Impact of HIV/AIDS on mortality and nutritional recovery among hospitalized severely malnourished children before starting antiretroviral treatment ()
1. INTRODUCTION
In low income countries, severe acute malnutrition (SAM) remains a major killer of children under five years of age. To cover large numbers of children with severe acute malnutrition, treatment approach combines, today, community-based approach with ready-to-use therapeutic foods or other nutrient-dense foods, at home, without being admitted to a health facility or a therapeutic feeding centre, and inpatient treatment with a facilitybased approach for those malnourished children with medical complications [1]. In low income countries, despite efforts, numbers of infants continue to be born with HIV, as less than 35% of pregnant women received HIV testing and less than 48% pregnant women are receiving effective treatment for preventing mother-tochild transmission. Severe acute malnutrition (SAM) remains a major problem for HIV-infected children and an important risk factor for mortality [2-8].
Observational studies reported high HIV prevalence among malnourished children [9-12]. A systematic review and meta-analysis of children presented with SAM in sub-Saharan Africa reported an HIV seroprevalence of 29% with data from 17 studies [13]. If severely malnourished uninfected children can be successfully treated in community based approach, those who are HIV/AIDS infected, seriously ill, need facility based treatment. Challenges, for facilities and feeding therapeutic centers, are case management for HIV/AIDS infected SAM children. This study aims to measure case fatality rate and nutritional recovery during nutritional rehabilitation, among severely malnourished HIV/AIDS uninfected and infected children before starting antiretroviral treatment, and to show urgent need for specific intervention needed for integrating HIV management in the area of SAM’s community-based treatment approach.
2. MATERIAL AND METHODS
2.1. Study Design and Site
This was a retrospective cohort study conducted from data of severely malnourished children hospitalized, between 2006-2009, at a feeding therapeutic center, based on inpatient treatment approach, in Ouagadougou. At this center, trained care providers staff, leaded by a medical doctor, was in charge of the treatment. Case management and follow-up care were based on WHO guidelines for inpatient treatment of severely malnourished children.
2.2. Study Population
During the considered period, severe acute malnutrition (SAM) diagnostic is based on severe wasting, as a weight-for-height below −3 SD or below 70% of median (based on NCHS reference) or the presence of nutritional oedema affecting both feet.
For HIV testing, the child blood sample were collected and identified by a single code and immediately transferred to Ouagadougou pediatric hospital laboratory for analyses. To reduce testing cost, a first level antibody tests was used and polymerase chain reaction (PCR) test was used when antibody test was positive.
2.3. Standard of Care
Patients received standard inpatient treatment for severely malnourished children with initial stabilization phase and rehabilitation phase. Treatment procedures were similar for marasmus and kwashiorkor. For feeding, daily and hourly volume was adapted to the child weight and presence of oedema.
HIV/AIDS infected children was referred to pediatric hospital to be integrated to HIV/AIDS follow up cohort and eligible’s patients received antiretroviral treatment.
All nutritional treatment, antiretroviral treatment and opportunistic infections management were offered, using national guidelines. Testing including PCR and transport to pediatric hospital were offered.
2.4. Study Samples Size
Data of 521 severely malnourished children, tested for HIV have been considered for analysis.
2.5. Data Collection
Trained research nurses collected data on children’s socio-demographic (sex, age, parent residence), feeding, anthropometry and clinical signs at admission. Anthropometry was daily measured. The child age was determined using date of birth recorded from its mother pregnancy card and date of admission. Weight was measured in kg using recommended scale with a precision of 0.1 kg (100 g). Length of less than 2 years old child was measured in centimeters using length board (horizontal infantometer) with a precision 0.1 cm (1 mm) and height of 2 years or older child able to stand was measured in cm using height board (vertical stadiometer) with a precision 0.1 cm (1 mm). If the child was not able to stand for any reason, length was measured using length board and subtract 0.7 cm to convert in to height.
Oedema of both feet was automatically considered as severely malnourished case.
Mid-upper arm circumference (MUAC) (cm) was recorded for completed 3 months children.
After discharge, a monthly visit was organized for children.
2.6. Laboratory Analyses
Anti body test and PCR for HIV diagnosis were performed for all children at Ouagadougou pediatric hospital laboratory.
2.7. Study Outcomes
The study aimed to analyze the impact of HIV/AIDS mortality rate and nutritional recovery, during nutritional rehabilitation among severely malnourished HIV-infected and uninfected children, before starting antiretroviral treatment.
2.8. Statistical Analyses
Usual statistics methods were applied. We used Pearson’s Chi square test or Fisher’s exact test to compare proportions; and Student’s independent t-test to compare means. General linear model has been used to analyze repeated measurements. Mortality relatives risks with confidence interval (CI 95%) have been calculated to estimate the impact of HIV on mortality rate. KaplanMeir survival curves and Cox proportional hazard models has been used to investigate the impact of HIV infection on mortality rate.
The following lower and upper standard deviation (SD) boundaries have been used: WHZ (−4, +6), HAZ (−6, +6) and WAZ (−6, +6). Weight gain was calculated as g/kg/day.
The data were analyzed using SPSS software version 20.
3. RESULTS
During the considered period, SAM community-based treatment approach with ready-to-use therapeutic foods was not common. Children were addressed from rural facilities to feeding therapeutics centers. We tested HIV status of 521 admitted severely malnourished children, 73 (14.0%) was HIV/AIDS infected (not prevalence, as testing was not systematic for all SAM children).
The proportion of HIV/AIDS infected children did not differ between sex categories (% male HIV infected = 14.30, and % of female HIV infected = 13.60, p = 0.81) and between age categories (% 0 - 11 mo HIV infected = 13.80; % 12 - 23 mo HIV infected = 13.30; % 24 - 35 mo HIV infected = 18.10, % >35 mo HIV infected = 6.70, p = 0.40).
At admission, WHZ, WAZ and MUAC means differed significantly between HIV/AIDS infected and uninfected SAM children (Table 1).
Case fatality rate differed significantly from SAM HIV uninfected (10.7%) and HIV infected children (39.7%), p < 0.001. Mortality relative risk was 3.71, 95% IC [2.51 - 5.47] for HIV infected children. Kaplan Meir
Table 1. HIV infected and uninfected children anthropometry at admission to the therapeutic feeding center.
survival curves differed significantly between the two groups, (p Log Rank < 0.001) (Figure 1).
From Cox regression, variables for adjustment were: HIV status, age categories, admission WHZ categories, admission WAZ categories and admission MUAC categories. Variables entered step by step using backward stepwise (p for entry = 0.05); variables in the equation at step 3 were: HIV status, admission WHZ categories and admission MUAC categories.
Adjusted mortality relative risk of HIV infected children was 4.27, CI: 2.55 - 7.15, Wald Chi square p-value < 0.001) (Tables 2(a) and (b)).
At discharge, mean weight gain (g/kg/d) differed significantly between infected children (weight gain = 4.64 (2.82)) and uninfected children (weight gain = 9.04 (5.04)), p < 0.001.
From admission to discharge, anthropometric Z-scores means evolution differed significantly between HIV infected and uninfected children and within each group’s subjects: WHZ (between group: p < 0.001; within subject: p < 0.001), WAZ (between group: p < 0.001; within subject: p < 0.001) (Figures 2 (a) and (b)).
4. DISCUSSION
The study aimed to analyze the impact of HIV/AIDS mortality rate and nutritional recovery during nutritional rehabilitation among severely malnourished HIV-infected and uninfected children, before starting antiretroviral treatment.
From the 521 severely malnourished children tested, 14.0% was HIV/AIDS infected and their mother HIV status was unknown. According to 2010 UNAIDS statistics, in low and middle-income countries, 35% of pregnant women received HIV testing and 48% received ART for preventing mother-to-child transmission. HIV infection undermines nutritional status by metabolic changes. In this study, intra hospital mortality rate was
(a) 
(b)
Table 2. (a) Univariate mortality analysis and Cox proportional hazard model; (b) Cox proportional hazard model.
approximately four times higher in severely malnourished HIV-infected children (39.7%) than in non-infected children (10.7%); and mortality relative risk was 3.71 times higher for HIV infected children. Authors reported excess mortality risk associated to HIV infection among malnourished children [14-16].
(a)
(b)
Figure 2. (a) and (b) From admission to discharge anthropometric Z-scores means evolution within each group subjects and between groups.
Many of the metabolic responses are described in severe malnutrition, but the responses in HIV-infected severely malnourished children are unknown [17]. Both severely malnourished uninfected and HIV infected children present co-morbidity [14] but may have deferent treatment, due to complex pathophysiological, metabolic, and pharmacological interactions.
Multiples infections and metabolic complications have synergism on death occurrence in sever acute malnutrition [18]. When associated to HIV infection, case fatality rate increases many times [19]. The challenge is great in the first week of the intra hospital treatment of SAM HIV infected children, as death occurred largely during this period. HIV infected children metabolic changes and nutrients can lead to death and needs must be considered in therapeutic and care guidelines.
In our study, at discharge, mean weight gain (g/kg/d) anthropometric Z-scores means evolution, differed significantly between HIV infected and uninfected severely children. Weight gain and anthropometric index evolution were very slow for SAM HIV infected children. In SAM HIV infected children, anorexia remaining common and specific diet is may be needed for more nutritional recovery. Young HIV-infected severely malnourished children, perinatally infected with HIV may have poor response to management as set out in current guidelines.
Antiretroviral therapy (ART) becomes increasingly available globally in the world, not in all the low incomes countries. The impact of highly active antiretroviral therapy on HIV infected children survival becomes evident [20]. In the context of delay to ART initiation for children admitted in feeding therapeutic centers or in rural facilities. Evidence of ART role on improving nutritional status is clearer. Due to delay (diagnosis, procedures, socio-cultural context), initiation to ART for SAM HIV infected cannot be before several weeks. There is no evidence on efficacy and impact on mortality rate to start ART immediately or after stabilization phase or rehabilitation phase. Optimum timing of ART initiation remains a challenge [21].
5. CONCLUSION
Effective interventions, updated and adapting to local country context to improve survival of severely malnourished HIV/AIDS infected children in HIV and SAM prevalent settings are urgently needed.
6. ACKNOWLEDGEMENTS
Commission Universitaire pour le Développement (CUD), Belgium, laboratory analysis, medicines for opportunistic diseases.