Management and Prevention of Common HIV-Related Manifestations

David H. Spach, MDProfessor of MedicineDivision of Infectious Diseases University of WashingtonSeattle, WA

Disclosures

Dr. Spach has no disclosures

Management and Prevention of Common HIV-Related Manifestations

• Opportunistic infections

• Community Acquired Pneumonia

• Hepatitis B Immunization

• Prevention of Hepatitis A virus

Opportunistic Infections

Candidiasis (Mucocutaneous)

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.

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

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

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.

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

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)

MAC Prophylaxis

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

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

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

Cryptococcal Meningitis

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.

Polling Question 4

• When should you start antiretroviral therapy?

1. Immediately

2. In 1 week

3. Defer for 2-4 weeks

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

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

Community-Acquired Pneumonia in Persons with HIV

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.

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

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

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

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

HBV Vaccine

HBV Vaccine Non-Responders

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

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.

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

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

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

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

HBV Vaccine Non-Responders

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

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)?

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?

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

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

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

Hepatitis A Prevention Update

Source: Nelson NP, et al. MMWR. July 3, 2020

HAV U.S., 2013–2017

Polling Question 7

• Should all adults with HIV who are not immune to HAV receive HAV vaccine?

1. Yes

2. No

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.

Polling Question 8

• Should you perform post-vaccination serologic testing in persons with HIV who receive HAV vaccine?

1. Yes

2. No

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.

Polling Question 9

• Should you defer giving HAV vaccine if CD4 count low (less than 200 cellsmm3)?

1. Yes

2. No

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.

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.

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.

Questions