Abstract
Background: In 2012, Uganda adopted option B+ strategy where all HIV-infected mothers irrespective of their CD4 count are initiated on ART for life to reduce the risk of mother to child transmission. This requires continued engagement with the health care system; however, previous PMTCT strategies in the country reported high levels of lost to follow up (LTFU) especially after pregnancy and this is unknown beyond the postpartum period in the option B+ error.
Objective: To determine the magnitude of Lost to follow up and its associated factors after pregnancy among Option B+ mothers.
Methods: The study was a retrospective cohort with a qualitative component conducted at Kisenyi HCIV a primary health care unit in Uganda. Quantitative data were analyzed using cox and modified poison models while for qualitative we used content analysis.
Results: Out of 452 mothers, 131 (29% ,95% CI 24.9 – 33.3) were LTFU after pregnancy. The incidence of LTFU was 10.51 per 100 person years of observation time with median follow-up of 28.4 months. LTFU was associated with tested positive and initiated ART at a later date (HR=0.49, P 0.024). The major reason for LTFU among Option B+ mothers after pregnancy was none disclosure.
Conclusion: LTFU after pregnancy among option B+ mothers is high. ART initiation on the day when a mother tests positive increases the risk of LTFU. Option B+ programs should give mothers ample time between the day they test positive and ART initiation and adopt deliberate strategies that promote disclosure especially to sexual partners.
Keywords loss to follow-up, option B+, pregnancy and prevention of mother-to-child transmission
INTRODUCTION
Uganda is still classified as a high HIV burden country with790, 000 HIV positive women, more than 120,000 deliveries to HIV positive mothers and 7600 new HIV infections among children 90% of which are acquired through mother-to-child transmission[1, 2]. To prevent mother to child transmission (PMTCT) and improve maternal health, Uganda in 2012 adopted the option B+ strategy where all HIV-infected mothers are initiated on ART irrespective of CD4 count and maintained on this therapy for life. This requires continued engagement with the healthcare system because from hence forth the mother has to be on ARVs and monitored regularly. However, one major concern from previous PMTCT strategies in Uganda was retention with up to 50% of the mothers being lost to follow up (LTFU) after pregnancy[3, 4]. Furthermore, studies in Sub-Saharan Africa show that women initiated on ART based on option B+ strategy are 5 times more likely to be LTFU than their counterparts initiated based on Low CD4[5].
ART clients who are LTFU experience treatment interruptions placing them at substantial risk for mortality, drug resistance and virologic failure[6]. Furthermore, “women who are LTFU may not present to care again until necessitated by illness or until a subsequent pregnancy, both of which may have implications for effective initiation of subsequent PMTCT services”[7-9]. There is also an increased risk of HIV mother to child transmission when treatment is disrupted during the postpartum period.
Life after pregnancy presents multiple factors which may increase the risk of LTFU; caring for a newborn is time intensive and potentially overwhelming, leaving little time for self-care. Some mothers do not disclose their HIV status to their partners making it hard to go to the clinic more frequently especially after the child has completed his/her immunization schedule. In some cases, the worry around delivering a healthy infant has passed, leading to changes in motivation for remaining in care [10], In addition, mothers with high CD4 levels may not have experienced AIDS related conditions and do not perceive themselves to be at risk of adverse outcomes further increasing risk of LTFU.
Studies on LTFU under the Option B+ erra conducted in Uganda have examined continued engagement up to the end of the postpartum period, none has looked at LTFU beyond period [3, 11]. This study sought to assess LTFU after pregnancy beyond the postpartum period and its associated factors among Option B+ mothers attending Kisenyi HC IV in Kampala.
METHODS
Study design
The study was a retrospective cohort where mothers enrolled on program at Kisenyi HCIV between January 2013 – December 2014 were followed up to assess LTFU from HIV care up to a minimum of 12 months after delivery. The study also included a qualitative component to explore the reasons for the observed LTFU pregnancy among mothers enrolled on ART based on Option B+ at Kisenyi HCIV.
Study setting
Kisenyi HCIV is the busiest Primary Health Care (PHC) Unit located in Kampala central division that serves a peri-urban and slum population. Between January 2013 and December 2014, 705 pregnant mothers were started on ART at the facility to prevent mother to child transmission(PMTCT). Provision of PMTCT services is a collaborative effort, led by Kampala City Council Authority together with Infectious Disease Institute (IDI) as an implementing partner. ART initiation is done at the antenatal care clinic (ANC)for every pregnant mother who is willing and diagnosed with HIV. Mothers continue in care at the ANC clinic until the time of delivery. At the time of delivery some mothers opt for other facilities while others stay at Kisenyi HCIV. Those who stay are transferred to the early infant diagnosis (EID) care point after delivery where they are followed up with their babies for one year and six months, after which mothers are transferred to the general HIV care unit for routine monitoring. Monitoring and follow up of mothers is done through scheduled visits which range from two weeks after initiating ART and thereafter one to three months depending on medical conditions. Mothers who miss a scheduled visit are called by peer mothers and if they do not respond within a month they are physically traced by community teams. During the visits mothers are given health education, screened for STIs, treated for opportunistic infections, given FP services and have their drugs refilled. They are also assessed for drug adherence and immunity status. This information is documented regularly in HIV care cards, registers and an electronic data base (Electronic Medical records).
Quantitative data collection and analysis
We reviewed HIV care cards for mothers enrolled who started on ART based on Option B+ at Kisenyi HCIV between January 2013 and December 2014. We consecutively enrolled mothers into the study until the required sample size was obtained.
We classified a mother as LTFU if she had missed her last scheduled clinic visit for three consecutive months or more after pregnancy and were neither transfers-out nor dead. Time-to-event analysis was used to assess loss to follow-up after delivery by estimating person-time in this period. Person-time began accruing at time of delivery and ended at (1) loss to follow-up, (2) transferred out, (3) dead (4) Censored on 31st December 2016. We described mothers’ characteristics using means and standard deviations for continuous variables, proportions and interquartile ranges for categorical variables.
At Bivariate analysis, a cox proportional regression model was used to assess the association between each variable and LTFU and the effect measured as hazard ratios (HR) and the corresponding 95% CI. All variables with a P-value < 0.20 at bivariate analysis were considered significant for multivariate analysis.
At multivariate analysis, joint association between all significant independent variables at bivariate analysis and LTFU were assessed, those with P-value <0.05 were considered statistically significant. The predictors were assessed for interaction using the chunk test and for confounding.
Qualitative data collection and analysis
Qualitative information was obtained using Key Informant Interviews (KIIs), In-depth interviews (IDIs) and Focus Group Discussions (FGDs). FGDs were held with mothers enrolled on the Option B+ program at Kisenyi HCIV. KIIs were conducted for Health care professionals from Kisenyi HCIV, IDIs with mothers who have ever missed an appointment over the study period, those who were LTFU at one point, traced and currently in care.
A total of three FGDs each containing 6-8 members were held by the principal investigator and a trained research assistant at the Antenantal clinic waiting area. Members of the FGD were obtained by snow balling where one peer mother was identified, and she then helped the study team to get other mothers to join the discussions. Discussions were regulated by the principal investigator using a preset topic guide, and the research assistant that captured additional information like; gestures and body language displayed during the discussion.
A total of eight face to face Interviews were held by the principle investigator with three purposively selected Health Care Professionals (Clinical head HIV care and treatment Infectious Disease Institute, one clinical officer, one midwife responsible for Option B+ at Kisenyi HCIV and five mothers who had ever missed an appointment, those who were LTFU at one point over the study period, traced and currently in care.
Topic guides for IDIs and FGDs were translated from English to Luganda while those for the KIIs were only in English. They comprised of open ended questions to prompt dialogue and unmediated opinions on: mothers, health care professionals experiences with option B+, challenges and constraints encountered, potential promoters of LTFU under option B+ program. Data collection and the subsequent analysis were conducted as an iterative process and the last FGD, KII and IDI were established by informational redundancy when the discussions or interviews were generating no new information. Audio-taped interviews and focus groups data were transcribed verbatim then edited to remove any identifiers. Transcripts were read thoroughly several times prior to coding and analysis using open code software. Coding and analysis followed a thematic analysis approach. Content analysis was used to analyze this data based on emerging themes and sub themes in line with the study objective. The coding framework was based on the literature, topics from interview guides, and emerging themes from transcripts.
Ethical approval
Ethical approval for the study was sought from Makerere University School of Medicine Research and Ethics Committee (SOMREC). A waiver of consent to review existing medical records was sought from SOMREC because mothers who are LTFU are not in care and all couldn’t be traced within the study period. Permission to conduct the study was obtained from KCCA and the In-Charge of Kisenyi HCIV. Similarly, oral consent was sought from the participants for the qualitative study prior to start of discussion and audio recording of the dialogues.
RESULTS
Out of 705 pregnant mothers enrolled on Option B+ program at Kisenyi HCIV between January 2013 and December 2014, 656 files were available and reviewed for this study. In addition, 177/656 mothers were LTFU before delivery, 24 mothers did not have properly documented appointment dates, 3 mothers had leverage values greater than 0. 2 at the time of analysis and were considered outliers; these were excluded from the study thus leaving an analytical sample size of 452.
The mean age of the mothers was 28.98 years (SD: ± 4.87) and about 84.3% (368/452) were married or living with a partner. Most of the mothers started ART on the same day they tested HIV positive 84% (348/452), and 48% (215/452) were below 25 years of age at the time ART initiation. Approximately 16% (71/452) had one or more opportunistic infections at the time of ART initiation and 77% (349/452) had HIV negative exposed infants see Table1.
131/452 (29%, 95% CI 24.9 – 33.3) were LTFU and 77.6% (95% CI 73.6- 81.3) kept at least 80% of their scheduled appointments after delivery. The incidence of LTFU after pregnancy was 10.51 per 100-person years (pyrs)of observation time with median follow-up of 28.4 months. The incidence of LTFU was highest among mothers who did not have a treatment supporter on enrollment into care (1.97/100 pyrs), then those who tested positive and initiated ART on the same day (1.18/100pyrs) and marrieds (1.11/100 pyrs). Tested positive and started ART later (HR= 0.49, P -0.024, 95% CI; 0.26 – 0.91) was significantly associated with LTFU after pregnancy See Table 2.
When mothers were asked after delivery to identify reasons why some Option B+ mothers may not return for HIV care, the most frequently cited barriers were lack of disclosure of the mother’s HIV status (30%), lack of transport (18%) and stigma (10%) see Table 3.
DISCUSSION
The proportion of option B+ mothers LTFU after pregnancy (29%) is high compared to the global target of 15% for all ART clients[6]. Our LTFU findings are higher compared to those reported in Malawi (13%) [5], in England, Wales, and Northern Ireland 12.5% [12]. However, they are lower than those reported in South Africa 47.9% [13] and in Uganda 40.6% [11]. The observed difference in the two Ugandan studies could partly be explained by differences in the timing of the studies. Ahoul etal considered a study period of 2000- 2005 when Uganda was implementing Option A and mothers who could afford not to breast feed opted out of the PMTCT program if the child tested negative on the first Polymerase chain reaction (PCR) hence a higher LTFU after pregnancy. Malawi, England, Wales and Northern Ireland started ART initiation for all mothers earlier than Uganda and have probably adapted better strategies to decrease LTFU under Option B+ program hence lower LTFU proportions.
Option B+ mothers who tested positive and initiated ART at a later date, were 0.49 times less likely to get LTFU after pregnancy than those initiated on the same day. Our findings are similar to those reported in many African countries[14]. Mothers who start ART immediately after testing positive may not have been adequately counselled, have little time to accept and disclose their HIV status to their partners or relatives[15], yet individuals who do not disclose their HIV status are twice as likely to be LTFU compared to those who disclose [16, 17].
Gestation age at ART initiation was not associated with LTFU after pregnancy. Similar findings were reported in Malawi, England, Wales and Northern Ireland [12, 18]. However they contradict those reported in South Africa, where the risk of LTFU increased with increase in gestation age [19]. The difference in the findings could be explained by a difference in the follow-up periods of participants while Phillips considered up to 12 months after ART initiation the other studies considered more than 24 months.
Noteworthy, factors associated with LTFU were studied with a limited sample size. Therefore, irrespective of tested positive and started ART on the same day, several factors could be significant if the sample size issue is addressed. In Uganda, for example where 25% of women aged 15-24 years are mothers are pregnant with their first child coupled with 7.6% HIV prevalence in the same group, young age at ART initiation would be one of those factors that could influence LTFU after pregnancy. Such findings have been reflected in Sub-Saharan Africa, England, Wales, and Northern Ireland where the probability of LTFU is higher among Option B+ mothers of younger age at ART initiation than in those who are older [5, 12, 16, 20].
Several reasons were mentioned for LTFU after pregnancy including; non-disclosure, negative HIV exposed infant final status, transport costs, partner support, gender-based violence, stigma, wok place policies, and stock outs of ARVs. The reasons for LTFU after pregnancy are remarkably similar to those reported in the literature[21-25]. Although, negative HIV exposed infant was not attributed to LTFU after pregnancy, participants in the FGDs and KIIs reported that it was an important reason for LTFU. The misconception that the mother’s health is unimportant once the exposed infant has a negative HIV result jeopardizes continuation in care, as women initiating ART when they are well may see less reason to remain in care after delivery. Several studies have also documented similar lack of motivation to remain in HIV care after a healthy delivery among women participating in Option B+ and other PMTCT programs [21, 22, 24].
All participants from the FGDs, KIIs and IDIs reported that non-disclosure of HIV status to the people you live was the major reason for LTFU after pregnancy. Such findings’ have also been reflected in Kenya and Uganda, where women who kept their status a secret, were more likely to get LTFU [25, 26]. According to Hermman etal, only 46.2% of PMTC mothers disclose their HIV status to their partners[27].This is because disclosure of HIV status threatens a woman’s relationship with her spouse and family. HIV-positive status calls a woman’s behavior into question. In doing so, it also calls into question her ability to be a wife and mother and to care for her family[28]. Disclosure is of particularly importance because it is a precondition for physical and emotional support which are critical for LTFU. Participants also acknowledged to this fact that mothers who have not disclosed find it difficult to get transport, cope up with short appointment schedules during ARV stock-out periods and to obtain permission from work to attend clinic days.
Finally, participants from FGDs acknowledged that the reason why their peers get LTFU is because they are not supported by their partners . The findings are consistent with those reported in a systematic review in Sub Saharan Africa where HIV positive mothers often felt a need for their partners’ permission to initiate, adhere to, and be retained in ART care. This is because mothers in Sub-Saharan Africa economically depend on their husbands; it is the man to provide transport needed to seek care[23]. However, partner support can only be got after disclosure and yet few disclose their HIV status to their partners.
In conclusion, LTFU among Option B+ mothers after pregnancy is high and ART initiation on the day a mother tests positive increases the risk of LTFU. The major reason for LTFU among Option B+ mothers after pregnancy is none disclosure. Our findings suggest the need for Ugandan government to consider giving mothers ample time between the day they test HIV positive and ART initiation.
The strength of this study is that we looked at LTFU beyond the postpartum period among Option B+ mothers. In addition, reasons for LTFU from Option B+ mothers seeking services during the study period, those who missed an appointment or were LTFU at one point over the study period, traced and currently in care and health workers captured a comprehensive picture of the issue. Option B+ programs, should adopt deliberate strategies that promote disclosure especially sexual partners.
The study has sevral limitations including, lacked information on some key variables like education levels, occupation and parity. However, information bias may have been minimal considering that the quantitative study findings were supported by the qualitative that comprehensively captured reasons for LTFU after pregnancy. Our sample size (452 versus 581) was too small to detect all factors significantly associated with LTFU after pregnancy.
ACKNOWLEDGEMENT
We thank the management of Kampala Capital City Authority for granting us permission to work with its facility, specifically the administration of Kisenyi HC IV where we conducted the study. The mothers, health workers and research assistants who participated in the study.
Authors’ contributions
YK participated in the conception, design, and implementation of the study, statistical analysis, interpretation and drafting of manuscript. JK and PM participated in study conception, design, statistical analysis and interpretation. All authors read and approved the final manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
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