Primary prophylaxis in humman immuno defieincy virus

Prophylaxis to Prevent First Episode of Opportunistic Diseases in HIV (Human Immune deficiency Virus) Infected Patients

Dr . Hythum Salah H.Mohamed - NGHA-KAMC-Riyadh 2nd September 2014

Introduction

• HIV-related immunosuppression significantly increases the risk for

acquiring opportunistic infections due to bacteria, viruses, fungi, and

protozoa.

• These opportunistic infections are a major source of morbidity and

mortality in HIV-infected patients .

• The widespread use of potent antiretroviral therapy (ART) has led

to a dramatic decline in the incidence of opportunistic infections .

www.uptodate.com

http://www.uptodate.com/

Opportunistic infections (OIs) associated with human immunodeficiency virus (HIV) infection

• Pneumocystis pneumonia

• Toxoplasma gondii encephalitis

• Cryptosporidiosis• Microsporidiosis• Mycobacterium

tuberculosis (TB) infection and disease

• Disseminated Mycobacterium avium complex (MAC) disease

• Bacterial respiratory disease• Bacterial enteric disease

www.guideline.gov (DHHS (U.S. Department of Health & Human Services)).

• Mucocutaneous candidiasis• Cryptococcosis• Histoplasmosis• Coccidioidomycosis• Aspergillosis• Cytomegalovirus (CMV)

disease• Herpes simplex virus (HSV)

disease• Human herpesvirus-8 (HHV-

8) disease• Varicella-zoster virus (VZV)

disease• Human papillomavirus (HPV)

disease• Syphilis• Bartonellosis

http://www.guideline.gov/

• Hepatitis B virus (HBV) infection

• Hepatitis C virus (HCV) infection

• Progressive multifocal leukoencephalopathy/JC virus infection

• Geographic OIs of specific consideration including

1-malaria

2-Penicilliosis marneffei

3- leishmaniasis

4- isosporiasis

5- Chagas disease.

www.guideline.gov (DHHS (U.S. Department of Health & Human Services)).

http://www.guideline.gov/

CD4 cell

• CD4 (cluster of differentiation

4) is a glycoprotein found on

the surface of immune cells

such as T helper cells,

monocytes, macrophages, and

dendritic cells.

• It was discovered in the late

1970s and was originally

known as leu-3 and T4 before

being named CD4 in 1984.

Alain Bernard (1984). Leucocyte typing: human leucocyte differentiation antigens .

Crystallographic structure of the V-set and

C2 domains of human CD4

• CD4 is a co-receptor that assists the T cell receptor (TCR) in

communicating with an antigen-presenting cell .

• HIV uses CD4 to gain entry into host T-cells and achieves this

through its viral envelope protein known as gp120 .

• HIV infection leads to a progressive reduction in the number of T

cells expressing CD4.

• A normal CD4 count in a healthy, HIV-negative adult can vary but is

usually between 500 and 1500 CD4 cells/mm3 .

• Factors other than HIV can affect CD4 count including infections,

time of day, smoking, stress .

www.aidsmap.com

http://www.aidsmap.com/

• Women living with HIV may find their CD4 count varies at different

points in the menstrual cycle, and taking oral contraceptives can

also affect the CD4 count.

• Only about 2% of the body's CD4 cells are in the blood; the rest are

in tissues such as lymph nodes.

• A CD4 percentage that is greater than 29% usually means that your

immune system is functioning normally ( CD4 count is roughly >500

cells/mm3).

www.aidsmap.com

http://www.aidsmap.com/

Pneumocystis Pneumonia (PCP)

• Indications of Primary Prophylaxis

• CD4 T-lymphocyte (CD4) count <200 cells/mm3 (AI), or

• Oropharyngeal candidiasis (AII), or

• CD4% <14% (BII),

• History of acquired immunodeficiency syndrome (AIDS)-defining illness (BII).

aidsinfo.nih.gov/guidelines (DHHS Guidelines)

• CD4 count >200 but <250 cells/mm3 and if CD4 cell count

monitoring (e.g., every 3 months) is not possible (BII)

• Patients who are receiving pyrimethamine/sulfadiazine for treatment

or suppression of toxoplasmosis do not require additional

prophylaxis for PCP (AII).

• Preferred Therapy

• Trimethoprim-sulfamethoxazole (TMP-SMX), 1 double strength (DS)

orally (PO) dailya (AI), or

• TMP-SMX, 1 single strength (SS) PO dailya (AI).


Alternative Therapy

• TMP-SMX 1 DS PO thee time weekly (TIW)a (BI), or

• Dapsoneb 100 mg PO daily or 50 mg PO twice daily (BID) (BI), or

• Dapsoneb 50 mg PO daily + (pyrimethamine 50 mg + leucovorin 25

mg) PO weekly (BI), or

• (Dapsoneb 200 mg + pyrimethamine 75 mg + leucovorin 25 mg) PO

weekly (BI), or

• Aerosolized pentamidine 300 mg via Respirgard II™ nebulizer

every month (BI), or

• Atovaquone 1500 mg PO daily with food (BI), or

• (Atovaquone 1500 mg + pyrimethamine 25 mg + leucovorin 10 mg)

PO daily with food (CIII).aidsinfo.nih.gov/guidelines (DHHS Guidelines)

Indication for Discontinuing Primary Prophylaxis

• CD4 count increased from <200 cells/mm3 to ≥200 cells/mm3 for at least 3 months in response to ART (AI) .

Indication for Restarting Primary Prophylaxis

• CD4 count <200 cells/mm3 (A) .

• Note: Patients who develop PCP despite TMP-SMX prophylaxis usually can be treated effectively with standard doses of TMP-SMX(BIII).

• For Moderate to Severe PCP—Total Duration = 21 Days (AII).


Toxoplasma gondii Encephalitis

Indications for Initiating Primary Prophylaxis

• Toxoplasma immunoglobulin G (IgG) positive patients with CD4 count <100 cells/mm3 (AII).

• Toxoplasma seronegative patients receiving a PCP prophylaxis regimen not active against toxoplasmosis should have toxoplasma serology retested if CD4 count declines to <100 cells/mm3 (CIII).

• Prophylaxis against toxoplasmosis should be initiated if seroconversion occurred (AII).


• Note: All the recommended regimens for preventing 1st episode of

toxoplasmosis are also effective in preventing PCP.

Preferred Regimen

• TMP-SMX 1 DS PO daily (AII)

Alternative Regimens

• TMP-SMX 1 DS PO TIW (BIII), or

• TMP-SMX SS PO daily (BIII), or

• Dapsonea 50 mg PO daily + (pyrimethamine 50 mg + leucovorin 25

mg) PO weekly (BI), or

• (Dapsonea 200 mg + pyrimethamine 75 mg + leucovorin 25 mg) PO

weekly (BI).


• Atovaquoneb 1500 mg PO daily (CIII)


• CD4 count >200 cells/mm3 for >3 months in response to ART (AI)


• CD4 count <100 to 200 cells/mm3 (AIII) .


Disseminated Mycobacterium aviumComplex (MAC) Disease .

Indications for Primary Prophylaxis

• CD4 count <50 cells/mm3 after ruling out disseminated MAC disease based on clinical assessment (which may include mycobacterial blood culture for some patients) (AI).


Scanning electron micrograph of M. paratuberculosis. Image courtesy of Johne's Information Center , University of Wisconsin

Preferred Regimen

• Azithromycin 1200 mg PO once weekly (AI), or

• Clarithromycin 500 mg PO BID (AI), or

• Azithromycin 600 mg PO twice weekly (BIII)

Alternative regimen

• Rifabutin 300 mg PO daily (BI).


Note: Active TB should be ruled out before starting rifabutin.


• CD4 count >100 cells/mm3 for ≥3 months in response to ART (AI)


• CD4 count <50 cells/mm3 (AIII).


Histoplasmosis (Histoplasma capsulatumInfections)

Indications for Primary

Prophylaxis

• CD4 count <150 cells/mm3 and

at high risk because of

occupational exposure or living

in a community with a

hyperendemic rate of

histoplasmosis (>10 cases/100

patient-years) (BI).


Preferred Regimen

Itraconazole 200 mg PO once daily (BI).

Discontinue Primary Prophylaxis

• If used, may discontinue if CD4 count ≥150 cells/mm3 for 6 months on ART (BIII).


• CD4 count <150 cells/mm3 (BIII).


Coccidioidomycosis

Indication of Primary Prophylaxis

• A new positive immunoglobulin

M (IgM) or IgG serologic test in

patients who live in a disease-

endemic area and with CD4

counts <250 cells/μL (BIII).

Regimen

• Fluconazole 400 mg PO once

daily (BIII).aidsinfo.nih.gov/guidelines (DHHS Guidelines)

Penicillium marneffei Infection

Indication for Primary Prophylaxis

• Patients with CD4 count <100 cells/mm3 who reside or stay for a long period in northern Thailand, Vietnam, and Southern China, in particular in rural areas (BI).

Preferred Therapy

• Itraconazolea 200 mg PO once daily (BI)

Alternative Therapy

• Fluconazole 400 mg PO once weekly (BII) .



• CD4 count >100 cells/mm3 for ≥6 months in response to ART (CII).


• CD4 count decreases to <100 cells/mm3 (BIII).


Treating Latent Tuberculosis Infection (LTBI) (to Prevent TB Disease)

Indications

• (+) screening test for LTBI, no

evidence of active TB, and no

prior history of treatment for

active or latent TB (AI)

• Close contact with a person

with infectious TB, regardless

of screening test result (AII).


TB chest x-ray. Credit: Gustoimages/Science Photo Library

Preferred Therapy (Duration of Therapy = 9 Months)

• Isoniazid (INH) 300 mg PO daily + pyridoxine 25 mg PO daily (AII), or

• INH 900 mg PO twice weekly (BIW) (by directly observed therapy [DOT]) + pyridoxine 25 mg PO daily (BII)

Alternative Therapies

• Rifampin (RIF) 600 mg PO daily x 4 months (BIII), or

• Rifabutin (RFB) (dose adjusted based on concomitant ART) x 4 months (BIII)

• For persons exposed to drug-resistant TB, select anti-TB drugs after consultation with experts or with public health authorities (AII).


Preventing Streptococcus pneumoniaeInfectionsIndications for Pneumococcal Vaccination

• All HIV-infected persons regardless of CD4 count

*** Vaccination Recommendations for Individuals Who Have Not Received Any Pneumococcal Vaccination

Preferred Vaccination

• One dose of 13-valent pneumococcal conjugate vaccine (PCV13) (AI), followed by:

• For patients with CD4+ count ≥200 cells/μL: 23-valent pneumococcal polysaccharide vaccine (PPV23) should be given at least 8 weeks after receiving PCV13 (AII), or

• For patients with CD4 count <200 cells/μL: PPV23 can be offered at least 8 weeks after receiving PCV13 (CIII) or can await increase of CD4 count to >200 cells/μL on ART (BIII).


Vaccination Recommendations for Individuals Who Have Previously Received PPV23

• One dose of PCV13 should be given at least 1 year after the last receipt of PPV23 (AII)

Re-vaccination of PPV

• A dose of PPV23 is recommended for individuals 19–64 years old if ≥5 years have elapsed since the first dose of PPV(BIII).

• Another dose should be given for individuals 65 years or older, if at least 5 years have elapsed since previous PPV23 dose(BIII).

• Vaccine Dosing

• PCV13: 0.5 mL IM

• PPV23: 0.5 mL IM.


Preventing Influenza and Bacterial Pneumonia as a Complication of Influenza

Indication for Influenza Vaccination

• All HIV-infected persons during influenza season (AIII)

Vaccination

• Inactivated influenza vaccine per recommendation of the

season (AIII)

• Note: Live attenuated influenza vaccine is contraindicated in HIV-

infected persons (AIII).


Syphilis (Treponema pallidum Infections)

Indication for Treatment

• An individual who was exposed sexually within 90 days preceding the diagnosis of primary, secondary, or early-latent syphilis in a sex partner (AII).

Individuals exposed >90 days before syphilis diagnosis in a sex partner, if serologic test results are not available immediately and the opportunity for follow-up is uncertain (AIII).aidsinfo.nih.gov/guidelines (DHHS Guidelines)

Treatment

• Same as for early stage syphilis listed below.

General Considerations for Treating Syphilis

• The efficacy of non-penicillin alternatives has not been well-evaluated in HIV-infected persons and should be undertaken only with close clinical and serologic monitoring.

• The Jarisch-Herxheimer reaction is an acute febrile reaction accompanied by headache and myalgias that can occur within the first 24 hours after therapy for early syphilis.

Treatment Recommendations Depending on Stage of Disease

Early Stage (Primary, Secondary, and Early-latent Syphilis)

Preferred Therapy

• Benzathine penicillin G 2.4 million units IM for 1 dose (AII)

• Alternative Therapy (For Penicillin-allergic Patients)

• Doxycycline 100 mg PO BID for 14 days (BII), or

• Ceftriaxone 1 g IM or IV daily for 10–14 days (BII), or

• Azithromycin 2 g PO for 1 dose (BII).


Varicella Zoster Virus (VZV) Diseases

Pre-Exposure Prevention of VZV Primary Infection

Indications

• Adult and adolescent patients with CD4 count ≥200 cells/mm3 without documentation of vaccination, health-care provider diagnosis or verification of a history of varicella or herpes zoster, laboratory confirmation of disease, or persons who are seronegativefor VZV (CIII).

Note: Routine VZV serologic testing in HIV-infected adults and adolescents is not recommended.

Vaccination

• Primary varicella vaccination (Varivax™), 2 doses (0.5 mL subcutaneously [SQ]) administered 3 months apart (CIII).

• If vaccination results in disease because of vaccine virus, treatment with acyclovir is recommended (AIII).

• VZV-susceptible household contacts of susceptible HIV-infected persons should be vaccinated to prevent potential transmission of VZV to their HIV-infected contacts (BIII).

• If post-exposure varicella zoster immune globulin (VariZIG™) has been administered, wait at least 5 months before varicella vaccination (CIII).

• If post-exposure acyclovir has been administered, wait at least 3 days before varicella vaccine (CIII).


Human Papillomavirus(HPV) infection Preventing 1st Episode of HPV Infection

Indications for HPV Vaccination

• Note: Please refer to Pediatric OI guidelines for vaccination of boys and girls under age 13 years.

• HIV-infected; aged 13–26 years (BIII)

• Vaccination Schedules

For Females

• HPV recombinant vaccine quadrivalent (Types 6, 11, 16, 18) 0.5 mL IM at 0, 1–2, and 6 months (BIII), or

• HPV recombinant vaccine bivalent (Types 16, 18) 0.5 mL IM at 0, 1–2, and 6 months (BIII)

For Males

• HPV recombinant vaccine quadrivalent (Types 6, 11, 16, 18) 0.5 mL IM at 0, 1–2, and 6 months (BIII).


Hepatitis A virus (HAV)infection

• HAV-susceptible patients with chronic liver disease, or who are

injection-drug users, or MSM (AII) .

• Hepatitis A vaccine 1 mL IM x 2 doses at 0 and 6–12 months (AII) .

• IgG antibody response should be assessed 1month after

vaccination; non-responders should be revaccinated when CD4

count >200 cells/µL. (BIII) .


Hepatitis B Virus (HBV) Infection

Indications for HBV Vaccination

• Patients without chronic hepatitis B or without immunity to HBV (anti-hepatitis B surface antibody [anti-HBs] <10 IU/mL)(AII).

• Patients with isolated anti-hepatitis B core antibody (anti-HBc) and with negative HBV deoxyribonucleic acid (DNA) (BII).

• Early vaccination is recommended before CD4 count falls below 350 cells/mm3 (AII), as low CD4 count at time of vaccination has been associated with poor response to the vaccine.

• However, in a patient with low baseline CD4 cell count, vaccination should not be deferred until CD4 reaches >350 cells/mm3, as some patients with CD4 <200 cells/mm3 do respond to vaccination (AII).

Vaccination Schedule

• Hepatitis B vaccine IM (Engerix-B® 20 μg/mL or Recombivax HB® 10 μg/mL) at 0, 1, and 6 months (AII), or

• Combined hepatitis A and hepatitis B vaccine (Twinrix®) 1 mL IM as a 3-dose series (at 0, 1, and 6 months) or as a 4-dose series (at days 0, 7, 21–30, and 12 months) (AII).

• Anti-HBs should be obtained 1 month after completion of the vaccine series, anti-HBs <10 IU/mL will be considered as non-responders. (BIII).


For Vaccine Non-responders

• Revaccinate with a second vaccine series (BIII).

• For patients with low CD4 count at the time of first vaccination

series, some experts might delay revaccination until after a

sustained increase in CD4 count with ART (CIII).

Alternative Vaccine Dose for Non-responders

• Some experts recommend revaccinating with 40 μg doses of either

vaccine (CIII).


Malaria• Preventing Malaria in Patients

Traveling to Endemic Areas

• Recommendations are the same for HIV-infected and HIV-uninfected patients.

• Specific recommendations are based on region of travel, malaria risks, and drug susceptibility in the region.

TMP-SMX has been shown to reduce malaria in HIV infected adults in Africa. However, it is not as effective as antimalarial prophylactic regimens. Therefore, HIV-infected travelersshould not rely on TMP-SMX for prophylaxis against malaria (AIII).aidsinfo.nih.gov/guidelines (DHHS Guidelines)

• No antimalarial drug is 100% protective and must be combined with the use

of personal protective measures, (i.e., insect repellent, long sleeves, long

pants, sleeping in a mosquito-free setting or using an insecticide-treated

bed net).

Atovaquone/Proguanil (Malarone)

• Good for last-minute travellers because the drug is started 1-2 days before

traveling to an area where malaria transmission occurs

• Cannot be used by women who are pregnant or breastfeeding a child less

than 5 kg .

• 250 mg atovaquone and 100 mg proguanil once daily started 1-2 days

before travel and for 7 days post last exposure. Very well tolerated medicine

side effects uncommon.

www.cdc.gov/malaria/resources

Chloroquine

• Cannot be used in areas with chloroquine or mefloquine resistance

• Can be used in all trimesters of pregnancy

• 500 mg salt (300 mg base) , One tablet orally, Once weekly , 1-2 weeks before exposure and 4 weeks post exposure .

Doxycycline

• Cannot be used by pregnant women and children <8 years old

• Good for last-minute travellers because the drug is started 1-2 days before traveling.

• 100 mg once daily , 1-2 days before exposure and then daily and for 4 weeks after exposure

Mefloquine (Lariam)

• Good choice for long trips because it is taken only weekly

• Cannot be used in patients with certain psychiatric conditions ,seizure and cardiac conduction abnormalities .

• once weekly ,2-3 weeks before exposure and for 4 weeks post exposure

• can be used in pregnancy .

www.cdc.gov/malaria/resources

Health & Medicine

Primary prophylaxis in humman immuno defieincy virus