1. Prophylaxis of Opportunistic Infections
HAIVN
Harvard Medical School AIDS
Initiative in Vietnam
M1-07-Prophylaxis of Opportunistic Infections-EN HAIVN Module 1, Revised April 2012

2. Learning Objectives
By the end of this session, participants should be able to:
Differentiate between primary and secondary prophylaxis
Explain the benefits and indications of cotrimoxazole prophylaxis
Describe the process of cotrimoxazole desensitization
Describe how to provide isoniazid (INH) prophylaxis

3. Relationship Between CD4 Count and Opportunistic Infections
The lower a person’s CD4 count is, the more vulnerable he/she is to opportunistic infections (OIs)
Different infections can occur based on how weak a person’s immune system is
The level of the CD4 count determines the OIs a person is at risk for
REMIND patients that the risk of OI is directly related to the CD4 cell count.

4. Sample OIs per CD4 Count CD4 Count OI / Condition Candidal vaginitis
> 500/mm3
Candidal vaginitis
Persistent generalized lymphadenopathy
/mm3
Pneuomoccal pneumonia
Pulmonary tuberculosis
Herpes zoster
Oropharyngeal candidiasis (Thrush)
< 200/mm3
Pneumocystis jiroveci pneumonia
Miliary/extrapulmonary TB
< 100/mm3
Candida Esophagitis
Penicilliosis
Toxoplasmosis
Cryptococcosis
< 50/mm3
Mycobacterium avium complex (MAC)
Disseminated cytomegalovirus (CMV)
POINT OUT, in particular, the CD4 counts that patients become at risk for PCP, TB, and Toxoplasmosis
REFER participants to Handout M1S7.1: Relationship Between Opportunistic Infections and CD4 Count for more information (a fuller list).
REMIND participants that syndromes that present at higher CD4 counts generally occur with increasing frequency at low CD4 counts.

5. Two Types of OI Prophylaxis
Primary prophylaxis:
Giving medication to prevent an OI from occurring in the first place
Secondary prophylaxis:
Giving medication after an OI is treated to prevent it from recurring
Also known as maintenance therapy
EXPLAIN the definitions of primary and secondary prophylaxis.

6. Cotrimoxazole Prophylaxis (CTP)

7. Cotrimoxazole (1) Can prevent: PCP Cerebral toxoplasmosis Malaria
Parasitic diarrheas
Non-typhoid salmonelloses
Streptococcus pneumoniae pneumonia
STATE that studies of CTX prophylaxis has shown again and again that the death rate and the OI rate of patients falls dramatically when taking CTX.

8. Cotrimoxazole (2) The benefits greatly outweigh the risks Benefits
Decreases morbidity and mortality
Inexpensive
Well tolerated
Prepares patient for daily medication taking (adherence)
Concerns
Hypersensitivity (allergic) rash
Anemia
EXPLAIN that studies in Africa show that CTX prophylaxis decreases OI, decreases hospital admissions, and decreases mortality among HIV infected patients.
EXPLAIN that CTX, when given at the low doses used in prophylaxis, has few side effects.
Some patients may experience anemia, or it may contribute to anemia in addition to the other drugs or conditions affecting the patient.
STRESS that the major side effect is hypersensitivity rash, which is common.
The benefits greatly outweigh the risks

9. Cotrimoxazole Allergy (1)
Clinically:
Maculopapular rash
Can have fever
Usually within first few weeks of treatment
Epidemiology
No studies in Asia
In Africa, about 2% had allergy to CTX*
Resolves when drug is stopped
EXPLAIN that there are no published studies of CTX allergy in Asia, but the experience of Tropical Disease Hospital in HCMC is that only a very small percent (1-2%) of patients have allergy to CTX.
In the study from Africa, 9/509 patient (2%) had CTX allergy.
8/9 (89%) were able to take CTX without allergy when started again.
Source: Lancet Oct 16-22;364(9443):
* Lancet Oct 16-22;364(9443):

10. Cotrimoxazole Allergy (2) – How to Manage?
Vietnam MOH guidelines on treatment of HIV/AIDS, 2009
Grade
Management
I – II
Continue CTX
Give antihistamines
Follow closely
III
Stop CTX
Consider desensitization or switch to alternate prophylaxis IV
Stop and do not use CTX again
Use alternate prophylaxis regimen with dapsone
EMPHASIZE that most grade I-II reactions will resolve even when continuing the medication.

11. Cotrimoxazole Desensitization
Desensitization is a rechallenge following an adverse reaction starting with low doses and gradually escalating
Review patient daily or give instructions on how to respond to any reaction:
Type of reaction
Action
No reaction
Progress to the next stage
Minor reaction
Continue same dose for 1 extra day or until the reaction subsides
Once reaction subsides: progress to the next stage
Severe, worsening or persistent reaction
Stop CTX
REFER participants to Handout M1S7.2: MOH Guidelines for HIV/AIDS Diagnosis and Treatment: Co-trimoxazole Desensitization in Adults for reference
EXPLAIN instructions for the desensitization protocol
Most patients will be able to progress through the protocol without any reaction
Offer antihistamines to patients
Any patient who gets a severe reaction must stop immediately.
Any patient who develops a minor reaction should delay going up to the next step.
That means they continue on the same dose for another day or two until the reaction subsides.
When it subsides they can go up to the next dose. If it doesn’t subside or it gets worse the regimen should be stopped.

12. When to Start CTP in Vietnam?
Indications:
CD4 ≤ 350 (any clinical stage)
WHO Stage 3 or 4 regardless of CD4 count
If CD4 testing is not available: clinical stage 2, 3, 4
Pregnant women can use CTX for entire pregnancy
Dose:
Adult: 960 mg/day or 960mg 3x /week
Pediatric: 5 mg/kg/day
Source: Vietnam MOH guidelines on treatment of HIV/AIDS, 2009 and MOH Decision No. 4139

13. When to Stop CTP in Vietnam?
No ARV: continue lifelong
With ARV: stop cotrimoxazole when CD4 > 350
Source: Vietnam MOH guidelines on treatment of HIV/AIDS, 2009 and MOH Decision No. 4139

14. What Should You Do When You Cannot Use Cotrimoxazole?
ASK participants what should you do when you cannot use Cotrimoxazole?
ALLOW time for them to respond, then go to next slide to show the answer.

15. Dapsone Indications: Dose: Note: not effective against other OIs
Prophylaxis of PCP in patients with allergy or adverse reaction to cotrimoxazole
Dose:
Adults: 100 mg daily
Pediatrics: 2 mg/kg once a day
Note: not effective against other OIs
Side effects (uncommon): rash, haemolytic anemia, hepatitis
INTRODUCE that Dapsone is available in Vietnam now. It comes in 50mg tablets and is given as two tablets one time per day.
EXPLAIN that it can cause a rash and hepatitis. In patients with G6PD deficiency it can cause haemolytic anemia. Most importantly it is less effective than CTX in preventing PCP and it does not protect against the large range of infections which CTX does.

16. TB Prophylaxis Therapy

17. Isoniazid Preventive Therapy (IPT)
Indication:
PLHIV with negative TB screening
Dose: Isoniazid 300 mg (5 mg/kg) once daily for 9 months
Must exclude active TB
EXPLAIN that the 2009 Vietnam MoH guidelines recommend IPT for all PLHIV with no active tuberculosis on TB screening.
Source: Vietnam MOH guidelines on treatment of HIV/AIDS, 2009

18. Case Study: Duong Duong, a 23-year-old man is newly diagnosed with HIV
He is clinical stage 1
His initial CD4 count returns at 89 cells/mm3
You perform a TB symptom screen:
He denies fever, cough, sweats, and weight loss
What OIs is he at risk for?
What prophylaxis would you start?
HAVE a participant read the case study presented on this slide.
ASK participants “what OIs is he at risk for?”
ALLOW time for participants to respond.
Answer: CD4 < 100: Tuberculosis, PCP, Candidiasis, Toxoplasma, Cryptococcal meninigits, Penicilliosis. Can refer participants back to Handout M1S7.1: Relationship Between Opportunistic Infections and CD4 Count for more information.
ASK participants “what prophylaxis would you start?”
Answer: (1) Cotrimoxazole for PCP and Toxoplasma; and (2) INH for TB

19. Primary Prophylaxis for Select OIs
Disease/ Agent
Indication
Primary Prophylaxis
When to stop?
Pneumocystis jiroveci
CD4 < 200 or
WHO Stage 3 or 4
Cotrimoxazole (960mg tab) once daily
CD4 > 200 cells/ml for more than 6 months
Toxoplasma gondii
CD4 < 100 or
WHO Stage 4
Mycobacterium tuberculosis
Negative TB screening tests
INH 300 mg daily x 9 months
After treatment course
EXPLAIN that primary prophylaxis in this table is for specific etiologies (Pneumocystis jiroveci, Toxoplasma gondii, Mycobacterium tuberculosis). For general primary prophylaxis, according to MOH Decision No. 4139, CPT in adult patients should be started when CD4<350 and stopped when CD4 > 350 for more than 6 months.
Source: National Guidelines for the Diagnosis and Treatment of HIV/AIDS. MOH, Vietnam

20. Secondary Prophylaxis

21. Secondary Prophylaxis of OIs (1)
Also called “Maintenance Therapy”
OI medication is continued to prevent relapse
Continued for life or until the patient:
starts ART
has an increase in CD4 count which persists over a specified period of time
EXPLAIN that after any acute OIs, the patient has a high risk for recurrent infection. Secondary prophylaxis is used to prevent the recurrence of an infection that a patient has already had.

22. Secondary Prophylaxis of OIs (2)
OIs which require secondary prophylaxis include:
PCP
Cerebral toxoplasmosis
Systemic fungal infections
Disseminated MAC infection
CMV disease
EXPLAIN to participants that systemic fungal infections include cryptococcosis and penicilliosis.

23. Secondary Prophylaxis for Select OIs
Disease / Agent
Indication
Secondary Prophylaxis
When to stop?
Pneumocystis jiroveci
Prior history of PCP
CTX (960mg)
1 tablet daily
CD4 > 200 cells/ml for more than 6 months
Toxoplasma gondii
Prior history of
Toxoplasma encephalitis
Cryptococcus neoformans
cryptococcosis
Fluconazole
mg/day
Penicillium marneffei
penicilliosis
Itraconazole
200 mg daily
EXPLAIN that in general, patients can stop secondary prophylaxis once their CD4 increases above 200 for more than 6 months
MENTION that secondary prophylaxis for other OIs not included on this chart are:
MAC: Clarithromycin (500 mg twice daily) plus Ethambutol (15 mg/kg/day)
CMV: Ganciclovir IV 5mg/kg/day, Valganciclovir orally 900mg/day, or weekly ganciclovir intravitreal injections (for CMV retinitis)
Source: National Guidelines for the Diagnosis and Treatment of HIV/AIDS. MOH, Vietnam

24. Case Study: Nga
Nga, a 25-year-old woman, presents to your clinic for follow-up of penicillium infection
She is about to complete 10 weeks of intensive phase treatment (Itraconazole 400 mg/day)
She has recently been started on ART
She is feeling well and wants to know whether she can stop the Itraconazole at the end of the 10 week course
What should you recommend regarding the Itraconazole?
When can she safely stop it?
HAVE a participant read the case study presented on this slide.
ASK participants “what should you recommend regarding the Itraconazole?”
ALLOW time for participants to respond.
Answer: She needs to stay on itraconazole for secondary prophylaxis. Her dose can be reduced to 200 mg/day
ASK participants “When can she safely stop it?”
Answer: When her CD4 count is greater than 200 cells/mm3 for more than 6 months

25. Key Points
Many OIs can be prevented with the use of primary or secondary
CTP is inexpensive, effective against many OIs, and reduces overall morbidity and mortality
IPT can prevent latent TB from becoming active TB

26. Thank you!
Questions?