December 2001OI Guidelines 11/28/01 2001 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected With Human Immunodeficiency

December 2001 OI Guidelines 11/28/01

2001 USPHS/IDSA Guidelines for the Prevention of

Opportunistic Infections in Persons Infected With Human

Immunodeficiency Virus

Module 1:

Prophylaxis Core

A Training Slide Set Prepared by the AETC National Resource Center


Disclaimer

These slides were developed using the most recent treatment guideline information at the time of production. However, in the rapidly changing field of HIV care this information could become out of date quickly. The user is encouraged to compare the date of this slide set with the date of the most recent guidelines. Also, it is intended that these slides be used, as prepared, without changes in either content or attribution. Users are asked to honor this intent.

AETC National Resource Center


Summary of OIs for Which Prevention Is Recommended

Primary ProphylaxisP. carinii*Tuberculosis*T. gondii*M. avium*Varicella zoster*S. pneumoniae†

Hepatitis A & B†

Influenza †

Secondary ProphylaxisP. carinii*T. gondii*M. avium*Cryptococcosis*Histoplasmosis*Coccidioidomycosis*Cytomegalovirus*Salmonella bacteremia

* Standard of care† Generally recommended


OIs for Which Prevention Is Not Routinely Indicated

Primary Prophylaxis

Bacteria (Neutropenia) †

Cryptococcosis†

Histoplasmosis†

Cytomegalovirus †

Secondary Prophylaxis

Herpes simplex virus §

Candida §

† Evidence for Efficacy but Not Routinely Indicated

§ Recommended only if subsequent episodes are frequent or severe


OI Guidelines November, 2001Comparison of Indications to Discontinue

Primary and Secondary Prophylaxis

Agent Recommendation

PCP 1o CD4 > 200 X 3 months

2o CD4 > 200 X 3 months

Toxo. 1o CD4 > 200 X 3 months

2o CD4 > 200 X 6 months + initial Rx + asymptomatic

MAC 1o CD4 > 100 X 3 months

2o CD4 > 100 X 6 months + 12 mo Rx + asymptomatic


OI Guidelines November, 2001

OIs for Which Primary and Secondary Prophylaxis Is Recommended


P. carinii Pneumonia

Primary ProphylaxisIndication: CD4 < 200 or thrush

When stop: CD > 200 for > 3 moWhen restart: CD4 falls to < 200

Secondary prophylaxisSame as primary


P. carinii Pneumonia

Preferred Regimens:• TMP-SMX DS 1/d*• TMP-SMX SS 1/dAlternative Regimens:• Dapsone 100 mg/d• Dapsone 50 mg/d + Pyrim 50 mg/wk + Leucovorin 25

mg /wk*• Dapsone 200 mg/wk + Pyrim 75 mg/wk + Leuco 25 mg/wk*• Atovaquone 1500 mg/d*• Aerosol pentamidine 300 mg/mo• TMP-SMX DS 3/wk

* Adequate for toxoplasmosis (CD4 <100 + pos serology)


Toxoplasmosis: Primary Prophylaxis

Indication: Pos lgG Toxo + CD4 < 100

When to stop: CD4 > 200 X 3 mo

When to restart: CD4 falls to < 100-200


Toxoplasmosis: Primary Prophylaxis

Preferred Regimen:

TMP – SMX DS 1/d po

Alternative Regimen:

• TMP – SMX SS 1/d

• Dapsone 50 mg/d + Pyrim 50 mg/wk + Leuco 25mg /wk

• Dapsone 200 mg/wk + Pyrim 75 mg/wk + Leuco 25/wk

• Atovaquone 1500 mg/d + Pyrim 25 mg/d + leuco10 mg/d


Toxoplasmosis:Secondary Prophylaxis

Indication:Completion of therapy for toxoplasmosis unless immune reconstitution occurs with HAART.

When to stop: CD4 > 200 X 6 mo + completed initial treatment + asymptomatic

When to restart: CD4 falls to < 200


Toxoplasmosis:Secondary Prophylaxis

Preferred Regimen :• Sulfadiazine 500-1000 mg qid + Pyrimethamine

25-50 mg/d + Leucovorin 10-25 mg/d

Alternative Regimen : • Clindamycin 300-450 mg q 6-8 hr +

Pyrimethamine 25-50 mg/d+ leucovorin10-25 mg/d

• Atovaquone 750 mg q 6-12 hr + Pyrimethamine 25 mg/d + leucovorin 10 mg/d


MAC:Primary Prophylaxis

Indication: CD4 < 50

When to stop: CD4 > 100 for > 3 month

When to restart: CD4 falls to < 50-100


MAC:Primary Prophylaxis

Preferred Regimen:

• Azithromycin 1200 mg/wk or

• Clarithromycin 500 mg bid


• Rifabutin* 300 mg/d or

• Azithromycin 1200 mg/wk + Rifabutin* 300 mg/d

* Dose adjusted for concurrent PI or NNRTI


MAC: Secondary Prophylaxis

Indication: Hx MAC

When to stop: CD4 > 100 X > 6 mo and Rx 12 mo and asymptomatic

When to restart: CD4 falls to < 100


MAC: Secondary Prophylaxis

Preferred Regimen:

Clarithromycin 500 mg bid + Ethambutol 15 mg/kg/d ± Rifabutin* † 300 mg/d


Azithromycin 500 mg/d + Ethambutol 15 mg/kg/d ± Rifabutin* 300 mg/d

* Dose adjusted for concurrent PI..NNRTI† Rifabutin reduces levels of clarithromycin by 50%



OIs for Which Only Primary Prevention Is Generally Recommended


Tuberculosis: Latent Infection

Screening: (5-TU) purified protein derivative

(PPD) by the Mantoux method • When HIV infection is first recognized.• Annual test if TST negative on initial evaluation

and continued risk.• Routine evaluation for anergy is not

recommended.


Tuberculosis: Treatment of Latent Infection

Indications: • PPD > 5 mm induration at 48-72h• Hx PPD + no Rx• TB contact (D/C if PPD neg at 12 wks)

All PPD positives should be evaluated for active TB including chest x-ray.


Treatment of Latent TB Infection: CDC/ATS Guidelines, August 2001*

Recommended Regimens:

• No HIV: INH X 9 mo.• HIV: INH X 9 mo. (if compliance assured)

RIF-PZA X 2 mo.

Alternative: RIF/RBT alone X 4 mo.

* Am J Resp Crit Care 2001; 164:1319



Rationale for RIF-PZA in HIV Co-infection:• Compliance & risk of active disease.• Risk of ALT greater with INH vs RIF-PZA in

HIV co-infected.• 21 reported cases severe RIF-PZA

hepatotoxicity, none had HIV.• Well tolerated in HIV co-infected patients.




RIF-PZA Regimen:HAART: Use RBT & dose adjustmentAdmonitions:• Not recommended: Liver disease or hx INH

hepatotoxicity• Caution: Other hepatotoxic drugs or EtOHPrescription: Only 2 week supply




RIF-PZA Regimen:Monitoring:• Clinical: at 2,4,6,& 8 weeks.• Lab: ALT & Bili at baseline, 2,4, & 6 weeks.Discontinue: 1) Sx + ALT

2) ALT > 5X ULN, or 3) Bili.



Tuberculosis: Treatment of Latent Infection - Regimens

HAART/No HAART:INH 300 mg/d + pyridoxine 50 mg/d X 9 mo (270 doses) †

INH 900 mg + pyridoxine 100 mg 2 X wk X 9 months (76 doses †

† Assuming completion of treatment can be assured.


Tuberculosis: Treatment of Latent Infection - Regimens

HAART:

Rifabutin* daily X 4 months

Rifabutin* + Pyrazinamide 20 mg/kg/d X 2 months (60 doses)

No HAART:

Rifampin 600 mg/d X 4 months

Rifampin 600 mg/d + Pyrazinamide 20 mg/kg/d X 2 months (60 doses)

* Dose adjusted for PI or NNRTI


Tuberculosis: Treatment of

Latent Infection

When to restart: patients previously treated for TB infection or TB disease do not require retreatment based upon diminished immune function alone. Patients with known exposure or suspected of acquiring TB infection may need retreatment. In these instances consultation with experts is strongly recommended.


Rifabutin Dose Modifications With ART Agents

PI/NNRTI

Rifabutin

Daily 2-3 X / Wk

IDV 1000 mg q 8h 150 300

NFV 1250 mg bid 150 300

APV 1200 mg bid 150 300

RTV/SQV 400/400 mg - 150

LPV/RTV 400/100 - 150 qod

NVP 200 mg bid 300 -

EFV 600 hs 450 600


Tuberculosis Prophylaxis Therapeutic Monitoring

Drug Clinical Laboratory Intervention

INH Review monthly for sx hepatitis

LFTs at baseline & 3 mo

D/C if ALT > 5 x ULN

RIF/

PZA

Clinical evaluation at wk 2, 4, 6 & 8

ALT & Bili at 2, 4 & 6 wks or with sx

D/C if:•sx + abn ALT/ AST, or

•ALT/AST > 5 x ULN, or Bilirubin


Varicella-Zoster Virus Disease

Varicella vaccine contraindicated in HIV-infected adults.

Varicella zoster immune globulin (VZIG) for susceptible HIV-infected children and adults. Give ASAP but 96 hours after close contact with a person who has chickenpox or shingles.

No preventive measures are currently available for shingles.


VACCINES: ROUTINE USE

Agent Indication

Hepatitis B Anti-HBc neg

Hepatitis A Risk * + neg anti-HAV

S. pneumoniae CD4 > 200

Influenza Annually, Oct – Nov

* Risk = IDU, MSM, hemophilia, chronic HBV or HCV


VACCINES: OTHER

Give if indicated:

Cholera, Japanese encephalitis, Lyme disease, Tetanus-diptheria, Typhoid inactivated (Typhim V1)


VACCINES: OTHER

Contraindicated (live virus):

Varicella, Yellow Fever, Typhoid live (Ty21a), Measles, Vaccinia



OIs for Which Only Secondary Prevention Is Generally Recommended


Cytomegalovirus Disease

Chronic maintenance therapy following inductionPreferred Regimen:• Ganciclovir IV or PO• Foscarnet IV• Ganciclovir implant + PO (for retinitis)Alternative Regimen:• Cidofovir IV + probenecid PO• Fomivirsen injection in vitreous• Valganciclovir PO

When to stop: CD4 >100-150 X 6 mo + no active disease + negative ophthal exam.

When to restart: CD4 < 100-150


* Consider if CD4 < 100 + endemic area (>10 cases/100 pts-yrs)** CD4 > 100-200 X 6 mo + complete initial therapy + asymptomatic

Prophylaxis Summary: Fungal Agents

Prophylaxis

Infection Primary Secondary D/C 2o Restart 2o

Candida No Severe/

Frequent

? -

Histoplasma No * Yes No -

Cryptococcus No Yes Yes ** CD4 <100

Coccidiodes No Yes No -


Cryptococcosis

Chronic Maintenance Therapy

Regimen: Preferred: Fluconazole (AI). Alternate: Amphotericin B, itraconazole

When to stop: completed initial treatment + asymptomatic + CD4 >100 - 200 X 6 mo on HAART

When to restart: CD4 falls to < 100 - 200


Histoplasmosis

Lifelong Suppressive Therapy

Indication: Completion of therapy for histoplasmosis

Agents: itraconazole (200 mg twice a day).When to stop: Insufficient data (? CD4+ >100

cells/µL)


Coccidioidomycosis

Lifelong Suppressive Therapy

Indication: Completion of therapy for coccidioidomycosis

Regimen: fluconazole PO or itraconazole. Patients with meningeal disease require consultation with an expert.

When to stop: Insufficient data (? CD4+ >100 cells/µL )


Salmonella

Prevention of Reccurrence:Indication: Salmonella septicemia Regimen: Preferred: Fluoroquinolones

(ciprofloxacin) for susceptible organisms.Other Management: Household contacts should

be evaluated for carriage so that hygienic measures and/or antimicrobial therapy can be instituted and recurrent transmission prevented. (Optional)



Infections Requiring Other Management Strategies


Hepatitis C Virus Infection

Prevention of Disease• Recommend screening-if positive: do RIBA/ HCV PCR, then:

– Avoid excessive amounts of alcohol – Vaccinate against hepatitis A – Evaluated for chronic liver disease and for the

possible need for treatment. – Monitor liver enzymes on patients on HAART.– HAART should not be routinely withheld from

patients co-infected with HIV and HCV


Human Papillomavirus Infection

Prevention of DiseaseGenital Epithelial Cancers in HIV-infected Women

Pelvic exam + PAP X 2 in first year after HIV Dx. If normal, repeat PAP annually If abnormal, follow Interim Guidelines for

Management of Abnormal Cervical Cytology (NCI)

Prevention of Recurrence Careful follow-up and monitoring after treatment No specific therapy recommended.



Cost Considerations


Drug Costs Of PCP Prophylaxis

* Administration costs need to be considered.

Agent Dose Annual Cost

TMP – SMX 1 DS/d $ 135

Dapsone 100 mg/d $ 72

Aerosolized pentamidine

300 mg/mo $ 1,185 *

Atovaquone 1500 mg/d $ 11,627


VACCINE COSTS *

* Average Wholesale Price

Vaccine Cost

Influenza $ 3

S. pneumoniae $ 13

Hepatitis A (2 doses) $124

Hepatitis B (3 doses) $ 70


Drug Costs Exceeding $10,000/yr*

* Average Wholesale Price

Agent Dose Annual CostAtovaquone 1500 mg/d $11,627

Valganciclovir 900 mg/d $21,582

IV ganciclovir 5 mg/kg/d $13,093

IV foscarnet 90 mg/kg/d $27,770

Cidofovir 375 mg qow $20,904

Fomivirsen 1 vial q 4 w $12,000


For Additional Information:

Sources of Complete Guidelines:– AETC Resource Center: www.aids-etc.org– AIDS Treatment Information Service:

www.hivatis.org

http://www.aids-ed.org/

http://www.hivatis.org/


OI Guideline SlidesDecember 2001

Author: John G. Bartlett, M.D.

Editor: Richard W. Dunning, M.H.S.

Reviewers:– Renslow Sherer, M.D.– Caroline Teter, PAC, M.P.H.

Documents

December 2001OI Guidelines 11/28/01 2001 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected With Human Immunodeficiency