Management and Prevention of Common HIV-Related …
Transcript of Management and Prevention of Common HIV-Related …
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Management and Prevention of Common HIV-Related Manifestations
David H. Spach, MDProfessor of MedicineDivision of Infectious Diseases University of WashingtonSeattle, WA
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Disclosures
Dr. Spach has no disclosures
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Management and Prevention of Common HIV-Related Manifestations
• Opportunistic infections
• Community Acquired Pneumonia
• Hepatitis B Immunization
• Prevention of Hepatitis A virus
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Opportunistic Infections
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Candidiasis (Mucocutaneous)
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Case History
Photograph Source: David H. Spach, MD
• A 31-year-old man with HIV has been off antiretroviral therapy for about 6 months.
• He now presents to clinic with white patches in his oral mucosa and is diagnosed with oral candidiasis.
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Polling Question 1
• Based on the OI Guidelines, which one of the following would be preferred therapy?
1. Clotrimazole 10 mg troche 5x/day x 7-14 days
2. Nystatin suspension 4-6 mL 4x/day for 7-10 days
3. Fluconazole 100 mg PO x 7-14 days
4. Fluconazole 200 mg PO x 3 days
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Adult Opportunistic Infections GuidelinesTreatment of Oropharyngeal Candidiasis
Source: Opportunistic Infections Guidelines. May 26, 2020.
Oropharyngeal Candidiasis: Initial Episodes (Duration: 7–14 days) RatingPreferredFluconazole: 100 mg PO once daily AIAlternativeClotrimazole 10 mg troche 5x/day BIMiconazole 50 mg buccal tablet once daily BIItraconazole solution 200 mg once daily BIPosaconazole oral suspension 400 mg BID x 1d, then 400 mg daily BINystatin suspension 4-6 mL (or 1-2 pastilles) 4x/day BIIGentian violet (0.00165%) topical application twice daily BI
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Case History
• A 24-year-old woman with HIV was recently diagnosed with HIV 4 weeks ago after when HIV screening was performed at an initial pregnancy visit. She is estimated to be 10 weeks of gestation. She has a CD4 count of 210 cells/mm3 and is receiving RAL +TDF-FTC.
• At the visit she reports vaginal itching and burning and a pelvic examination shows vulvovaginal candidiasis.
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Polling Question 2
• Based on the OI Guidelines, which one of the following would be preferred therapy for treatment of the vulvovaginal candidiasis for this woman?
1. Clotrimazole 2% cream (intravaginal) x 3 days
2. Fluconazole 150 mg PO x 1
3. Fluconazole 100 mg x 3 days
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Adult Opportunistic Infections Guidelines Candidiasis (Mucocutaneous)
Source: Opportunistic Infections Guidelines. May 26, 2020.
• Treatment of Candidiasis in Pregnancy- Oral candidiasis: topical therapy preferred- Vulvovaginal candidiasis: topical therapy essential- Avoid ANY DOSE of fluconazole in first trimester
• RISK When Using Fluconazole During FIRST Trimester- Spontaneous abortion even with single 150 mg dose- Cardiac septal closure defects with higher exposures (>150 mg)
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MAC Prophylaxis
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Polling Question 3
• A 27-year-old woman is newly diagnosed with HIV. Her CD4 count is 34 cells/mm3 and HIV RNA 78,240 copies/mL. She is immediately starting on Bictegravir-TAF-FTC.
• What is recommended regarding MAC prophylaxis?
1. Start daily azithromycin
2. Start once weekly azithromycin
3. Start daily azithromycin + rifabutin
4. Do not start prophylaxis
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Adult Opportunistic Infections GuidelinesPrimary Prophylaxis for Disseminated MAC Disease
Source: Opportunistic Infections Guidelines. February 15, 2019.
Preventing First Episode of Disseminated MAC Disease (Primary Prophylaxis) Rating
Primary prophylaxis is not recommended for adults and adolescents who immediately initiate ART AII
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Primary MAC Prophylaxis while on Combination ART
Incident MAC Rate Per 100 Person Years
Source: Yangco BG, et al. AIDS Patient Care STDs. 2014;28:280-3.
0.56
0.69
0.43
0.0
0.2
0.4
0.6
0.8
1.0
ALL No MAC Prophylaxis MAC Prophylaxis
Inci
dent
MAC
Rat
e pe
r 100
Pe
rson
Mon
ths
11/369 7/194 4/175
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Cryptococcal Meningitis
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Cryptococcal Meningitis
• A 37-year-old homeless man is admitted to the hospital with fever, confusion, and headache. He is diagnosed with cryptococcal meningitis and HIV.
• Initial laboratory studies show an HIV RNA level of 245,000 copies/mL and CD4 count 68 cells/mm3. An HIV drug resistance genotype is ordered.
• He is immediately started on amphotericin + 5-flucytosine.
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Polling Question 4
• When should you start antiretroviral therapy?
1. Immediately
2. In 1 week
3. Defer for 2-4 weeks
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Opportunistic Infection
Immune Reconstitution Inflammatory Syndrome (IRIS)
1
10
100
1,000
10,000
100,000
1,000,000
0 4 8 12 16 20 24 28 32 36 40 44 48 52
HIV
RN
A (c
opie
s/m
L)
Weeks
50
Antiretroviral Therapy
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Starting Antiretroviral Therapy with Cryptococcal Meningitis
Source: Opportunistic Infections Guidelines. Cryptococcosis. August 17, 2016.
Induction Consolidation Maintenance
≥2 weeks ≥8 weeks ≥1 year
Typical Course of Antifungal Treatment for Cryptococcal Meningitis
Defer ART Consider ART ART
0 Week 2 Week 10
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Community-Acquired Pneumonia in Persons with HIV
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Treatment of CAP in Persons with HIV
• A 38-year-old woman with HIV is seen in clinic in the month of August with a 2-day history of cough, fever, and mild dyspnea on exertion. A COVID-19 test (NP swab) was performed the prior day and is negative.
• She is taking bictegravir-TAF-FTC. Recent HIV RNA level <40 copies/mL and CD4 count 430 cells/mm3. She has no other medical problems.
• Chest radiograph shows a focal right lower lobe infiltrate and she is diagnosed with community acquired pneumonia (CAP). She is not acutely ill.
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Polling Question 5
• Based on OI Guidelines, what oral antibiotic treatment should be given for out-patient management of this woman with CAP?
1. Trimethoprim-sulfamethoxazole2. Amoxicillin-clavulanate plus Azithromycin3. Amoxicillin-clavulanate4. Azithromycin
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Adult Opportunistic Infections GuidelinesOut-Patient Treatment of CAP in Persons with HIV
Source: Opportunistic Infections Guidelines. CAP. October 10, 2019.
Empiric Out-Patient Treatment of CAP in Persons with HIV Rating
Preferred
*Beta-lactam plus Macrolide (Azithromycin or Clarithromycin) AI
Respiratory Fluoroquinolone (Levofloxacin or Moxifloxacin) AI
Alternative
^Beta-lactam plus Doxycycline BIII*Preferred beta-lactam = amoxicillin (high-dose) or amoxicillin-CA^Alternative beta-lactam = cefpodoxime or cefuroxime
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Community Acquired Pneumonia in Persons with HIVCommon Bacterial Pathogens
Source: Opportunistic Infections Guidelines. CAP. October 10, 2019.
• Streptococcus pneumoniae
• Haemophilus species
• Mycoplasma pneumoniae
• Chlamydia pneumoniae
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Why Not Use Macrolide Monotherapy?Pneumococcal Antimicrobial Susceptibility Surveillance Data
Source: CDC. Active Bacterial Core Surveillance Data, 2016.
100.0
99.8
97.5
96.0
87.8
81.7
69.3
0 20 40 60 80 100
Vancomycin
Levofloxacin
Cefotaxime
Penicillin
Tetracycline
TMP-SMX
Erythromycin
Streptococcus pneumoniae Antimicrobial Susceptibility
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HBV Vaccine
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HBV Vaccine Non-Responders
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HHS Opportunistic Infections GuidelinesHBV Screening in Persons with HIV
Source: Opportunistic Infections Guidelines. November 13, 2018.
• All persons with HIV should be screened for HBV with:- HBsAg- Anti-HBs- Anti-HBc
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HBV “Isolated Core Antibody”
• A 28-year-old trans woman (she/her/hers) recently moved and has a visit to new clinic. She has taken DTG plus TAF-FTC x 6 months.
• Initial clinic labs show CD4 count 824 cells/mm3, HIV RNA <40 copies/mL, HBsAg (-), anti-HBs (-), and anti-HBc (+). She has never received hepatitis B vaccine.
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Polling Question 6
• Based on HHS OI Guidelines, what would you recommend now to address the isolated anti-HBc?
1. Give 1 standard dose HBV vaccine & check anti-HBs in1-2 months
2. Give 3-dose series of standard dose HBV vaccine & check anti-HBs 1-2 months after series completed
3. Check HBV DNA level4. She is immune and no further action is needed
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Adult Opportunistic Infections GuidelinesApproach to Isolated Anti-HBc in Persons with HIV
Source: Opportunistic Infections Guidelines. November 13, 2018.
Isolated Anti-HBc Positive
Single dose HBV Vaccine
Check anti-HBs in 1-2 Months
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Adult Opportunistic Infections GuidelinesApproach to Isolated Anti-HBc in Persons with HIV
Isolated Anti-HBc Positive
Single dose HBV Vaccine
Anti-HBs ≥100 mIU/mLAnti-HBs <100 mIU/mL
Immune to HBV
Check anti-HBs in 1-2 Months
Complete HBV Vaccine Series
Check anti-HB in 1-2 Months
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Rational for Guideline Cut-off of 100 IU/mL
Source: Piroth L, et al. J Infect Dis. 2016:213:1735-42.
Persons with HIV and Isolated anti-HBc
• Anti-HBs response for >18 months after Hep B Vaccine Booster Dose
100% in those who achieved a titer of 100 IU/mL after booster
23% of those who achieved a titer of 10-100 IU/mL after booster
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HBV Vaccine Non-Responders
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Adult Opportunistic Infections GuidelinesHepatitis B Vaccines In Persons with HIV
Source: Opportunistic Infections Guidelines. November 13, 2018.
Month 0 62 41 3 5
HepB (Eng-B) (20 μg HBsAg/dose)
21 3
21 3HepB (Rec-HB)(10 μg HBsAg/dose)
HepB (Eng-B) (40 μg HBsAg/dose)
21 3
21 4HepB (Rec-HB)(20 μg HBsAg/dose)
3
21HepB (CpG)
SD
HD
HD
SD
SD
4
SD = standard dose; HD = high dose
AII
AII
BI
BI
CIII
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Hepatitis B Vaccine: Topics
• What do you do when a person with HIV does not respond to a standard hepatitis B vaccine series (anti-HBs <10 mIU/mL)?
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Adult Opportunistic Infections GuidelinesApproach to HBV Vaccine Nonresponders
Source: HHS. Opportunistic Infections Guidelines. November 13, 2018.
• Preferred Approach for Vaccine Nonresponders- Revaccinate with a second standard dose vaccine series (BIII).- If CD4 count low, consider defer revaccination until after a sustained increase in CD4 count with ART (CIII).
• Alternative Vaccine Dose and Duration for Nonresponders- Double dose, 4-dose series (Eng-B or Rec-HB) (BI)
Role of HepB CpG for non-responders?
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B-Enhancement of HBV Vaccination in Persons Living With HIV (BEe-HIVe): Study Design
Entry Criteria Group A and B- HIV-1- Age 18-70 years- On ART & HIV RNA <1,000 copies/mL
- CD4 >100 cells/mm3
Group A (Vaccine Non-Responders)- Serum Hep B antibody <10 mIU/mL
- HBV vaccination (>168 days prior)
Group B (Vaccine Naïve)- Hep B antibody negative (<45 days)
Source: ClinicalTrials.gov Identifier NCT04193189
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B-Enhancement of HBV Vaccination in Persons Living With HIV (BEe-HIVe): Study Design
Entry Criteria Group A and B- HIV-1- Age 18-70 years- On ART & HIV RNA <1,000 copies/mL
- CD4 >100 cells/mm3
Group A (Vaccine Non-Responders)- Serum Hep B antibody <10 mIU/mL
- HBV vaccination (>168 days prior)
Group B (Vaccine Naïve)- Hep B antibody negative (<45 days)
Source: ClinicalTrials.gov Identifier NCT04193189
HepB (CpG) 3 doses: 0, 4, and 24 weeks
HepB (Eng-B) 3 doses: 0, 4, and 24 weeks
HepB (CpG) 2 doses: 0, 4 weeks
HepB (CpG) 3 doses: 0, 4, and 24 weeks
Group A: Vaccine Non-Responders
Group B: Vaccine Naive
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BEe-HIVe: Vaccine Non-Responders Study Design
Source: ClinicalTrials.gov Identifier NCT04193189
Month 0 62 41 3 5
HepB (Eng-B) (20 μg HBsAg/dose
21 3
21HepB (CpG)
SD
SD
21HepB (CpG) 3SD
SD = standard dose
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Hepatitis A Prevention Update
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Source: Nelson NP, et al. MMWR. July 3, 2020
HAV U.S., 2013–2017
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Polling Question 7
• Should all adults with HIV who are not immune to HAV receive HAV vaccine?
1. Yes
2. No
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Hepatitis A Vaccine: Topics
Source
• Should all adults with HIV who are not immune to HAV receive HAV vaccine?
YES
• ACIP recommends for ALL persons with HIV ≥1 year of age
Source: Nelson NP, et al. MMWR, 2020;69:1-38.
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Polling Question 8
• Should you perform post-vaccination serologic testing in persons with HIV who receive HAV vaccine?
1. Yes
2. No
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Hepatitis A Vaccine: Topics
• Should you perform post-vaccination serologic testing in persons with HIV who receive HAV vaccine?
• YES
ACIP recommends postvaccination serologic testing for all persons with HIV ≥1 month after completing HepA vaccine series. Note: seroconversion (e.g. ≥10 mIU/mL) delayed ≥6 months in some
Source: Nelson NP, et al. MMWR, 2020;69:1-38.
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Polling Question 9
• Should you defer giving HAV vaccine if CD4 count low (less than 200 cellsmm3)?
1. Yes
2. No
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Hepatitis A Vaccine: Topics
• Should you defer giving HAV vaccine if CD4 count low (less than 200 cellsmm3)?
NO
ACIP recommends HAV vaccine should not be delayed until the CD4 count exceeds a certain thresholdNote: persons with low CD4 count have lower responses to HAV vaccine and revaccination may be required when CD4 count higher
Source: Nelson NP, et al. MMWR, 2020;69:1-38.
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Polling Question 10
• How do you manage HAV exposure* in HAV nonimmune persons with HIV?
1. HAV vaccine
2. Immune globulin
3. HAV vaccine + Immune globulin
*Example-sexual, household, or food source exposure to HAV <2 weeks prior.
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Hepatitis A Vaccine: Topics
• How do you manage HAV exposure in HAV nonimmune persons with HIV —HAV vaccine, IG, or both?
BOTH: Hepatitis A vaccine + Immune globulin (0.1 mL/kg)
Notes: 1) Give vaccine and IG at separate body sites2) Complete HAV vaccine series if needed
Source: Nelson NP, et al. MMWR, 2020;69:1-38.
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Questions