Rapidly expanding access to antiretroviral therapy (ART) and universal initiation of lifelong ART for all pregnant and postpartum women (the World Health Organization's Option B+ approach)1 have contributed to major increases in ART uptake and prevention of mother-to-child transmission (PMTCT).2–4 Pregnancy represents a time-limited opportunity for the timely initiation of ART and promotion of optimal adherence, which is imperative for both maternal and child health. However, pregnant and postpartum women's adherence to ART remains a concern in many settings,5–7 and poor adherence could limit the benefits of ART for prevention and treatment.
HIV-status disclosure is widely believed to have beneficial effects, reflected in guidelines recommending that all women living with HIV be encouraged to disclose.8 These effects may include improved adherence to ART and increased levels of social support and psychological well-being.9,10 Conversely, limited disclosure is a commonly cited barrier to adherence in the context of PMTCT.11–13 However, many women express fears around disclosing, including abandonment after disclosing to a partner and anticipated stigma after disclosing to community members,14 although some reports indicate that negative reactions to disclosure may be relatively uncommon.15,16 Given the perceived benefits, counseling services routinely encourage women to disclose. However, the current evidence for a beneficial effect on adherence has limitations.
A major concern is that most studies have relied on cross-sectional data, making causality difficult to determine. From cross-sectional data, it is unclear whether disclosure leads to better adherence or whether individuals who have higher levels of adherence are more likely to disclose. Furthermore, disclosure is a process that occurs over time, and it is plausible that the impact of disclosure may change over time. Notably, numerous cross-sectional studies in Africa have reported associations between disclosure and adherence in the context of PMTCT,17–21 but significant associations are less frequently reported in longitudinal studies.22 Prospective investigations are needed to provide high-quality evidence for the association between disclosure and adherence, and to explore the possibility of changes in this association over time.
Further limitations in this literature include a reliance on self-reported adherence and few considerations of subgroups or differences in the effects of disclosure to different individuals. Self-reported adherence measures suffer from recall and social desirability biases,23 but few studies in the context of PMTCT have explored the impact of disclosure on HIV viral suppression, a more robust biological measure and a strong indication of ART adherence. The few existing studies suggest that nondisclosure to a male partner is associated with elevated viral load (VL) at delivery in South Africa24 and in France,25 and at approximately 4 years postpartum in Uganda.26 However, only one of these studies assessed the impact of disclosure to family members on VL. We have previously shown that disclosure to male partners and to family/community members form separate dimensions.27 It is plausible that disclosure to different individuals may have different effects on medication-taking behaviors, and thus on VL, and that the effect of disclosure may differ in different subgroups, but these possibilities require further consideration.
There is an urgent need to help women maintain optimal adherence to achieve and maintain viral suppression during pregnancy and while breastfeeding, and disclosure may confer these benefits. Further investigations that use longitudinal data to explore the association between disclosure and VL are clearly needed, as well as investigations of how disclosure in different subgroups and to different individuals may change this association. To address this gap, we explored the impact of disclosure on VL among 2 groups of women in Cape Town, South Africa: (1) women already on ART when entering antenatal care, using cross-sectional analyses; and (2) women initiating ART during pregnancy and followed through pregnancy and postpartum, using longitudinal data.
These analyses draw on a multi-phase implementation science study (the MCH-ART study), which evaluated strategies for delivering HIV care and treatment services during pregnancy and postpartum (ClinicalTrials.gov NCT01933477). The design, methods, and primary findings of the study have been previously described.28,29 Briefly, the study was conducted at one antenatal care clinic in the former township of Gugulethu, and included a cross-sectional evaluation of pregnant women living with HIV who were entering antenatal care; an observational cohort study following women who initiated ART during the pregnancy through their first postpartum clinic visit (for up to 3 additional study visits); and an intervention study evaluating strategies for delivering HIV care during the postpartum period (for up to 6 additional study visits). Only breastfeeding women were included in the intervention study. ART eligibility was determined based on local guidelines: Until June 2013, eligibility was determined based on CD4 cell count or clinical disease staging; from July 2013 onward, all pregnant women living with HIV were eligible to initiate lifelong ART under Option B+ guidelines.
For the broader MCH-ART study, consecutive pregnant women living with HIV who were entering antenatal care were recruited and enrolled; for the current analyses, women who had tested HIV-positive before the pregnancy and were already on ART were included in cross-sectional analyses. Women who initiated ART during the pregnancy were followed through delivery in the broader study, and women opting to breastfeed were followed through the postpartum period. For the current analyses, all women initiating ART and followed as part of the broader study were included in longitudinal analyses through 12 months (m) postpartum. All women provided written informed consent before enrollment, and the study was approved by the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee and by Columbia University Medical Center Institutional Review Board.
Study measures were administered by trained interviewers at study visits separate from routine HIV or antenatal/postpartum care. All measures were translated into and administered in isiXhosa, the predominant local language. Measures were back-translated before the study using standard procedures to ensure accuracy.30 Basic sociodemographic characteristics were assessed at enrollment, and a composite poverty score was calculated based on current employment, housing type, and access to household assets.31 Gestation was assessed using ultrasound. Women self-reported their date of HIV diagnosis and their date of ART initiation. Disclosure to male partners and to family/community members was assessed at all study visits. Family/community members included: mother; father; sister; brother; uncle; aunt; male cousin; female cousin; other male family member; other female family member; friend; and spiritual leader. This list was developed for the purposes of this study. At each study visit, disclosure to each category was assessed using response options of “Yes,” “No,” or “Not Applicable.” Given that our intention was to compare women who had disclosed to those who had not disclosed, either through deciding not to disclose to a specific individual or because this individual is not present in their life, we combined the response options “No” and “Not applicable” in analyses. CD4 enumeration via flow cytometry (Beckman Coulter, Brea, CA) was conducted as part of routine care at entry into antenatal care, and women underwent phlebotomy at every study visit for batched HIV VL testing (Abbott RealTime HIV-1 assay, Abbott Laboratories, Lake Bluff, IL) conducted by the South African National Health Laboratory Services.
Data were analyzed using Stata 12 (StataCorp, Inc., College Station, TX). Throughout, we explored disclosure using 2 separate constructs: (1) disclosure to a male partner and (2) disclosure to ≥1 family/community member, given that these disclosure events form separate dimensions in this sample.27 Based on the thresholds for viral suppression and treatment failure in the South African National ART guidelines,32 we defined elevated VL as ≥50 and ≥1000 copies/mL in sensitivity analyses. Results were similar in sensitivity analyses, thus we present only results using ≥50 copies/mL.
Among women who had tested HIV-positive before the pregnancy and were established on ART, we examined the impact of disclosure on elevated VL at entry into antenatal care in logistic regression models. Among women initiating ART during pregnancy (including those who had tested HIV-positive before the pregnancy as well as those who tested HIV-positive during the pregnancy), we examined the impact of disclosure on elevated VL at (1) delivery and (2) 12 m postpartum in Poisson regression models with robust error variance.33 For these analyses, we used cumulative reports of disclosure through delivery and 12 m postpartum, and stratified analyses by the timing of HIV diagnosis (before vs. during the pregnancy). For the analyses of VL at delivery, we excluded women who had not been on ART >12 weeks (and >16 weeks in sensitivity analyses) to exclude women who may not have had a sufficient duration of ART use to reach viral suppression. Finally, we explored the impact of missing data by assuming that women who were lost from the study prior to delivery or 12 m postpartum had (1) suppressed and (2) elevated VL; these assumptions did not appreciably change the results.
Sociodemographic and Clinical Characteristics
We included 1187 pregnant women living with HIV, enrolled between March 2013 and June 2014. A total of 559 women who had tested HIV-positive before the pregnancy and were already on ART at entry into antenatal care (median age: 31.5 years; median time since diagnosis: 4.6 years) were included in cross-sectional analyses. Data from 628 women who were initiating ART during the pregnancy (median age overall: 28.0 years; 56% diagnosed HIV-positive during the pregnancy) were included in longitudinal analyses. Sociodemographic and clinical characteristics are described in Table 1. Low levels of married and/or cohabiting relationship status and intended pregnancy were observed in both groups. Overall, women had entered antenatal care at a median gestation of 20 weeks (inter-quartile range: 15–26 weeks).
Women Established on ART: Impact of Disclosure on VL
Among women already on ART at entry into antenatal care, 21% had an elevated VL ≥50 copies/mL (Table 2); and 12% had an elevated VL ≥1000 copies/mL. Disclosure to a male partner was reported by 85% of women, and 95% had disclosed to ≥1 family/community member. Neither disclosure to a male partner nor disclosure to ≥1 family/community member was associated with VL ≥50 copies/mL in unadjusted or adjusted models. This lack of association persisted when models were stratified by relationship status and by age categories.
Women Initiating ART: Impact of Disclosure on VL at Delivery
Of 628 women who were initiating ART during the pregnancy, only 30 (5%) were lost from the study before delivery. Of the women retained at study measurement visits, 147 (25%) had not been on ART >12 weeks at delivery and were excluded from analysis, as they may not have had a sufficient duration of ART use to reach viral suppression. No differences in disclosure to a male partner were observed between those excluded and those included (64% vs. 65%; P = 0.899; see Table 1, Supplemental Digital Content, https://links.lww.com/QAI/B305), but women who were excluded from analysis were less likely to have disclosed to ≥1 family/community member by delivery (64% vs. 75%; P = 0.013; see Table 1, Supplemental Digital Content, https://links.lww.com/QAI/B305).
Among women who tested HIV-positive before the pregnancy and who were included in analysis (20% with elevated VL ≥50 copies/mL at delivery, and 8% with VL ≥1000 copies/mL), neither disclosure to a male partner nor disclosure to ≥1 family/community member was associated with elevated VL ≥50 copies/mL at delivery (Table 3). By delivery, 73% of this group had disclosed to their male partner, and 84% had disclosed to ≥1 family/community member. Among the women who tested HIV-positive during the pregnancy and who were included in analyses (21% with elevated VL ≥50 copies/mL at delivery, and 9% with VL ≥1000 copies/mL), disclosure to ≥1 family/community member by delivery was not associated with VL ≥50 copies/mL, but disclosure to a male partner was associated with a reduced risk of elevated VL at delivery. By delivery, 57% and 66% of this group had disclosed to a male partner and to ≥1 family/community member, respectively. The impact of disclosure to a male partner on VL persisted after adjustment [adjusted risk ratio (aRR): 0.56; 95% confidence interval (CI): 0.31 to 1.01], and results were similar when restricted to women who had been on ART >16 weeks at delivery (aRR: 0.58; 95% CI: 0.26 to 1.29). This impact appeared to be modified by relationship status: among women who were married and/or cohabiting, disclosure to a male partner was strongly associated with a reduced risk of elevated VL at delivery in adjusted models (aRR: 0.20; 95% CI: 0.08 to 0.55), but no effect was observed among women who were neither married nor cohabiting (aRR: 0.80; 95% CI: 0.43 to 1.49; P-value for interaction = 0.006).
Women Initiating ART: Impact of Disclosure on VL at 12 m Postpartum
Of 471 breastfeeding women who were enrolled into postpartum follow-up, 60 women were excluded from analysis: 59 women (13%) were lost from the study, and one woman did not have a VL measure at 12 m postpartum. No differences in disclosure by the time of delivery were observed between those excluded from analysis and those retained (see Table 2, Supplemental Digital Content, https://links.lww.com/QAI/B305).
Among women diagnosed before the pregnancy and included in analyses (36% with elevated VL ≥50 copies/mL at 12 m postpartum, and 28% with VL ≥1000 copies/mL), no association between elevated VL ≥50 copies/mL and either disclosure to a male partner or disclosure to ≥1 family/community member was observed (Table 4). By 12 m postpartum, disclosure to a male partner was reported by 74% of these women, and disclosure to ≥1 family/community member by 86%. Among women diagnosed during the pregnancy and included in analyses (32% with elevated VL ≥50 copies/mL at 12 m postpartum, and 25% with VL ≥1000 copies/mL), no association was observed between disclosure to a male partner and elevated VL ≥50 copies/mL, but disclosure to ≥1 family/community member appeared to reduce the risk of elevated VL at 12 m postpartum in adjusted models (aRR: 0.69; 95% CI: 0.48 to 0.97). By 12 m postpartum, 60% of women in this group had disclosed to their male partner, and 73% had disclosed to ≥1 family/community member.
In this sample of pregnant and postpartum women in South Africa, high levels of disclosure were reported; however, the association between disclosure and VL was complex. Disclosure did not appear to have an impact on VL at any time point assessed among women who tested HIV-positive before the pregnancy. Yet among women who were newly diagnosed HIV-positive during the pregnancy and initiated ART, disclosure to a male partner appeared to be associated with a reduced risk of elevated VL at delivery among women who were married and/or cohabiting. In this group of women who tested HIV-positive during the pregnancy, we also observed an association between disclosure to ≥1 family/community member and a reduced risk of elevated VL at 12 m postpartum. Altogether, though we observed high levels of both disclosure and viremia in this cohort, nondisclosure does not seem to be a primary driver of elevated VL.
The few existing studies of disclosure to a male partner and viral suppression in the context of PMTCT suggest a beneficial effect.24–26 Our findings suggest a more nuanced association: Here, disclosure has a beneficial effect on viral suppression only among some women, and only in some circumstances. This is consistent with qualitative research, suggesting that many women manage to maintain ART adherence regardless of nondisclosure.34 Studies of disclosure and VL among adults in Africa have yielded mixed results, with some showing that disclosure reduces the odds of virologic failure,35 others finding no association between disclosure and VL,36,37 and still others showing higher levels of treatment failure among individuals reporting disclosure.38 Through our use of longitudinal data and nuanced disclosure measures, as well as our consideration of subgroups, our results may help put these mixed findings into context. We propose that the impact of disclosure on VL is modified by 3 factors: (1) the timing of HIV diagnosis (before vs. during the pregnancy); (2) relationship to the person(s) to whom women disclose; and (3) in the case of disclosure to a male partner, relationship status. We explore each of these proposed modifying factors below.
Significant associations between disclosure and adherence have been observed less frequently in longitudinal compared with cross-sectional research.22 Here, we show that the impact of disclosure differs across the timing of HIV diagnosis, and across time points of assessment. Our results suggest that there is a critical window during which disclosure to a male partner helps newly-diagnosed women to establish optimal adherence behaviors. Women who are diagnosed HIV-positive during pregnancy face a triple burden: they must quickly adjust to the pregnancy, a new HIV diagnosis, and the need to start lifelong ART.39 Qualitative work in Uganda has suggested an evolution of coming to terms with an HIV diagnosis and developing coping strategies.40 Our results suggest that the benefits of disclosure to a married or cohabiting male partner may change over time. Disclosure may be most beneficial during the critical window immediately after an HIV diagnosis, as it engages the male partner as an important treatment supporter early in the woman's coping process. These results suggest that counseling should consider how the benefits of disclosure may change over time41 and encourage early disclosure where appropriate.
The reasons for disclosing to different categories of people may differ,34,42 and our results suggest that disclosure to different individuals may have different effects. In previous research among pregnant women in South Africa, both disclosure to a male partner and disclosure to family members have been found to be associated with improved ART adherence,43 but different effects of disclosure to male partners and to family/community members on the use of PMTCT services have been demonstrated in Kenya.44 Similarly, disclosure to a partner has been shown to increase linkage to HIV care among males in Kenya, whereas disclosure to family members has increased linkage among females.45 In this study, disclosure to family/community members seemed to play an important role only among newly diagnosed women at 12 m postpartum, although the effects were relatively modest.
We observed an association between disclosure to a male partner and VL at delivery only among women who were married and/or cohabiting, suggesting that an individual's living situation may moderate both the patterns and the consequences of disclosure.46 Married and/or cohabiting relationship status is a well-documented predictor of disclosure to a male partner47–50; here, we demonstrate that relationship status additionally affects the impact of disclosure on VL. Disclosure to a male partner has been previously shown to only affect adherence to antiretrovirals for PMTCT under certain conditions51 including delivering at home versus in a health facility.52 For women who are neither married nor cohabiting, maintaining high levels of adherence may be easier because of the relative ease of maintaining secrecy around ART use. Alternatively, the mediating processes that happen as a result of disclosure, rather than the disclosure event alone, may be critical in affecting outcomes9,10; here, women in married and/or cohabiting relationships may be provided with greater support after disclosing, leading to improved outcomes, whereas nondisclosure may contribute to poorer ART outcomes.
A strength of this study is the inclusion of longitudinal analyses, and the inclusion of a robust biological and clinical endpoint. Our analysis included a large sample of pregnant women recruited from a primary care antenatal clinic in South Africa, but further research is needed to extrapolate our findings to other countries and to contexts outside of pregnancy. A limitation of this analysis is that disclosure was assessed using self-report and may be subject to recall and social desirability bias, but this is common to all disclosure research. Thus, we used nuanced disclosure measures and extend the literature by assessing both disclosure to a male partner and to family/community members. We did not assess women's reports of individuals' reactions to disclosure, which may determine whether disclosure is beneficial,9,10 and did not ask women about their reasons for not disclosing. Levels of disclosure were high among women diagnosed before the pregnancy, potentially limiting our ability to detect differences between groups. We used VL as an objective measure of adherence, but VL may be influenced by other factors such as drug resistance. Women who were lost to follow-up were excluded from analysis, although we used sensitivity analyses to explore the impact of these missing data. Finally, a fairly large proportion of women (25%) did not have a sufficient duration of ART use and were excluded from analyses of VL at delivery; these results are thus restricted to women who had initiated ART earlier in the pregnancy.
Despite some limitations, these results are notable. Although disclosure may have other benefits, we argue that the widely-held belief that disclosure always has a beneficial impact on adherence needs to recognize that this relationship is more nuanced: disclosure may be beneficial for some women, at some time points, but these benefits are dependent on 3 critical factors: (1) the timing of HIV diagnosis (before vs. during the pregnancy); (2) relationship to the person(s) to whom women disclose; and (3) in the case of disclosure to a male partner, relationship status. Further research is needed to explore the causality and mechanisms of these unique findings. We recommend that counseling about disclosure should ideally be tailored to individual women's circumstances, particularly during pregnancy and the postpartum period. Although individualized counseling may not be feasible in busy primary care settings, our results suggest that there are particular subgroups, such as newly diagnosed women, for whom tailored counseling may be most beneficial.
The authors would like to thank the women who participated in this study, as well as the study staff for their support of this research.
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