CLINICAL HIV AND AIDS JOURNAL (ISSN:2633-5476)

Back ground: The majority of infants born to HIV-infected women are HIVexposed uninfected (HEU). Effective clinical management of these children will prevent seroconversion, severe illness and malnutrition. To ensure quality care the Ministry of health has guidelines for standard evidence based care that all providers follow.

Objectives: A clinical audit to determine proportion of HEU children aged less than 24 months enrolled in Lea Toto program that accessed and adhered to Kenyan National guidelines in the following components: early infant HIV diagnosis (EID), anti-retroviral prophylaxis, immunization, retention in care, and management of nutrition and infectious co-morbidity.

Methods-design, setting and participants: This was a clinical audit conducted at Lea Toto program a faith based NGO which has for the past 20 years provided health services to families of children affected by HIV and currently serves up to 3,100 HIV-positive childrens and up to 15,000 family members annually. The study participants were HEU children 0 to 24 months old on follow up in 2016-2017. Children were classified as HEU on the basis of their first HIV PCR test being negative. After informed consent a standardized clinical audit tool was used to abstract data from the electronic medical records of the HEU infants. The tool was used to collect information on timing and results of the early infant HIV diagnosis, ART prophylaxis, nutrition status, morbidity, immunization and adherence to follow up.

Results: A total of 322 electronic medical records of HEU infants at Lea Toto program were evaluated. Age on enrolment into the program was from 3 days of age to 20 months of age. The mean age of first HIV PCR test was 2.01 months. A total of 287 (89.13%) of the first HIV PCR were done at Lea Toto. Overall 299 (92.8%) of the 322 participants received ART prophylaxis, 144 (44.7%) the recommended combined Zidovudine (AZT)+Nevirapine (NVP) prophylaxis, and 155 (48%) only NVP. Only 217 (67.39%) participants started ART prophylaxis on first day of life and up to 219 (68.01%) HEU were on the ART prophylaxis for 3 months, while 25 (7.8%) receive a shorter course of prophylaxis because of loss to followup or no longer at risk, and 78 (24.2%) received more than 3 months prophylaxis due to heightened risk of infection from maternal viral non-suppression. The 23 (7%) who did not received ART prophylaxis were enrolled into the program after they had been weaned off breastfeeding and reports of ART prophylaxis could not be verified. Overall 265 (82.3%) received Co-Trimoxazole prophylaxis. There were 214 (66.45%) participants who reported exclusive breastfeeding for 6 months, 58 (18%) for 5 months and only 10 (3%) for less than a month. Overall 72 (22.4%) had some malnutrition including 43 (13%) moderate malnutrition, 13 (4%) stunted, 9 (3%) wasted, while 7 (2%) both wasted and stunted. Only 26 (8.1%) of the 322 participants were admitted to hospital during the period of audit. Only 4 (1.2%) children seroconverted. Factors associated with seroconversion were late enrolment, inappropriate ART prophylaxis and incomplete HIV testing. 

Conclusion and Recommendation: Children enrolled in the Lea Toto program are accessing the essential HIV care package. Late enrollment into the program was associated with increased likelihood of malnutrition and HIV infection. There is need for continuing medical education (CME) to address the observed low PCR testing rate at 9 months and inappropriate use of CTX before the age of 6 weeks of life.

HIV exposed uninfected children; Clinical management; Lea Toto program; Kenya

With increasingly effective PMTCT (Prevention of Mother to Child Transmission), the population of HEU infants is growing. HEU children are at increased risk of mortality, morbidity and slower early growth than their HIV-unexposed counterparts [1,2]. Nine out of ten HIV infected children acquired the virus from their infected mothers during pregnancy, delivery, or through breast-feeding [3]. Without treatment, the likelihood of HIV passing from mother-tochild is 15% to 45%. With specific interventions such as combination antiretroviral treatment (cART) in non-breastfeeding populations, the risk of MTCT can be reduced to less than 2%, and to 5% or less in breastfeeding populations [4].

Since 2011 to 2015 globally the annual number of HIV-infected children has declined by 50%. Kenya reduced number of new HIV infections among children by 49% between 2013 and 2015[5].

The purpose of this study was to conduct a clinical audit to determine proportion of HEU children aged less than 24 months enrolled in Lea Toto program that accessed and adhered to Kenyan National guidelines in the following components:

1. Recommended infant ART prophylaxis for 12 weeks, with Zidovudine and nevirapine for 6 weeks, followed by nevirapine for 6 weeks.
2. Early infant HIV diagnosis-at 6 weeks age or first contact if seen after 6 weeks age using DNA PCR. 
3. Co-Trimoxazole prophylaxis-from 6 weeks of age to 6 weeks after exclusive breastfeeding stops.
4. Adherence exclusive breastfeeding for 6 months then addition of appropriate complementary feeds while continuing to breastfeed for at least 12 months. 
5. Recommended immunization schedule as per National Vaccination and Immunization Programme. 
   

Study design

This was a clinical audit to evaluate management of HEU children according to Kenyan national HIV guidelines.

Study population

The study population was HEU children followed up in the first 2 years of life in 2016 and 2017 in Lea Toto program and had been in the program for at least 3 months and were confirmed HIV negative on initial PCR testing. Potential study participants were identified by proportionate stratified random sampling from the 8 facilities.

Data abstraction

A standardized structured questionnaire was used to abstract de-identified data from electronic medical records of the patients. Specifically the tool collected data on the demographic characteristics (age, sex, whether orphaned, maternal education status and use of cART), early infant HIV diagnosis (defined as DNA PCR testing at 6-8 weeks of life), subsequent HIV testing, ART prophylaxis (drugs used and duration), feeding and nutrition status (duration of exclusive breastfeeding, timing of complementary feeds, anthropometric measurements of the child), morbidity (cause of illness and hospitalization), immunization and adherence to follow up.

Statistical analysis

Electronic data was cleaned before embarking on data analysis. We used STATA 9.2 for statistical analysis. Descriptive statistics were used to summarize the study population characteristics, ART prophylaxis, early infant and subsequent HIV testing. Adequacy of care was estimated by level of adherence to Kenyan HIV treatment guidelines. Prevalence was tabulated and association between incomplete HIV care and poor outcomes (including seroconversion, malnutrition and sever illness) was determined using Chi square test of independence.

Ethical considerations

Written consent was obtained from custodians of electronic medical records (board of management-Lea Toto program) before data collection. The study was conducted after approval from the Research and Ethics Committee of Kenyatta National Hospital and the University of Nairobi.

A total of 322 electronic medical records of HEU infants at Lea Toto program were evaluated. The study was conducted in January and February 2018. The current age of the children was from 3 to 24 months during study period. The median age of enrolment into program of 1.5 months and there was a male to female ratio of 1:1. Just over half of the children had been referred to the program, 125 (38.8%) by community health workers and 58 (18.1%) from other health facilities. Half of the mothers 151(51.7%) were unemployed, while 47 (31.12%) were single parents.

Majority of the participants at 265 (82.3%) were on CoTrimoxazole prophylaxis. The prophylaxis was started as early as day 1 of life to 9 months of age. The majority of participants 178 (55.28%) were started at 4-6 weeks of age. There were 57 children whose records didn’t include Co-Trimoxazole prophylaxis received. This was especially for children lost to follow up.

There were 26 (8.1%) children admitted to hospital in the period of observation among them 16 (4.9%) with diagnosis of gastroenteritis, 12 (3.7%) ARI, 2 (0.6%) for tuberculosis, 4 (1.5%) for neonatal conditions as seen in Table 3.

Overall 72 (22.4%) experienced some malnutrition including 43 (13%) with moderate malnutrition [Weight for age (W/A) range -1 to -2 standard deviation (SD)], 13 (4%) stunted [height for age (H/A) Z score<-3], 9 (3%) wasted [weight for height (W/H/) Z score<-3], while 7 (2%) both wasted and stunted. The median age for diagnosis of wasting was 13 months and the range was 2-24 months. The median age of stunting was 14 months with a range of 10-24 months. Out of 29 participants with severe malnutrition, 26 (89.65%) were appropriately diagnosed and managed. The plotting of child’s weight and height in recommended growth charts was not regularly done (Table 3).

The HEU children with severe malnutrition were compared to those that were well nourished. They were comparable in terms of mother’s education status as well as employment status. A similar proportion of children (both well-nourished and not) were exposed to exclusive breastfeeding for 6 months. The only difference between well-nourished and poorly nourished HEU was the age at which they enrolled into the program. Only 20% of the malnourished HEU enrolled into the program by 6 months of age compared to 93.4% of the well-nourished HEU. Children enrolled in the program after the age of 6 months had 27 fold increased risk of being malnourishedOR=27.5 [(95% CI 11.2, 65.5), p<0.001 Fischer’s exact test].

All children who seroconverted were malnourished compared to 77 of the 318 children who were not infected and this difference was significant (p=0.008 Fischer’s exact test). The infected children experienced a higher hospital admission rate compared to those who were not infected 2 (50%) compared to 19 (5.9%) OR=15.7 (2.1, 117.9).

Table 5 shows the performance of the program over the period of observation. There was effective coverage of the essential HIV care package for the children enrolled into the program other than the 9 month HIV test.  

The majority of study participants 294 (91.3%) were enrolled at 0-6 months of age, mainly at 6 weeks of age 86 (26.8%). This corresponds to the timing of first or second HIV PCR test. These children also come for refill of their prophylaxis and adjusting of doses at 6 weeks of age.

The children’s caregivers were mainly both parents 182 (56.5%) but majority were separated. Most parents were unemployed or in casual labor. Most mothers at 151 (51.7%) were unemployed, 47 (31.12%) of these mothers were single parents. The socioeconomic status of the families of HEU children is critical for their care. 

The program receives children after they have been delivered in other facilities and already on ART prophylaxis. This proved to be challenging. Sometimes one has to rely on mother’s history on when prophylaxis was started and if the medicines are adhered to.

The program is different from research based programs. The program’s facilities are located in the community, increasing accessibility. Furthermore the program works with CHWs to ensure community involvement. It is also run by local (Kenyan) technical staff, with guidance from national guidelines. This makes the model more sustainable.

Despite the national HIV guidelines amendment to include zidovudine (AZT) as part of prophylaxis, most children enrolled early 2016 were on nevirapine (NVP) prophylaxis only. There were only 144 (45%) on AZT+NVP. The program staff then has to start the zidovudine later than recommended. This is critical as appropriate ART prophylaxis ensures HEU children don’t seroconvert. The program needs to give feedback to referring health facilities if the children are not on appropriate ART [6-8].

The duration of ART prophylaxis for some participants was not appropriate. For instance its recommended if a breastfeeding mother refuses to start ART but agrees to provide infant ARV prophylaxis, provide 6 weeks of AZT+NVP, followed by daily NVP until 6 weeks after complete cessation of breastfeeding. If mother has viral load ≥ 1,000 bcopies/micromoles, continue infant prophylaxis until confirmed viral suppression or 6 weeks after complete cessation of breastfeeding. These special recommendations were not followed in the above mentioned circumstances and these children were put on similar prophylaxis as children whose mothers were on HAART and virally suppressed. This is challenging since the mothers are not managed at the program.

The national guidelines recommend that all HIV exposed infants should receive Co-Trimoxazole prophylaxis from 6 weeks of age to 6 weeks after exclusive breastfeeding stops. WHO estimate that only 8% of children exposed to HIV were initiated on Co-Trimoxazole prophylaxis by two months of age. Similarly at the program some children (17%) were not on Co-Trimoxazole prophylaxis at any point of management.

There were challenges with early infant HIV diagnosis. The tests were conducted when the child was enrolled at first contact, for 287 (89.13%) participants especially if not done at referring facility. This may not be the same timings as recommended by national guidelines. For instance a child enrolled at 5 months age will have a PCR test at enrolment. The same child is expected to have HIV PCR at 6 months age. Some children were no longer brought to the clinic once their PCR test turned negative and child was not breastfeeding. This resulted in low turnout for the 18 month antibody tests. However the social worker and CHWs organize for home visits to ensure children resume follow up.

The turnaround time for HIV PCR results was as long as 2 months. For instance there were 3 infants who were initially managed as HEU as results were pending, but their first HIV PCR turned positive. These children had initial high viral loads due to late start of HAART

The above mentioned challenges hindered full turn out of the recommended HIV tests. In our study there was only 79% uptake of the 6 week PCR test. Similarly in a review by Celleti [9] only 39% of children in low-income countries were estimated to have access to HIV testing within the recommended 2 months of birth.

According to a study by Ashiono E et al. [10] in a retrospective cross-sectional study that analyzed 2,642 records of HIV-exposed infants in north rift Kenya, (42.4%) infants had DNA PCR within the first 6 weeks of age. In that study only 72.1% infants received prophylactic antiretroviral, in this study ART prophylaxis was given to 92.8% of participants at Lea Toto program.

According to the ZVITAMBO trial [11] compared with notexposed infants, sick clinic visits were 1.2 times more common among HEU infants. In this current study at Lea Toto HEU children were seen severally for various diseases, some even before scheduled appointments. There were study participants who ended up being admitted due to the severity of their illness. There were others who required further specialized treatment e.g. recurrent eye discharge not responding to treatment.

In a study by Gichuhi et al. [12] that followed 351 HEU infants from neonatal period up to 1 year of age, common medical conditions included bronchopneumonia, diarrhea and failure to thrive. These were similar to the medical conditions leading to hospital admissions in this current study at Lea Toto.

Malnutrition was observed in majority of study participants. The children who were not exclusively breastfed had higher risk of malnutrition OR=1.84 95%CI 0.85-3.96 and severe illness. More than half (56%) of the participants with wasting were not exclusively breastfed. Among the children who were treated for severe illness requiring admission and specialist follow up, 58.1% (OR: 1.22; 95% CI: 0.99 p) were not exclusively breastfed for 6 months.

The immunization status of the children was mainly recorded in the first visit to the program. The follow up immunizations after first visit was not recorded for most of the children. The immunization of HEU infants is critical in ensuring disease prevention. HEU infants have altered cell-mediated and humoral immunity, this coupled with lack of immunization increases their risk to acquire severe childhood illnesses which are preventable.

The children lost to follow up before official discharge, majority 13 out of 23 did not resume follow up. There was no documentation on home visits or phone call to ascertain child’s whereabouts.

The seroconversion rate in this study was 1.24% (95% CI: 0.34, 3.15). Factors associated were late enrolment to program, incomplete EID and inappropriate ART prophylaxis. A meta-analysis including 9 studies, 3688 mother-baby pairs in Ethiopia [13], the pooled prevalence of MTCT of HIV was 9.93%. Associated factors with MTCT of HIV include: mixed feeding, absence of infant ARV prophylaxis, home delivery, and absence of maternal PMTCT intervention.

I would like to acknowledge the Board of management and staff at Lea Toto program for their support. Of special mention are Prof. Rachel Musoke and Prof. Ruth Nduati who have provided critical guidance and supervision throughout the duration of this study. I would also like to thank the data team at Lea Toto program for all the assistance with data collection and analysis.

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