Safety of Cotrimoxazole in HIV- and HAART-exposed Infants

Study Overview
=================
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.

Official Title
-----------------
Safety of Cotrimoxazole in HIV- and HAART-exposed Infants in Botswana

Conditions
-----------------
Acquired Immunodeficiency Syndrome, Infant, Newborn, Anemia, Neutropenia, HIV Infections

Intervention / Treatment
-----------------
* Drug: cotrimoxazole


Participation Criteria
=================
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
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cotrimoxazole<br> | Drug: cotrimoxazole<br>* Daily oral cotrimoxazole suspension from 1 to 6 months of age at the following weight-based doses: less than 5kg: 100mg sulfamethoxazole, 20mg trimethoprim greater than 5kg: 200mg sulfamethoxazole, 40mg trimethoprim<br>* Other names: trimethoprim-sulfamethoxazole;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of severe or life-threatening anemia | incidence of severe or life-threatening anemia (as defined by DAIDS toxicity tables, 2004) between 1 and 6 month of life | between 1 to 6 months of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of severe or life-threatening neutropenia | incidence of severe or life-threatening neutropenia (as defined by DAIDS toxicity tables, 2004) between 1 and 6 month of life | between 1 to 6 months of life | 
| composite severe morbidity and mortality | Composite of severe morbidity (grade 3 or 4 illnesses, DAIDS toxicity tables, 2004), hospitalization, and mortality. | between 1 and 6 months of life | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Antiretroviral Therapy, Highly Active, Trimethoprim-Sulfamethoxazole Combination, anemia, neutropenia, safety, hematologic toxicity