Medication adherence in pregnant women with human immunodeficiency virus receiving antiretroviral therapy in sub-Saharan Africa: a systematic review

The most commonly investigated socio-demographic factors included maternal age and education. A number of the quantitative studies (2 RCTs and 11 observational studies) found no association between maternal age and adherence to medication [10, 20‐31]. Three observational studies reported a significant association between maternal age and ART adherence [32‐34] while a cross sectional study conducted in Nigeria found that pregnant women aged 40 years and older, were less likely to adhere to ART compared with younger women [34]. On the other hand, a cohort study conducted in Malawi demonstrated that women aged 15–29 years were less likely to adhere to ART during pregnancy [32] compared with older women. Overall, the studies showed inconsistent results regarding the effects of maternal age on medication adherence during pregnancy.

Education was the second most investigated socio-demographic factor. Four observational studies reported that a low educational level was significantly associated with maternal non-adherence to medication, in particular, not completing secondary education [29, 35, 36] or primary education [34]. One study also showed that the husbands’ level of education was significantly associated with maternal non-adherence to ART [34]. However, a longitudinal study conducted in Uganda found that mothers with education above secondary level were significantly less likely to accomplish 95% adherence [10]. An inability to read and write in the primary language was also found to be significantly associated with non-adherence in a clustered RCT conducted in Zambia [37]. Studies investigating education showed lack of completion of secondary schooling adversely affected medication adherence. However, pregnant women with high levels of education beyond secondary school also showed low levels of adherence due to their desire to make independent decisions about their medication-taking behavior.

Two qualitative studies that utilized in-depth interviews and focus groups provided insights about how mothers’ knowledge and beliefs impacted on adherence to ART. A study carried out in South Africa highlighted how some women, because of misinterpretation of information they received, took incorrect dosage of their medication despite counseling being conducted in the local language [38]. In a Ugandan study, participants believed that they had sufficient knowledge about HIV/AIDS and ART to continue or terminate their treatment themselves, without following their prescribers’ intent [39]. In two cross sectional studies conducted in rural and urban settings, one in Nigeria and the other in South Africa, women’s knowledge about MTCT was significantly associated with maternal adherence to ART medications [27, 31]. Being well informed about HIV and prevention of MTCT among women appeared to encourage adherence to ART during pregnancy, although misinterpretation of health professionals’ counseling led to inappropriate decisions made by pregnant women about their medication-taking activities.

Qualitative research provided useful insights on the impact of the emotional and psychological state of pregnant women following a diagnosis of HIV. In-depth interviews and focus groups conducted in Mozambique showed that pregnant women were not emotionally or socially ready to continue lifelong treatment due to high levels of HIV related stigma in their communities [40]. Similarly, in-depth interviews and focus groups conducted in Kenya revealed that the shock experienced from being diagnosed as HIV positive remained a barrier to pregnant women’s ability to initiate and adhere to ART [30, 41]. Refusal by pregnant women to accept their HIV sero-status was also identified as an obstacle to ART adherence, because of fear that family members and friends may isolate or stigmatize them [42]. However, interviews conducted in Cote d’ Ivoire, in western Africa, revealed that the motivation to protect their unborn baby was more pronounced in mothers who had previously lost young children to HIV. They were determined to prevent losing another child to the disease by seeking to maintain good adherence to ART during pregnancy [42]. Likewise, interviews conducted in Kenya showed that HIV positive women who longed for motherhood, viewed taking and adhering to ART during pregnancy as a way of bearing HIV negative children [41]. For some women in Malawi, the desire to prevent HIV from infecting their unborn children, to maintain their health, and to be able to work, motivated them to adhere to ART [43]. In essence, the shock of receiving an HIV positive result during pregnancy had the potential to unsettle the emotional state of women, thereby interfering with adherence negatively. Nevertheless, the desire to ensure that the unborn child is protected from HIV infection, was an important motivator for women to adhere to ART during pregnancy, especially for those who had already lost a child to the disease.

Women’s belief systems, as demonstrated by the value placed on religion and their role in taking on family responsibilities, also influenced medication-taking behavior. Interrupted personal routines associated with been away from home, attending church, a funeral or a party, were reasons given for missed doses of ART in a study conducted in South Africa [38]. Religious belief was reported as a barrier to adherence in a qualitative study [44], whereas a case-control study showed no association between religious affiliation and adherence in HIV positive pregnant women [29]. A qualitative study conducted in Kenya provided insight on how the cultural environment comprising women’s customs, beliefs and behaviors, influenced the use of traditional medicine together with ART [45]. A sub-analysis of a RCT and an observational study in Zambia and Congo, Brazzaville showed that use of traditional medicine was significantly associated with non-adherence to ART during pregnancy [46, 47]. Traditional medicines were sometimes used as a substitute for ART as women sought to find what they perceived to be more effective, or safe alternatives. Religious activities appeared to have a mixed influence on medication adherence.

Two cross sectional studies showed that multi-parity (4th baby and above) was associated with non-adherence in HIV positive pregnant women [34, 36] although this association was not demonstrated in other similar studies [21, 24, 25, 30, 31]. One possible reason could be related to studies being conducted in different countries. In two studies that were conducted in Nigeria, the research was undertaken in two different regions of Nigeria, which had distinct socio-cultural outlooks.

A qualitative study using in-depth interviews demonstrated that women who had previous experience with prevention of MTCT were better prepared and more compliant with taking ART in their current pregnancy [41]. However, observational studies conducted in South Africa and Nigeria did not show an association of previous maternal exposure to prevention of MTCT and adherence to ART [31, 35].

Diagnosis of HIV either immediately before, or during, pregnancy was found to be a predictor of non-adherence to ART. A cohort study in Zambia showed that women newly diagnosed with HIV during pregnancy were more likely to be non-adherent than those with a known HIV status before pregnancy [22]. An association with a positive HIV diagnosis during pregnancy with non-adherence to ART was also found in a cross sectional study conducted in Nigeria [34]. In Burkina Faso, a significant association of knowledge of HIV status immediately before pregnancy and adherence to ART was found in a cohort study [33]. Consequently, the knowledge of a positive HIV diagnosis immediately before and during pregnancy was a major predictor of non-adherence in women taking ART. On the other hand, previous experience with prevention of MTCT was shown to improve adherence among women during their current pregnancy.

Opportunistic infections occur from progressive damage to the immune system. Up to that point, there is an asymptomatic phase of the disease where the person may not experience any symptoms. During this asymptomatic phase, women live in denial and may not perceive the need to commence or continue ART. In a study involving in-depth interviews, Malawian HIV positive pregnant women were reluctant to initiate ART because they were not experiencing symptoms related to the disease [44].

Two observational studies conducted in Ethiopia and Malawi found the WHO clinical staging of HIV in women was associated with adherence to ART [32, 48]. The WHO clinical stage 1 signifies women are asymptomatic, or have persistent generalized lymphadenopathy, while those in the clinical stage 4 signifies severe signs and symptoms of the disease. In Malawi, women in the clinical state 3 were less likely to adhere to treatment than those in WHO clinical stage 1 [32]. Similarly, Ethiopian women in the clinical stage 1 or 2 were also found to be more likely to be adherent than women in the clinical stage 3 or 4 [48]. Evidence suggests that non-adherence in advanced HIV disease may be as a result of increased opportunistic infections and HIV complications requiring many medicines to treat these conditions [49].The immunological status (CD4+ cell count) of women was also linked with adherence to ART in pregnancy [48]. This is because as the CD4+ cell count increased, adherence to ART improved. It appears as though there are mixed results in terms the influence of disease progression on medication adherence.

Two qualitative studies based on in-depth interviews reported the influence of ART side effects on adherence during pregnancy. The first study, conducted in Cote d’Ivoire, highlighted that pregnant women complained of side effects, such as tiredness and weakness, but these effects did not prevent them from continuing with their medication [42]. Side effects were also a reported barrier to ART adherence in the second study, which was carried out in Malawi. Almost all women experienced side effects such as dizziness, hallucinations, nightmares, nausea and vomiting. Results from this study further revealed that women reported worsening of ART side effects in the absence of food. Some stopped taking their ART occasionally due to their inability to consume food from a lack of availability. The authors posited that women had poor adherence during times of food scarcity and when side effects were too severe to manage [44]. A cross analytical study conducted in the Democratic Republic of Congo found no association between ART side effects and adherence [46].

Two qualitative studies, using in-depth interviews, reported on perceived effectiveness of ART among women during pregnancy, thus facilitating adherence to medication [41, 42]. Previous successful experiences of mothers taking ART that resulted in giving birth to healthy children, served as a source of confidence, which facilitated adherence to medication. Side effects of ART, coupled with food shortage, appeared to be major obstacles to adherence during pregnancy. The perceived efficacy of ART also facilitated adherence to ART among the women.

Four qualitative studies, utilizing in-depth interviews and focus groups, showed that limited finances, specifically relating to the cost for transportation to the health care clinics and hospitals, was a barrier to adherence. Financial constraint emerged as the greatest hindrance to taking ART in a RCT conducted in Uganda [39]. In that study, the high cost of transportation from the pregnant women’s home to the clinic was the most prevalent barrier to enrolling in the preventative MTCT Plus Program and adherence to ART [39]. Other qualitative studies [28, 30, 44] conducted in Swaziland, Kenya and Malawi also reported transportation barriers due to lack of finances. However, cross sectional and longitudinal studies, carried out in Democratic Republic of Congo and Uganda, found no association between lack of finances for transportation to the clinic and medication adherence [10, 46]. Financial constraint to buying food was also a major barrier to adherence in many women, as revealed in three qualitative studies [38, 39, 44]. As a result of financial limitations, women were unable to purchase sufficient food to ensure they took ART with food as they were concerned about taking ART on an empty stomach.

Several observational studies and one RCT reported no association between income generating activities, or people’s occupation on adherence to ART during pregnancy [10, 21, 26, 30, 31, 35, 36]. However, one cross sectional study conducted in Nigeria reported an association of occupation and non-adherence. The study reported that women who were artisans, or full-time housewives, were more likely to be non-adherent compared with women working in a trade or the public service. Women who were students were adherent to their ART [34]. The poor financial state of women proved to be a major obstacle to ART adherence in terms of consuming enough food to take their medication at the required time, and in terms of inhibiting transportation to scheduled ART refill appointments.

The issue of women empowerment was examined during in-depth interviews carried out in Uganda, where women reported economic dependence on their husbands. These women were unable to independently determine when to buy food or related household items that could assist with medication adherence [39]. It was posited that a lack of female economic empowerment was a limiting factor over treatment-seeking behavior and ability to initiate and adhere to ART [39]. A cohort study undertaken in South Africa demonstrated that not receiving financial support from a partner, or a husband, was significantly associated with incomplete adherence in women receiving ART during pregnancy [35].

In an in-depth interview study conducted in South Africa, domestic violence, which included both actual physical abuse or threatening behavior, was mentioned by many women as interfering with adherence to ART [38]. Intimate partner violence was significantly associated with non-adherence to antiretroviral drugs during pregnancy, especially sexual violence, as reported in a cross-sectional study undertaken in Zambia [21].

Male involvement was associated with maternal nevirapine and ART adherence in cross sectional studies conducted in Ethiopia and South Africa [48, 50]. By contrast, lack of male involvement was not associated with ART adherence in a longitudinal study conducted in Uganda [10]. One qualitative study, using in-depth interviews, reported lack of male involvement as part of the overall challenges facing the delivery of a comprehensive MTCT service in Swaziland [28].

Qualitative studies highlighted the extreme difficulties that most pregnant women faced regarding disclosure of HIV status to partners, family and friends. An in-depth interview study in Kenya described HIV disclosure to spouses to be a dreadful experience for women because of negative consequences on the women’s marriage, such as violence and accusations of infidelity, as well on their health and well-being, including taking ART [41]. One study, using focus groups and interviews in Uganda, reported that non-disclosure was a common barrier to enrolling in an MTCT program and continuing ART because of fear of blame, domestic violence, divorce, abandonment and loss of economic support that might follow. The study also highlighted the fear of HIV positive pregnant women in exposing their status to their partners by suggesting the use of safe sex practices [39]. Some women faced outright obstructive behaviors from their spouse, such as throwing away their pills after HIV disclosure, as revealed during in-depth interviews in a Malawian study [44]. A similar study in South Africa reported women being afraid of disclosing their HIV status to family members because of fear of discrimination [38]. In studies conducted in Malawi and Mozambique, the fear of disclosure to partners and spouses was highlighted as a barrier [40, 43].

In qualitative studies undertaken in South Africa and Kenya, as a consequence of fear of disclosure, many women resorted to hiding their ART in their homes, away from partners and family [38, 45]. Fear of disclosure also presented a problem when hidden medications needed to be brought to the health facility for pill counts [38]. However, there are studies describing the supportive roles of partners and family members with respect to adherence of medication when women disclosed their HIV status [45, 51]. Quantitative research conducted across several of the sub-Saharan African countries, including Nigeria, Rwanda, Ethiopia, Kenya, Tanzania, Zambia, and South Africa demonstrated an association between disclosure to partners, family and friends and maternal adherence to ART. Seven observational studies and a RCT showed that disclosure was associated with good maternal adherence [21, 25, 27, 30, 48, 52‐54] while non-disclosure was associated with non-adherence in two observational studies [29, 34]. A cross sectional study in Nigeria showed an association between disclosure of a partner’s HIV status and women’s adherence to medication, particularly if the partner was also HIV positive [34]. Fear of disclosure of HIV infection status and the negative consequences that came with such disclosure was a major barrier to ART adherence during pregnancy. However, male partners who were HIV positive and those who accepted the HIV status of their female partners tend to be supportive of their spouse’s adherence to ART.

The initiation, adherence and retention of ART were largely influenced by stigma and fear of discrimination. Qualitative studies showed the complexities around the issue of stigma and women’s adherence to ART. In a study in Malawi where focus groups and in-depth interviews were conducted, women reported shame as the reason why they would not return to the MTCT clinic after testing HIV positive. For those who continued treatment, they devised means of concealing their HIV status in order to avoid stigma, such as travelling to distant health care facilities to ensure anonymity and hiding their ART [43]. Research conducted in Malawi, showed the fear of stigma hindered women from taking their nevirapine at home as prescribed [55]. However, in a recent Malawi study involving in-depth interviews, while stigma was acknowledged by HIV positive pregnant women, there were few reports of overt discrimination and only one patient stopped ART because of stigma [44]. Similarly, women interviewed in Kenya expressed fears of being rejected by their partners and causing shame to their loved ones. They therefore travelled long distances to attend MTCT clinics, located outside of their local communities [41]. Likewise, in another Kenya study, women discussed fear of stigma if their HIV infection status was disclosed. The women recounted that they were able to attend their clinical appointments and adhered to taking their medicines because the community was unaware of their HIV status [45]. A qualitative study also reported stigma as a major challenge to delivering comprehensive MTCT services in Swaziland [28]. Nevertheless, most pregnant women recognized that HIV/AIDS stigma was prevalent within their communities, but the women claimed that the community view of HIV infected persons had no bearing on their decision to commence or continue ART, as shown in an interview study in Uganda [39]. In essence, evidence suggests that stigma and discrimination are strong barriers to ART adherence during pregnancy.

In interviews conducted in South Africa, women reported that HIV-infected relatives stole their ART from their home. They attributed the discrepancies in their ART-taking behavior to theft of the medications, hence limiting their adherence [38]. Focus group research in Kenya also highlighted how women shared their medications with partners, which led to poor adherence to ART [30].

An important facilitator identified during focus groups and interviews, was women observing positive outcomes in the health and wellbeing of other women taking ART within communities in Kenya and Malawi [41, 43, 56]. In a cohort study conducted in Uganda, the place of residence comprising a village environment where individuals were exposed to large amounts of information about prevention of MTCT, was associated with good maternal adherence to nevirapine. In this study, women were exposed to information about prevention of MTCT [57]. Conversely, in a cross sectional study conducted in Ethiopia, living in a rural or urban setting was not associated with adherence to ART. In this study, women were not exposed to extensive information about prevention of MTCT [48]. Attending a support group, and having partner support were found to be positively associated with maternal adherence to medication in observational studies carried out in Ethiopia [48], South Africa [50, 52] and Nigeria [31].

Quantitative research conducted in Zambia demonstrated that the odds of ingesting a single dose of nevirapine was greater among pregnant women who attended three or more antenatal care visits compared with women who attended two or fewer visits [58]. A significant association was found between more than two antenatal care visits and adherence to a single dose of nevirapine in a study completed in South Africa [27]. A similar study involving attendance by pregnant women of at least one antenatal care clinic was also found to be significantly associated with adherence to ART in Ethiopia [48]. Health facility delivery and term delivery was also linked with maternal adherence to a single dose of nevirapine in a cross sectional study conducted in South Africa [27].

A subgroup analysis of one RCT demonstrated that structured counseling by health care workers was a facilitating factor for pregnant women to adhere to their medication. A cross sectional study in Ethiopia documented that mothers who were given accurate counseling on the appropriate intake of ART had 4.7 times higher odds of adhering to option B+ care and support than women who were not correctly counseled [48]. A similar study conducted in South Africa showed evidence of association between adherence to single nevirapine dose and the quality of HIV counseling [27]. Qualitative studies utilizing focus groups and interviews indicated the benefits of health care providers’ counseling to help pregnant women optimize the benefits of ART. A study in Tanzania showed nurses provided high quality psycho-social support to women that resulted in good adherence to antiretroviral (ARV) drugs [59]. Pregnant women in studies undertaken in Uganda and Cote d’Ivoire also reported positive interactions with antenatal care staff that facilitated adherence to ART [42, 51].

Nevertheless, qualitative research has also described the negative impact of health care workers’ attitude and behavior on the ability of women to initiate, adhere and continue ART. Focus groups conducted in Kenya revealed that mistreatment by midwives was one of the reasons women reported difficulties in the use of zidovudine [30]. Women feared that midwives would not provide the required assistance during delivery if they knew their HIV infection status. During focus groups and interviews conducted in Malawi and Uganda, poor interaction with health workers was identified as a major barrier to ART adherence [39, 43]. Poor interactions included disrespectful behaviors such as shouting and making rude comments. Well-structured and accurate counseling on the benefits of ART, good rapport and provision of effective psycho-social support by health professionals were major enablers of ART adherence during pregnancy. Conversely, negative attitudes of health professionals towards women were barriers to ART adherence.

Qualitative studies using focus groups and interviews showed that prolonged counseling to initiate ART treatment, or prevention of MTCT prophylaxis, was perceived by health care providers as being counterproductive because it increased the nonattendance rate and disease progression among pregnant women [28]. In addition, long waiting times, poor counseling due to short contact time between health care providers and women all impacted negatively on the ability of mothers to continue and adhere to ART in Swaziland, Uganda and Tanzania [39, 59]. Lack of privacy and not trusting health workers to keep women’s HIV status confidential were cited by many women as reasons for not initiating or continuing ART [28, 59]. Unpredictable shortages or delayed re-supply of ART were found to reduce patient adherence in Swaziland, Cote d’Ivoire and Tanzania [28, 42, 59].