Introduction
Women who are pregnant and living with Human Immunodeficiency Virus (HIV) are recognised as part of the HIV key and vulnerable population group [
1,
2]. During pregnancy, antiretroviral therapy (ART) is recommended for HIV infected women for viral suppression and reduction of perinatal HIV transmission [
3,
4]. It is not simply the provision of the ART that is recommended but also the adherence regimen associated with ART. In this case, adherence to ART is defined as patients taking their medication as prescribed, as even minor deviations from this regimen can be detrimental to maternal and neonatal health [
5].
The importance of adherence to ART for HIV has been documented in research literature [
4‐
8]. Studies have found that ART adherence lower than 95% can be associated with the development of viral resistance to medications whereas adherence above 95% is associated with no opportunistic infection nor deaths [
9,
10]. Reasons for ART non-adherence include side-effects, being away from home, lack of food and medication, non-disclosure of HIV status to partner, stigma, and work-related demand [
11]. Interestingly, longitudinal studies in Argentina, Brazil, Peru [
4] and in Switzerland [
5] found that self-reported adherence among HIV infected pregnant women decreased significantly post-partum.
Similar findings are reported by Nachega et al. [
12] in his meta-analysis of 51 articles of pre- and post-natal HIV infected women from across the world, including seven from South Africa. It was found that overall, that is during and after pregnancy, an estimated 74% of pregnant women were adequately (> 80%) adherent to their ART regime. Adherence was much higher during pregnancy then after pregnancy (76% vs 53% respectively) [
12]. The decrease in ART adherence during the post-partum period was clarified as the mother’s concern regarding the transmission of her HIV to her fetus during pregnancy and birth had abated [
12]. This is explained by the necessity concerns framework which postulates that a person will adhere to the medication regime if they see a necessity to take the medication and have no concerns about its adverse effects [
13,
14]. If no necessity is experienced anymore and a concern about adverse effects is seen, medication adherence will decrease.
As of 2016, South Africa had the biggest HIV epidemic in the world with 7.1 million people living with HIV, 270,000 new infections annually, 110,000 AIDS related deaths, and the largest ART program in the world with 56% of adults on ART [
15]. In terms of HIV infected pregnant women, 95% received ART in 2016 and mother-to-child transmission (MTCT) of HIV fell from 3.6% to 1.5% between 2011 and 2016 [
16]. As such, it is possible to eliminate MTCT in South Africa. Peltzer et al. [
17] noted that successful PMTCT interventions in South Africa have included mother-to-mother peer mentoring as well as cognitive behavioral interventions [
18]. Male involvement in PMTCT was also seen as improving PMTCT outcomes [
19] as well as interventions that involved numerous text messages and telephone calls to pregnant women reminding them of PMTCT [
20]. In the 51 study meta-analysis of ART adherence during and after pregnancy, facilitators of better adherence included higher education, higher income, knowledge about PMTCT, previous PMTCT, disclosure of HIV status, positive partner support, support groups, and being on lifelong ART [
12]. Barriers to ART adherence include but not limited to being younger, drug use, depression, home births, and number of pills [
12].
Little is known about longitudinal ART adherence among HIV infected pregnant women in South Africa. The present study aimed to longitudinally examine the impact of a prevention of mother to child transmission (PMTCT) uptake intervention on ART adherence among HIV infected pregnant women in Mpumalanga province, South Africa. It was hypothesised that in the experimental condition mothers would be significantly more likely to adhere to ART protocol medications as prescribed compared to control condition mothers when comparing pre-natal and post-partum adherence rates.
Results
Attrition Analysis
A total of 683 HIV infected pregnant women completed a baseline assessment and 403 completed a 12 month post-partum assessment. In multivariable logistic regression, education (AOR = 1.68, p = 0.014], decreased depression (AOR = 0.69, p = 0.045], and antiretroviral adherence (AOR = 1.47, p = 0.045] were associated with retention in PMTCT care (all ps < 0.05), after controlling for HIV-related stigma and infant HIV status. No other variables were associated with attrition. Variables associated with attrition were included as covariates if they were associated with the outcomes.
Baseline Differences Between Conditions
Age, education, relationship status, monthly income, number of children, depressive symptoms, and adherence were not different between conditions at baseline. However, the partners of women in the control condition were marginally more likely to be HIV infected (28.4% versus 21.7%, p = 0.052). Variables that were statistically different between conditions at baseline were included as covariates if they were associated with the outcomes.
Sample Characteristics at Baseline
The mean age of the women was 28.40 (SD = 5.71) years (see Table
1), with a range of 18 to 46 years. A total of 194 women or 29% had completed school, 83% were not employed, 45% earned less that R600 per month, and 59% were not married and living separately. Just over half (53%) of women reported that this current pregnancy was unplanned and a fifth (20%) reported that they had no children. Of those that have children, 5% reported to know that their child is HIV infected. Over half (54%) of the women were diagnosed with HIV during this pregnancy with the majority (60%) having disclosed their HIV status to their partner. The mean time since ART initiation among women was 13.27 (SD = 24.35) months. Over half (54%) of women reported male involvement during this pregnancy and 13% reported that they had drunk three or more alcoholic beverages on at least one occasion in the past month.
Table 1
ART adherence by socioeconomic, reproductive, HIV, partner, alcohol use, stigma and depression at baseline (N = 683)
Sociodemographics |
Age (m, SD) | 28.40 (5.71) | 28.87 (5.77) | 28.17 (5.67) | 1.514, 0.131 |
Educational attainment |
Grade 0–9 | 148 (21.7%) | 67 (29.9%) | 81 (17.7%) |
14.998, 0.001
|
Grade 10–11 | 339 (49.8%) | 107 (47.8%) | 232 (50.8%) |
Grade 12 or more | 194 (28.5%) | 50 (22.3%) | 144 (31.5%) |
Relationship status |
Not married, living separate | 403 (59.2%) | 129 (57.6%) | 274 (60.0%) | 0.382, 0.826 |
Not married, living together | 153 (22.5%) | 53 (23.7%) | 100 (21.9%) |
Married | 125 (18.4%) | 42 (18.8%) | 83 (18.2%) |
Employment status |
Not employed | 562 (82.5%) | 185 (82.6%) | 377 (82.5%) | 0.001, 0.976 |
Employed, Volunteer or Student | 119 (17.5%) | 39 (17.4%) | 80 (17.5%) |
Income (ZAR) per month |
< 600 | 308 (45.2%) | 97 (43.3%) | 211 (46.2%) | 0.499, 0.480 |
≥ 600 or more | 373 (54.8%) | 127 (56.7%) | 246 (53.8%) |
Reproductive |
Number of children |
None | 139 (20.4%) | 35 (15.6%) | 104 (22.8%) |
4.707, 0.030
|
One or more | 542 (79.6%) | 189 (84.4%) | 353 (77.2%) |
Unplanned pregnancy |
No | 320 (47.0%) | 95 (42.5%) | 225 (49.2%) | 2.810, 0.094 |
Yes | 361 (53.0%) | 129 (57.6%) | 232 (50.8%) |
HIV issues |
Diagnosed with HIV in this pregnancy | | | | |
No, before | 314 (46.1%) | 120 (53.6%) | 194 (42.5%) |
7.481, 0.006
|
Yes | 367 (53.9%) | 104 (46.4%) | 263 (57.5%) |
Months since ART initiation | 13.27 (24.35) | 16.41 (27.09) | 11.73 (22.76) |
− 4.146, < 0.001*
|
Partner issues |
Disclosed HIV status to partner | | | | |
No | 279 (41.0%) | 71 (31.7%) | 208 (45.5%) |
11.867, 0.001
|
Yes | 402 (59.9%) | 153 (68.3%) | 249 (54.5%) |
Male involvement (cut of ≥ 8 (median score of male involvement)) |
No | 313 (46.0%) | 102 (45.5%) | 211 (46.2%) | 0.024, 0.876 |
Yes | 368 (54.0%) | 122 (54.5%) | 246 (53.8%) |
Intimate partner violence |
Psychological partner violence | 3.24 (5.31) | 3.86 (5.63) | 2.94 (5.14) |
− 4.718, 0.007
|
Physical partner violence | 1.14 (3.68) | 2.07 (5.15) | 0.69 (2.57) |
–3.498, < 0.001
|
Alcohol use, stigma and depression |
Alcohol use of more than 2 drinks on at least on one occasion in the past 4 weeks |
No | 587 (86.2%) | 178 (79.5%) | 409 (89.5%) |
12.716, < 0.001
|
Yes | 94 (13.8%) | 46 (20.5%) | 48 (10.5%) |
Stigma | 0.773 (1.36) | 0.69 (1.28) | 0.97 (1.49) |
− 2.541, 0.011*
|
Depression |
EDS score of 0–12 | 349 (51.2%) | 87 (38.8%) | 262 (57.3%) |
20.572, < 0.001
|
EDS score of 13 and more | 332 (48.8%) | 137 (61.2%) | 195 (42.7%) |
Intervention |
Standard of care | 345 (50.7%) | 100 (44.6%) | 245 (54.6%) |
4.836, 0.028
|
Enhanced intervention | 336 (49.3%) | 124 (55.4%) | 212 (46.4%) |
In Table
1, ART adherence at baseline assessment was positively associated with higher educational attainment, number of children, disclosure of HIV status to partner, and low reported alcohol use. The findings show that physical partner violence, time since ART initiation in months, psychological partner violence, and stigma were negatively associated with adherence to ART.
ART Adherence Change
Table
2 below presents the multinomial logistic regression analyses, which shows the odds of women with sustained adherence, changing to adherent and changing to non-adherent from baseline (8–24 weeks prenatal) to 12 months post-partum. In predicting sustained adherence, a significant effect of condition was found suggesting that women in the enhanced intervention condition were less likely to sustain ART adherence over time than women in the standard care condition, after controlling for alcohol use, intimate partner violence, and depressive symptoms. In predicting if women become adherent over time, the intervention condition had no impact on women becoming adherent when controlling for other factors. The intervention condition was significantly associated with change to non-adherence from baseline to 12-month follow-up, which may indicate that the intervention had no long term effect on remaining adherent.
Table 2
Multinomial logistic regressions with “Stable non-adherence” (prenatal and 12 months postnatal) as reference group (n = 39)
Fixed effects
|
Intervention |
0.528 [0.355, 0.785]**
|
0.601 [0.396, 0.911]*
| 1.196 [0.748, 1.912] | 1.021 [0.629, 1.658] |
2.474 [1.353, 4.526]**
|
2.182 [1.177, 4.050]*
|
Covariates (baseline) |
Age | 0.982 [0.948, 1.018] |
–
| 1.018 [0.976, 1.062] |
–
| 1.013 [0.962, 1.067] | – |
Educational attainment (ref = up to 10 years) | | | | |
10 to 11 years | 1.489 [0.892, 2.484] | 1.452 [0.847, 2.487] | 0.637 [0.355, 1.142] | – | 1.047 [0.507, 2.158] | – |
12 years or more |
2.186 [1.234, 3.872]**
| 1.810 [0.995, 2.487] | 0.679 [0.355, 1.298] | – | 0.686 [0.292, 1.612] | |
Monthly income | 1.386 [0.928, 2.071] | – | 0.915 [0.568, 1.475] | – | 0.608 [0.342, 1.082]^ | 0.709 [0.385, 1.307] |
Relationship status (ref = unmarried living separate) |
Unmarried, living together | 1.153 [0.700, 1.899] | – | 1.389 [0.773, 2.495] | – | 0.412 [0.168, 1.012]^ | 0.508 [0.203, 1.271] |
Married | 1.054 [0.620, 1.790] | – | 1.750 [0.961, 3.186] | – | 0.778 [0.357, 1.694] | 0.922 [0.411, 2.070] |
Pregnancy Unplanned | 0.743 [0.501, 1.102] | – |
1.694 1.046, 2.746]*
| 1.625 [0.993, 2.658]^ | 0.856 [0.483, 1.520] | – |
Diagnosed during this pregnancy | 1.358 [0.917, 2.013] | – | 0.770 [0.481, 1.232] | – | 1.059 [0.597, 1.879] | – |
Months since ART initiation | 1.001 [0.993, 1.009] | – | 1.002 [0.993, 1.011] |
–
| 0.990 [0.975, 1.004] | – |
Alcohol use |
0.364 [0.199, 0.666]**
|
0.440 [0.236, 0.820]*
|
1.924 [1.032, 3.584]*
| 1.829 [0.969, 3.352]^ |
2.382 [1.178, 4.815]*
| 1.950 [0.932, 4.078]^ |
Stigma | 0.938 [0.805, 1.093] | – | 1.014 [0.847, 1.215] | | 0.894 [0.692, 1.153] | – |
Disclosure of HIV status to partner | 0.760 [0.508, 1.136] | – | 1.140 [0.704, 1.1845] |
–
| 0.750 [0.421, 1.334] | – |
Male involvement | 0.997 [0.936, 1.063] | – | 0.955 [0.886, 1.029] |
–
| 1.001 [0.912, 1.099] | – |
Psychological intimate partner violence | 0.965 [0.930, 1.002]^ | 1.011 [0.960, 1.065] | 0.991 [0.947, 1.037] | – |
1.050 [1.004, 1.098]*
| 1.043 [0.995, 1.094]^ |
Physical intimate partner violence |
0.873 [0.797, 1.956]**
|
0.886 [0.794, 0.988]*
| 1.001 [0.932, 1.075] | – | 1.054 [0.985, 1.128] | – |
Depression |
0.521 [0.350, 0.776]**
|
0.604 [0.397, 0.21]*
|
2.155 [1.334, 3.481]**
|
2.031 [1.245, 3.311]**
| 1.084 [0.611, 1.925] | – |
Model fit
|
− 2LL (deviance) | − 374.101 | − 314.773 | − 375.482 |
Number of parameters | 9 | 6 | 8 |
AIC/BIC | 764.20/793.73 | 645.55/673.69 | 760.96/779.42 |
Sustained adherence was also associated with decreased alcohol use (AOR 0.440; 95% CI 0.236, 0.820), decreased depressive symptoms (AOR 0.604; 95% CI 0.397, 0.21), and decreased physical intimate partner violence (AOR 0.886; 95% 0.794, 0.988). Change to adherent was associated with increased depressive symptoms (AOR 2.031; 95% CI 1.245, 3.311) and change to non-adherent was not associated with any covariates at 95% or better.
Reason for Missing ART
Table
3 below presents the reasons, by those who were non-adherent, for missing ART by time and condition. Overall, when comparing baseline to 12 month post-partum, the proportion of those giving varying reasons for non-adherence decreased for the majority of reasons. In the control condition, however, increases from baseline to 12 months post-partum were observed for reasons such as “simply forgot”, “had too many pills to take”, and “felt sick or ill.” In the enhanced intervention condition, increases from baseline to 12 months post-partum was observed for reasons such as “had problems taking pills at specified times (with meals, on an empty stomach, etc.)”, “had problems taking medication due to lack of food” and “ran out of pills.”
Table 3
Reason for missing ART by time point and condition
Reasons | % | % | % | % |
Were away from home | 49.1 | 31.1 | 57.5 | 50.7 |
Were busy with other things | 46.2 | 44.4 | 52.2 | 33.3 |
Had a change in routine | 37.7 | 35.6 | 38.1 | 31.9 |
Simply forgot |
34.0
|
42.2
| 44.8 | 30.4 |
Did not want others to notice you taking medication | 42.5 | 28.9 | 40.4 | 29.0 |
Had problems taking pills at specified times (with meals, on an empty stomach, etc.) | 39.6 | 20.0 |
34.3
|
36.2
|
Fell asleep or slept through dose time | 33.0 | 31.1 | 38.1 | 33.3 |
Felt depressed or overwhelmed | 35.8 | 35.6 | 43.3 | 26.1 |
Felt like the drug was toxic or harmful | 39.6 | 20.0 | 35.8 | 34.8 |
Wanted to avoid the side effects | 32.1 | 26.7 | 43.3 | 23.2 |
Had too many pills to take |
30.2
|
37.8
| 40.3 | 23.2 |
Had problems taking medication due to lack of food | 27.4 | 17.8 |
32.8
|
33.3
|
Felt sick or ill |
26.4
|
33.3
| 30.6 | 23.2 |
Ran out of pills | 16.0 | 13.3 |
24.6
|
29.0
|
Discussion
The study examined the impact, over time, of a multi-session cognitive behavioral PMTCT intervention, including ART adherence, among HIV-infected pregnant women in South Africa. Adherence to antiretroviral medication, which is provided free of charge to all living in South Africa, was defined as taking all ART medication over the last 4 days. This study found that adherence to ART at baseline was associated with higher educational attainment, number of children, time since ART initiation in months, disclosure of HIV status to partner, both psychological and physical partner violence, the use of alcohol, increased stigma, and increased depression. Similar findings are reported in a meta-analysis among women during and after pregnancy [
12].
Between the baseline (8–24 weeks pregnant) assessment and the 12 month post-partum assessment, women in the enhanced intervention group underwent two group and three individual cognitive behavioral PYF intervention sessions. The PYF intervention did not have the desired outcome on remaining adherent nor did it have an impact on becoming adherent over time, which was likely due to the
significantly greater proportion of nonadherent women in the experimental condition at baseline (55 versus 46%). Because this was a cluster-randomized trial, it is likely that clinics randomized to the experimental condition were more likely to have geographic or area-specific factors that may have negatively impacted adherence, with these factors remaining stable by the 12-month follow-up. The study found that there was a change to nonadherence over time. These results, although distressing for the intervention effect, mimic the findings reported in longitudinal studies among HIV infected women in South America [
4], Switzerland [
5], and in the meta-analysis of 51 articles from across the world [
12]. These studies show that self-reported adherence among HIV infected women decreased significantly post-partum.
The reason for the decrease in ART adherence post-partum was postulated in the meta-analysis which found that the mothers concern surrounding the transfer of HIV to her fetus had abated once the baby was born [
12]. The necessity-concerns framework [
13,
14] clarifies that the mother adhered to her ART regime as she deemed it necessary to protect the fetus from HIV and thus the concerns for the unborn baby far outweighed the concerns about taking the medication. Once the child was born HIV-negative, the mother had no concern for the transfer of HIV from mother to child and therefore may not have been motivated to continue taking her ART medication. At this juncture, the concerns regarding taking ART far outweighed the necessity for taking it. Once this occurred, post-partum ART adherence decreased.
The intervention in this study, as seen in Fig.
1 above, mainly concentrated on adherence during the pre-natal phase and had only one individual session at 6-weeks post-partum. The lack of adherence reinforcement during the post-partum intervention sessions could have negatively impacted the study outcome. At the 6-week post-partum session, high loss to follow up was experienced due to mothers travelling back to their parents’ home for birth. During the study period, the South African government enacted a policy change where Polymerase Chain Reaction (PCR) testing for HIV changed from 6 weeks post-partum to at-birth [
37]. This possibly further led to the high loss to follow up that was experienced at 6 weeks post-partum. The high loss to follow up at 6-weeks meant that women did not receive the adherence intervention post-partum.
Although the ART adherence intervention component of PYF did not have the desired overall outcome of increasing adherence over time as mentioned above, it is important to state that the results did show that for those who sustained their ART adherence over time, this was associated with decreased alcohol use, decreased depressive symptoms, and decreased physical intimate partner violence. These associations were also reported elsewhere in literature [
12]. In terms of depression, the PYF intervention was effective at reducing depressive symptoms among the study participants [
38] which could have led sustained ART adherence. The PYF intervention also had a desired positive outcome on reducing stigma among study participants [
39] which is a known determinant of non-adherence.
Reasons given by the most number of women in the enhanced intervention group for missing their ART was that they were away from their home when they needed to take their medication. This is similar to a finding in an Eastern Cape study, which stated that being away from home was their second most important reason for missing ART [
11]. In that study population, like this one, when women travelled outside their regular place of treatment, they often travelled without their clinic refill prescription records and thus could not receive ART medication at another clinic. This not only affect those women who travelled in the short term but also those who relocated [
11] and as such, women in both the Eastern Cape study and this study ran out of pills. The reason of running out of medication in this study was one of three reasons that increased in proportion from baseline to 12 months post-partum.
The remaining two reasons in the enhanced intervention group that increased in proportion from baseline to 12 months post-partum include having problems taking their medication at specified times and, having problems taking their medication due to the lack of food. These reasons were also stated in the Eastern Cape [
11] where the lack of food lead women, who had sufficient ART, to not take their medication. The lack of food worsens ART side effects [
11] and thus it would lead women not to adhere to their regimen.
Limitations of the Study
The study suffered from high loss-to-follow-up due to the migrant population in Mpumalanga. Although the RCT gathered intermediate measures at 32 weeks pre-natal, 6 weeks and 6 months post-natal, the loss to follow-up was too high to warrant analyses of that data for this paper. The number of participants though at baseline and at 12 months post-partum were sufficient for analysis. The measures utilized were subject to self-report recall bias. Some bias was mitigated by utilizing ACASI. The inclusion criteria biased against women without partners as this study was limited only to women who had a partner. The woman’s partner though were not required to be the biological father of the child. Because nonadherence was associated with attrition, it is possible that women who were not adherent may have not been followed up with. Lastly, variables such as knowledge, attitude, norms, skills may have been important to evaluate as these may have influenced adherence.
Conclusion
The study found that the enhanced intervention had no desired effect on ART adherence over time. It also found that ART adherence decreased post-partum. The high loss to follow up and limited post-partum ART adherence intervention could have led to this outcome. Interventions are thus needed to show the necessity of taking ART post-partum and an increased number of ART adherence interventions are needed during the post-partum phase. Better retention strategies are also necessary at the CHCs as this study was CHC based and structured in such a manner as to only interview women when they came for their regular pre- or post-natal CHC visits. Our high loss-to-follow-up also points to a high loss-to-follow-up of CHC post-partum visits.
Sustained ART adherence was associated with decreased alcohol use, decreased depressive symptoms, and decreased physical intimate partner violence. Due to this finding we recommend that interventions are required to address alcohol use during and after pregnancy, as well as interventions to reduce depression and to increase positive male involvement during and after pregnancy.
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