Introduction
Worldwide, over 2 million children are infected with HIV, 90% of whom live in sub-Saharan Africa [
1]. Many HIV-infected infants and children die from HIV related causes without their HIV status being known, or receiving HIV care [
2]. Without access to cotrimoxazole prophylaxis, antiretroviral therapy (ART) and supportive care, about a third of infants die by 1 year of age and a half by age 2 years [
3]. Early initiation of ART is associated with better treatment outcomes and increased survival in children born to HIV infected mothers [
4‐
8].
The goal of early infant diagnosis (EID) is to identify HIV infected infants prior to the development of clinical disease to facilitate treatment and follow up. For infants who are virologically negative, it provides an opportunity to plan and counsel on appropriate feeding to reduce the risk of infection whilst maintaining adequate nutrition. Throughout Africa, the diagnostic challenge of HIV-exposure in infants is being addressed by scaling up virological testing using dried blood spots (DBS) for polymerase chain reaction (PCR) [
2,
9,
10].
Despite this scale up, there are few data describing the uptake and implementation of EID. Available data suggest that only 8% of infants born to women with HIV infection receive a virological test within the first 2 months of life [
2]. More than three quarters of infants born to HIV infected mothers who register for care drop out before 6 months of age and up to 85% by the 12th month of follow up [
11,
12]. The majority of infants and children who enroll into HIV care are referred from acute or chronic care services [
13]. This means most newly acquired infections in children are not diagnosed early enough to benefit from early ART [
14].
We aimed to describe the uptake, key drop out points and completion rates for early infant testing in a rural Kenyan setting during the recommended follow up to 18 months of age. To interpret the quantitative findings, we examined service providers and caregivers’ knowledge, attitude and perceptions of the EID process.
Methods
Study Setting
EID was introduced in Kenya under the prevention of mother to child transmission (PMTCT) programme by the Ministry of Health in 2006. The service is offered free of charge in more than 190 centers including private health centers, government clinics and public health care institutions [
10]. A testing algorithm for infants under 18 months was developed and implemented by the National AIDS and Sexually transmitted disease Control Programme (NASCOP). It recommends that all HIV exposed infants should be tested by PCR at 6 weeks of age (or at first contact), by an antibody test at 12 months (if PCR negative) and a confirmatory antibody test at 18 months (if a previous antibody test was negative and continued breastfeeding). In August 2008, in view of data suggesting poor infant outcomes [
15], national policy changed to offer ART to all infants with HIV infection confirmed by PCR.
The study was conducted at the HIV clinic in Kilifi District Hospital. Kilifi District is predominantly rural and is located along the Kenyan coast. DBS samples are collected and couriered as a weekly batch to a central laboratory in Nairobi, approximately 560 km away, for analysis. Detailed sample collection, transport, analysis and feedback of results have been previously described [
10]. Data on clinic registration follow up visits, treatment and blood test results were prospectively recorded on a computer database for all clients attending the clinic.
Study Population
We included data from all HIV-exposed infants enrolling for care in the clinic between August 2006 (when EID was initiated) and August 2008 (when the algorithm changed to promptly initiate ART for any positive PCR test). To fully assess completion, we excluded infants who had not reached 18 months of age by August 2008. We also assessed infant-caregiver couples for mothers/caregivers who had ever enrolled for care at the clinic. For qualitative research, we recruited i) caregivers of infants still in follow up in the clinic, identified from the database and purposively sampled on their next routine visit over a 4 week period, and ii) service providers including nurses, counselors and clinical officers involved with implementing EID.
Study Design and Analysis
We used an observational study design involving mixed methodology. A historic cohort study was used to determine uptake and drop out. We examined data on enrolment and follow up since 2006 using a dynamic model to illustrate intake, drop out and completion at different ages of entry (in 2 month strata). Continuous data are presented using medians and interquartile ranges while categorical data are presented in frequencies and percentages. To determine factors related to drop out in both infants and their mothers, we used the Kruskal–Wallis rank sum test and Pearson’s χ2 test as appropriate. Analysis was performed using STATA version 9.0 (Stata Corp., TX, USA).
This was complemented by a qualitative descriptive study to determine knowledge, attitudes and perceptions of service providers and caregivers regarding the early infant testing process. Qualitative data collection comprised six non-participatory observations of the early infant testing and care process, in-depth interviews with ten caregivers (all mothers) and six service providers (two PMTCT counselors, two clinic nurses, a nutritionist and a clinical officer) directly involved in provision of EID services. Experienced female interviewers fluent in the local languages, Swahili and Giriama, conducted the interviews and transcribed the recordings. Two investigators separately identified the main themes. The resulting findings were presented back to the clinic staff to elicit further information, and validation. Data were grouped using an access framework considering three dimensions of accessibility: availability (physical access), acceptability (cultural access) and affordability (financial access) [
16].
The study was approved by the Kenya National Scientific Steering Committee and the National Ethics Review Committee. Verbal consent was sought for the observations and written informed consent was obtained for the interviews.
Discussion
Our findings suggest several weaknesses in the implementation of EID in rural Kenya. We found frequent late entry and high drop out among infants enrolling for care and EID. This appears to be, in part, due to lack of knowledge and understanding of EID by service providers and consequently, caregivers. Service providers were inadequately prepared to effectively implement EID despite having undergone PMTCT training. This finding is supported by the current PMTCT training curriculum, which is limited in dealing with EID as part of the strategy to prevent transmission or progression of HIV [
17].
The majority of infants enrolled after 2 months of age, with more than 80% being referred for care from acute or chronic clinical services. This suggests that infants were referred and enrolled when they fell sick, rather than for scheduled follow up of PMTCT. This is also evident from the high proportion of positive PCRs compared to the Kenyan national figure of 15.4%, or to 9.4% from South Africa [
10,
18]. PMTCT has the potential to reduce transmission rates from 35 to 40% to less than 5% [
19,
20]. That almost half of the infants who had a virological test never came back for their results supports the suggestion that caregivers were inadequately prepared for EID.
Two-thirds of the infants who dropped out had mothers who were also ‘lost to follow up’ for HIV care. Indeed, a study evaluating the PMTCT programme in rural Malawi revealed a progressive loss to follow up of HIV positive mothers of up to 81% postnatally [
21]. Household and community factors influenced retention, including stigma and constrained social support networks. Ineffective access to, or utilization of, support networks including partners and community groups because of stigma has been reported elsewhere [
22]. Given the high level of poverty in our setting [
23], travel and other indirect costs associated with repeated visits to the hospital were important.
A limitation to our study was that in our setting, as elsewhere in rural Africa, many women opt to deliver at home, and not all attend antenatal clinic [
24,
25]. Consequently we were unable to determine the overall number of infants born to HIV infected mothers for comparison. For practical and ethical reasons, we only interviewed caregivers who were still in follow up, most of whose children had completed the recommended follow up period. This is a weakness of the study, but these caregivers were able to discuss likely challenges for those who had not completed follow up.
Fully integrating EID into PMTCT has the potential to improve uptake and retention by including more specific EID training within the PMTCT syllabus to empower service providers with adequate knowledge and understanding of EID. Moreover, as has been applied in ART adherence counseling, specific EID adherence counseling is needed. This could be implemented at two important time points: during the last trimester of pregnancy when the mothers need to be prepared for the arrival of the baby, and postnatally, at the enrolment of the infant into care to emphasize the importance of follow up.
In our setting, HIV-exposed infants are enrolled and cared for in exclusive HIV clinics. An alternative is to incorporate EID services and postnatal testing within MCH services, offered together with immunizations, growth monitoring and other maternal child health care services [
18]. This is a potentially attractive strategy considering high levels of immunization coverage [
26], and the possibility of reducing costs to caregivers by combining visits. Several African countries have revised child health cards to include HIV-related information, making tracking of exposed children easier and increasing the likelihood that HIV-exposed infants are referred for virological testing and put on treatment [
27]. An approach through MCH services would also allow maternal or infant antibody testing to detect HIV infections occurring during pregnancy or in the post-partum period.
Conclusion
Scaling up early infant testing in resource limited setting is an important step in improving survival among HIV infected infants. However, this scale up should go hand in hand with training and infrastructure for EID to be embedded within the PMTCT program, consideration of integration of EID with MCH services and broader initiatives aimed at increasing early uptake and decreasing dropout rates for those enrolled in care.
Acknowledgments
The authors would like to thank the health care staff and the patients at the Comprehensive Care and Research Clinic, Kilifi District Hospital for their participation in this study. We also acknowledge the assistance of Jane Kahindi and Gladys Sanga in conducting and transcribing the interviews. This paper is published with the permission of the director of the Kenya Medical Research Institute.