HIV-Associated Histoplasmosis in Guatemala

Juan Luis Rodriguez Tudela

Disclosure• My trustee position in GAFFI is 100%

voluntary;• Since my retirement in 2012, I have not

received any compensation from diagnostic or pharmaceutical companies because of talks, research projects, advisory committees or any other activities;

• I pay for my travelling and accommodation.

GAFFI is the only NGO dealing with fugal infections in the world

1. Global access to diagnosis and treatment of fungal infections;

2. Educate Health care professionals;3. Measure the impact of serious fungal

diseases.

www.GAFFI.org

Lessons learned from a Project done in Guatemala with PLWHIV for the

diagnosis and treatment of fungal OIs

2015 Situation• PLWHIV in Guatemala

are attended in HIV units

• There were 16 HIV units across de country without communication among them and very limited access to diagnosis & treatment of Fungal OIs

2015 situation• Asking for which OIs they

had…..

Lots ofTuberculosis

Little Histoplasmosis & Cryptococcosis

PneumocistosisMight be!!!

Main Objective

•Following WHO recommendations provide access to diagnosis and treatment for PLWHIV:•Active finding of OI cases;•Patients w/o OI: quick start of ARVT

Setting up a “Diagnostic Laboratory Hub” in

Guatemala City

Setting up a network of HIV

units13 out of 16 HIV units agreed to

participate

• Patients:• New cases;• Patients who have been out of care;• On ART and looking for care.

• Strategy:• Screening for all:

• With or without CD4 count;• Regardless of CD4 count number;• 6 month follow-up.

• Results so far:• Three cohorts 2017, 2018, 2019 with around 6,000 patients;• Primary analysis of 2017 and 2018 cohort;• Finishing 2019 cohort data base.

TB

Cryptococcosis

AIDS

FOCUS ON THESE INFECTIONS

TB

Cryptococcosis

AIDS

Pneumocystosis

FOCUS ON THESE INFECTIONS

in a separate cohort because no enough budget to make full screening (Real time PCR)

Primary Care

HistoplasmosisTuberculosis

Pneumocystosis NTM

Cryptococcosis

TTO

Primary Care

Diagnostic Laboratory

Hub

TTO

HistoplasmosisTuberculosis

Pneumocystosis NTM

Cryptococcosis

Experts

Videoconference&

E-learningPrimary Care

TTO

Diagnostic Laboratory

Hub

HistoplasmosisTuberculosis

Pneumocystosis NTM

Cryptococcosis

• 52% of new HIV cases had advanced HIV• 29% without CD4 count

Lessons learned in Guatemala

Histoplasmosis patient’s characteristics

Histoplasmosis Without OIn=271 n=3529

No. % No. %Sex

Male 172 63.5% 2201 62.4%Female 97 35.8% 1291 36.6%Transsexual 2 0.7% 37 1.0%

Age (years)n 271 100% 3517 99.6%Median, IQR 35 (29-43) 34 (27-44)

Sexual orientationHeterosexual 232 85.6% 2642 74.9%Homosexual 22 8.1% 602 17.1%Bisexual 9 3.3% 207 5.9%Unknown 8 3.0% 78 2.2%

Ethnic groupLadino 192 70.8% 2504 71.0%Mayan 41 15.1% 542 15.4%Other 0 0.0% 20 .6%Unknown

ResidenceUrban 90 34.1% 1653 48.7%Rural 174 65.9% 1743 51.3%

Histoplasmosis Without OIn=271 n=3529

No. % No. %Sex

Male 172 63.5% 2201 62.4%Female 97 35.8% 1291 36.6%Transsexual 2 0.7% 37 1.0%

Age (years)n 271 100% 3517 99.6%Median, IQR 35 (29-43) 34 (27-44)

Sexual orientationHeterosexual 232 85.6% 2642 74.9%Homosexual 22 8.1% 602 17.1%Bisexual 9 3.3% 207 5.9%Unknown 8 3.0% 78 2.2%

Ethnic groupLadino 192 70.8% 2504 71.0%Mayan 41 15.1% 542 15.4%Other 0 0.0% 20 .6%Unknown

ResidenceUrban 90 34.1% 1653 48.7%Rural 174 65.9% 1743 51.3%

Type of patient

Newly HIV-diagnosed 163 60.1% 1742 49.4%

On ART 54 19.9% 1134 32.1%

Out of care 54 19.9% 641 18.2%

CD4 (cells/mm3)

< 200 120 71.0% 595 23.5%

< 350 140 82.8% 1104 43.5%

≥ 350 11 6.5% 767 30.2%

Viral load (copies/mL)

n 171 63.1% 2355 66.7%

Log10 Median, IQR 5.2 (4.7-5.7) 4.6 (3.4-5.1)

Histoplasmosis Without OIn=271 n=3529

No. % No. %

Type of patient

Newly HIV-diagnosed 163 60.1% 1742 49.4%

On ART 54 19.9% 1134 32.1%

Out of care 54 19.9% 641 18.2%

CD4 (cells/mm3)

< 200 120 71.0% 595 23.5%

< 350 140 82.8% 1104 43.5%

≥ 350 11 6.5% 767 30.2%

Viral load (copies/mL)

n 171 63.1% 2355 66.7%

Log10 Median, IQR 5.2 (4.7-5.7) 4.6 (3.4-5.1)

Histoplasmosis Without OIn=271 n=3529

No. % No. %

16.2% of patients with Histoplasmosis had coinfections

n %H + TB 24 54.5%Cryp + H 15 34.1%H + NTM 3 6.8%Cryp + H+ TB 2 4.5%Total 44 100.0%

OIsOverall

incidence

Interval CD4 cell count

Unknown <50 50-99 100-199 200-350 >350

Tuberculosis 7.8% 9.8% 12.1% 11.9% 8.5% 2.7% 4.1%

NTM 1.3% 1.2% 2.2% 1.0% 1.7% 0.8% 1.3%

Histoplasmosis 6.7% 8.9% 17.7% 7.2% 3.4% 2.6% 1.4%

Cryptococcosis 4.5% 4.2% 13.3% 6.9% 4.0% 1.5% 0.8%

Total 20.3% 24.1% 45.3% 27.0% 17.6% 7.6% 7.6%

Overall incidence of Histoplasmosis compared with other OIs. Full cohort

OIsOverall

incidence

Interval CD4 cell count

Unknown <50 50-99 100-199 200-350 >350

Tuberculosis 7.8% 9.8% 12.1% 11.9% 8.5% 2.7% 4.1%

NTM 1.3% 1.2% 2.2% 1.0% 1.7% 0.8% 1.3%

Histoplasmosis 6.7% 8.9% 17.7% 7.2% 3.4% 2.6% 1.4%

Cryptococcosis 4.5% 4.2% 13.3% 6.9% 4.0% 1.5% 0.8%

Total 20.3% 24.1% 45.3% 27.0% 17.6% 7.6% 7.6%

Overall incidence of Histoplasmosis compared with other OIs. Full cohort

OIsOverall

incidence

Interval CD4 cell count

Unknown <50 50-99 100-199 200-350 >350

Tuberculosis 7.8% 9.8% 12.1% 11.9% 8.5% 2.7% 4.1%

NTM 1.3% 1.2% 2.2% 1.0% 1.7% 0.8% 1.3%

Histoplasmosis 6.7% 8.9% 17.7% 7.2% 3.4% 2.6% 1.4%

Cryptococcosis 4.5% 4.2% 13.3% 6.9% 4.0% 1.5% 0.8%

Total 20.3% 24.1% 45.3% 27.0% 17.6% 7.6% 7.6%

Overall incidence of Histoplasmosis compared with other OIs. Full cohort

OIsOverall

incidence

Interval CD4 cell count

Unknown <50 50-99 100-199 200-350 >350

Tuberculosis 7.8% 9.8% 12.1% 11.9% 8.5% 2.7% 4.1%

NTM 1.3% 1.2% 2.2% 1.0% 1.7% 0.8% 1.3%

Histoplasmosis 6.7% 8.9% 17.7% 7.2% 3.4% 2.6% 1.4%

Cryptococcosis 4.5% 4.2% 13.3% 6.9% 4.0% 1.5% 0.8%

Total 20.3% 24.1% 45.3% 27.0% 17.6% 7.6% 7.6%

Overall incidence of Histoplasmosis compared with other OIs. Full cohort

OIsOverall

incidence

Interval CD4 cell count

Unknown <50 50-99 100-199 200-350 >350

Tuberculosis 7.8% 9.8% 12.1% 11.9% 8.5% 2.7% 4.1%

NTM 1.3% 1.2% 2.2% 1.0% 1.7% 0.8% 1.3%

Histoplasmosis 6.7% 8.9% 17.7% 7.2% 3.4% 2.6% 1.4%

Cryptococcosis 4.5% 4.2% 13.3% 6.9% 4.0% 1.5% 0.8%

Total 20.3% 24.1% 45.3% 27.0% 17.6% 7.6% 7.6%

Overall incidence of Histoplasmosis compared with other OIs. Full cohort

Overall incidence of Histoplasmosis compared with other OIs in newly HIV patients

OIsOverall

incidence

Interval CD4 cell count

Unknown <50 50-99 100-199 200-350 >350

Tuberculosis 7.1% 9.8% 11.5% 10.8% 7.5% 2.7% 2.9%

NTM 1.1% 1.5% 2.4% 0.5% 1.9% 0.3% 0.0%

Histoplasmosis 7.9% 14.1% 19.7% 7.0% 4.1% 2.4% 1.1%

Cryptococcosis 4.8% 5.3% 14.3% 7.4% 3.3% 1.5% 0.3%

Total 21.0% 30.6% 47.9% 25.8% 16.8% 6.8% 4.3%

Overall incidence of Histoplasmosis compared with other OIs in newly HIV patients

OIsOverall

incidence

Interval CD4 cell count

Unknown <50 50-99 100-199 200-350 >350

Tuberculosis 7.1% 9.8% 11.5% 10.8% 7.5% 2.7% 2.9%

NTM 1.1% 1.5% 2.4% 0.5% 1.9% 0.3% 0.0%

Histoplasmosis 7.9% 14.1% 19.7% 7.0% 4.1% 2.4% 1.1%

Cryptococcosis 4.8% 5.3% 14.3% 7.4% 3.3% 1.5% 0.3%

Total 21.0% 30.6% 47.9% 25.8% 16.8% 6.8% 4.3%

Overall incidence of Histoplasmosis compared with other OIs in newly HIV patients

OIsOverall

incidence

Interval CD4 cell count

Unknown <50 50-99 100-199 200-350 >350

Tuberculosis 7.1% 9.8% 11.5% 10.8% 7.5% 2.7% 2.9%

NTM 1.1% 1.5% 2.4% 0.5% 1.9% 0.3% 0.0%

Histoplasmosis 7.9% 14.1% 19.7% 7.0% 4.1% 2.4% 1.1%

Cryptococcosis 4.8% 5.3% 14.3% 7.4% 3.3% 1.5% 0.3%

Total 21.0% 30.6% 47.9% 25.8% 16.8% 6.8% 4.3%

6 month survival curves

Category MortalityCoinfection 41.9%Crypto 29.2%Histo 28.6%TB 22.9%NTM 15.8%Negative 5.2%Global 8.8%

6 month survival curves

MortalityOIs Non OIS

2017 29.6 4.32018 25.3 5.9

OIs contribution to mortality in newly HIV patients

Unknown 24.9%Histoplasmosis 17.3%Tuberculosis 15.1%Cryptococcosis 10.3%Coinfections 7.3%NTM 1.6%

Lessons learned in Guatemala

OIs contribution to mortalityTuberculosis 15.1%NTM 1.6%Histoplasmosis 17.3%

27.6%Cryptococcosis 10.3%Coinfections 7.3%

Unknown 24.9% PCP, Toxo, CMV, Bacteria, Other?

Lessons learned in Guatemala

Treatments for Histoplasmosis

Treatment n %AmB_Then_ITZ 85 31.4%

AmB 59 21.8%

ITZ 39 14.4%

FZ 9 3.3%

AntiTB+AmB 6 2.2%

AntiTB 4 1.5%

AmB_Then_FZ 4 1.5%

AmB+Antibiotics 4 1.5%

AntiTB+AmB+FZ 3 1.1%

AmB+FZ then FZ 3 1.1%

AntiTB+FZ 2 0.7%

AmB+FZ 2 0.7%

AntiTB+ITZ 1 0.4%

AntiTB+AmB+ITZ 1 0.4%

FZ+Antibiotics 1 0.4%

No treatment 38 14.0%

Unknown 10 3.7%

Total 271 100.0%

Summary of Guatemala´s findings

• Global screening was a wise decision because 29% of patients were managed without CD4 cell count; 37.6% of those with Histoplasmosis;

• Without the commercial Ag test, 35% of disseminated histoplasmosis would not have been diagnosed;

• Histoplasmosis was the most frequent OI among newly HIV-diagnosed patients;

• Histoplasmosis is more frequent in rural areas;• In one year, the diagnostic program has reduced OIs associated mortality a

4.3%;• Liposomal amphotericin B and flucytosine would likely have a major impact

in reducing deaths.