opportunistic infections - eacsociety · opportunistic infections sanjay pujari, md, fidsa...
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Opportunistic infectionsSanjay Pujari, MD, FIDSA
Institute of Infectious Diseases, Pune India
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Outline
• The problem
• Mycobacterial
• Fungal
• Viral
• Protozoal
• Bacterial
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AIDS related deaths globally: The ART impact
UNAIDS data 2019
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Incidence of OI’s in the ART era
Clin Infect Dis 2016;62:595-603
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Late presenters in single center Belgian center
Sci Rep. 2018 Jun 5;8(1):8594
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Factors associated with late presentation
Sci Rep. 2018 Jun 5;8(1):8594
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Late/Advanced presentation to care: Central/Eastern Europe (2014)
Int J Infect Dis. 2018 May;70:121-130
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Late entry into care: Poland
HIV Med 2019 Jun 28. [Epub ahead of print]
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Late/advanced presentation to care:South Africa
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Trends in IF on ART: Ethiopia
BMJ Open 2018;8:e017413.
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Outline
• The problem
• Mycobacterial
• Fungal
• Viral
• Protozoal
• Bacterial
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HIV prevalence in new and relapsed TB: 2017
Global TB report 2018
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Countries with major burden of TB/MDRTB/HIV
Global TB report 2018
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Trends in HIV/TB incidence and deaths
Global TB report 2018
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Mortality amongst HIV/TB
Global TB report 2018
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Estimated number of deaths
Global TB report 2018
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XpertMTB/Rif and mortality
Lancet Glob Health. 2019 February ; 7(2): e191–e199.
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XpertMTB/Rif vs XpertMTB/Rif ultra in PLHIV
Cochrane Databse Syst Rev 2019 Jun; 2019(6): CD009593
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FujiLAM vs AlereLAM for diagnosing TB
Lancet Infect Dis 2019;19:852-61
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FujiLAM vs AlereLAM for diagnosing TB
Lancet Infect Dis 2019;19:852-61
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WGS for TB diagnosis
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Low body weight leads to sub-optimal TB drug concentrations
Antimicrob Agents Chemother 2019 May 24;63(6).
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Low body weight leads to sub-optimal TB drug concentrations
Antimicrob Agents Chemother 2019 May 24;63(6).
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RAFA: High dose RMP in induction phase
2017 INTERTB Symposium, London, UK;
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RAFA: High dose RMP in intensive phase (CD4<100)
2017 INTERTB Symposium, London, UK;
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DTG bid efficacy with RMP
Clin Infect Dis March 2019 (epub).
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TAF with RMP
Open Forum Infectious Diseases, February 2019, 6:2, ofz035,
0
20000
40000
60000
80000
100000
120000
140000
TAF + RMP TDF
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REFLATE 2 trial: RAL + RMP
• RAL 400 mg BID + 3TC/TDF did not meet criteria for noninferior efficacy vs EFV 600 mg QD + 3TC/TDF
Virologic Outcomes (FDA Snapshot) RAL-EFV Treatment Difference (95% CI)
-13.9 3.7-5.1
-12% NI margin
-12 -8 -4 0 4 8
RAL + 3TC/TDFEFV + 3TC/TDF
12-16 -14Virologic Nonresponse
HIV-1 RNA < 50 c/mL
No Virologic Data
Patie
nts (
%)
60
100
80
20
40
0
6661
2229
1210
RAL + 3TC/TDFEFV + 3TC/TDF
De Castro. IAS 2019. Abstr MOAB0101. Reproduced with permission.
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Doubling DRV/r with RMP: Liver safety (ALT)
CROI 2019; abstr 81
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DRV trough concs across dosing regimens with RMP
CROI 2019; abstr 81
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RBT concentrations with ATV/r
Indian J Tuberc. 2019 Jan;66(1):129-133
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PRED-IRIS study
N Engl J 2018 Nov 15;379(20):1915-1925
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ART coverage and TB incidence
Bull World Health Organ 2019;97:405–414
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BRIEF TB/A5279: INH/RPT x 1 mo for preventing TB
N Engl J Med 2019;380:1001-11.
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BRIEF TB/A5279: INH/RPT x 1 mo for preventing TB
N Engl J Med 2019;380:1001-11.
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DOLPHIN: 3HP + DTG
CROI 2019; abstr 80
CROI 2019; abstr 80
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DTG trough concs: alone and with 3HP
CROI 2019; abstr 80
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STREAM: short regimen for MDRTB
N Engl J Med 2019;380:1201-13.
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STREAM: short regimen for MDRTB
N Engl J Med 2019;380:1201-13.
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WHO: Components of longer MDRTB regimens
WHO consolidated guidelines 2019
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NIXTB trial: design
TB alliance, 2018
BPaL
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NIXTB trial: Primary outcome (mITT)
TB alliance, 2018
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NIXTB trial: Primary efficacy by HIV status (mITT)
TB alliance, 2018
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TB: Some research ideas
• High dose Anti-TB drugs to optimize treatment • DDIs of high dose RMP with ARVs
• Outcomes of rifabutin based treatment for TB
• Impact of newer rapid POC screening tests on morbidity/mortality
• Outcomes of newer recommended MDRTB regimens in PLHIV
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Outline
• The problem
• Mycobacterial
• Fungal
• Viral
• Protozoal
• Bacterial
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Annual incidence of cryptococcal infection
Lancet Infect Dis 2017 Aug;17(8):873-881
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ScRAG positive mortality
Clin Infect Dis. 2019 Jun 8
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ACTA: Treatment of CM in PLHIV
N Engl J Med 2018; 378:1004-1017
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Ambition-CM trial: design
PLHIV with CM
Single dose
L-AmpB 10 mg/kg/day on day 1
2 doses
L-AmpB 10 mg/kg/day on day 1
L-AmpB 5mg/kg/dayOn day 3
3 doses
L-AmpB 10 mg/kg/day on day 1
L-AmpB 5mg/kg/dayOn day 3 & 7
Control
L-AmpB 3 mg/kg/day for 14 days
+ fluconazole 1200 mg/day x 14 days
Clin Infect Dis 2019 Feb;68:3:393-401
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EFA with L-AmB short course
Clin Infect Dis 2019 Feb;68:3:393-401
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Efficacy of short course L-AmpB
Clin Infect Dis 2019 Feb;68:3:393-401
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Histoplasmosis vs TB in Brazil
Open Forum Infect Dis 2019 Apr 13;6(4):ofz073
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Clinical prediction of histoplasmosis
Open Forum Infect Dis 2019 Apr 13;6(4):ofz073
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PjPCR and Betaglucan in serum in PCP
BMC Infect Dis 2019 Jul 23;19(1):658
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PCRct values and B-glucan levels and severity of PCP
BMC Infect Dis 2019 Jul 23;19(1):658
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Echinocandins for PCP
0
5
10
15
20
25
30
35
all cause mortality PCP-death mild PCP Mod-severe PCP Echinocandin+TMP-SMX Echinocandin mono
AIDS 2019, 33:1345–1351
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Fungal: Some research ideas
• Optimal regimen for pre-emptive treatment of cryptococcemia
• Clinical Scoring tool for differentiating histoplasma vs TB
• Optimal management of histoplasmosis in PLHIV
• Non-invasive diagnosis of PCP
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Outline
• The problem
• Mycobacterial
• Fungal
• Viral
• Protozoal
• Bacterial
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Pembrolizumab for PML
New Engl J Med 2019 Apr 25;380(17):1597-1605
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Pembrolizumab for PML
New Engl J Med 2019 Apr 25;380(17):1597-1605
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Zostavax in PLHIV with CD4>200: Efficacy
Clin Infect Dis 2018 Nov 13;67(11):1712-1719
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Zostavax in PLHIV with CD4>200: Safety
Clin Infect Dis 2018 Nov 13;67(11):1712-1719
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Viral: Some research ideas
• Exploring immunomodulating treatment in PML
• Role of newer HZ vaccine in PLHIV
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Outline
• The problem
• Mycobacterial
• Fungal
• Viral
• Protozoal
• Bacterial
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Combi LAmB + miltefosine for HIV-VL
29 58
PLoS Negl Trop Dis. 2019 Jan 17;13(1):e0006988
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Outline
• The problem
• Mycobacterial
• Fungal
• Viral
• Protozoal
• Bacterial
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Pulmonary infections etiology using sputum multiplex PCR
Clin Infect Dis 2019 Apr 26. [Epub ahead of print]
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HIV associated with higher mortality in Sepsis: sSA
Critical Care (2019) 23:212
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Immunogenicity of PCV-13 with CD4 counts<350
Hum Vaccin Immunother. 2019 Aug 23:1-7
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COSTOP:CTX prophylaxis in PLHIV with CD4>250- efficacy
PLOS One 2018; 13(12): e0206907.
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COSTOP:CTX prophylaxis in PLHIV with CD4>250-safety
PLOS One 2018; 13(12): e0206907.
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Summary
• OI’s: Going, going, but not gone
• Continued need to be vigilant • Late presentation• Failing ART
• Great potential for further refining and optimizing treatment and prevention of OI’s
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