The purpose of this study is to evaluate the effect of starting anti-HIV drugs in HIV infected patients who are being treated for opportunistic infections (OIs). This study will follow two patient groups: those who received anti-HIV drugs soon after being diagnosed with an OI and patients with OIs who deferred beginning anti-HIV drugs until after recovering from the OI.

Condition	Treatment or Intervention	Phase
HIV Infections AIDS-Related Opportunistic Infections	Drug: Lopinavir/ritonavir  Drug: Stavudine	Phase IV

Further Study Details: 

Expected Total Enrollment:  282

Despite the advent of highly active antiretroviral therapy (HAART), many HIV infected patients without access to antiretroviral therapy (ART) present with acute OIs. Such presentations pose a management problem, as there are currently no data available as to whether initiating HAART during the acute presentation is of benefit. Reports of an immune reconstitution inflammatory syndrome (IRIS) marked by increasing hypoxia and/or new pulmonary infiltrates have been associated with the initiation of ART in patients with AIDS. There is also concern as to drug interactions between ART and antimicrobials used to treat the presenting OI. This study will evaluate the possible benefits and costs of initiating ART in HIV infected patients who present with an AIDS defining OI.

Patients in this study will be randomized to one of two study arms. Arm A will receive ART within 2 weeks of starting therapy for the acute OI. Arm B will have ART deferred until at least 4 weeks and no more than 32 weeks after beginning therapy for the acute OI. All patients will be offered the study-provided antiretroviral drugs: lopinavir/ritonavir in combination with stavudine. A third or fourth antiretroviral drug is at the discretion of the study official, although lamivudine is strongly recommended. Drug regimen additions and substitutions will be made on a case-by-case basis. Patients will be followed for 48 weeks and will have 10 study visits. Study visits will include a physical exam, blood tests, and patient questionnaires.

Patients in Arm A are eligible for a substudy to evaluate the pharmacokinetics of the study drugs in patients with Pneumocystis carinii pneumonia, bacterial pneumonia, or other respiratory infections.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria for Step 1:

• HIV-1 infection
• Currently being treated for OI (including Pneumocystis carinii pneumonia [PCP]; cryptococcal meningitis; disseminated histoplasmosis; disseminated Mycobacterium avium complex [MAC]; cytomegalovirus [CMV] retinitis; CMV encephalitis; toxoplasmic encephalitis; other atypical non-tuberculous, non-MAC mycobacterial infections; or other serious, invasive bacterial infections). Participants with bacterial pneumonia or serious bacterial infection must have a CD4 count less than 200 cells/mm3 within 30 days prior to study entry.
• Able to take oral medications
• Able and willing to give written informed consent
• Willing to use acceptable methods of contraception

Exclusion Criteria for Step 1:

• Any ART within 8 weeks prior to study entry
• 31 or more days of any antiretroviral within 6 months prior to entry
• History of more than one virologic, immunologic, or clinical treatment failure while on a HAART regimen, or a history of more than one regimen change for unknown reasons
• Pregnant or breastfeeding
• Systemic cancer chemotherapy within 30 days prior to study entry
• Immunomodulators within 30 days prior to study entry, including growth factors, immune globulin, interleukins, and interferons (unless for HCV or Kaposi’s sarcoma)
• Investigational antiretroviral agents at study entry
• Systemic investigational agents (except antiretroviral drugs) within 30 days prior to study entry will be allowed at the study official’s discretion
• Anticipated use of certain medications
• Renal failure requiring dialysis
• Drug or alcohol use that, in the opinion of the study official, would interfere with the study
• Treatment for current OI or bacterial infection for more than 14 days prior to study entry
• Known resistance to ART that prohibits administration of an effective ART regimen
• Current OI has recurred within 90 days prior to study entry. Recurrent bacterial infections are not excluded.

California
      Stanford Univ, Stanford,  California,  94305-5107,  United States; Recruiting
      San Mateo County AIDS Program, Stanford,  California,  94305-5107,  United States; Recruiting
      Willow Clinic, Stanford,  California,  94305-5107,  United States; Recruiting
      Santa Clara Valley Medical Ctr, Stanford,  California,  94305-5107,  United States; Recruiting
      San Francisco General Hosp, San Francisco,  California,  94110,  United States; Recruiting
      Univ of California, Davis Med Ctr, Sacramento,  California,  95814,  United States; Recruiting
      UC Davis Med Ctr, Sacramento,  California,  95814,  United States; Recruiting
      Harbor General/UCLA, Torrance,  California,  90502-2052,  United States; Recruiting
      University of California, San Diego Antiviral Rese, San Diego,  California,  92103,  United States; Recruiting
Colorado
      Univ of Colorado Health Sciences Ctr, Denver, Denver,  Colorado,  80262-3706,  United States; Recruiting
Florida
      Univ of Miami, Miami,  Florida,  33136-1013,  United States; Recruiting
Georgia
      Emory University, Atlanta,  Georgia,  30308,  United States; Recruiting
Illinois
      Northwestern University, Chicago,  Illinois,  60611-3015,  United States; Recruiting
      Cook County Hospital Core Center, Chicago,  Illinois,  60612,  United States; Recruiting
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  46202-5250,  United States; Recruiting
      Methodist Hospital of Indiana, Indianapolis,  Indiana,  46202-1261,  United States; Recruiting
      Wishard Hosp, Indianapolis,  Indiana,  46202,  United States; Recruiting
Maryland
      University of Maryland, Institute of Human Virology, Baltimore,  Maryland,  21201,  United States; Recruiting
      Johns Hopkins University, Baltimore,  Maryland,  21287-8106,  United States; Recruiting
Massachusetts
      Brigham and Womens Hospital, Boston,  Massachusetts,  02215,  United States; Recruiting
      Harvard (Massachusetts General Hospital), Boston,  Massachusetts,  02114,  United States; Recruiting
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States; Recruiting
Minnesota
      Hennepin County Medical Clinic, Minneapolis,  Minnesota,  55455-0392,  United States; Recruiting
Missouri
      Washington Univ (St. Louis), St. Louis,  Missouri,  63108-2138,  United States; Recruiting
      St. Louis Connect Care, St. Louis,  Missouri,  63108-2138,  United States; No longer recruiting
New York
      Columbia Univ, New York,  New York,  10021,  United States; Recruiting
      NYU/Bellevue, New York,  New York,  10016-6481,  United States; Recruiting
      Univ of Rochester Med Ctr, Rochester,  New York,  14642-0001,  United States; Recruiting
      Community Health Network, Inc., Rochester,  New York,  14642-0001,  United States; Recruiting
      Beth Israel Medical Center, New York,  New York,  10003,  United States; Recruiting
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  27514,  United States; Recruiting
      Duke University Medical Center, Durham,  North Carolina,  27710,  United States; Recruiting
Ohio
      Ohio State University, Columbus,  Ohio,  43210,  United States; Recruiting
      University of Cincinnati, Cincinnati,  Ohio,  45267-0405,  United States; Recruiting
      Case Western Reserve University, Cleveland,  Ohio,  44106-5083,  United States; Recruiting
Pennsylvania
      University of Pennsylvania, Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
      Presbyterian Medical Center - Univ. of PA, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
Rhode Island
      The Miriam Hospital, Providence,  Rhode Island,  02906,  United States; Recruiting
Tennessee
      Comprehensive Care Clinic, Nashville,  Tennessee,  37203,  United States; Recruiting
Texas
      Univ of Texas, Galveston, Galveston,  Texas,  77555-0435,  United States; Recruiting
South Africa, Johannesburg
      University of Witwatersrand, PARKTOWN,  Johannesburg,  South Africa; Recruiting

Study chairs or principal investigators

Andrew R. Zolopa, MD,  Study Chair,  Stanford University   

Study ID Numbers:  ACTG A5164
Record last reviewed:  April 2005
Last Updated:  April 7, 2005
Record first received:  February 19, 2003
ClinicalTrials.gov Identifier:  NCT00055120
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08