Cotrimoxazole Prophylaxis for HIVExposed Infants

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Cotrimoxazole Prophylaxis for HIV-Exposed
Infants
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Objectives

• This presentation discusses
• Definition of cotrimoxazole (CTX) prophylaxis
• Rationale for CTX prophylaxis
• Which infants and children should receive
  cotrimoxazole
• How cotrimoxazole prophylaxis should be
  prescribed
• How cotrimoxazole prophylaxis should be monitored

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What is Cotrimoxazole (CTX)?

• Cotrimoxazole is a combination antibiotic
• Trimethoprim/ sulfamethoxazole (TMP/SMX)
• Bactrim
• Septrim
• Widely available, inexpensive and safe
• Cotrimoxazole is used to treat many different
  types of infection

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What is CTX prophylaxis?

• Use of CTX to prevent the occurrence of
  infections including
• Pneumocystis pneumonia (PCP)
• Other bacterial pneumonias
• Some forms of diarrhea
• Malaria

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Pneumocystis pneumonia (PCP)

• PCP is one of the most common opportunistic
  infections among infants and children with
  HIV/AIDS
• PCP is a deadly infection seen in both adults and
  children with HIV/AIDS
• Studies from Africa show that 10-40 of
  HIV-infected children with respiratory illness
  have PCP infection
• Diagnosis is challenging
• Mortality is very high

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Pneumocystis pneumonia
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Diagnosis of PCP in HIV-Infected Children with
Respiratory Disease
PCP
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Pneumocystis pneumonia (PCP)

• PCP occurs very early in life
• Median age of children with PCP is 3-6 months
• In most settings, this is well before a
  definitive diagnosis of HIV has been made

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PCP is common, peak incidence is between 3-6
months and occurs before infant is identified as
HIV-infected
Number of cases
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Why is CTX prophylaxis recommended for
HIV-exposed infants?

• PCP is
• common
• deadly
• preventable with CTX prophylaxis

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Why else is CTX prophylaxis recommended?

• CTX prophylaxis also protects against infections
  other than PCP
• Bacterial pneumonia
• Diarrheal illness
• Malaria

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CTX decreases mortality and hospitalizations

• The CHAP Trial
• A randomized placebo-controlled trial of 541
  children in Zambia showed that the use of CTX
• Decreased mortality by 43
• Decreased hospitalizations by 23
• Did not increase adverse drug effects

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CTX decreases mortality and hospitalizations
The CHAP Trial

• At a median follow-up of 19 months
• mortality in the CTX group 28
• mortality in the placebo group 42

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CTX prevents malaria in endemic areas

• CHAMP trial in Uganda evaluated efficacy of CTX
  in preventing malaria in HIV-infected children
• 300 HIV-infected children, all on CPT and 88
  used ITN compared with a cohort of 561 non
  HIV-infected children, only 12 used ITN, and
  non received CPT
• Presence of mutations associated with antifolate
  resistance was common in both groups
• 100 in HIV-infected children compared to 75 in
  the HIV-uninfected children
• CTX alone decreased malaria risk by 35
• CTX and ITN decreased malaria risk by 97

Gasasira A et.al., CROI 2007 Abstract 78
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Which infants should receive CTX?

• All HIV-exposed infants should receive CTX
• e.g., all infants born to women known to be
  HIV-infected, or infants with positive rapid
  antibody test
• Starting at 4 - 6 weeks of age or at first visit
  in the clinic
• Until no longer breastfeeding and HIV has been
  definitively excluded

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Why provide CTX prophylaxis to infants whose HIV
status is unknown?

• PCP presents and kills early (3-6 months)
• HIV is often diagnosed late (15-18 months)
• CTX is safe and effective
• If you wait for a definitive diagnosis of HIV,
  you will lose the opportunity to save many lives

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How should CTX be prescribed?

• Dosing guidelines are varied, as multiple
  regimens have been shown to be safe and effective
• Use simplified age based dosing recommended by
  WHO

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Cotrimoxazole Prophylaxis Dosing Recommendations
Or one double strength tablet
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Side Effects

• CTX is generally very well tolerated in children
• Check for tolerance and adherence at every visit
• Side effects and toxicities are more common in
• Adults gt children
• Advanced disease gt early stages of disease
• HIV-infected gt HIV-exposed children

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Information for prescribers - 1

• CTX is usually well tolerated, but should be
  regularly monitored
• Check for tolerance and adherence at every visit
• Side effects are uncommon when CTX is used for
  prophylaxis
• The most common side effects are gastrointestinal
  (nausea, vomiting, diarrhea). Rash and fever are
  less common but also occur.
• Side effects are uncommon in infants

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Information for prescribers - 2

• CTX can cause marrow suppression leading to
  neutropenia (low white blood cell count) and
  anemia (low red blood cell count)
• Use caution when prescribing with other medicines
  known to have hematologic toxicity
• Start CTX after infant has completed AZT
  prophylaxis
• CTX can also cause hepatitis (inflammation of the
  liver) or transaminitis (asymptomatic increase in
  liver enzymes)
• When possible, initiation of CTX and
  nevirapine-containing ART should be separated by
  8-12 weeks

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Information for prescribers - 3

• Contraindications to CTX include
• Allergy to sulfa medications
• Severe renal insufficiency (creatinine gt 3 x
  normal)
• Severe hepatic insufficiency (LFTs gt 5x normal)
• Dapsone may be used in place of CTX for
  patients with sulfa allergy

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Information for caretakers - 1

• CTX is an antibiotic that can keep your baby
  healthy.
• CTX can help prevent your baby from getting
  pneumonia, diarrhea and other problems many
  babies can get.
• You will have to give your baby this medicine for
  the first year of his or her life. Youll get a
  new prescription each time you bring your baby to
  the doctor/nurse.
• CTX is not an antiretroviral medicine and does
  not treat or cure the HIV virus

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Information for caretakers - 2

• The dose of CTX will increase as your child
  grows.
• CTX may be taken with or without food.
• CTX is safe, but can sometimes cause side
  effects. Make sure to tell your health care
  provider if your child has any problems,
  particularly diarrhea, fever, and/or rash.

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Information for Caretakers- 3

• CTX can be given with food
• Tabs can be crushed and mixed with clean water or
  breast milk for infants, jelly or jam for older
  children
• If suspension is available instruct caretakers
  to
• Use a spoon or syringe to accurately measure the
  dose
• Always use the same clean utensil to administer
  dose

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Adherence support is important
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How should CTX be monitored?

• Monitoring for adherence
• Assessment of adherence should be performed at
  every visit
• Monitoring for tolerance and toxicity
• Advice parents to bring the child back if they
  have problems, particularly nausea, diarrhea,
  fever, and/or rash.

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Few HIV-Exposed Infants are Receiving CTX
HIV-Exposed Infants Receiving CTX in countries
with HIV-Related U5M, 2005
UNICEF, 2006
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Why are few exposed infants receiving CTX?

• What are the barriers to the systematic use of
  cotrimoxazole prophylaxis for infants and
  children in this program?

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Potential barriers and solutions
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Potential barriers and solutions
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Pediatric CTX prophylaxis

• Safe and well tolerated
• Inexpensive
• Relatively simple
• Extremely effective
• Strongly recommended
• Saves Lives!