Safety of Cotrimoxazole in HIV- and HAART-exposed Infants

Sponsor

Harvard School of Public Health (HSPH) (Other)

Overall Status

Completed

CT.gov ID

NCT01086878

Collaborator

National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Fogarty International Center of the National Institute of Health (NIH), Harvard Initiative for Global Health (Other), The American Society of Tropical Medicine and Hygiene (Other)

222

Enrollment

Locations

Arm

19.9

Duration (Months)

111

Patients Per Site

5.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acquired Immunodeficiency Syndrome Infant, Newborn Anemia Neutropenia HIV Infections	Drug: cotrimoxazole	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

222 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Feb 1, 2009

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cotrimoxazole	Drug: cotrimoxazole 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 Other Names: Bactrim Septrim Cotrim Septra trimethoprim/sulfamethoxazole trimethoprim-sulfamethoxazole

Arm

Intervention/Treatment

Experimental: Cotrimoxazole

Drug: cotrimoxazole

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

Other Names:

Bactrim

Septrim

Cotrim

Septra

trimethoprim/sulfamethoxazole

trimethoprim-sulfamethoxazole

Outcome Measures

Primary Outcome Measures

incidence of severe or life-threatening anemia [between 1 to 6 months of life]
incidence of severe or life-threatening anemia (as defined by DAIDS toxicity tables, 2004) between 1 and 6 month of life

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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