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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.
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