Clinical trial NCT01086878: Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
Official title: Safety of Cotrimoxazole in HIV- and HAART-exposed Infants in Botswana
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acquired Immunodeficiency Syndrome
Infant, Newborn
Anemia
Neutropenia
HIV Infections
Keywords: Antiretroviral Therapy, Highly Active
Trimethoprim-Sulfamethoxazole Combination
anemia
neutropenia
safety
hematologic toxicity
Lead sponsor: Harvard School of Public Health (HSPH)
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Fogarty International Center of the National Institute of Health
name: Harvard Initiative for Global Health
name: The American Society of Tropical Medicine and Hygiene
First posted: 2010-03-15
Enrollment: 222
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine if prophylactic cotrimoxazole makes severe anemia or neutropenia more common in infants exposed to maternal HIV and combination antiretroviral therapy.

Detailed description: Each year, more than 2 million children are born to HIV-infected women. The World Health Organization (WHO) recommends that these infants receive cotrimoxazole (CTX) prophylaxis starting at 4-6 weeks of age until the period of infant HIV transmission risk is over, and the infant is known to be HIV-uninfected. There is also increasing interest in studying CTX prophylaxis given to all infants of HIV-infected women at the time of initiation of replacement feeding, regardless of infant HIV infection status, to mitigate the high risk of infant morbidity and mortality associated with formula feeding in the developing world. However, infant in utero exposure to maternal antiretroviral drugs can lead to hematologic toxicities in infants. It is critical to know whether infant CTX prophylaxis exacerbates the hematologic toxicity associated with perinatal ARV exposure. This question, with broad public health implications, has never been studied.

We will study the hematologic toxicity associated with CTX prophylaxis given to infants exposed to maternal HAART in Botswana. We will use existing data from a large cohort that did not receive CTX, and enroll a smaller cohort that does receive CTX according to Botswana national guidelines.

Eligibility criteria: Both maternal and infant criteria need to be met:

Maternal Inclusion Criteria:

* documented HIV infection
* taking 3-drug highly active antiretroviral therapy at any point during pregnancy (note: can include 2 NRTI+NNRTI, 2NRTI+PI, or 3 NRTI)
* 21 years of age or older, and able and willing to sign informed consent
* Proof of Botswana Citizenship

Maternal Exclusion Criteria:

* involuntary incarceration

Infant Inclusion Criteria:

* younger than 42 days of age
* able to be brought to regular visits at study clinic until at least 6 months postpartum

Infant Exclusion Criteria:

* known pre-existing birth anomalies resulting in a high probability that the baby will not survive to 6 months
* known hypersensitivity to cotrimoxazole

Primary outcomes:
measure: incidence of severe or life-threatening anemia
timeFrame: between 1 to 6 months of life
Secondary outcomes:
measure: incidence of severe or life-threatening neutropenia
timeFrame: between 1 to 6 months of life
measure: composite severe morbidity and mortality
timeFrame: between 1 and 6 months of life
Other outcomes:
Locations:
city: Molepolole
country: Botswana
facility: Scottish Livingstone Hospital
state: Kweneng
city: Gaborone
country: Botswana
facility: Princess Marina Hospital
Study officials:
affiliation: Harvard School of Public Health (HSPH)
name: Shahin Lockman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dryden-Peterson S, Jayeoba O, Hughes MD, Jibril H, McIntosh K, Modise TA, Asmelash A, Powis KM, Essex M, Shapiro RL, Lockman S. Cotrimoxazole prophylaxis and risk of severe anemia or severe neutropenia in HAART-exposed, HIV-uninfected infants. PLoS One. 2013 Sep 23;8(9):e74171. doi: 10.1371/journal.pone.0074171. eCollection 2013.