Determining standardized causes of death of infants, children, and adolescents living with HIV in Asia

Sohn, Annette H.; Lumbiganon, Pagakrong; Kurniati, Nia; Lapphra, Keswadee; Law, Matthew; Viet, C.; Nguyen, Lam Van; Truong, Khanh Huu; Wati, Dewi Kumara; Ounchanum, Pradthana; Puthanakit, Thanyawee; Sudjaritruk, Tavitiya; Ly, Penh Sun; Yusoff, Nik Khairulddin Nik; Fong, Sieu M; Mohamed, Thahira Jamal; Nallusamy, Revathy; Kumarasamy, N.; Kariminia, Azar; Asia-Pacific, for IeDEA

doi:10.1097/qad.0000000000002583

Cited by 13 publications

(6 citation statements)

References 26 publications

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“…Malnutrition was the leading underlying cause of death among HIV-uninfected decedents but was more frequent in the causal chain of HIV-infected decedents as HIV disease with wasting syndrome or as morbid conditions. This finding is in line with recent studies from Asia and Uganda that reported increased mortality among HIV-infected children who have severe acute malnutrition [52,53]. The increased risk of death could be because of the synergistic immunosuppressive effects of both diseases rendering the child vulnerable to fatal infections.…”

Section: Discussionsupporting

confidence: 91%

Causes of death in HIV-infected and HIV-uninfected children aged under-five years in western Kenya

Onyango

Akelo

Sande

et al. 2021

Aids

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Objectives: Describe the causes of death among infants and children less than 5 years stratified by HIV status.Design: Cross-sectional analysis of causes of death ascertained through minimally invasive tissue sampling (MITS) in the Kenya Child Health and Mortality Prevention Surveillance site. Methods:We included decedents aged 28 days to less than 5 years, whose death was reported within 36 h, underwent MITS, and had HIV test results and causes of death determined. MITS specimens were tested using Taqman Array Cards, culture, cytology, histopathology and immunohistochemistry and HIV PCR. A panel evaluated epidemiologic, clinical, verbal autopsy and laboratory data to assign causes of death using ICD-10 guidelines. Causes of death and etiological agents were stratified by HIV status.Results: Of 176 included decedents, 14% (n ¼ 25) were HIV-infected, median viral load was 112 205 copies/ml [interquartile range (IQR) ¼ 9349-2 670 143). HIV-disease (96%; n ¼ 24) and malnutrition (23%; n ¼ 34) were the leading underlying causes of death in HIV-infected and HIV-uninfected decedents, respectively. Malnutrition was more frequent in the causal chain of HIV-infected (56%; n ¼ 14) than HIV-uninfected decedents (31%; n ¼ 49) (P value ¼ 0.03). Viral pneumonia was twice as common in HIV-infected (50%; n ¼ 9) than HIV-uninfected decedents (22%; n ¼ 7) (P value ¼ 0.04). Conclusion:Nearly all HIV-infected decedents' underlying cause of death was HIV disease, which was associated with malnutrition. Our findings underscore the need for strengthening early identification and management of HIV-infected children. Prevention, early diagnosis and treatment of malnutrition could be instrumental in improving the survival of HIV-infected and HIV-uninfected children.

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Section: Discussionsupporting

confidence: 91%

Causes of death in HIV-infected and HIV-uninfected children aged under-five years in western Kenya

Onyango

Akelo

Sande

et al. 2021

Aids

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“…However, the burden observed in this current study remains high and could be explained by either undocumented previous therapeutic failure or vertical transmission of resistant viruses [36]. Regarding the immunological profile, CD4 nadir was found to be a predictor of ADRMs, with nearly three‐quarters of ALHIV with a CD4 nadir < 350 cells/μl archiving mutations in HIV‐1 reservoirs [37], highlighting the fact that close monitoring of CD4 is necessary in this vulnerable population in order to prevent the emergence of opportunistic infections [38]. Furthermore, the most prevalent ADRMs were selected by NNRTIs.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of archived drug resistance mutations in HIV‐1 DNA among vertically infected adolescents under antiretroviral treatment in Cameroon: Findings during the COVID‐19 pandemic

et al. 2023

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Background With the success of antiretroviral therapy (ART), children born with HIV are more likely to reach adolescence. However, frequent non‐adherence to ART in adolescents living with HIV (ALHIV) leads to viral replication. Notably, a viraemic infection might lead to archived drug resistance mutations (ADRMs). Hence, within the context of the COVID‐19 pandemic, we aimed to compare the patterns of ADRMs in viraemic and non‐viraemic vertically infected ALHIV and to assess their immunity to and diagnosis of SARS‐CoV‐2. Methods A comparative study was conducted among COVID‐19‐unvaccinated ALHIV receiving ART in Yaoundé‐Cameroon over the period October 2021 to March 2022. Plasma HIV‐RNA was measured using Abbott® m2000rt; HIV‐1 genotyping was performed on buffy‐coat (HIV‐1 DNA) and ADRMs were interpreted using HIVdb.v9.0.1. Patterns of HIV‐1 ADRMs were compared between viraemic (≥ 1.60 log10HIV‐1 RNA copies/ml) and non‐viraemic (< 1.60 log10copies/ml) individuals. SARS‐CoV‐2 antibodies were assessed on whole blood using Abbott Panbio COVID‐19 immunoglobulin G/M (IgG/IgM) rapid test and COVID‐19 polymerase chain reaction test was performed using nasopharyngeal swab samples. Results Of the 60 ALHIV [aged 17 (16–19) years, 51.6% female], median ART duration was 14 (12–16) years; 31/55 (56.3%) were exposed to nonnucleoside reverse transcriptase inhibitor (NNRTI)‐based first‐line ART (of whom 19/31 transitioned to dolutegravir‐based ART in 2020) and 24/55 (43.6%) were on second‐line ART. Forty‐two out of 60 (70.0%) ALHIV were non‐viraemic; 43/60 (71.6%) were successfully sequenced. Overall the ADRM rate was 62.7% (27/43), with 69.2% (9/13) viraemic and 60.0% (18/30) non‐viraemic (p = 0.56). NNRTI‐ADRMs were significantly higher among viraemic ALHIV (69.2% vs. 46.7%, p = 0.030). Regarding immunity, those with CD4 nadir < 350 cells/μl had significantly higher rates of ADRMs [adjusted odds ratio (aOR) = 3.20 (1.36–95.53), p = 0.03]. In relation to COVID‐19 immunity, overall SARS‐CoV‐2 IgG seropositivity was 28.3% (17/60), whereas 0% (0/60) were seropositive to IgM; in particular, those with CD4 count nadir ≥ 350 cells/μl had higher odds of SARS‐CoV‐2 IgG seropositivity [OR =7.85 (2.03–30.28), p < 0.01]. No significant association was found between SARS‐CoV‐2 IgG seropositivity and HIV‐RNA (non‐viraemic, 33.3%; viraemic, 16.7%; p = 0.18). SARS‐CoV‐2 RNA prevalence was 4.5% (2/44). The two positive participants were with low‐levels of viral load (Ct > 30) and seropositive to IgG. Conclusion In the context of virological success, the majority of ALHIV harbour ADRMs, essentially driven by NNRTI mutations and low CD4 nadir. During the current pandemic, about one‐third of ALHIV were previously exposed to SARS‐CoV‐2. However, some children might have been exposed and uninfected and others might have been infected but showed no serological response at sampling. These findings support the use of NNRTI‐sparing regimens and the implementation of COVID‐19 barrier measures targeting ALHIV during such a pandemic.

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“…Acquired immunodeficiency syndrome (AIDS) is an important public health concern worldwide, and deprives hundreds of thousands of people of their lives each year. AIDS is the fourth major cause of human death and the leading cause of death due to infectious disease [ 1 ]. Serious opportunistic infections (OIs) are the prominent cause of death in patients with advanced AIDS, with many such infections posing a serious threat to the health of human immunodeficiency virus (HIV)/AIDS patients [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular identification and genetic characteristics of Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in human immunodeficiency virus/acquired immunodeficiency syndrome patients in Shanghai, China

et al. 2023

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Background Opportunistic infections are a ubiquitous complication in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are common opportunistic intestinal pathogens in humans. In China, despite the number of HIV/AIDS patients being extremely large, only a few studies have investigated opportunistic infections caused by intestinal pathogens in this patient population. The aims of this study were to elucidate the occurrence and genetic characteristics of Cryptosporidium spp., G. duodenalis, and E. bieneusi in HIV/AIDS patients. Methods We collected fecal specimens from 155 HIV/AIDS patients (one from each patient). All of the specimens were examined for the presence of the pathogens by genotyping using polymerase chain reaction and sequencing of the small subunit ribosomal RNA gene for Cryptosporidium spp.; the triosephosphate isomerase, β-giardin and glutamate dehydrogenase genes for G. duodenalis; and the internal transcribed spacer region of the rRNA gene for E. bieneusi. The Cryptosporidium-positive specimens were further subtyped by polymerase chain reacion and sequencing of the 60-kDa glycoprotein gene. Results Six (3.9%), three (1.9%), and eight (5.2%) HIV/AIDS patients were positive for Cryptosporidium spp., G. duodenalis, and E. bieneusi, respectively. No statistical differences were observed in occurrence rate between the groups by gender, clinical symptom (diarrhea), and CD4+ cell count. Four Cryptosporidium species were identified: Cryptosporidium hominis (n = 2), Cryptosporidium parvum (n = 1), Cryptosporidium meleagridis (n = 1), and Cryptosporidium andersoni (n = 2). Furthermore, two C. hominis subtypes (IeA12G3T3 and IaA28R4) were detected. Three G. duodenalis-positive specimens were successfully amplified and sequenced at the triosephosphate isomerase and β-giardin loci, which led to the identification of assemblages C and B, respectively. Seven genotypes (D, Type IV, EbpC, Peru11, EbpD, A, and I) were identified in E. bieneusi-positive specimens. Conclusions Our findings should increase awareness of AIDS-related opportunistic intestinal pathogens, and indicate the need for routine examination in clinical practice for the detection of Cryptosporidium spp., G. duodenalis, and E. bieneusi. Homology analyses of the three intestinal pathogens at the nucleotide and/or amino acid levels indicated their zoonotic potential. Graphical Abstract

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Determining standardized causes of death of infants, children, and adolescents living with HIV in Asia

Cited by 13 publications

References 26 publications

Causes of death in HIV-infected and HIV-uninfected children aged under-five years in western Kenya

Causes of death in HIV-infected and HIV-uninfected children aged under-five years in western Kenya

Evaluation of archived drug resistance mutations in HIV‐1 DNA among vertically infected adolescents under antiretroviral treatment in Cameroon: Findings during the COVID‐19 pandemic

Molecular identification and genetic characteristics of Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in human immunodeficiency virus/acquired immunodeficiency syndrome patients in Shanghai, China

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