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HIV-Associated Histoplasmosis in Guatemala
Juan Luis Rodriguez Tudela
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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.
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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
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Lessons learned from a Project done in Guatemala with PLWHIV for the
diagnosis and treatment of fungal OIs
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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
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2015 situation• Asking for which OIs they
had…..
Lots ofTuberculosis
Little Histoplasmosis & Cryptococcosis
PneumocistosisMight be!!!
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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
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Setting up a “Diagnostic Laboratory Hub” in
Guatemala City
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Setting up a network of HIV
units13 out of 16 HIV units agreed to
participate
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• 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.
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TB
Cryptococcosis
AIDS
FOCUS ON THESE INFECTIONS
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TB
Cryptococcosis
AIDS
Pneumocystosis
FOCUS ON THESE INFECTIONS
in a separate cohort because no enough budget to make full screening (Real time PCR)
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Primary Care
HistoplasmosisTuberculosis
Pneumocystosis NTM
Cryptococcosis
TTO
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Primary Care
Diagnostic Laboratory
Hub
TTO
HistoplasmosisTuberculosis
Pneumocystosis NTM
Cryptococcosis
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Experts
Videoconference&
E-learningPrimary Care
TTO
Diagnostic Laboratory
Hub
HistoplasmosisTuberculosis
Pneumocystosis NTM
Cryptococcosis
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• 52% of new HIV cases had advanced HIV• 29% without CD4 count
Lessons learned in Guatemala
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Histoplasmosis patient’s characteristics
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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%
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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%
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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. %
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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. %
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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%
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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
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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
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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
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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
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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
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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%
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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%
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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%
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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%
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6 month survival curves
MortalityOIs Non OIS
2017 29.6 4.32018 25.3 5.9
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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
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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
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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%
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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.