This study compares 2 different treatments administered to try to prevent serious bacterial infections (such as pneumonia) in HIV-positive children. A combination of drugs (azithromycin plus atovaquone) will be compared to sulfamethoxazole-trimethoprim (SMX/TMP) alone. This study also evaluates the long-term safety and tolerance of these different drugs. SMX/TMP is a commonly prescribed drug for the prevention of bacterial infections. However, the combination of azithromycin and atovaquone may be safer and more effective than SMX/TMP. This study compares the 2 treatments.

Condition	Treatment or Intervention	Phase
Bacterial Infections Pneumonia, Pneumocystis carinii HIV Infections	Drug: Azithromycin  Drug: Atovaquone  Drug: Sulfamethoxazole-Trimethoprim	Phase II

Further Study Details: 

Expected Total Enrollment:  690

Although SMX/TMP remains the drug of choice for PCP prophylaxis, drug sensitivity may limit its use. Atovaquone has demonstrated greater safety than SMX/TMP and thus is suitable as a candidate drug for treatment and prophylaxis of PCP. Azithromycin, with a broad anti-microbial spectrum (including mycoplasma and atypical mycoplasma), is an attractive prophylactic agent for use in children with HIV infection, due to its relative safety and once-daily dosing regimen. Therefore, the combination of atovaquone and azithromycin may offer broader antimicrobial coverage and greater safety than SMX/TMP.

Patients are randomized to receive either SMX/TMP or combination micronized atovaquone/azithromycin. Crossover to the alternative regimen may occur if serious toxicity is observed. Patients are monitored for occurrence of serious bacterial infections or PCP breakthrough, and when a serious bacterial infection occurs, patients are crossed over to the alternative regimen. Treatment continues until 2 years after the last patient is enrolled. The first 30 patients will undergo a pharmacokinetic profile. Patients are followed every 4 weeks for the first 4 months, then every 8 weeks thereafter. [AS PER AMENDMENT 05/28/99: This study was closed to infants and children age 19 months and older on 2/15/99; the study is now open to infants age 3 to 18 months (Stage II). Patients who are age 24 months or older at the time of Stage I closure will have end-of-study evaluations and will no longer be followed on protocol. Patients who are less than 24 months of age at the time of Stage I closure will be allowed to continue in the current version of the protocol. Enrollment for children age 3 to 18 months will continue until 50 subjects have been randomized. Because Stage II is an unblinded study, patients who are less than 24 months of age currently enrolled on Version 4.0 will have their study medication regimen unblinded and their atovaquone dose increased.]

Ages Eligible for Study:  3 Months   -   18 Months,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Children may be eligible for this study if they:

• Are HIV-positive.
• Are between the age of 3 months and 18 months (consent of parent or guardian required). (This study has been changed. In an earlier version, patients up to 19 years old were eligible.)
• Are at risk for developing pneumonia and need preventive treatment.
• Have a CD4 count of less than 1,500 cells/mm3 if under 1 year of age or a CD4 count of less then 500 cells/mm3 if between 1 and 2 years of age.

Exclusion Criteria

Children will not be eligible for this study if they:

• Have an infection that requires treatment.
• Are allergic to atovaquone, azithromycin, or SMX/TMP.
• Have serious diarrhea for more than 1 week.

Alabama
      Univ of South Alabama, Mobile,  Alabama,  36604,  United States
      Univ of Alabama at Birmingham - Pediatric, Birmingham,  Alabama,  35233,  United States
California
      UCSF / Moffitt Hosp - Pediatric, San Francisco,  California,  941430105,  United States
      UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla,  California,  920930672,  United States
      Harbor - UCLA Med Ctr / UCLA School of Medicine, Los Angeles,  California,  905022004,  United States
      Children's Hosp of Oakland, Oakland,  California,  946091809,  United States
      UCLA Med Ctr / Pediatric, Los Angeles,  California,  900951752,  United States
      Children's Hosp of Los Angeles/UCLA Med Ctr, Los Angeles,  California,  900276016,  United States
      Cedars Sinai / UCLA Med Ctr, Los Angeles,  California,  900481804,  United States
      Long Beach Memorial (Pediatric), Long Beach,  California,  90801,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
Colorado
      Children's Hosp of Denver, Denver,  Colorado,  802181088,  United States
Connecticut
      Yale Univ Med School, New Haven,  Connecticut,  06504,  United States
      Connecticut Children's Med Ctr, Farmington,  Connecticut,  060303805,  United States
      Univ of Connecticut / Farmington, Farmington,  Connecticut,  06032,  United States
District of Columbia
      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States
Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States
      Univ of Florida Health Science Ctr / Pediatrics, Jacksonville,  Florida,  32209,  United States
      North Broward Hosp District, Fort Lauderdale,  Florida,  33311,  United States
      Univ of Florida Gainesville, Gainesville,  Florida,  32610,  United States
      Palm Beach County Health Dept, Riviera Beach,  Florida,  33404,  United States
Georgia
      Emory Univ Hosp / Pediatrics, Atlanta,  Georgia,  30306,  United States
      Med College of Georgia, Augusta,  Georgia,  30912,  United States
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  United States
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
      Univ of Illinois College of Medicine / Pediatrics, Chicago,  Illinois,  60612,  United States
      Univ of Chicago Children's Hosp, Chicago,  Illinois,  606371470,  United States
Louisiana
      Tulane Univ / Charity Hosp of New Orleans, New Orleans,  Louisiana,  701122699,  United States
      Earl K Long Early Intervention Clinic, New Orleans,  Louisiana,  70112,  United States
Maryland
      Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore,  Maryland,  21201,  United States
      Johns Hopkins Hosp - Pediatric, Baltimore,  Maryland,  212874933,  United States
Massachusetts
      Children's Hosp of Boston, Boston,  Massachusetts,  021155724,  United States
      Boston City Hosp / Pediatrics, Boston,  Massachusetts,  02118,  United States
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States
      Univ of Massachusetts Med School, Worcester,  Massachusetts,  016550001,  United States
Michigan
      Children's Hosp of Michigan, Detroit,  Michigan,  48201,  United States
Mississippi
      Univ of Mississippi Med Ctr, Jackson,  Mississippi,  39213,  United States
New Jersey
      Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark,  New Jersey,  071032714,  United States
      UMDNJ - Robert Wood Johnson Med School / Pediatrics, New Brunswick,  New Jersey,  089030019,  United States
      Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl, Newark,  New Jersey,  07103,  United States
      Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl, Camden,  New Jersey,  08103,  United States
New York
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
      SUNY - Brooklyn, Brooklyn,  New York,  11203,  United States
      Cornell Univ Med College, New York,  New York,  10021,  United States
      North Shore Univ Hosp, Great Neck,  New York,  11021,  United States
      Schneider Children's Hosp, New Hyde Park,  New York,  11040,  United States
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
      Mount Sinai Med Ctr / Pediatrics, New York,  New York,  10029,  United States
      Metropolitan Hosp Ctr, New York,  New York,  10029,  United States
      Children's Hosp at Albany Med Ctr, Albany,  New York,  12208,  United States
      SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse,  New York,  13210,  United States
      Bronx Lebanon Hosp Ctr, Bronx,  New York,  10457,  United States
      Incarnation Children's Ctr / Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
      State Univ of New York at Stony Brook, Stony Brook,  New York,  117948111,  United States
      Children's Hosp Pact Prog / Children's Hosp of Buffalo, Buffalo,  New York,  14222,  United States
      Montefiore Med Ctr Adolescent AIDS Program, Bronx,  New York,  10467,  United States
      Beth Israel Med Ctr / Pediatrics, New York,  New York,  10003,  United States
      Univ of Rochester Med Ctr, Rochester,  New York,  146420001,  United States
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  277103499,  United States
Ohio
      Columbus Children's Hosp, Columbus,  Ohio,  432052696,  United States
Pennsylvania
      Children's Hosp of Philadelphia, Philadelphia,  Pennsylvania,  191044318,  United States
      Saint Christopher's Hosp for Children, Philadelphia,  Pennsylvania,  191341095,  United States
South Carolina
      Med Univ of South Carolina, Charleston,  South Carolina,  294253312,  United States
Tennessee
      Saint Jude Children's Research Hosp of Memphis, Memphis,  Tennessee,  381052794,  United States
      Vanderbilt Univ Med Ctr, Nashville,  Tennessee,  372322581,  United States
Texas
      Hermann Hosp / Univ Texas Health Science Ctr, Houston,  Texas,  77030,  United States
      Texas Children's Hosp / Baylor Univ, Houston,  Texas,  77030,  United States
Virginia
      Children's Hosp of the King's Daughters, Norfolk,  Virginia,  23507,  United States
      Med College of Virginia, Richmond,  Virginia,  23219,  United States
Washington
      Children's Hospital & Medical Center / Seattle ACTU, Seattle,  Washington,  981050371,  United States
Puerto Rico
      San Juan City Hosp, San Juan,  009367344,  Puerto Rico
      Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan,  009365067,  Puerto Rico
      Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon,  00956,  Puerto Rico

Study chairs or principal investigators

Wayne M Dankner,  Study Chair
Ram Yogev,  Study Chair
Walter T Hughes,  Study Chair

Study ID Numbers:  ACTG 254; PACTG 254
Record last reviewed:  October 2004
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000811
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08