Study of Anti-HIV Therapy Intensification
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
First received: April 22, 2002
Last updated: May 17, 2012
Last Verified: May 2012
History of Changes
The purpose of this study is to see how the body's immune system changes after replacing and
adding new anti-HIV drugs to a patient's current anti-HIV therapy. This study will also see
whether adding drugs is safe. Patients who take part in A5136 are also eligible to take part
in 2 substudies. The purpose of substudy A5140s is to see how many latently infected cells
(cells in which the HIV virus survives) are in the lymph node (small, rounded structures that
make disease-fighting cells). Substudy A5155s will be performed to see how many latently
infected cells are in the blood before and after replacing and adding anti-HIV drugs.
ACTG A5136 is a follow-up study to ACTG 315 and ACTG 375, which were designed to examine the effects of highly active antiretroviral therapy (HAART) in certain HIV-infected patients. Many HIV-infected patients have undergone long-term anti-HIV therapy and have had the virus suppressed. However, most of these patients still have problems with their immune systems. The reason for these problems is unknown. This study may help researchers understand what causes immune system problems in people who have low levels of HIV in their blood.
Drug : Lopinavir/Ritonavir
Drug : Lamivudine/Zidovudine
Drug : Tenofovir disoproxil fumarate
Biological : Pneumococcal Vaccine, Polyvalent (23-valent)
Drug : Lamivudine
Drug : Stavudine
Drug : Zidovudine
Drug : Didanosine
Biological : Lyme Disease Vaccine Recombinant OspA
Biological : Haemophilus B Conjugate Vaccine
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Immunologic Consequences of Antiretroviral Therapy Intensification in Subjects With Moderately Advanced HIV-1 Disease: A Follow-Up Study to ACTG 315/375|
Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):
|Study Completion Date:||June 2006|
ACTG 315 and its follow-up study, ACTG 375, were designed to examine the immunologic and
virologic consequences of highly active antiretroviral therapy (HAART) in patients with
moderately advanced HIV-1 disease. At the conclusion of ACTG 375, patients eligible for
participation in ACTG A5136 will have received over 5 years of antiretroviral therapy.
Despite long-term therapy and long-term maximal viral suppression in most patients,
significant immune defects such as impaired response to antigens, including HIV, abnormally
low CD4 cell counts, abnormally high immune activation, and decreased expression of CD28
persist. It is uncertain whether these defects persist as a result of irreversible damage
inflicted by HIV infection or ongoing immune perturbation resulting from continuous low-level
HIV replication. Cellular reservoirs of HIV that persist (despite undetectable plasma viral
load) may contribute to persistent immune activation and impaired immune function. A great
deal of information on the relationship between low-level viral replication and persistent
immune impairment may be gained by investigating these patients before and after
intensification of their antiretroviral therapy regimens.
Patients continue to receive their ACTG 375 antiretroviral therapy until they register to A5136. Following entry evaluations, patients replace the protease inhibitors (PIs) in their ACTG 375 regimen with lopinavir/ritonavir (LPV/r), add tenofovir disoproxil fumarate (TDF) to their regimen, and maintain the rest of their ACTG 375 regimen for 48 weeks. Patients have clinic visits at entry and at Weeks 4, 12, and 16. After 24 weeks, patients have clinic visits every 12 weeks. Blood is drawn at these visits for viral load, immune response, and other routine tests. A skin test, a urine sample collection, and a pregnancy test (for women of reproductive potential) are also performed at entry. Patients also receive immunizations. At Weeks 12 and 16, a lyme vaccine, polyvalent is administered. At Week 36, lyme vaccine, polyvalent; pneumococcal vaccine, polyvalent; and haemophilus b conjugate (HIB) vaccine are administered [AS PER AMENDMENT 05/14/02: Lyme disease vaccine has been removed from the study due to unavailability]. At Week 48, skin tests are performed. Week 52 is the final clinic visit, at which blood is drawn and a urine sample is taken.
Patients who participate in substudy A5140s undergo 2 lymph node aspirates, at entry and at Week 48. Patients participating in substudy A5155s have blood drawn at screening and Week 48.
|Ages Eligible for Study:||Child, Adult, Senior|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Patients may be eligible for this study if they:
- Have completed ACTG 375 within 2 weeks of finishing Week 230.
- Have a viral load less than 400 copies/ml within 90 days prior to study entry.
- Agree not to become pregnant or to impregnate during the study. The female patient/male partner must use acceptable methods of contraception while receiving study drugs and for 1 month after stopping the drugs. Women and men who cannot have children are eligible without requiring the use of contraception, but they must provide acceptable documentation of menopause, sterilization, or lack of sperm cells.
- Need to use certain drugs within 30 days of study entry.
- Have taken any immunomodulatory therapies within 30 days prior to study entry unless approved by the protocol chairs.
- Have a history of serious kidney problems.
- Are allergic or sensitive to the study drugs.
- Are pregnant or breast-feeding.
- Have an alcohol or drug dependency that, in the opinion of the investigator, would
Patients may not be eligible for this study if they:
Contacts and LocationsChoosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00034086
Locations Show More
|United States, Colorado|
|University of Colorado Hospital CRS|
|Aurora, Colorado, United States|
|United States, Illinois|
|Rush Univ. Med. Ctr. ACTG CRS|
|Chicago, Illinois, United States, 60612|
|United States, Ohio|
|Cleveland, Ohio, United States, 44106|
Sponsors and CollaboratorsNational Institute of Allergy and Infectious Diseases (NIAID)
|Study Chair:||Kimberly Smith|
|Study Chair:||Hernan Valdez|
|Responsible Party:||National Institute of Allergy and Infectious Diseases (NIAID)|
|ClinicalTrials.gov Identifier:||NCT00034086 History of Changes|
|Other Study ID Numbers:||A5136|
|ACTG A5140s- Substudy|
|ACTG A5155s- Substudy|
|Study First Received:||April 22, 2002|
|Last Updated:||May 17, 2012|
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):Lopinavir
HIV Protease Inhibitors
CD4 Lymphocyte Count
Additional relevant MeSH terms:
Lamivudine, zidovudine drug combination
Heptavalent Pneumococcal Conjugate Vaccine
ClinicalTrials.gov processed this data on March 27, 2020
This information is provided by ClinicalTrials.gov.