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Journal of Epidemiology and Global Health logoLink to Journal of Epidemiology and Global Health
. 2024 Nov 14;14(4):1453–1463. doi: 10.1007/s44197-024-00321-6

The Impact of Undernutrition and Anemia on HIV-Related Mortality Among Children on ART in Sub-Saharan Africa: A Systematic Review and Meta-Analysis

Sisay Moges 1,, Bereket Aberham Lajore 1, Abera Feyisa Oleba 2, Abraham Samuel Godebo 3, Mengistu Lodebo Funga 4
PMCID: PMC11652469  PMID: 39541033

Abstract

Background

Although there have been significant advancements in providing HIV-infected children with access to antiretroviral therapy (ART), the mortality rates have remained unacceptably high. Inadequate nutrient intake or absorption is a widespread problem in several African nations, resulting in undernutrition and anemia. However, the pooled effect of malnutrition and anemia on HIV-related death related to children receiving ART was not investigated in sub-Saharan Africa.

Methods

We searched multiple electronic databases (PubMed/MEDLINE, Embase, CINAHL, and Web of Science) for observational studies published between January 1, 2010, and April 24, 2024 that reported the risk factors or effects of undernutrition and, anemia on HIV-related mortality among children. Study selection, data extraction, and quality evaluation were carried out separately by two reviewers. A meta-analysis was conducted using random effect models.

Results

The review included 27 studies with a combined total of 61,796 study participants. The study findings showed that severe wasting (HR: 2.49; 95% CI: 1.87–3.30), being underweight (HR: 2.11; 95% CI: 1.64–2.72), and Anemia (HR: 2.58; 95% CI: 2.08–3.19) were highly linked to HIV-related death among children. The risk of death due to anemia was greater among children under the age of 5 years than older children.

Conclusion

Undernutrition and anemia in sub-Saharan African children increased the risk of HIV-related death. The impact of malnutrition and anemia among under 5 years old children with HIV/AIDS was more pronounced, suggesting that these conditions at this early age can have more serious consequences for a child’s survival. The importance of combining nutrition with HIV treatment programs in sub-Saharan African countries is crucial.

Keywords: Effect of undernutrition, Effect of anemia, Risk factor for HIV mortality, Children, Sub-saharan Africa

Background

The HIV/AIDS epidemic continues to be a significant public health challenge in sub-Saharan Africa, with children being particularly vulnerable to its impacts [1]. Although there has been significant advancement in providing HIV-infected children in this area with access to antiretroviral therapy (ART), the mortality rates have remained unacceptably high [2]. According to the World Health Organization (WHO), in the African region, an estimated 1.3 million children aged 0–14 were living with HIV at the end of 2022, and approximately 69,000 children died of AIDS-related illnesses [3]; a mortality rate of 7.9% was reported in sub-Saharan African countries [4]. Although ART has greatly increased the survival rates and quality of life of HIV-infected individuals, its effectiveness in children is frequently impacted by factors such as undernutrition and anemia [5].

Inadequate nutrient intake or absorption is a widespread problem in several African nations, resulting in undernutrition and anemia [6]. Undernutrition in the presence of HIV can worsen the disease, weaken the immune system, and decrease the effectiveness of antiretroviral medications [7]. The complex interplay between HIV and undernutrition forms a harmful cycle, with each condition worsening the effects of the other, possibly resulting in higher rates of illness and death [8, 9]. However, malnutrition and anemia are not the sole causes of HIV-related mortality among children but serve as critical markers in a complex interplay of factors. They indicate underlying vulnerabilities, such as weakened immune systems and poor overall health, which make children more susceptible to opportunistic infections and hinder their response to antiretroviral therapy (ART) [1012]. This interplay involves co-existing infections, delayed ART initiation, and inadequate healthcare access, all contributing to higher mortality risks [13, 14]. While malnutrition and anemia reflect these broader issues, they are part of a multifaceted web of clinical and socio-economic factors driving poor health outcomes in HIV-infected children. Anemia, a frequent coexisting condition in children with HIV, is defined by a lower amount of hemoglobin in the bloodstream, which can lead to tiredness, lack of strength, and decreased cognitive abilities [15, 16]. Anemia in HIV-infected children has diverse causes, including decreased red blood cell production, increased rates of blood cell destruction, and a lack of nutrients [17, 18].

Previous studies in Africa have inconsistent across different settings. For example studies, such as [13, 19, 20], reported a non-significant association between malnutrition and HIV-related mortality among children, while others found a significant link, highlighting the variability in outcomes across different settings [2123]. Similarly, for anemia, certain studies [24, 25] observed no significant association with mortality, whereas others demonstrated a strong correlation between anemia and increased risk of death in children with HIV [21, 22]. These mixed findings emphasize the need to interpret the results within the specific contexts and populations studied. Nevertheless, it is uncertain how applicable these results are to the wider sub-Saharan African setting and how they specifically relate to children receiving ART. This issue becomes more complex due to the socioeconomic conditions in sub-Saharan Africa. Poverty, lack of food, and restricted healthcare access are common issues that can worsen undernourishment and anemia and make managing HIV difficult [26, 27]. Therefore, this review.provide valuable insights into the role of malnutrition and anemia in HIV-related mortality among children, highlighting key knowledge gaps and guiding evidence-based interventions and policies. The findings have the potential to inform clinical practice, support program development, and shape policy creation in this critical area of child health.

Methods and Materials

Eligibility Criteria

Studies were included based on predefined criteria regarding population, comparators, outcomes, study design, settings, period, and language. The target population comprised HIV-infected children (aged 0–15 years) receiving ART, and studies must have included participants from one or more countries in sub-Saharan Africa. Undernutrition, including wasting and underweight, as well as anemia (hemoglobin < 10 g/dL), were considered key exposure factors. The primary outcome was all-cause mortality, used to assess and compare the risk of death associated with these specific exposures. The eligible studies included retrospective cohort, case-control, and cross-sectional studies. Moreover, theses and dissertations were also included. Studies involving both study participants with TB and HIV infection simultaneously, single case reports, case series, reviews, commentaries, editorials, studies not reporting the association between malnutriton and/or anemia with HIV related mortality, and studies with insufficient data to calculate effect estimates were excluded. Studies carried out in countries in sub-Saharan Africa after 2010 until now and released in the English language were included. Furthermore, any studies that could not be accessed after two attempts at communication with the main author or corresponding author were also not included in the review. The inclusion and exclusion criteria aimed to pinpoint important and high-quality research focused on risk factors in pediatric patients with HIV infection.

Search Strategy and Information Sources

We searched multiple electronic databases such as PubMed/MEDLINE, Hinari CINAHL, Embase, Google Scholar, African Journals Online (AJOL), OpenGray and Science Direct databases for peer-reviewed articles published from January 1, 2010, to April 24, 2024. We selected the period from January 2010 to April 24, 2024, because 2010 marks the introduction of more robust and effective ART combinations by the WHO, along with a significant shift in treatment strategies. Furthermore, prospective articles of interest were manually searched through the reference lists of eligible studies. Two authors (SM and BAL) independently searched. The search strategy was developed in consultation with a medical librarian and will include a combination of Medical Subject Headings (MeSH) terms and free-text keywords. The search terms were grouped into four main categories: 1) population: HIV-infected children; 2) exposure: undernutrition and anemia; 3) outcome: mortality; and 4) setting: sub-Saharan Africa. The following keywords were used: HIV/AIDS; death OR survival; predictor OR associated factor OR risk factors; OR determinants; effect of undernutrition; effect of anemia; antiretroviral therapy OR ART; pediatrics OR children; under five years OR 15 years [African countries]. Methodological terms such as prospective, retrospective, cohort, and cross-sectional studies were also included. Using Boolean operators (AND, OR), these keywords were combined to generate extensive search strings that will find pertinent research in a variety of databases. For example, the following search strategy was employed in the PubMed database: (HIV[MeSH] OR HIV Infections [MeSH] OR HIV [tiab] OR Human Immunodeficiency Virus[tiab] OR AIDS [tiab]) AND (Child[MeSH] OR Pediatrics[MeSH] OR Child * [tiab] OR Pediatric* [tiab] OR Pediatrics* [tiab]) AND (Malnutrition[MeSH] OR Nutritional Status [MeSH] OR Anemia [MeSH] OR Malnutrition [tiab] OR Undernutrition[tiab] OR Nutritional Deficiency* [tiab] OR Anemia [tiab] OR Anemia[tiab]) AND (Mortality[MeSH] OR Death[MeSH] OR Mortality* [tiab] OR Death* [tiab] OR Survival [tiab]) AND (Antiretroviral Therapy, Highly Active [MeSH] OR Anti-Retroviral Agents[MeSH] OR Antiretroviral Therapy* [tiab] OR ART [tiab] OR HAART[tiab]) AND (Africa South of the Sahara” [MeSH] OR Sub-Saharan Africa* [tiab] OR names of individual sub-Saharan African countries). The retrieved studies were imported and managed using EndNote XX reference management software. The search was conducted between January 2024 and April 2024 to identify potentially eligible studies for the systematic review and meta-analysis. This search strategy will be adapted for use in other databases, taking into account their specific indexing systems and search functionalities.

Screen and Selection Process

The screening and selection of studies followed systematic and rigorous approaches. Two reviewers (SM and BAL) independently reviewed the titles and abstracts of all retrieved records from the databases and manually searched them against the predefined eligibility criteria. All identified articles were entered into the EndNote XX database, and any duplicated entries were eliminated. Documentation of the reasons for exclusion was completed at this point. Any discrepancies or disagreements in selection between the two reviewers were resolved through discussion and consensus.

Risk of Bias and Quality Assessment

The risk of bias and quality of the studies included in our review were meticulously evaluated by two independent reviewers utilizing the Newcastle‒Ottawa Scale (NOS) [21] for observational studies. The NOS assesses the risk of bias in three domains, including the selection of the study groups, the comparability of the groups, and the ascertainment of the outcome of interest. The NOS framework allows for a comprehensive assessment, allocating up to four stars for ‘Selection,’ two for ‘Comparability,’ and three for ‘Outcome’ categories. The results are presented in the ‘Summary of Findings’ table.

Data Extraction

A Microsoft Excel spreadsheet was used for data extraction. Two authors (SM and BAL) independently extracted data from the included studies using a predefined checklist. The following data were extracted from each primary study: first author’s name, publication year, study country, and sample size. To ensure consistency in the data extraction process, both reviewers independently extracted data from the first three eligible articles. Any discrepancies or disagreements in selection between the two reviewers were resolved through discussion and consensus. Subsequently, they met to compare results, clarify any discrepancies, and refine the abstraction form if necessary. After this initial calibration, one reviewer extracted data from the remaining articles, and the second reviewer verified the extracted information.

Outcome Variables and Effect Measures

This research focused on the pooled impact of severely wasting, underweight and anemia on HIV related mortality, as documented in primary studies among children on ART in sub-Saharan African nations. Severe wasting is defined as a weight for height (WHZ) measurement of < -3 SD, underweight is defined as a weight for age (WHZ) measurement of < -2 SD [28], and anemia is defined as a hemoglobin level of less than 10 g/dl [29]. The hazard ratio (HR) was a suitable measure of effect for our study. A random-effects model was used to combine the mortality risk for each selected exposure variable from various studies, taking into account potential heterogeneity between the studies.

Data Synthesis and Analysis

A narrative synthesis summarized the study characteristics, populations, study countries, outcome assessments, and key findings. A meta-analysis was conducted using Stata software version 17 to estimate the role of undernutrition and anemia on HIV-related mortality. The hazard ratios (HRs) with 95% confidence intervals (CIs) were computed. Hazard ratio (HRs) from primary studies were log-transformed (logHR) to obtain the effect sizes and corresponding standard errors. Forest plots visually display the pooled estimates. Heterogeneity was assessed using Cochran’s Q statistic, the I2 statistic, and the chi-square test (P < 0.05). Heterogeneity levels were classified as low (I2: 0–25%), moderate (I2: 25–50%), or high (I2: ≥50%) [30, 31]. The DerSimonian‒Laird method was used to estimate variance in random effects models. Subgroup analyses explored potential sources of heterogeneity, considering study countries and study participant age. The report is presented in the text, tables and figures.

Results and Discussion

Selection of Studies

A comprehensive literature search across multiple databases yielded 275 relevant publications: 101 from PubMed, 86 from Google Scholar, and 78 from other sources. After removing duplicates and screening titles, 152 articles were excluded. Review of 81 abstracts led to the exclusion of 42 more. A full-text assessment of the remaining studies, focusing on predictors of mortality in children under 15, resulted in 27 articles meeting eligibility criteria. Twenty-four studies were excluded due to missing outcomes or data. Finally, 29 studies were included in the systematic review and meta-analysis. The selection process, guided by a PRISMA flow diagram, involved several stages of refinement [32] (Fig. 1).

Fig. 1.

Fig. 1

PRISMA flow diagram of the selection of studies, a systematic review of the role of malnutrition and anemia on mortality among Children on ART in sub-Saharan Africa

Characteristics of the Studies

This systematic review included 27 studies that were conducted across various sub-Saharan African countries between 2010 and the present(2024) and involved a total of 61,796 patients. All studies employed a retrospective cohort design. This review analyzed the impact of severe wasting in 15 studies, underweight in 8 studies and, anemia in 22 studies on HIV mortality. The reviewed studies encompassed a diverse range of sub-Saharan African countries. Ethiopia was the most represented, with 20 studies [10, 13, 2025, 3344], two from Kenya [12, 14], and one from South Africa [45]; multicounty studies were also included: one encompassing Malawi, Uganda, and Kenya [46]; another covering Malawi, South Africa, Zambia, and Zimbabwe [47]; and single-country studies conducted in Cote d’Ivoire [48], Tanzania [49], the Democratic Republic of Congo (DRC) [50], Nigeria [51], and Zimbabwe [52] (Table 1).

Table 1.

Characteristics of the studies included in the review, a systematic review of the role of malnutrition and anemia on mortality among children on ART in sub-saharan Africa

Authors Study participants outcome variables assessed Country Sample size
Ebissa et al., 2015 [40] < 5 years Sever wasting & Anemia Ethiopia 556
Koye et al., 2012 [43] < 5 years Sever wasting Ethiopia 549
Chekole et al., 2022 [39] < 15 years Sever wasting & Anemia Ethiopia 588
Ebonyi et al., 2014 [19] < 15 years Sever wasting Nigeria 691
Bitew et al., 2017 [24] < 15 years Sever wasting & Anemia Ethiopia 228
Mekonnen et al., 2023 [23] < 5 years Sever wasting & Anemia Ethiopia 415
Alebel et al., 2020 [21] < 15 years Sever wasting & Anemia Ethiopia 553
Tagesse & Abebe, 2020 [44] < 15 years Sever wasting Ethiopia 410
Adem et al., 2014 [33] < 15 years Underweight & Anemia Ethiopia 560
Abrams et al., 2017 [45] < 5 years Sever wasting South African 272
Mulugeta et al., 2017 [10] < 15 years Anemia Ethiopia 757
Auld et al., 2014 [48] < 15 years Anemia Cote d’Ivoire’ 2110
Ben-Farhat et al., 2017 [46] < 15 years Under weight Malawi, Uganda and Kenya 3949
Sidamo et al., 2017 [13] < 15 years Sever wasting & Anemia Ethiopia 421
Marie et al., 2022 [22] < 5 years Sever wasting Ethiopia 376
Davies et al., 2014 [47] < 15 years Underweight & Anemia Malawi, South Africa, Zambia & Zimbabwe 12,655
McHugh et al., 2017 [52] < 15 years Sever wasting Zimbabwe 385
Biyazin et al., 2022 [38] < 15 years Sever wasting & Anemia Ethiopia 251
Nyandiko et al., 2022 [12] < 15 years Under weight Kenya 6234
Gebremedhin et al., 2013 [42] < 15 years Anemia Ethiopia 432
Arage et al., 2019 [36] < 5 years Sever wasting Ethiopia 426
Mwiru et al., 2015 [49] < 15 years Sever wasting & Anemia Tanzania 3144
Andargie & Asmleash, 2018 [35] < 15 years Anemia Ethiopia 269
Oumer et al., 2019 [25] < 15 years Underweight & Anemia Ethiopia 243
Molla et al., 2022 [20] < 15 years Sever wasting, Underweight & Anemia Ethiopia 721
Nugent et al., 2014 [50] < 15 years Underweight & Anemia DRC 1010
Alemu et al., 2022 [34] < 5 years Anemia Ethiopia 415

Quality Assessment and Risk of Bias

Two independent reviewers evaluated the risk of bias in the included studies using the Newcastle‒Ottawa Scale (NOS) for observational studies [53]. The NOS rates research based on three areas selection (up to 4 stars), comparability (up to 2 stars), and outcome (up to 3 stars)—for a total maximum score of 9 stars. High NOS scores indicate stronger methodological quality, with better control for biases such as selection and confounding. In terms of the selection area, the majority of research papers received a rating of 3 out of 4 stars, showing overall satisfactory representativeness and selection methods. Nevertheless, certain studies, such as the one by Ebissa et al. [40], received a lower rating (2 stars) because of possible selection bias, which could impact the representativeness of the study population, indicating potential problems with sample selection or representativeness. Studies with a 3-star rating, such as Koye et al. [43] and Alebel et al. [21], likely had stronger methods for assessing outcomes and, longer tracking periods, whereas some studies [10, 13, 22, 24, 36, 40, 42, 44, 49] were given 2 stars, suggesting varying measurements of outcomes, particularly for anemia. In general, most studies were deemed high quality, receiving a score of 7 stars or higher.

The Association Between Severe Wasting and HIV-Related Mortality

The impact of severe wasting was assessed in 15 studies involving 9,162 participants. A random-effects meta-analysis was conducted due to moderate heterogeneity (I²=44.16%), showing that severe wasting was associated with more than a twofold increase in the risk of HIV-related death (HR: 2.49; 95% CI: 1.87–3.30). Subgroup analysis by age revealed a higher risk of mortality for children under 5 years (HR: 3.40) compared to those under 15 years (HR: 2.17). Country-based subgroup analysis indicated the greatest effect size in Tanzania (HR: 3.36), followed by Ethiopia (HR: 2.80) and South Africa (HR: 2.43). However, Kenya, Nigeria, and Zimbabwe showed nonsignificant effect sizes. Meta-regression showed that sample size did not significantly influence the pooled estimate (P = 0.57), suggesting that heterogeneity was mainly due to age and country differences. Publication bias was assessed through a funnel plot, Begg’s test, and Egger’s test. The funnel plot indicated some studies outside the 95% CI, but with both positive and negative effect sizes. Begg’s and Egger’s tests suggested the presence of publication bias, with p-values < 0.05, indicating small study effects and potential bias (Fig. 2).

Fig. 2.

Fig. 2

The association between severe wasting and HIV-related mortality, a systematic review of the role of malnutrition and anemia on mortality among Children on ART in sub-Saharan Africa

The Association Between Underweight and HIV-Related Mortality

The association between underweight and HIV-related mortality was evaluated in 8 studies [12, 20, 25, 33, 37, 46, 47, 50] involving 1,010 participants. A random-effects meta-analysis was used due to heterogeneity (I²=58.54%). The analysis showed that underweight children had a twofold increased risk of HIV-related mortality (HR: 2.11; 95% CI: 1.64–2.72) (Fig. 3). Subgroup analysis revealed the highest effect in multicounty studies from Malawi, South Africa, Zambia, and Zimbabwe, followed by other regions. Meta-regression showed no significant effect of sample size (P = 0.126). Publication bias was not indicated by the funnel plot, Begg’s test (P = 0.6398), or Egger’s test (P = 0.9015), showing no evidence of small-study effects or bias.

Fig. 3.

Fig. 3

Effect of underweight on HIV-related mortality, a systematic review of the role of malnutrition and anemia on mortality among Children on ART in sub-Saharan Africa

The Association Between of Anemia and HIV Related Mortality

Anemia was analyzed in 22 studies involving 26,842 participants using a random-effects model due to significant heterogeneity (I²=53.72%). The analysis revealed that children with anemia had more than twice the risk of mortality (HR: 2.58; 95% CI: 2.08–3.19) (Fig. 4). Subgroup analysis showed a higher risk of death in children under 5 years (HR: 3.31) compared to those under 15 years (HR: 2.45). The largest effect was reported in Kenya (HR: 3.00), followed by Côte d’Ivoire (HR: 2.95) and Ethiopia (HR: 2.83). Meta-regression indicated that smaller sample sizes significantly increased the pooled estimate of mortality risk (P = 0.002). Publication bias was assessed through a funnel plot, Begg’s test, and Egger’s test. The funnel plot suggested minimal risk of bias, although a few studies fell outside the 95% CI. Egger’s test indicated publication bias (P = 0.0000), while Begg’s test did not show statistical significance (P = 0.2363). Since Egger’s test has greater power, it suggests the presence of some publication bias despite Begg’s test showing otherwise.

Fig. 4.

Fig. 4

The association between anemia and HIV-related mortality, a systematic review of the role of malnutrition and anemia on mortality among Children on ART in sub-Saharan Africa

Discussion

The review indicated that undernutrition, such as severe wasting and underweight, as well as anemia, was a significant predictor of HIV-related mortality among children. The present analysis revealed a significant association between severe wasting and an increased risk of HIV-related mortality among children on ART in Africa, with a hazard ratio (HR) of 2.49 (95% CI: 1.87–3.30), and underweight, with a twofold increased risk of death (95% CI: 1.64–2.72). These findings underscore the critical impact of malnutrition on the survival of HIV-infected children, especially those under five years old. Several studies corroborate these findings. For instance, a study conducted in India [54] and other countries [55] revealed that severe wasting significantly increased the risk of mortality in HIV-infected children. Similarly, this finding is supported by evidence from East Africa [56], where the pooled prevalence of underweight among HIV-positive children was 41.63%. Malnutrition can be linked to increased HIV-related mortality due to its negative effects on the immune system, treatment effectiveness, and vulnerability to infections. Children who are extremely malnourished and thin typically have a weakened immune system, which hinders their ability to effectively fight viruses and heal from infections [7, 57, 58]. These consistent results highlight the universal impact of malnutrition on the mortality of HIV-infected children, regardless of geographic location. The study’s findings underscore the significant role of malnutrition in increasing HIV-related mortality among children in sub-Saharan Africa, particularly through severe wasting and underweight. Malnutrition compromises the immune system, making HIV-infected children more vulnerable to opportunistic infections and reducing the effectiveness of antiretroviral therapy (ART). This indicates that the challenges of providing malnutrition care among HIV-infected children receiving antiretroviral treatment in Africa are still critical issues, as malnutrition can affect the immunity of the affected children [59]. The context of undernutrition in HIV-infected children is often exacerbated by poverty, food insecurity, and limited healthcare access, all of which make it difficult to provide the necessary nutritional support. Current interventions, such as nutritional rehabilitation and supplementation, integrated with ART, have shown promise in improving survival outcomes [60]. However, challenges in scaling these interventions persist, particularly in rural areas [61]. Further research is required to assess the long-term benefits of integrating nutritional care into routine HIV treatment and to identify the most effective strategies for combating malnutrition in these vulnerable populations.

The current study showed that anemia was a strong indicator of HIV-related death in children, and the risk of death was 2.5 times greater in HIV-infected children with baseline hemoglobin levels less than 10 g/dl than in those with hemoglobin levels greater than or equal to 10 g/dl (HR: 2.52; 95% CI: 2.08–3.19). Studies from multiple centers in Europe have confirmed this discovery [62]. Furthermore, consistent with this report, previous reviews [63, 64] revealed that children with HIV infection who also had anemia had a doubled chance of dying. Anemia is common during the course of HIV infection. This condition further weakens the body’s ability to fight infections, complicating HIV management and worsening health outcomes. In the context of HIV treatment, anemia makes it more difficult for children to recover and respond to ART, increasing the likelihood of poor survival outcomes [29]. It may result directly from being infected with HIV, or it could be caused by nutritional deficiencies, other infections such as systemic fungal and mycobacterium infections, and opportunistic diseases such as lymphoma. Moreover, adverse reactions to antiretrovirals and other drugs can inhibit bone marrow function, causing anemia, thrombocytopenia, and leukopenia [16, 65]. This makes it more difficult for HIV-positive children to survive while receiving antiretroviral therapy (ART). Furthermore, the results show that younger children, especially those under five years old, face a much greater chance of death when suffering from severe malnourishment or anemia. One possible explanation is that younger children have weaker immune systems than older children, making them more vulnerable to the combined impact of HIV, malnutrition, and anemia. The initial five years of life are critical for both physical and cognitive growth [66]. Malnutrition and anemia during this period can have more severe and lasting impacts on a child’s overall health and survival. Therefore, studies should explore the role of micronutrient supplementation and anemia treatment in improving survival outcomes. There is also a pressing need to understand the socioeconomic barriers that prevent malnourished HIV-positive children from receiving comprehensive care. Addressing these gaps will be key to improving the survival and quality of life for children living with HIV in sub-Saharan Africa.

Limitation of the Study

This review is limited to certain forms of malnutrition, such as severe wasting and undernutrition, while the impact of stunting on HIV-related mortality was not included, potentially reducing the comprehensiveness of the findings. Additionally, since all the included studies were observational, establishing a causal relationship between malnutrition, anemia, and mortality remains challenging.

Conclusion

This comprehensive analysis, which examined 27 studies in sub-Saharan Africa, offers compelling evidence of the impact of malnutrition and anemia on HIV-related death in children. According to the analysis, severe malnutrition and underweight status had a notable impact on HIV-related death rates. Additionally, anemia was found to be a key factor in predicting HIV-related deaths. Young children under 5 years old were at greater risk of death, showing that malnutrition and anemia during this time could have longer-lasting and more severe consequences on a child’s health and chances of survival. Therefore, the significant link between nutritional status and HIV-related death highlights the importance of combined nutrition and HIV treatment programs in sub-Saharan African countries. Policies should emphasize nutritional support in HIV treatment plans, especially for children under five years of age. Furthermore, health resources need to be used to address both HIV treatment and nutritional support.

Acknowledgements

Not applicable.

Author Contributions

SM, AFG, AFO and BAL were responsible for developing the protocol and were involved in various aspects of the study, including designing the study, selecting the eligible studies, SM and BAL involved extracting the data, and performing the statistical analyses, MLF contributed to drafting the initial versions of the manuscript and revising the manuscript. SM prepared and edited the final draft of the manuscript, which was subsequently read and approved by the all author.

Funding

Not applicable.

Data Availability

All the data analyzed during this study are included in this published article.

Declarations

Ethics Approval and Consent to Participate

This section is not applicable because it was conducted using secondary data.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Footnotes

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  • 1.Enane LA, et al. Traversing the cascade: urgent research priorities for implementing the ‘treat all’strategy for children and adolescents living with HIV in sub-saharan Africa. J Virus Eradication. 2018;4:40–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Sartorius B, et al. Subnational mapping of HIV incidence and mortality among individuals aged 15–49 years in sub-saharan Africa, 2000–18: a modelling study. Lancet HIV. 2021;8(6):e363–75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.World health Organization(WHO). HIV/AIDS WHO Africa Report. 2023 [cited 2024 April 22]; https://www.afro.who.int/health-topics/hivaids#:~:text=Treatment%20and%20care%20in%20children,died%20of%20AIDS%2Drelated%20illnesses
  • 4.Ahmed I, Lemma S. Mortality among pediatric patients on HIV treatment in sub-saharan African countries: a systematic review and meta-analysis. BMC Public Health. 2019;19(1):149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Muenchhoff M, et al. Malnutrition in HIV-infected children is an indicator of severe disease with an impaired response to antiretroviral therapy. AIDS Res Hum Retroviruses. 2018;34(1):46–55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Elmighrabi NF, et al. A systematic review and meta-analysis of the prevalence of childhood undernutrition in North Africa. PLoS ONE. 2023;18(4):e0283685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Fuseini H, et al. Undernutrition and HIV infection in sub-saharan Africa: health outcomes and therapeutic interventions. Curr HIV/AIDS Rep. 2021;18:87–97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Thimmapuram R, et al. Correlation of nutrition with immune status in human immunodeficiency virus outpatients. Mo Med. 2019;116(4):336. [PMC free article] [PubMed] [Google Scholar]
  • 9.Sashindran VK, Thakur R. Malnutrition in HIV/AIDS: aetiopathogenesis. Nutrition and HIV/AIDS-Implication for treatment. Prevention and Cure [series online]; 2020.
  • 10.Mulugeta A, et al. Determinants of survival among HIV positive children on antiretroviral therapy in public hospitals, Addis Ababa, Ethiopia. Qual Prim Care. 2017;25(4):235–41. [Google Scholar]
  • 11.Nlend AEN, Loussikila AB. Predictors of mortality among HIV-infected children receiving highly active antiretroviral therapy. Med et maladies Infectieuses. 2017;47(1):32–7. [DOI] [PubMed] [Google Scholar]
  • 12.Nyandiko W et al. Predictors of mortality among children and adolescents living with HIV on Antiretroviral Therapy in Western Kenya. JAIDS J Acquir Immune Defic Syndr, 2022: pp. 10–1097. [DOI] [PMC free article] [PubMed]
  • 13.Sidamo N et al. Incidence and predictors of mortality among children on anti-retroviral therapy in public health facilities of Arba Minch town, Gamo Gofa Zone, southern Ethiopia; retrospective cohort study. Clin Mother Child Health. 2017;14(3).
  • 14.Wamalwa DC, et al. Predictors of mortality in HIV-1 infected children on antiretroviral therapy in Kenya: a prospective cohort. BMC Pediatr. 2010;10(1):33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Cao G et al. Prevalence of anemia among people living with HIV: a systematic review and meta-analysis. EClinicalMedicine 2022;44. [DOI] [PMC free article] [PubMed]
  • 16.Obeagu EI, Obeagu GU. Anemia in HIV: The Role of Erythropoietin in Disease Progression. Elite Journal of Haematology, 2024;2(4):51–67.
  • 17.Wagnew F, et al. Burden of anemia and its association with HAART in HIV infected children in Ethiopia: a systematic review and meta-analysis. BMC Infect Dis. 2019;19:1–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Duffy C, et al. Multiple concurrent illnesses associated with anemia in HIV-infected and HIV-exposed uninfected children aged 6–59 months, hospitalized in Mozambique. Am J Trop Med Hyg. 2020;102(3):605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Ebonyi AO et al. Predictors of mortality in a clinic cohort of HIV-1 infected children initiated on antiretroviral therapy in Jos. Nigeria J AIDS Clin Res. 2014;5(12). [DOI] [PMC free article] [PubMed]
  • 20.Molla M, et al. Effects of Undernutrition and predictors on the Survival Status of HIV-Positive children after started antiretroviral therapy (ART) in Northwest Ethiopia. Int J Pediatr. 2022;2022(1):1046220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Alebel A, et al. Mortality rate among HIV-positive children on ART in Northwest Ethiopia: a historical cohort study. BMC Public Health. 2020;20(1):1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Marie BT, Argaw WS, Bazezew BY. Time to death among HIV-infected under-five children after initiation of anti-retroviral therapy and its predictors in Oromiya Liyu Zone, Amhara region, Ethiopia: a retrospective cohort study. BMC Pediatr. 2022;22:1–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Mekonnen E, et al. Time to death and its predictors among under-five children on antiretroviral treatment in public hospitals of Addis Ababa, Addis Ababa, Ethiopia, a retrospective follow up study. PLoS ONE. 2023;18(7):e0288475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Bitew S, Mekonen A, Assegid M. Predictors on mortality of human immunodeficiency virus infected children after initiation of antiretroviral treatment in Wolaita Zone health facilities, Ethiopia: retrospective cohort study. J AIDS HIV Res. 2017;9(4):89–97. [Google Scholar]
  • 25.Oumer A, Kubsa ME, Mekonnen BA. Malnutrition as predictor of survival from anti-retroviral treatment among children living with HIV/AIDS in Southwest Ethiopia: survival analysis. BMC Pediatr. 2019;19:1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Shimanda PP, Amukugo HJ, Norström F. Socioeconomic factors associated with anemia among children aged 6–59 months in Namibia. J Public Health Afr. 2020;11(1). [DOI] [PMC free article] [PubMed]
  • 27.Yang F, Liu X, Zha P. Trends in socioeconomic inequalities and prevalence of anemia among children and nonpregnant women in low-and middle-income countries. JAMA Netw open. 2018;1(5):e182899–182899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.WHO, Assessing and Managing Children at Primary Health-Care. Facilities to prevent overweight and obesity in the context of the double burden of Malnutrition: updates for the Integrated Management of Childhood Illness (IMCI). Table 1, World Health Organization (WHO) classification of nutritional status of infants and children. World Health Organization.: Geneva; 2017. [PubMed]
  • 29.World Health Organization. Iron deficiency anemia: assessment, prevention, and control: a guide for program managers. 2001.
  • 30.Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58. [DOI] [PubMed] [Google Scholar]
  • 31.Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10(1):101–29. [Google Scholar]
  • 32.Page MJ, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg. 2021;88:105906. [DOI] [PubMed] [Google Scholar]
  • 33.Adem AK, Alem D, Girmatsion F. Factors affecting survival of HIV positive children taking antiretroviral therapy at Adama Referral Hospital and Medical College, Ethiopia. J AIDS Clin Res. 2014;5(3).
  • 34.Alemu GG, et al. Survival time and predictors of death among HIV infected under five children after initiation of anti-retroviral therapy in West Amhara Referral hospitals, Northwest Ethiopia. BMC Pediatr. 2022;22(1):670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Andargie AA, Asmleash Y. Survival time of human immunodeficiency virus (HIV) infected children under 15 years of age after initiation of antiretroviral therapy in the University of Gondar Comprehensive Specialized Hospital, Ethiopia. J AIDS HIV Res. 2018;10(4):49–55. [Google Scholar]
  • 36.Arage G, et al. Survival rate of HIV-infected children after initiation of the antiretroviral therapy and its predictors in Ethiopia: a facility-based retrospective cohort. SAGE open Med. 2019;7:2050312119838957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Belachew A. Predictors of Survival Time among children on antiretroviral therapy in Dilchora Referral Hospital. East Ethiopia: Dire Dawa; 2019. [Google Scholar]
  • 38.Biyazin Y, et al. Survival and predictors of mortality among HIV-positive children on antiretroviral therapy in public hospitals. J Pharm Policy Pract. 2022;15(1):48. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Chekole B, et al. Survival status and predictors of mortality among HIV-positive children initiated antiretroviral therapy in Bahir Dar town public health facilities Amhara region, Ethiopia, 2020. SAGE Open Med. 2022;10:20503121211069477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Ebissa G, Deyessa N, Biadgilign S. Predictors of early mortality in a cohort of HIV-infected children receiving high active antiretroviral treatment in public hospitals in Ethiopia. AIDS Care. 2015;27(6):723–30. [DOI] [PubMed] [Google Scholar]
  • 41.Edessa D, Asefa F, Sheikahmed J. Early mortality among HIV-positive children initiated anti-retroviral therapy in eastern Ethiopia: a retrospective cohort study. Sci Technol Arts Res J. 2015;4(2):157–63. [Google Scholar]
  • 42.Gebremedhin A, et al. Predictors of mortality among HIV infected children on anti-retroviral therapy in Mekelle Hospital, Northern Ethiopia: a retrospective cohort study. BMC Public Health. 2013;13:1–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Koye DN, Ayele TA, Zeleke BM. Predictors of mortality among children on antiretroviral therapy at a referral hospital, Northwest Ethiopia: a retrospective follow up study. BMC Pediatr. 2012;12(1):1–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Tagesse N, Abebe W. Predictors of Mortality in children and adolescents living with HIV on antiretroviral therapy, Ethiopia: a retrospective cohort study. Ethiop J Pediatr Child Health. 2020;15(2).
  • 45.Abrams EJ, et al. Despite access to antiretrovirals for prevention and treatment, high rates of mortality persist among HIV-infected infants and young children. Pediatr Infect Dis J. 2017;36(6):595–601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Ben-Farhat J, et al. Mortality and clinical outcomes in children treated with antiretroviral therapy in four African vertical programmes during the first decade of paediatric HIV care, 2001–2010. Tropical Med Int Health. 2017;22(3):340–50. [DOI] [PubMed] [Google Scholar]
  • 47.Davies M-A, et al. Prognosis of children with HIV-1 infection starting antiretroviral therapy in Southern Africa: a collaborative analysis of treatment programs. Pediatr Infect Dis J. 2014;33(6):608–16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Auld AF, et al. Temporal trends in mortality and loss to follow-up among children enrolled in Cote D’ivoire’s national antiretroviral therapy program. Pediatr Infect Dis J. 2014;33(11):1134–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Mwiru RS, et al. Nutritional status and other baseline predictors of mortality among HIV-infected children initiating antiretroviral therapy in Tanzania. J Int Association Providers AIDS Care (JIAPAC). 2015;14(2):172–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Nugent J, et al. Predicting mortality in HIV-infected children initiating highly active antiretroviral therapy in a resource-deprived setting. Pediatr Infect Dis J. 2014;33(11):1148–55. [DOI] [PubMed] [Google Scholar]
  • 51.Anigilaje EA, Aderibigbe SA. Mortality in a cohort of HIV-infected children: a 12‐month outcome of antiretroviral therapy in Makurdi, Nigeria. Adv Med. 2018;20181:6409134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.McHugh G et al. Clinical outcomes in children and adolescents initiating antiretroviral therapy in decentralized healthcare settings in Zimbabwe. Afr J Reprod Gynaecol Endoscopy. 2017;20(1). [DOI] [PMC free article] [PubMed]
  • 53.Herzog R, et al. Newcastle-Ottawa scale adapted for cross-sectional studies. BMC Public Health. 2013;13:154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Washington R et al. Nutrition, morbidity and mortality status in a cohort of children (0–14 years) exposed to maternal HIV in south India. 2023.
  • 55.Savadogo LGB et al. Impact of HIV/AIDS on mortality and nutritional recovery among hospitalized severely malnourished children before starting antiretroviral treatment. Open Journal of Pediatrics. 2013;2013.
  • 56.Abate BB, Aragie TG, Tesfaw G. Magnitude of underweight, wasting and stunting among HIV positive children in East Africa: a systematic review and meta-analysis. PLoS ONE. 2020;15(9):e0238403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Haider BA, et al. Anemia, iron deficiency, and iron supplementation in relation to mortality among HIV-infected patients receiving highly active antiretroviral therapy in Tanzania. Am J Trop Med Hyg. 2019;100(6):1512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Huibers MHW, et al. Severe anaemia complicating HIV in Malawi; multiple co-existing aetiologies are associated with high mortality. PLoS ONE. 2020;15(2):e0218695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Jesson J, Leroy V. Challenges of malnutrition care among HIV-infected children on antiretroviral treatment in Africa. Med et maladies Infectieuses. 2015;45(5):149–56. [DOI] [PubMed] [Google Scholar]
  • 60.Morales F, et al. Effects of malnutrition on the immune system and infection and the role of nutritional strategies regarding improvements in children’s health status: a literature review. Nutrients. 2023;16(1):1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Prendergast AJ, Evans C. Children who are HIV-exposed and uninfected: evidence for action. Aids. 2023;37(2):205–15. [DOI] [PubMed] [Google Scholar]
  • 62.Mocroft A, et al. Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe. Aids. 1999;13(8):943–50. [DOI] [PubMed] [Google Scholar]
  • 63.Ambarwati D, Dewi YLR, Murti B. The Effect of Iron Deficiency Anemia on the child death related to HIV/AIDS infection: Meta-Analysis. J Epidemiol Public Health. 2021;6(2):158–69. [Google Scholar]
  • 64.Wubneh CA, Belay GM. Mortality and its association with CD4 cell count and hemoglobin level among children on antiretroviral therapy in Ethiopia: a systematic review and meta-analysis. Trop Med Health. 2020;48:1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Tydeman-Edwards R, Van Rooyen FC, Walsh CM. Obesity, undernutrition and the double burden of malnutrition in the urban and rural southern Free State, South Africa. Heliyon. 2018;4(12). [DOI] [PMC free article] [PubMed]
  • 66.Kotecha PV. Nutritional anemia in young children with focus on Asia and India. Indian J Community Med. 2011;36(1):8–16. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

All the data analyzed during this study are included in this published article.


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