Evidence map›Paper›PMID 41002116›Full record

SynthesisHIV medicine2026

Diagnostic accuracy of the WHO clinical staging system for detection of immunologically defined advanced HIV disease: A systematic review and meta-analysis.

Hussein H Twabi, Akitoshi Ueno, Josephine Ives, Ross Murtagh, Madalo Mukoka, Seyed Alireza Mortazavi, David S Lawrence, Augustine T Choko, Robina Semphere, Kelvin Balakasi and 4 more

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in HIV medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Hussein H TwabiPublic Health Group, Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.
Akitoshi UenoClinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
Josephine IvesPublic Health Scotland, Glasgow, UK.
Ross MurtaghSchool of Infection and Immunity, University of Glasgow, Glasgow, UK.
Madalo MukokaPublic Health Group, Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.
Seyed Alireza MortazaviSchool of Health & Wellbeing, University of Glasgow, Glasgow, UK.
David S LawrenceClinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
Augustine T ChokoPublic Health Group, Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.
Robina SempherePublic Health Group, Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.
Kelvin BalakasiPublic Health Group, Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.
Ajay RangarajWorld Health Organization, Global HIV, Hepatitis and Sexually Transmitted Infections Programmes, Geneva, Switzerland.
Nathan FordWorld Health Organization, Global HIV, Hepatitis and Sexually Transmitted Infections Programmes, Geneva, Switzerland.
Joseph N JarvisClinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
Peter MacPhersonClinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.

Funding

Wellcome Trust 304666World Health Organization 001
6 · The paper itself

Abstract

introductionPeople with advanced HIV disease face high risks of severe illness and death. CD4 testing enables timely diagnosis and appropriate care, yet access remains limited in many settings. This review investigated the diagnostic accuracy of the WHO clinical staging for identifying advanced HIV disease.

methodsWe conducted a systematic review and meta-analysis of studies published between 1 January 1998 and 1 May 2024 that assessed both WHO clinical staging and CD4 counts in people living with HIV aged 5 years and older (PROSPERO: CRD42024558372). We pooled sensitivity and specificity estimates of WHO Stage 3/4 for detecting advanced HIV disease (CD4 <200 cells/μL) using bivariate random-effects meta-analysis. Risk of bias was assessed using QUADAS-2, and certainty of evidence was appraised using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE).

resultsOf 15,194 studies screened, 335 relevant studies were identified, from which 25 were included in evidence synthesis and 21 in the meta-analysis. Most studies were from the WHO African (19/25) and South-East Asian (5/25) regions. Risk of bias was moderate to high in 88% of studies, primarily due to issues with clinical staging assessment. Pooled sensitivity and specificity of WHO Stage 3/4 were 60.7% (95% CI: 48.0%-72.1%) and 72.4% (95% CI: 61.4%-81.3%), respectively. Specificity was significantly higher outside the African region (p < 0.001). In a population of 100,000 people living with HIV with 30% advanced HIV disease prevalence, WHO staging would miss 11,700 true advanced HIV disease cases and misclassify 19,600.

conclusionsWHO clinical staging alone shows low accuracy for detecting advanced HIV disease, risking both missed diagnoses and overtreatment. CD4 testing remains essential for accurately identifying and managing advanced HIV disease.

Indexed as

HIV InfectionsCD4 Lymphocyte CountHumansSensitivity and SpecificitySeverity of Illness IndexWorld Health Organizationclinical stagingdiagnostic accuracyHIVmeta‐analysisscreeningsystematic review

Identifiers

PMID41002116
PMCPMC7618267

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.