Hospital. All the participants in the baseline study signed written informed consent for their readiness to participate in the follow-up study. Additional informed consent was obtained from each participant either verbally (telephonic survey) or in writing (face-to-face interview) after they affirmed that they understood their right to participate in the study freely, and to refuse to answer any question they are not comfortable with or even drop out at any time. The rights of participants to privacy and confidentiality of medical information were respected throughout the study.

Statistical analysis

Descriptive statistics, including mean, frequency count and percentages, were used to summarise the data. We fitted adjusted and unadjusted logistic regression models to examine factors associated with complete adherence to ART during the postpartum period. 95% confidence intervals were reported for all analyses, and a p-value less than 0.05 was considered statistically significant. All analyses were conducted with the Statistical Packages for Social Sciences, version 24.0 (SPSS, Chicago, IL, USA).

Results

Socio-demographic characteristics

The analysis was performed on 485 participants who answered the questions on ART adherence. Of the 509 participants contacted, nine had died, and six refused to participate in the study, while nine did not answer the questions on adherence to ART, having withdrawn their participation from the study. The mean age of study participants was 32.91 (SD 5.74) years. Most participants were aged 25 years or more (92.6%), single (67%), had grade 12 education, unemployed (62.3%), received government’s social grant (93.6%), non-smokers, and never drank alcohol (64.3%). The mean duration of HIV infection was 6.7 years (SD = 4.1 years).

Descriptive findings

The overall postpartum adherence rate was 63.9% but varied by socio-demographic and behavioural characteristics. The distribution of adherence scores is presented in Fig 1. Adherence was lowest among women aged 24 years or less (36.1%), students (43.5%), women cohabiting (46.2%), alcohol users (50.9%) and smokers (51.2%). However, a higher level of adherence was reported among women who had disclosed their status to their partner (65.8%) and those who knew their partner’s status (69.0%). There was no significant difference in the level of adherence by infant feeding choices (Table 1).

Fig 1. Distribution of participants by adherence score.

Fig 1

Table 1. Chi-square statistics showing factors associated with complete adherence to ART.

Variables All participants Complete adherence Sub-optimal adherence p-value
Age
    24 years or less 36 (7.4) 13 (36.1) 23 (63.9) 0.003
    25–29 years 114 (23.5) 73 (64.0) 41 (36.0)
    30–34 years 144 (29.7) 89 (61.8) 55 (38.2)
    35–39 years 123 (25.4) 88 (71.5) 35 (28.5)
    40 years and above 68 (14.0) 47 (69.1) 21 (30.9)
Marital status
    Never married 325 (67.0) 202 (62.2) 123 (37.8) 0.039
    Currently married 126 (26.0) 89 (70.6) 37 (29.4)
    Cohabiting 26 (5.4) 12 (46.2) 14 (53.8)
    Previously married 8 (1.6) 7 (87.5) 1 (12.5)
Education level
    Grade 7 and less 29 (6.0) 22 (75.9) 7 (24.1) 0.220
    Grade 8–12 421 (86.8) 263 (62.5) 158 (37.5)
    Higher education 34 (7.2) 25 (71.4) 10 (28.6)
Employed in a salary paying job
    Yes 157 (32.4) 100 (63.7) 57 (36.3) 0.511
    No 328 (67.6) 210 (64.0) 118 (36.0)
Occupation in last 12 months
    Government employee 17 (3.5) 11 (64.7) 6 (35.3) 0.155
    Non-government employee 114 (23.5) 80 (70.2) 34 (29.8)
    Self employed 29 (6.0) 20 (69.0) 9 (31.0)
    Student 23 (4.7) 10 (43.5) 13 (56.5)
    Unemployed 302 (62.3) 189 (62.6) 113 (37.4)
Smoking
    Yes 43 (8.9) 22 (51.2) 21 (48.8) 0.050
    No 442 (91.1) 288 (65.2) 154 (34.8)
Drank alcohol in the past year
    Yes 173 (35.7) 88 (50.9) 85 (29.1) <0.001
    No 312 (64.3) 222 (71.2) 90 (28.8)
Know partner’s status
    Yes 319 (65.8) 220 (69.0) 99 (31.0) 0.001
    No 166 (34.2) 85 (53.8) 73 (46.2)
Disclosed status to partner
    Yes 400 (82.5) 263 (65.8) 137 (34.3) 0.027
    No 85 (17.5) 44 (53.7) 38 (46.3)
Breastfeeding duration
    0 month 187 (38.6) 121(64.7) 66 (35.3) 0.942
    1–3 months 105 (21.6) 64 (61.0) 41 (39.0)
    4–6 months 116 (23.9) 74 (63.8) 42 (36.2)
    7–12 months 44 (9.1) 28 (63.6) 16 (36.4)
    12 months and more 32 (6.6) 22 (68.8) 10 (31.3)
Number of years since HIV diagnosis
    1–5 years 206 (42.5) 124 (60.2) 82 (39.8) 0.312
    6–10 years 163 (33.6) 107 (65.6) 56 (34.4)
    11–17 years 116 (23.9) 79 (68.1) 37 (31.9)

Multivariable analyses

The results of the unadjusted logistic regression models show that younger age and alcohol use were associated with lower odds of postpartum adherence to ART. While knowing a partner’s status was associated with a higher likelihood of postpartum adherence to ART. However, infant feeding practices were not associated with postpartum adherence. The magnitude and direction of effects remain in the adjusted regression (Table 2). In the adjusted logistic regression, younger mothers were 70% less likely to report complete adherence to ART. Likewise, mothers who currently use alcohol were 53% less likely to report complete postpartum adherence to ART. However, mothers who knew their partner’s status were twice more likely to report complete postpartum adherence (AOR: 2.07; CI:1.25–3.41). Shorter duration of breastfeeding was not significantly associated with lower odds of complete adherence to ART.

Table 2. Adjusted and unadjusted binary logistic regression showing determinants of complete adherence to ART.

Variables Unadjusted odds Adjusted Odds
Age
    24 years and less 0.25 (0.11–0.59)* 0.30 (0.12–0.77)*
    25–29 years 0.80 (0.42–1.51) 0.85 (0.42–1.64)
    30–34 years 0.72 (0.39–1.34) 0.70 (0.36–1.34)
    35–39 years 1.12 (0.59–2.15) 1.09 (0.55–2.15)
    40 years and above 1 1
Marital status
    Currently married 1.50 (0.97–2.33) 1.13 (0.70–1.83)
    Never married or previously married 1 1
Education level
    Grade 7 and less 1.26 (0.41–3.87) 1.12 (0.33–3.77)
    Grade 8–12 0.67 (0.31–1.42) 0.81 (0.36–1.86)
    Higher education 1 1
Occupation in the past 12 months
    Employed 1.35 (0.90–2.04) 1.53 (0.98–2.39)
    Student 0.46 (0.20–1.08) 0.65 (0.25–1.73)
    Unemployed 1 1
Smoking status
    Yes 0.56 (0.30–1.05) 0.76 (0.38–1.53)
    No 1 1
Drank alcohol in the past year
    Yes 0.42 (0.29–0.62)*** 0.47 (0.31–0.72)***
    No 1 1
Disclosure of status to a partner
    Yes 1.55 (0.97–2.50) 0.89 (0.48–1.66)
    No 1 1
Knows partner’s HIV status
    Yes 1.88 (1.28–2.76)* 2.07 (1.25–3.41)*
    No 1 1
Breastfeeding duration
    0 month 0.83 (0.37–1.87) 0.90 (0.38–2.12)
    1–3 months 0.71 (0.31–1.65) 0.71 (0.29–1.75)
    4–6 months 0.80 (0.35–1.85) 0.79 (0.32–1.91)
    7–12 months 0.80 (0.30–2.09) 0.79 (0.28–2.20)
    12 months and more 1 1

*p-value <0.05

***p-value <0.001

Discussion

The study examined the level of and factors associated with postpartum adherence to ART in the Eastern Cape, South Africa. Our analysis shows that fewer than two-thirds of mothers self-reported complete adherence to ART at 18–24 months postpartum period. Even though a 100% rate of postpartum adherence is desirable, the 64% adherence level in this study is higher than the rate reported among postpartum mothers in a study in western Uganda [12] and in SSA [5]. Of concern, however, is the decline in the level of adherence among these women relative to the level reported during pregnancy [17]. The decline is even more pronounced among adolescent and young adults, with less than 37% adherence rate compared to 63.5% rate during pregnancy [17]. Compared to women aged 40 years or more, adolescents and young adults had a 70% lower odds of attaining complete adherence to ART. The finding is not surprising given that younger age has been reported previously to be associated with non-adherence to ART [15]. Thus, any intervention to improve postpartum adherence must prioritise adolescents and young adults in the study settings.

While we assumed that breastfeeding duration will positively influence adherence to ART among postpartum mothers with HIV, our analysis shows that the association is not statistically significant. In contrast to a study that links breastfeeding cessation with adherence challenges [21], our study did not find a significant difference in the level of adherence between mothers that did not initiate breastfeeding, breastfeed for a short duration or those who breastfed for a longer duration. Fear of infecting the baby is one of the main reasons for not initiating breastfeeding [17], and the group of women who did not breastfeed are likely to take adherence seriously, given their concern for not transmitting the virus. Likewise, mothers that breastfeed their babies knew the importance of adherence to ART to prevention of MTCT of HIV and are likely to use their medication to reduce their risk of transmitting HIV to their infants. Another plausible explanation could be that since South Africa is a largely breastfeeding country, with breastfeeding being practiced religiously in many rural communities [19], it is likely that the there is a uniform distribution of breastfeeding across communities and may, therefore, not be a good predictor of adherence.

Our study also shows that alcohol use significantly influenced postpartum adherence to ART, which is consistent with previous studies [17, 25, 26]. Alcohol users were fifty-three percent less likely to adhere to ART compared to non-users. The pathway through which alcohol use interfere with adherence to ART in the study setting has been explained in a previous study [17]. Alcohol users tend to drink in company of friends on nights out and in parties, which makes them forget to use their medications [17]. Also, it appears that people believe that they can not use their medication as well as take alcohol making them to sometimes forgo ART in order to take alcohol [25, 26]. Young people are more likely to use alcohol compared to adults [27], and this may explain why adherence is poor among young women compared to older adults. Screening for alcohol use may help to identify mothers with adherence challenges who might require adherence counselling during postnatal care and child immunisation.

Another important finding of this study is that knowing partner’s serostatus predicts postpartum ART adherence. Mothers who knew the status of their partners were twice more likely to adhere to ART compared to those who did not. Open and honest communication about HIV status can create environments conducive for adherence, with couples encouraging and supporting each other to achieve complete adherence. In such open and honest environment, there is a high tendency for the men to support their partners in ensuring complete adherence to ART in order to eliminate the risk of MTCT of HIV, a goal shared by both parents. In cases where both partners are not honest about their status, fear of stigma would hinder adherence to ART [17, 21].

Study limitations

This study has some limitations. The association reported in this study could not be interpreted as causation given the cross-sectional nature of the data. Also, our measure of adherence is based on self-reporting; thus, adherence level may have been exaggerated due to social desirability bias. Nevertheless, the use of multiple questions to assess adherence offers a more reliable approach to measuring this concept as demonstrated in previous studies [14, 28, 29].

Conclusion

Overall, postpartum adherence to ART is suboptimal in the study setting. Younger mothers and those who use alcohol have lower odds of reporting good adherence to ART. Knowing a partner’s status improves adherence, but infant feeding practices did not influence postpartum adherence behaviours. This study has re-iterated factors associated with adherence to ART which have been reported in different contexts within and outside South Africa. It is critical to design and strengthen interventions which target young mothers and alcohol users. Also, HIV sero-status disclosure should be encouraged among mothers to facilitate partner support.

Supporting information

S1 File. Study dataset.

(SAV)

Acknowledgments

The authors are greatful to the study participants for taking their time to share their experience and personal information for this project. Also we appreciate our amazing research assistants for their contribution during the data collection phase of this project.

Data Availability

All relevant data are within the manuscript and Supporting Information files.

Funding Statement

OVA is a receipient of the South African Medical Research Council Pilot Grant awarded to Walter Sisulu University. Research reported in this publication was supported by the South African AIDS Vaccine Initiative under the auspices of the South African Medical Research Council with funds received from the South African National Department of Health.

References

  • 1.HIV/AIDS JUNPo. Global AIDS update 2016. Geneva: UNAIDS; 2016. [Google Scholar]
  • 2.UNAIDS. Miles to Go—Closing Gaps, Breaking Barriers, Righting Injustices. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS; 2018. [Google Scholar]
  • 3.UNAIDS. Global HIV statistics: fact sheet July 2017. Geneva, Switzerland: UNAIDS; 2017. [Google Scholar]
  • 4.Davis NL, Miller WC, Hudgens MG, Chasela CS, Sichali D, Kayira D, et al. Maternal and Breast Milk Viral Load: Impacts of Adherence on Peri-Partum HIV Infections Averted-the BAN Study. Journal of acquired immune deficiency syndromes (1999). 2016;73(5):572 10.1097/QAI.0000000000001145 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Abuogi LL, Humphrey JM, Mpody C, Yotebieng M, Murnane PM, Clouse K, et al. Achieving UNAIDS 90-90-90 targets for pregnant and postpartum women in sub-Saharan Africa: progress, gaps and research needs. Journal of Virus Eradication. 2018;4(Suppl 2):33 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.World Health Organization Unicef. Guideline:Updates on HIV and infant feeding: the duration of breastfeeding, and support from health services to improve feeding practices among mothers living with HIV. Geneva: WHO; 2016 2016. [PubMed] [Google Scholar]
  • 7.Rollins N, Mahy M, Becquet R, Kuhn L, Creek T, Mofenson L. Estimates of peripartum and postnatal mother-to-child transmission probabilities of HIV for use in Spectrum and other population-based models. Sex Transm Infect. 2012;88(Suppl 2):i44–i51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Davis NL, Miller WC, Hudgens MG, Chasela CS, Sichali D, Kayira D, et al. Adherence to extended postpartum antiretrovirals is associated with decreased breastmilk HIV-1 transmission: Results of the BAN study. AIDS (London, England). 2014;28(18):2739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Nachega JB, Uthman OA, Anderson J, Peltzer K, Wampold S, Cotton MF, et al. Adherence to antiretroviral therapy during and after pregnancy in low-, middle and high income countries: a systematic review and meta-analysis. AIDS (London, England). 2012;26(16):2039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Bardeguez AD, Lindsey JC, Shannon M, Tuomala RE, Cohn SE, Smith E, et al. Adherence to antiretrovirals among US women during and after pregnancy. Journal of acquired immune deficiency syndromes (1999). 2008;48(4):408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Vaz MJR, Barros SMO, Palacios R, Senise JF, Lunardi L, Amed AM, et al. HIV-infected pregnant women have greater adherence with antiretroviral drugs than non-pregnant women. International journal of STD & AIDS. 2007;18(1):28–32. [DOI] [PubMed] [Google Scholar]
  • 12.Decker S, Rempis E, Schnack A, Braun V, Rubaihayo J, Busingye P, et al. Prevention of mother-to-child transmission of HIV: Postpartum adherence to Option B+ until 18 months in Western Uganda. PloS one. 2017;12(6):e0179448 10.1371/journal.pone.0179448 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Okawa S, Chirwa M, Ishikawa N, Kapyata H, Msiska CY, Syakantu G, et al. Longitudinal adherence to antiretroviral drugs for preventing mother-to-child transmission of HIV in Zambia BMC pregnancy and childbirth. 2015;15(1):258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Mekuria LA, Prins JM, Yalew AW, Sprangers MA, Nieuwkerk PT. Which adherence measure–self‐report, clinician recorded or pharmacy refill–is best able to predict detectable viral load in a public ART programme without routine plasma viral load monitoring? Tropical Medicine & International Health. 2016;21(7):856–69. [DOI] [PubMed] [Google Scholar]
  • 15.Kreitchmann R, Coelho DF, Kakehasi FM, Hofer CB, Read JS, Losso M, et al. Long-term postpartum adherence to antiretroviral drugs among women in Latin America. International journal of STD & AIDS. 2016;27(5):377–86. [DOI] [PubMed] [Google Scholar]
  • 16.Sileo KM, Kizito W, Wanyenze RK, Chemusto H, Reed E, Stockman JK, et al. Substance use and its effect on antiretroviral treatment adherence among male fisherfolk living with HIV/AIDS in Uganda. PloS one. 2019;14(6):e0216892 10.1371/journal.pone.0216892 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Ajayi AI, Adeniyi OV, Akpan WJBph. Use of traditional and modern contraceptives among childbearing women: findings from a mixed methods study in two southwestern Nigerian states. 2018;18(1):604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Zacharius KM, Basinda N, Marwa K, Mtui EH, Kalolo A, Kapesa A. Low adherence to Option B+ antiretroviral therapy among pregnant women and lactating mothers in eastern Tanzania. PloS one. 2019;14(2):e0212587 10.1371/journal.pone.0212587 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Adeniyi OV, Ajayi AI, Issah M, Owolabi EO, Ter Goon D, Avramovic G, et al. Beyond health care providers’ recommendations: understanding influences on infant feeding choices of women with HIV in the Eastern Cape, South Africa. International breastfeeding journal. 2019;14(1):7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.UNAIDS. Country factsheets | South Africa 2017 Geneva, Switzerland: UNAIDS; 2018. [cited 2019 26 June]. Available from: https://www.unaids.org/en/regionscountries/countries/southafrica. 10.21542/gcsp.2018.1 [DOI] [Google Scholar]
  • 21.Gill MM, Umutoni A, Hoffman HJ, Ndatimana D, Ndayisaba GF, Kibitenga S, et al. Understanding Antiretroviral Treatment Adherence Among HIV-Positive Women at Four Postpartum Time Intervals: Qualitative Results from the Kabeho Study in Rwanda. Aids patient care and Stds. 2017;31(4):153–66. 10.1089/apc.2016.0234 [DOI] [PubMed] [Google Scholar]
  • 22.Adeniyi O, Ajayi A, Selanto-Chairman N, Goon D, Boon G, Fuentes Y, et al. Demographic, clinical and behavioural determinants of HIV serostatus non-disclosure to sex partners among HIV-infected pregnant women in the Eastern Cape, South Africa. PloS one. 2017;12(8):e0181730 10.1371/journal.pone.0181730 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Stirratt MJ, Dunbar-Jacob J, Crane HM, Simoni JM, Czajkowski S, Hilliard ME, et al. Self-report measures of medication adherence behavior: recommendations on optimal use. Translational behavioral medicine. 2015;5(4):470–82. 10.1007/s13142-015-0315-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Morisky DE. Predictive validity of a medication adherence measure for hypertension control. 2008. [DOI] [PMC free article] [PubMed] [Retracted]
  • 25.Kader R, Govender R, Seedat S, Koch JR, Parry C. Understanding the impact of hazardous and harmful use of alcohol and/or other drugs on ARV adherence and disease progression. PLoS One. 2015;10(5):e0125088 10.1371/journal.pone.0125088 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Sileo KM, Simbayi LC, Abrams A, Cloete A, Kiene SM. The role of alcohol use in antiretroviral adherence among individuals living with HIV in South Africa: Event-level findings from a daily diary study. Drug and alcohol dependence. 2016;167:103–11. 10.1016/j.drugalcdep.2016.07.028 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Owolabi EO, Ter Goon D, Adeniyi OV, Seekoe E. Adult binge drinking: rate, frequency and intensity in Buffalo City Metropolitan Municipality, South Africa. South African Family Practice. 2018;60(2):46–52. [Google Scholar]
  • 28.Phillips T, Brittain K, Mellins CA, Zerbe A, Remien RH, Abrams EJ, et al. A self-reported adherence measure to screen for elevated HIV viral load in pregnant and postpartum women on antiretroviral therapy. AIDS and behavior. 2017;21(2):450–61. 10.1007/s10461-016-1448-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Wilson IB, Lee Y, Michaud J, Fowler FJ, Rogers WH. Validation of a new three-item self-report measure for medication adherence. AIDS and Behavior. 2016;20(11):2700–8. 10.1007/s10461-016-1406-x [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Tanya Doherty

20 Dec 2019

PONE-D-19-31896

Levels and determinants of postpartum adherence to Antiretroviral Therapy in the Eastern Cape, South Africa

PLOS ONE

Dear Dr Ajayi,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The reviewers note that this paper reports on an important outcome namely postpartum ART adherence. They note some changes that would strengthen the paper. Please respond to these comments and revise accordingly especially regarding how you defined adherence and how the adherence data was analysed and also address the issue of selection bias.

We would appreciate receiving your revised manuscript by Feb 02 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Tanya Doherty, PhD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

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

Reviewer #1: No

Reviewer #2: No

**********

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

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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: Summary:

This is a very well written paper and easy to read and understand. It presents an important long-standing issue of attempting to understand the reasons behind suboptimal adherence to antiretroviral therapy (ART) among HIV-positive postnatal women. They find that in the context of a community of the Eastern Cape province of South Africa, three factors are associated with ART adherence during the postnatal period. Young maternal age and alcohol use are associated with poor adherence while knowledge of partner’s HIV status is associated with better adherence. These associations are commonly observed in the rest of the country and other parts of Sub-Saharan Africa. However, the authors were mostly interested in how infant feeding practices influence adherence and they did not find a relationship between ART adherence and infant feeding practices.

Their results probably reflect that even though certain factors are commonly associated with ART adherence and should be addressed with confidence at a population level, the outcome related to the hypothesis behind exploring the influence of infant feeding practices on ART adherence could be masked by the local community’s societal and cultural influences. Future work incorporating perceptions around breastfeeding and HIV infection would be useful.

Although it is a brilliant study, the authors may consider looking into a few suggestions which could make the manuscript stronger. The suggestions are not major but do require the authors’ attention.

Minor Essential Revisions:

1. ABSTRACT – probably mention in a short sentence what method was used to measure adherence.

2. ABSTRACT: Be careful how you interpret results about feeding. There is no indication of statistical significance and the confidence intervals fully overlap a statistic of no significant (OR=0). Therefore, I would recommend you clearly state that there was not relationship between ART adherence and feeding rather than saying feeding ‘tended to reduce the odds of adherence’.

3. STATISTICAL METHODS AND RESULTS:

a. The way you measured adherence appears to be a strong and robust method but however the way you present the results has masked this robust approach. Your method of measuring adherence appears to report an ordered outcome variable with scores ranging from ‘0’ through to ‘6’. An important question is whether scoring a 1 reflects better adherence challenges compared to scoring a 6, on average? If this is true, then your outcome should be ordered from perfect adherence (score=0) to poorest/worst (score=6). It would make sense to have four ordered groups with adherences scores of 0, 1-2, 3-4 and 5-6. You would then check if the ordered logit model fits your data better than your current logistic regression model with a binary outcome (score 0 versus 1-6). You might need to include a supplementary file explaining how you decided the choose the final approach.

b. You need to include a distribution of the adherence scale results for the overall sample, probably in the form of a graph, in the main body of the results section. You mention that ~64% of participants adhered (abstract and discussion), but the reader does not see this clearly from the results section! Did 64% get an adherence score of 0? It is important for the reader to see what proportion of the sample fell into the different scores of the adherence scale 0, 1, 2, 3, 4, 5, 6 or stepwise groups 0, 1-2, 3-4, 5-6. This will also help the reader to understand why you chose a binary outcome over an ordinal outcome or vice-versa. Please add a paragraph describing the main outcome variable in the results section.

c. Under 'Postpartum Adherence to ART' paragraph, you mention that adherence was also lowest among 'students (43.2%)'. Where is this outcome in Table 2?

d. It will be useful to mention what statistic was done to get the p-value reported in Table 2. Yoy may add a table legend with this information.

4. DISCUSSION: In the paragraph which talks about feeding practices, consider discussing the reasons why this dataset did not reflect your hypotheses around feeding and ART adherence? Have you considered the possibility of socio-cultural perceptions around breastfeeding and the stigma associated with HIV if a woman does not breastfeed, in certain settings. If this is true, then breastfeeding will likely be more uniform across the community thus not be a good predictor of adherence. South Africa is largely a breastfeeding country and many rural communities practice breastfeeding religiously.

5. DISCUSSION: You mention that ‘young people are more likely to use alcohol ….’. This statement requires a qualification either from an external reference or from your dataset. Does your data show an association between young age and alcohol use? Otherwise I would not recommend the statement.

6. CONCLUSION: This study has re-iterated associations which have been reported in different contexts within and outside South Africa. Hence emphasis is needed on this and that it is time to focus on designing or strengthening interventions which deal with the risk of young maternal age and alcohol.

Reviewer #2: The study documents a cross sectional analysis of adherence to ARVs and determinants thereof among postpartum mothers with HIV who delivered at a hospital in the Eastern Cape, South Africa. Data collection takes place 18-24 months postpartum and this study appears to be one part of a larger study/ies based on the cohort “The East London Prospective Cohort Study after 18-24 months post-delivery”, although how this analysis fits in with this cohort and any other studies, if at all, is unclear

There are no line numbers, which makes it difficult to be clear about the recommended edits.

Overall: The study needs to be published as the information is useful to health practitioners and policy makers, and will be of interest to researchers. However the quality of the writing needs to be strengthened for publication in PLoS One

Abstract: Give a brief definition of adherence vs perfect adherence – see my point fi Introduction and be consistent throughout

Introduction

1. Please give a succinct account of what perfect adherence involves – daily medications at a specific time – or what – or is there a variation

2. Para 2, 3 and 4: Please can you attempt to rewrite with a more crisp style. Avoid words like “huge”. Also give dates for your statistics

3. Para5: “The Eastern Cape is a resource constrained… “- please correct

Methods

Design and setting

1. Please clarify how this analysis relates to the electronic database – is the database routine surveillance, or research driven. Don’t just refer to other literature.

2. 18-24 months is quite a long time – in the methods and in the results please specify how many months or weeks post delivery the participants were, and if a range – do a bivariate analysis on adherence and if this is significant, include in the MV analysis

Participants

3. Please clarify whether all women in the database were contacted to participate or a sub-sample. If a sub-sample – how were they selected?. If not able to be contacted, what are the characteristics of those who could not be contacted. Please address the question of selection bias thoroughly.

4. There is no sample size calculation – please include or explain why not

Measures

5. Rather than describing the questions, please include them verbatim. Also, I counted only 5 question descriptions .

6. Have the questions been validated against other measure of adherence that are not self-report or are they ‘de novo’– please give details and explanations

Statistical analysis

7. The first 2 sentences fit better into the results. Also include characteristics of those not included in the 509 as well as the 10/509 who did not answer the adherence questions – and give reasons why they didn’t

Para 2

8. Clarify the outcome – “perfect adherence”

9. Typo “A 95% confidence intervals..” – please correct

Results

1. Para 1“Receives” s/b received

2. Please add HIV duration and categories of months/years duration of HIV infection eg. 1.5-2yrs, 2-5 yrs, >5 - or some other meaningful division and include in the Tables , and comment on the result in the discussion. The same for months postpartum

3. Only keep this text if Table 1 is removed. Otherwise it is just a repeat

4. Postpartum adherence: Specify that you mean the overall perfect adherence rate in sentence 1 and thereafter wherever this is the case. Or define adherence earlier in the text to mean perfect and the be consistent throughout the paper only using the word adherence

5. Multivariable findings: Change to Multivariable analyses

6. Remove the word “at least” as it is inaccurate, and cite the 95% CI

Tables

1. Table 1 is unnecessary as the information can be incorporated as a column with n (%) in

2. Table 2: It would strengthen the paper if you divide suboptimal adherence into at least 2 categories – based on the score. The ORs can compare perfect to suboptimal adherence overall, but this additional information is worth informing the reader

3. Add footnotes to Table 3 to explain the *, **, ***

Discussion

1. Para 1 last sentence doesn’t make sense if you include “likely”. Please be specific

2. Para 2.Explain why you assumed breast feeding will influence adherence – perhaps in the introduction and refer back to that with clear reasoning

3. Par 3: Within this paragraph, you give details regarding decline – why not give these in Para1 and link these ideas

4. Study limitations: Replace sentence 1 with “This study has some limitations”

References:

1. Reference 17 is confusing – last author JJBid? no journal stated

**********

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Reviewer #1: No

Reviewer #2: Yes: Deborah Constant

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

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PLoS One. 2020 Feb 27;15(2):e0229592. doi: 10.1371/journal.pone.0229592.r002

Author response to Decision Letter 0


15 Jan 2020

PONE-D-19-31896

Levels and determinants of postpartum adherence to Antiretroviral Therapy in the Eastern Cape, South Africa

PLOS ONE

Dear Editor,

Thank you for considering our article and returning constructive comments that have helped us to further improve our paper. We have studied the comments and have responded to all comments below. We trust you will find our manuscript good enough for publication.

Best Regards

Anthony

Comments to the Author

________________________________________

Reviewer #1: Summary:

This is a very well written paper and easy to read and understand. It presents an important long-standing issue of attempting to understand the reasons behind suboptimal adherence to antiretroviral therapy (ART) among HIV-positive postnatal women. They find that in the context of a community of the Eastern Cape province of South Africa, three factors are associated with ART adherence during the postnatal period. Young maternal age and alcohol use are associated with poor adherence while knowledge of partner’s HIV status is associated with better adherence. These associations are commonly observed in the rest of the country and other parts of Sub-Saharan Africa. However, the authors were mostly interested in how infant feeding practices influence adherence and they did not find a relationship between ART adherence and infant feeding practices.

Their results probably reflect that even though certain factors are commonly associated with ART adherence and should be addressed with confidence at a population level, the outcome related to the hypothesis behind exploring the influence of infant feeding practices on ART adherence could be masked by the local community’s societal and cultural influences. Future work incorporating perceptions around breastfeeding and HIV infection would be useful.

Response

We thank the reviewer for the positive feedback.

Although it is a brilliant study, the authors may consider looking into a few suggestions which could make the manuscript stronger. The suggestions are not major but do require the authors’ attention.

Response

Many thanks to the reviewer for the important insights and comments.

Minor Essential Revisions:

1. ABSTRACT – probably mention in a short sentence what method was used to measure adherence.

Response

We have added a sentence on adherence measure in the abstract.

2. ABSTRACT: Be careful how you interpret results about feeding. There is no indication of statistical significance and the confidence intervals fully overlap a statistic of no significant (OR=0). Therefore, I would recommend you clearly state that there was not relationship between ART adherence and feeding rather than saying feeding ‘tended to reduce the odds of adherence’.

Response

We have effected this correction.

3. STATISTICAL METHODS AND RESULTS:

a. The way you measured adherence appears to be a strong and robust method but however the way you present the results has masked this robust approach. Your method of measuring adherence appears to report an ordered outcome variable with scores ranging from ‘0’ through to ‘6’. An important question is whether scoring a 1 reflects better adherence challenges compared to scoring a 6, on average? If this is true, then your outcome should be ordered from perfect adherence (score=0) to poorest/worst (score=6). It would make sense to have four ordered groups with adherences scores of 0, 1-2, 3-4 and 5-6. You would then check if the ordered logit model fits your data better than your current logistic regression model with a binary outcome (score 0 versus 1-6). You might need to include a supplementary file explaining how you decided to choose the final approach.

Response

Our goal is to determine the rate and determinants of complete adherence since child delivery. Our use of six-item questions focusing on whether mothers have defaulted in using their medication since child delivery is to ensure a close to accurate measure of adherence. A score of six may not necessarily mean more adherence challenge given that the content of the six questions. Put differently, a person who reported any instances of not using their medication, may or may not use the medication in the past month, or may or may not use the medication because of alcohol or travel. So, a score of 1 or 6 may not necesarily indicate more adherence challenges. Since our interest is in complete adherence, only a score of zero, those with complete adherence, is of interest to us. It is critical to ensure complete adherence among parturient women, especially breastfeeding population to ascertain that they adhere to the current ART. We have however presented the scores and explain why we favoured a binary classification over an ordinal classification. We fitted ordered logit model and the variables that were significant in the logistic regression model were all significant in the ordered logit model.

b. You need to include a distribution of the adherence scale results for the overall sample, probably in the form of a graph, in the main body of the results section. You mention that ~64% of participants adhered (abstract and discussion), but the reader does not see this clearly from the results section! Did 64% get an adherence score of 0? It is important for the reader to see what proportion of the sample fell into the different scores of the adherence scale 0, 1, 2, 3, 4, 5, 6 or stepwise groups 0, 1-2, 3-4, 5-6. This will also help the reader to understand why you chose a binary outcome over an ordinal outcome or vice-versa. Please add a paragraph describing the main outcome variable in the results section.

Response

This is an important suggestion and we have now added this as suggested.

c. Under 'Postpartum Adherence to ART' paragraph, you mention that adherence was also lowest among 'students (43.2%)'. Where is this outcome in Table 2?

Response

It is in Table under occupation, but it is 43.5% as we stated.

d. It will be useful to mention what statistic was done to get the p-value reported in Table 2. You may add a table legend with this information.

Response

We have added the statistical test from which the P-values were estimated.

4. DISCUSSION: In the paragraph which talks about feeding practices, consider discussing the reasons why this dataset did not reflect your hypotheses around feeding and ART adherence? Have you considered the possibility of socio-cultural perceptions around breastfeeding and the stigma associated with HIV if a woman does not breastfeed, in certain settings. If this is true, then breastfeeding will likely be more uniform across the community thus not be a good predictor of adherence. South Africa is largely a breastfeeding country and many rural communities practice breastfeeding religiously.

Response

We thank the reviewer for this suggestion. We did not consider this alternative explanation and have now added this.

5. DISCUSSION: You mention that ‘young people are more likely to use alcohol ….’. This statement requires a qualification either from an external reference or from your dataset. Does your data show an association between young age and alcohol use? Otherwise I would not recommend the statement.

Response

We have added references to the statement.

6. CONCLUSION: This study has re-iterated associations which have been reported in different contexts within and outside South Africa. Hence emphasis is needed on this and that it is time to focus on designing or strengthening interventions which deal with the risk of young maternal age and alcohol.

Response

We thank the reviewer for this important suggestion

Reviewer #2: The study documents a cross sectional analysis of adherence to ARVs and determinants thereof among postpartum mothers with HIV who delivered at a hospital in the Eastern Cape, South Africa. Data collection takes place 18-24 months postpartum and this study appears to be one part of a larger study/ies based on the cohort “The East London Prospective Cohort Study after 18-24 months post-delivery”, although how this analysis fits in with this cohort and any other studies, if at all, is unclear

There are no line numbers, which makes it difficult to be clear about the recommended edits.

Response

We have added line numbers.

Overall: The study needs to be published as the information is useful to health practitioners and policy makers, and will be of interest to researchers. However the quality of the writing needs to be strengthened for publication in PLoS One

Response

We thank the reviewer for the positive review of our paper and suggestions provided to help improve our paper.

Abstract: Give a brief definition of adherence vs perfect adherence – see my point fi Introduction and be consistent throughout

Response

We have now added a definition of complete adherence and sub-optimal adherence. For consistency, we have changed the word “perfect adherence” to complete adherence all through the manuscript. Our use of adherence reflects complete adherence to ART.

Introduction

1. Please give a succinct account of what perfect adherence involves – daily medications at a specific time – or what – or is there a variation

Response

It involves the use of ART regularly without any missing episodes. Our focus is not on hourly variation on a particular day, rather on days patients failed to use the medications. We have clarified this in the introduction.

2. Para 2, 3 and 4: Please can you attempt to rewrite with a more crisp style. Avoid words like “huge”. Also give dates for your statistics

Response

We have added dates to the statistics and rephrased the sentences where the word “huge” was used.

3. Para5: “The Eastern Cape is a resource constrained… “- please correct

Response

Thank you for calling our attention to this. We have corrected it.

Methods

Design and setting

1. Please clarify how this analysis relates to the electronic database – is the database routine surveillance, or research driven. Don’t just refer to other literature.

Response

We thank the reviewer for this comment. We have indicated this database is not routine but research driven. The database contains information of mothers who gave birth between September 2015 to May 2016 period only.

2. 18-24 months is quite a long time – in the methods and in the results please specify how many months or weeks post delivery the participants were, and if a range – do a bivariate analysis on adherence and if this is significant, include in the MV analysis

Response

We have specified that the months and weeks the participants were. It is a range of 18 -26months post partum. However, there is no information to calculate the date of delivery and the date of interview.

Participants

3. Please clarify whether all women in the database were contacted to participate or a sub-sample. If a sub-sample – how were they selected?. If not able to be contacted, what are the characteristics of those who could not be contacted. Please address the question of selection bias thoroughly.

Response

We attempted to contact all women in the database. However, the several of the mothers were unreachable through their mobile phones. Identifying information were kept separately from the baseline survey. We used the patients register and mobile phone numbers we obtained during the baseline survey for the follow up. The ethical approval did not allow us to keep identifying information in the database. As such, we are unable to match the baseline data to the follow up data. We have addressed this as a potential limitation to our study.

4. There is no sample size calculation – please include or explain why not?

Response

We have included a sample size calculation.

Measures

5. Rather than describing the questions, please include them verbatim. Also, I counted only 5 question descriptions .

Response

Done

6. Have the questions been validated against other measure of adherence that are not self-report or are they ‘de novo’– please give details and explanations

Response

The questions used to measure adherence in this study are pre-validated. Most evidence indicates that self-report adherence measures show moderate correspondence to other adherence measures and can significantly predict clinical outcomes.

Statistical analysis

7. The first 2 sentences fit better into the results. Also include characteristics of those not included in the 509 as well as the 10/509 who did not answer the adherence questions – and give reasons why they didn’t

Response

We have moved the sentences to the results section.

Para 2

8. Clarify the outcome – “perfect adherence”

Response

We changed this to complete adherence and have defined this in the introduction.

9. Typo “A 95% confidence intervals..” – please correct

Response

Done

Results

1. Para 1“Receives” s/b received

Response

Changed to “received”.

2. Please add HIV duration and categories of months/years duration of HIV infection eg. 1.5-2yrs, 2-5 yrs, >5 - or some other meaningful division and include in the Tables , and comment on the result in the discussion. The same for months postpartum

3. Only keep this text if Table 1 is removed. Otherwise it is just a repeat

Response

We have merged Table 1 and Table 2.

4. Postpartum adherence: Specify that you mean the overall perfect adherence rate in sentence 1 and thereafter wherever this is the case. Or define adherence earlier in the text to mean perfect and the be consistent throughout the paper only using the word adherence

Response

Done

5. Multivariable findings: Change to Multivariable analyses

Response

Done

6. Remove the word “at least” as it is inaccurate, and cite the 95% CI

Response

Done

Tables

1. Table 1 is unnecessary as the information can be incorporated as a column with n (%) in

Response

We have merged Table 1 and Table 2.

2. Table 2: It would strengthen the paper if you divide suboptimal adherence into at least 2 categories – based on the score. The ORs can compare perfect to suboptimal adherence overall, but this additional information is worth informing the reader

Response

We considered this and opted not to because the proportion of participants in the suboptimal category is not large. Further categorizing that group means we will loose statistical power. Also, there is no clinical relevance to do this. People with suboptimal adherence are likely to develop resistance and are to be targeted with interventions.

3. Add footnotes to Table 3 to explain the *, **, ***

Response

Done

Discussion

1. Para 1 last sentence doesn’t make sense if you include “likely”. Please be specific

Response

The word “likely” has been deleted

2. Para 2.Explain why you assumed breast feeding will influence adherence – perhaps in the introduction and refer back to that with clear reasoning

Response

The assumption is based on a study that shows that women with older children, most of whom stopped breastfeeding by 13–18 months, reported more barriers and missed doses than women with younger children. We have stated this in both the introduction and the discussion.

3. Par 3: Within this paragraph, you give details regarding decline – why not give these in Para1 and link these ideas

Response

We thank the reviewer for this suggestion. We have implemented this suggestion.

4. Study limitations: Replace sentence 1 with “This study has some limitations”

Response

Done

References:

1. Reference 17 is confusing – last author JJBid? no journal stated

Response

Corrected

Decision Letter 1

Tanya Doherty

11 Feb 2020

Levels and determinants of postpartum adherence to Antiretroviral Therapy in the Eastern Cape, South Africa

PONE-D-19-31896R1

Dear Dr. Ajayi,

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.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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

With kind regards,

Tanya Doherty, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

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Acceptance letter

Tanya Doherty

12 Feb 2020

PONE-D-19-31896R1

Level and determinants of postpartum adherence to Antiretroviral Therapy in the Eastern Cape, South Africa

Dear Dr. Ajayi:

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With kind regards,

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on behalf of

Professor Tanya Doherty

Academic Editor

PLOS ONE

Associated Data

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

    Supplementary Materials

    S1 File. Study dataset.

    (SAV)

    Data Availability Statement

    All relevant data are within the manuscript and Supporting Information files.


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