Safety of Cotrimoxazole in HIV- and HAART-exposed Infants

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Acquired Immunodeficiency Syndrome; Anemia; Neutropenia; Infant, Newborn
• Intervention / Treatment: Drug: cotrimoxazole

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 Type: Interventional
• Enrollment (Anticipated): 222
• Phase: Phase 4

Contacts and Locations

Study Locations

• Botswana
  • Gaborone, Botswana
    • Princess Marina Hospital
  • Kweneng
    • Molepolole, Kweneng, Botswana
      • Scottish Livingstone Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / 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; Septra; trimethoprim-sulfamethoxazole; Cotrim; Septrim; 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

Collaborators and Investigators

• Sponsor: Harvard School of Public Health (HSPH)
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Fogarty International Center of the National Institute of Health; Harvard Initiative for Global Health; The American Society of Tropical Medicine and Hygiene
• Investigators: Principal Investigator: Shahin Lockman, MD, Harvard School of Public Health (HSPH)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: March 12, 2010
• First Submitted That Met QC Criteria: March 12, 2010
• First Posted (Estimate): March 15, 2010

Study Record Updates

• Last Update Posted (Estimate): February 25, 2011
• Last Update Submitted That Met QC Criteria: February 24, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Antiretroviral Therapy, Highly Active; safety; anemia; neutropenia; Trimethoprim-Sulfamethoxazole Combination; hematologic toxicity
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Slow Virus Diseases; HIV Infections; Neutropenia; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Trimethoprim; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination
• Other Study ID Numbers: BHP031; 2P30AI060354-06 (U.S. NIH Grant/Contract); 3R24TW007988-01S1 (U.S. NIH Grant/Contract)