5/15/2017. What Does HIV/AIDS Look Like in DC in Potpourri of Challenges With Opportunistic Infections

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Potpourri of Challenges With Opportunistic Infections Henry Masur, MD Clinical Professor of Medicine George Washington University Washington, DC FORMATTED: 4/28/217 Learning Objectives After

1 Potpourri of Challenges With Opportunistic Infections Henry Masur, MD Clinical Professor of Medicine George Washington University Washington, DC FORMATTED: 4/28/217 Learning Objectives After attending this presentation, learners will be able to: Describe the incidence of new cases of HIV-infected individuals with CD4+ cell counts lower than /μl in the Disctrict of Columbia Describe the relationship between CD4+ cell counts and opportunistic infections in the current era Use polymerase chain reaction testing appropriately to diagnose respiratory illnesses Recognize the risks for discontinuing antiinfective therapy in patients whose HIV RNA levels are not fully suppressed Slide 3 of 48 What Does HIV/AIDS Look Like in DC in 217 Slide 4 of 48 1

2 HIV/AIDS In DC: Tremendous Progress But Tremendous Work To Do Slide 7 of 48 Lifetime Risk of HIV by State Slide 8 of Rate of HIV Cases Living in DC per 1, Persons Slide 9 of 48 2

3 Stage of Disease at First Lab in DC and in 215 Among Cases Presumed Living in DC District of Columbia 1% 2% Proportion of Cases 9% 8% 7% 6% 5% 4% 3% 36% 33% 29% 7% 23% 2% 1% 29% 42% % First Stage in DC Stage in 215 Slide 1 of 48 Stage 1 Stage 2 Stage 3 Unknown Opportunistic Infections Among HIV Infected Persons Are Declining But They Still Occur All 63,541 Patients, NA-ACCORD, 21, United States and Canada Incidence, events per 1 person-years Pneumocystis jiroveci pneumonia Candidiasis, esophageal MAC or M. kansasii infection, disseminated TB pulmonary Crypto CMV retinitis Toxoplasmosis All declines statistically significant (P<.5) Slide 11 of 48 Buchacz K et al. J Infect Dis 216;214: How Many People Are Accessing the Guidelines on the AIDSinfo Website? Data is from October 215 September 216 7, Page Views/Downloads by Guideline 6, 5, 4, 3,, 1, Adult ARV Adult OI Perinatal Pediatric Ped OI Page Views Downloads Slide 12 of 48 3

4 Opportunistic Infection Guideline Traffic from October 213 Present Guideline Page Views 1,6, 1,4, 1,, 1,, 8, 6, 4,, 19% 21% Oct Sept 214 Oct Sept 215 Oct Sept 216 Page Views Slide 13 of 48 Top Viewed Sections in Opportunistic Infection Guidelines 216 Rank Short Title Page views 1 What's New/Landing Page 57,19 2 PCP 35,787 3 Table 3 - TB Drug Dosing 28,12 4 MAC 19,419 5 Toxo 18,51 6 TB 11,674 7 CMV 1,856 8 HSV 1,684 9 Cryptococcosis 9,497 1 Table 2 - OI Treatment 7, Table 4 - Discontinuing Prophylaxis 7,66 12 PML/JVC 7, HPV 5, Syphilis 5, Candida 4,962 Slide 14 of 48 #1 Are Opportunistic Infections Occurring at Higher CD4 Counts Than Pre ART? Slide 15 of 48 4

5 Distribution of CD4+ Lymphocyte Counts at Diagnosis of Opportunistic Infection CD4+ T-Lymphocyte Count (/ L) MAC CMV CMV HISTO TOXO Crypt Cocci Cand PCP Crypt Diss HSV Strep Pulm Cervical Ret Other Esoph Spor TB Pneumo TB CA Slide 16 of 48 CD4+ T-cell Counts, Viral Load Data, and History of Antiretroviral Therapy (ART) Use Among 5,836 Patients Experiencing Any First OIs, NA-ACCORD, 21, United States and Canada Slide 17 of 48 Buchacz K et al. J Infect Dis 216;214: HIV-Related Opportunistic Infections Most OIs Occur at CD4< CD Most OIs Months Post HIV Months Post ART Slide 18 of 48 5

6 CD4+ T-cell Counts, Viral Load Data, and History of Antiretroviral Therapy (ART) Use Among 5,836 Patients Experiencing Any First OIs, NA-ACCORD, 21, United States and Canada Buchacz K et al. J Infect Dis 216;214: Slide 19 of 48 Some OIs Occur When ART is Initiated- IRIS and Unmasking CD ART Start IRIS Months Post HIV Months Post ART Slide 2 of 48 When Clinical Syndromes Occur Soon After Initiation of ART, Are They True Opportunistic Infections Due to Replicating Organisms or Are They Inflammatory Responses to Latent Organisms? Slide 21 of 48 6

7 Distribution of CD4 Counts Measured within 4 Months of PCP (N = 24; 942 followed x 8 months) CD4 Count % PCP Diagnosis 3 5.5% % % % Source: Chu et al. JAMA 3/95 Slide 22 of 48 #1 How Useful is PCR for Diagnosis Pneumonia PCP CMV Other CNS Lesions Toxoplasma EBV Cryptococcus Mycobacteria Slide 23 of 48 Case 46 year old MSM with chronic alcoholism Non adherent with ARVs and OI prophylaxis CD4 count = 16 (2%), VL = 295,648 Prior History esophageal candidiasis (azole R) Disseminated MAI (7) PCP (211) Presents in December with several days of cough which has become worse in past 24 hours with higher fever and new onset shaking chills Slide 24 of 48 7

8 Exam and Lab Physical Exam T 38.5 C; BP 12/8; P=12 Diffuse rales Laboratory O2 Sat on room air: 92% Sputum: scant, gram stain shows scanty mixed flora WBC 1.6 (9% polys) Slide 25 of 48 PA Chest Image Slide 26 of 48 CT Scan Slide 27 of 48 8

9 Laboratory Results Bronchoalveolar Lavage Gram stain and wet mount Negative Direct Immunofluorescent Stain Negative for pneumocystis Multiplex PCR Positive for Influenza Positive for Pneumocystis Positive for CMV Positive for Rhinovirus Slide 28 of 48 How to Establish Diagnosis of PCP Slide 3 of 48 Serologic Tests for PCP LDH Sensitivity depends on lung severity Non-specific Beta Glucan Not sensitive or specific Follow efficacy of therapy if positive? Slide 31 of 48 9

10 Plasma Beta-Glucan for Pneumocystis Pneumonia in AIDS Patients With Respiratory Symptoms (n=139) Slide 32 of 48 Sax, AIDS, March 213. Diagnosis of Pneumocystis Pneumonia Specimen Acquisition Open lung biopsy Transbronchial biopsy Bronchoalveolar lavage Induced sputum 1957 Organism Detection Methenamine silver Immunofluorescence Giemsa / Diff Quik PCR 217 Slide 33 of 48 Role of PCR for Diagnosis of Disease High negative predictive value Disappointing positive predictive value Slide 34 of 48 1

11 My Final Diagnosis Influenza pneumonia Probable Bacterial Pneumonia Unlikely pneumonia is due to PCP or CMV or Rhinovirus Slide 35 of 48 Slide 36 of 48 Figueiredo-Mello C, et al. Medicine 217;96:e5778. Finds of Microbiological Investigation in 224 Cases of Community- Acquired Pulmonary Infections in Hospitalized Patients Living with HIV Etiology Routine investigation N (%) Routine + extended investigation N (%) Fungi 17 (8) 58 (26) Pneumocystis jirovecii Histoplasma spp. 5 5 Bacteria 27 (12) 48 (21) Streptococcus pneumoniae Virus 14 (6) 48 (21) Influenza A non H1N1 9 7 Slide 37 of 48 Figueiredo-Mello C, et al. Medicine 217;96:e

12 Frequency of Mixed Etiology Findings Observed During Routine Plus Extended Microbiological Investigation of Community-acquired Pulmonary Infections in Hospitalized Patients Living With HIV Etiology N Mycoplasma pneumoniae + Pneumocystis jirovecii 4 Pneumocystis jirovecii + Rhinovirus 3 Pneumocystis jirovecii + Mycobacterium tuberculosis 3 Streptococcus pneumoniae + Rhinovirus 3 Adenovirus + Pneumocystis jirovecii 2 Chlamydophila pneumoniae + Pneumocystis jirovecii 2 Histoplasma spp. + Pneumocystis jirovecii + Rhinovirus 2 Mycoplasma pneumoniae + Streptococcus pneumoniae 2 Adenovirus + M. avium or M. colombiensis + Pneumocystis jirovecii 1 Adenovirus + Pneumocystis jirovecii + Pulmonary thromboembolism 1 Bordetella pertussis + Streptococcus pneumoniae + Staphylococcus aureus + Rhinovirus 1 Chlamydophila pneumoniae + Streptococcus pneumoniae 1 Chlamydophila pneumoniae + Streptococcus pneumoniae + Mycobacterium tuberculosis 1 Cytomegalovirus + Rhinovirus + Kaposi s sarcoma 1 Coronavirus + Pneumocystis jirovecii + Rhinovirus 1 Coronavirus OC43 + Rhinovirus 1 Histoplasma spp. + Mycobacterium tuberculosis 1 Slide 38 of 48 Figueiredo-Mello C, et al. Medicine 217;96:e5778. Conclusion PCR is very sensitive Some organisms can colonize without causing disease Some patients, especially immunosuppressed, can shed virus for months after acute infection Results need context for interpretation Slide 39 of 48 How Useful is PCR for Diagnosis? Pneumonia PCP Other CNS Lesions Toxoplasma EBV CMV Cryptococcus Mycobacteria Slide 4 of 48 12

13 #2 Early Termination of Prophylaxis Slide 41 of 48 Question 3 yo Female Baseline Labs: Initial/Current ART Current Labs Current OI Prophylaxis HIV RNA 78, c/ml CD4 count 8 cells/ul TDF / FTC /Lopinavir/Rit x 3 years HIV RNA < 5 c/ml (persistently) CD4 167 cells/ul (CD4 % = 12%) TMP-SMX 1 DS QD Slide 42 of 48 Slide 44 of 48 13

14 Slide 45 of 48 Undetectable CD4 1 Off TS On TS Miro JM. CROI 217. Slide 46 of 48 Author Conclusions In suppressed HIV-infected adult patients on ART, secondary TE prophylaxis can be safely discontinued in patients with CD4 cell counts > cells/mm3 However, in patients with detectable HIV RNA the risk of relapse may be substantial, even if the CD4 cell count is> cells/mm3 and prophylaxis should be maintained Secondary TE prophylaxis should not be stopped in virologically suppressed patients on ART with CD4 cell counts of 1- Slide 47 of 48 14

15 Bottom Line Stopping prophylaxis for any OI has some risk The risk for stopping prophylaxis at CD4 1- cells/ul and VL <5 PCP: Reasonable risk Toxoplasma: Higher risk Slide 48 of 48 15

16 Dr Masur Suggested Readings Activity #: HIV 17 DC (F) Page: 1 SUGGESTED READINGS 1. Buchacz K, Lau B, Jing Y, et al. Incidence of AIDS-defining opportunistic infections in a multicohort analysis of HIV-infected persons in the United States and Canada, -21. J Infect Dis. 216;214(6): Ref ID: Mocroft A, Reiss P, Kirk O, et al. Is it safe to discontinue primary Pneumocystis jiroveci pneumonia prophylaxis in patients with virologically suppressed HIV infection and a CD4 cell count < cells/microl? Clin Infect Dis. 21;51(5): Ref ID: Montesinos I, Delforge ML, Ajjaham F, et al. Evaluation of a new commercial real-time PCR assay for diagnosis of Pneumocystis jirovecii pneumonia and identification of dihydropteroate synthase (DHPS) mutations. Diagn Microbiol Infect Dis. 217;87(1): Ref ID: Alfonso Y, Fraga J, Cox R, et al. Conventional polymerase chain reaction for the diagnosis of neurotoxoplasmosis: comparison of three sets of primers for the B1 gene using CSF samples. Diagn Microbiol Infect Dis. 213;75(2): Ref ID: Figueiredo-Mello C, Naucler P, Negra MD, Levin AS. Prospective etiological investigation of community-acquired pulmonary infections in hospitalized people living with HIV. Medicine (Baltimore). 217;96(4):e5778. Ref ID: Karageorgopoulos DE, Qu JM, Korbila IP, Zhu YG, Vasileiou VA, Falagas ME. Accuracy of ß-D-glucan for the diagnosis of Pneumocystis jirovecii pneumonia: a meta-analysis. Clin Microbiol Infect. 213;19(1): Ref ID: 1576

Outline. Cryptococcosis Pneumocystosis Diarrhea. Case Histories: HIV Related- Opportunistic Infections in 2015

Outline. Cryptococcosis Pneumocystosis Diarrhea. Case Histories: HIV Related- Opportunistic Infections in 2015 AU Edited: 05/06/15 Case Histories: HIV Related- Opportunistic Infections in 2015 Henry Masur, MD Clinical Professor of Medicine George Washington University School of Medicine Bethesda, Maryland Washington,