Clinical Trial: When to Start Anti-HIV Drugs in Patients with Opportunistic Infections

This study is currently recruiting patients.

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)


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

MedlinePlus related topics:  AIDS;   Parasitic Diseases;   Viral Infections

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Official Title: A Phase IV Study of Antiretroviral Therapy for HIV Infected Adults Presenting with Acute Opportunistic Infections: Immediate Versus Deferred Initiation of Antiretroviral Therapy

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


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.

Location and Contact Information

      Stanford Univ, Stanford,  California,  94305-5107,  United States; Recruiting
Debbie Slamowitz  650-723-2804 

      San Mateo County AIDS Program, Stanford,  California,  94305-5107,  United States; Recruiting
Debbie Slamowitz  650-723-2804 

      Willow Clinic, Stanford,  California,  94305-5107,  United States; Recruiting
Debbie Slamowitz  650-723-2804 

      Santa Clara Valley Medical Ctr, Stanford,  California,  94305-5107,  United States; Recruiting
Debbie Slamowitz  650-723-2804 

      San Francisco General Hosp, San Francisco,  California,  94110,  United States; Recruiting
Michele Downing  415-514-0550  Ext. 354 

      Univ of California, Davis Med Ctr, Sacramento,  California,  95814,  United States; Recruiting
Nancy Fitch, NP  916-914-6322 

      UC Davis Med Ctr, Sacramento,  California,  95814,  United States; Recruiting
Nancy Fitch, NP  916-914-6322 

      Harbor General/UCLA, Torrance,  California,  90502-2052,  United States; Recruiting
Mario Guerrero, MD  310-222-3848 

      University of California, San Diego Antiviral Rese, San Diego,  California,  92103,  United States; Recruiting
Jill Kunkel, RN  619-543-8080 

      Univ of Colorado Health Sciences Ctr, Denver, Denver,  Colorado,  80262-3706,  United States; Recruiting
M. Ray  303-372-5535 

      Univ of Miami, Miami,  Florida,  33136-1013,  United States; Recruiting
Leslie Thompson  305-243-3838 

      Emory University, Atlanta,  Georgia,  30308,  United States; Recruiting
Ericka R. Patrick, RN  404-616-6313 

      Northwestern University, Chicago,  Illinois,  60611-3015,  United States; Recruiting
Baiba Berzins, MPH  312-695-5012 

      Cook County Hospital Core Center, Chicago,  Illinois,  60612,  United States; Recruiting
Joanne Despotes, RN, MPH, ACRN  (312) 572-4545 

      Indiana Univ Hosp, Indianapolis,  Indiana,  46202-5250,  United States; Recruiting
Beth Zwickl  317-274-8456 

      Methodist Hospital of Indiana, Indianapolis,  Indiana,  46202-1261,  United States; Recruiting
Sarah Ryan  317-929-2917 

      Wishard Hosp, Indianapolis,  Indiana,  46202,  United States; Recruiting
Scott Hamilton  317-630-6023 

      University of Maryland, Institute of Human Virology, Baltimore,  Maryland,  21201,  United States; Recruiting
Sandy Zaremba, RN, CCRC  410-706-1476 

      Johns Hopkins University, Baltimore,  Maryland,  21287-8106,  United States; Recruiting
Ilene P Wiggins, RN  410-614-2766 

      Brigham and Womens Hospital, Boston,  Massachusetts,  02215,  United States; Recruiting
Carolyn Koziol, RN  617-732-5635 

      Harvard (Massachusetts General Hospital), Boston,  Massachusetts,  02114,  United States; Recruiting
Teri Flynn, RN, ANP  617-724-3819 

      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States; Recruiting
Helen Fitch, RN, BSN  617-632-0785 

      Hennepin County Medical Clinic, Minneapolis,  Minnesota,  55455-0392,  United States; Recruiting
Ellen Kane, RN, BSN  612-347-2690 

      Washington Univ (St. Louis), St. Louis,  Missouri,  63108-2138,  United States; Recruiting
Michael Klebert  314-454-0058 

      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
Mykyelle Crawford  212-305-2665 

      NYU/Bellevue, New York,  New York,  10016-6481,  United States; Recruiting
Maura Laverty  212-263-6565 

      Univ of Rochester Med Ctr, Rochester,  New York,  14642-0001,  United States; Recruiting
Carol Greisberger  585-275-2740 

      Community Health Network, Inc., Rochester,  New York,  14642-0001,  United States; Recruiting
Carol Greisberger  585-275-2740 

      Beth Israel Medical Center, New York,  New York,  10003,  United States; Recruiting
Ann Marshak  212-420-4432 

North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  27514,  United States; Recruiting
Cheryl Marcus  919-843-8761    cjm@med. 

      Duke University Medical Center, Durham,  North Carolina,  27710,  United States; Recruiting
Suzanne Aycock, RN, BSN, CCRC  919-684-8216 

      Ohio State University, Columbus,  Ohio,  43210,  United States; Recruiting
Todd L. Lusch, BA  614-293-8112 

      University of Cincinnati, Cincinnati,  Ohio,  45267-0405,  United States; Recruiting
Tammy Powell, RN  513-584-8373 

      Case Western Reserve University, Cleveland,  Ohio,  44106-5083,  United States; Recruiting
Jane Baum, BSN, RN  216-844-2546 

      University of Pennsylvania, Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
Joseph Quinn, RN  215-349-8092 

      Presbyterian Medical Center - Univ. of PA, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
Joseph Quinn, RN  215-349-8092 

Rhode Island
      The Miriam Hospital, Providence,  Rhode Island,  02906,  United States; Recruiting
Joan Gormley, BSN  401-793-4396 

      Comprehensive Care Clinic, Nashville,  Tennessee,  37203,  United States; Recruiting
Janet Nicotera, RN, BSN  615-467-0154  Ext. 108 

      Univ of Texas, Galveston, Galveston,  Texas,  77555-0435,  United States; Recruiting
Carrier Derkowksi  409-747-0241 

South Africa, Johannesburg
      University of Witwatersrand, PARKTOWN,  Johannesburg,  South Africa; Recruiting
Pauline S. Vunandlala, BSc  01-27-11-717-2810 

Study chairs or principal investigators

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

More Information

Click here for more information on lopinavir/ritonavir

Click here for more information on stavudine

Haga clic aquí para ver información sobre este ensayo clínico en español.


Wislez M, Bergot E, Antoine M, Parrot A, Carette MF, Mayaud C, Cadranel J. Acute respiratory failure following HAART introduction in patients treated for Pneumocystis carinii pneumonia. Am J Respir Crit Care Med. 2001 Sep 1;164(5):847-51.

Bartlett JA, DeMasi R, Quinn J, Moxham C, Rousseau F. Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults. AIDS. 2001 Jul 27;15(11):1369-77.

Hamill RJ. Immune restoration syndrome in AIDS and mycoses. Program and abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16-19, 2001; Chicago, IL. Abtract 1272.

Nunez M, Asencio R, Valencia ME, Leal M, Gonzalez-Lahoz J, Soriano V. Rate, causes, and clinical implications of presenting with low CD4+ cell counts in the era of highly active antiretroviral therapy. AIDS Res Hum Retroviruses. 2003 May;19(5):363-8.

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

Cache Date: April 9, 2005