# An Enhanced Package of Care to Reduce Mortality in Persons with Advanced HIV Disease

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $618,989

## Abstract

Antiretroviral therapy (ART) is recommended for all people living with HIV (PLWH) – regardless of their CD4
cell count – to improve survival and reduce transmission. This “treat-all” approach benefits PLWH overall, but
also confers a risk of unmasking immune reconstitution inflammatory syndrome (IRIS) and death, particularly
for the 30-40% of people who present with advanced HIV disease (CD4 count <200 cells/µL) worldwide.
 In 2017, the World Health Organization (WHO) recommended that persons with advanced HIV disease be
screened for opportunistic infections (OIs) and given prophylaxis for tuberculosis (TB) and cryptococcal antigen
(CrAg). However, because this screening and prophylaxis package has never been validated in a clinical trial,
it is not consistently implemented in sub-Saharan Africa. Compounding the problem, funding for CD4 testing
has been reduced by stakeholders as CD4 testing is no longer needed for ART initiation. Consequently,
identification of persons with advanced HIV disease via CD4 testing and OI screening and prophylaxis often
does not occur in reality. As a result, early mortality after ART initiation remains high.
 Subsequent to the release of the initial 2017 WHO recommendations for OI screening and prophylaxis,
several novel point-of-care diagnostics and treatments for OIs have emerged:
● Visitect point-of-care CD4 assay provides a visual result of CD4 count >200 of <200 cells/µL, with a
 sensitivity of 92% and specificity of 89% in venous blood;
● Semi-quantitative CrAg lateral flow assay (CrAg-SQ LFA) can detect persons with CrAg titers who likely have
 disseminated infection and are at risk of meningitis/death despite standard of care antifungal therapy;
● Fujifilm SILVAMP TB LAM, a new point-of-care TB urinary test, has 70% sensitivity and 91% specificity;
● Isoniazid (INH) + Rifapentine given for one month for latent TB treatment is non-inferior to 9 months of INH.
 The objective of this proposal is to improve survival in persons with advanced HIV disease. We will
implement a 2x2 factorial, cluster-randomized trial in 24 Ugandan clinics to: (Aim 1) determine the survival
benefit of a novel point-of-care CD4 test compared with standard flow cytometry CD4 testing in persons with
advanced HIV disease; and (Aim 2) determine the survival benefit of an enhanced diagnostic OI screening and
prophylaxis strategy in persons with advanced HIV disease. The enhanced OI screening and prophylaxis
strategy will include point-of-care FujiFilm TB LAM, CrAg-SQ LFA, with enhanced prophylaxis for TB (1 month
of INH + rifapentine), and referral of plasma CrAg+ with high titers to hospital. Survival and retention-in-care
will be assessed at 6 months. Lastly, (Aim 3) we will evaluate the cost and cost-effectiveness of the CD4
testing strategies (described in Aim 1) and OI screening and prophylaxis strategies (described in Aim 2).
 Findings from this trial will have the potential to impact international HIV treatment guidelines on optimal
...

## Key facts

- **NIH application ID:** 10896964
- **Project number:** 5R01AI162181-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Radha Rajasingham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $618,989
- **Award type:** 5
- **Project period:** 2021-08-23 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896964

## Citation

> US National Institutes of Health, RePORTER application 10896964, An Enhanced Package of Care to Reduce Mortality in Persons with Advanced HIV Disease (5R01AI162181-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10896964. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*