This study will examine the effects of increases in HIV blood levels on the immune system. A
better understanding of how HIV alters the immune response may lead to development of
effective immune-based therapies against the virus.
Patients 18 years of age or older with HIV-1 infection who have been receiving highly active
antiretroviral therapy (HAART) may be eligible for this study. In order to study the effect
of increased levels of virus on the immune system, therapy will be stopped in these patients
temporarily. Therefore, only patients who have an appropriate level of understanding of the
potential benefits of therapy and the risks of stopping treatment will be considered for
enrollment. Pregnant women may not participate and women of childbearing potential must agree
not to become pregnant during the study. Candidates will be screened with a medical history,
physical exam, blood and urine tests and possibly a chest X-ray and electrocardiogram.
Upon entering the study, participants will have blood tests to measure the amount of virus in
the blood, CD4+ T cell counts, side effects of the medications, and how the patient s immune
system responds to HIV in the test tube. White cells will be collected through leukapheresis.
In this procedure, a needle is placed in an arm vein and blood flows from the vein through a
tube (catheter) into a cell separator machine, where the white cells are separated from the
rest of the blood by a spinning process. Some of the white cells are collected by the
machine, and the rest of the blood is returned to the body through a second needle placed in
the other arm. Patients will then have a physical examination and blood tests every 1 to 2
weeks and will be managed according to their viral load and CD4 cell counts as follows:
- If viral blood levels remain less than 5000 copies per milliliter, no medical
intervention is planned.
- If viral blood levels rise to 5,000 copies per ml or higher, patients will undergo a
second leukapheresis and re-start antiretroviral therapy. They will be monitored at
least monthly until viral load returns to pre-study levels.
- If the CD4 count rises or remains at pre-study levels, no intervention is planned.
- If the CD4 count decreases by 10 to 25 percent of pre-study levels, the counts will be
monitored every 2 weeks at least 3 times and then monthly.
- If the CD4 count decreases by 25 percent or more of pre-study values, antiretroviral
therapy will be re-started and counts will be monitored until they return to pre-study
If viral and CD4 levels do not return to pre-study levels promptly, patients will continue to
be monitored and will be advised about possible treatment changes. Alternatively, patients
whose viral and CD4 levels are similar to or better than pre-study values may be offered
laboratory testing every 3 months for at least 1 year if there is a scientific reason to
continue studying the patient s immune system. Patients may be asked to undergo additional
leukapheresis in the future, or another interruption of therapy in the future if it is felt
safe to do so.
Highly active antiretroviral therapy (HAART) has been successful in controlling HIV levels in
infected patients, but it is not effective in eliminating the virus from the patient and
life-long therapy is thought to be required. However, proper adherence to HAART regimens is
costly, results in inconveniences to patients, and is not without significant acute and
long-term risks. Many patients are interested in undergoing treatment interruption to relieve
these inconveniences and risks. This study seeks to identify these patients and to monitor
them for virologic and immunologic parameters during the treatment interruption. Patients
that meet the criteria for the study will discontinue all antiretroviral therapy
simultaneously, after which the patient will be monitored by a full panel of virologic,
immunologic, and safety parameters. Through this study, we will attempt to further
characterize the mechanisms by which HIV evades and/or suppresses an effective anti-viral
immune response and to identify features of the virus or the patients' immune responses that
are associated with virologic control following treatment interruption.
- INCLUSION CRITERIA:
Subjects greater than or equal to 18 years of age.
HIV infection confirmed by ELISA and Western blot.
Ability to sign informed consent and willingness to comply with study requirements and
In the judgment of the PI, patient has satisfactory knowledge of the benefits of continuing
HAART as well as the risks of discontinuing such treatment. The patient has a private
physician and the decision to interrupt antiretroviral therapy, the target point (i.e.
viral load or CD4+ T cell count) to reinitiate therapy, and the regiment of antiretrovirals
used upon re-initiation of therapy will be made with this private physician.
History of at least 2 months of ongoing HAART, defined as a minimum three drug regimen
consisting of at least two nucleoside analogs and one protease inhibitor or two nucleoside
analogs and one NNRTI or three nucleosides in place of other drug classes OR patients that
are currently off therapy who are planning on resuming or initiating a HAART regimen within
the next 3 months.
No baseline CD4 counts greater than or equal to 350 cells/microL, with confirmation, within
the last 3 months.
Asymptomatic for significant HIV-related illnesses, such as opportunistic infections and
malignancies other than mucocutaneous Kaposi's sarcoma.
For patients on IL-2 therapy, agreement to resume HAART while undergoing treatment cycles.
Psychiatric illness that, in the opinion of the PI, might interfere with study compliance.
Active substance abuse or history of prior substance abuse that may interfere with protocol
compliance or compromise patient safety.
Women who are pregnant or breastfeeding.
Creatinine greater than 2.
Liver function tests greater than 5 times the normal laboratory values.
Platelet count less than 100,000/mm(3), hemoglobin less than 9 mg/dL, neutrophils less than
PT or PTT (in the absence of documented anti-cardiolipin antibody) prolonged by greater
than 2 seconds.
Known underlying bleeding disorder.
Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS disease as
detectable on routine history, physical examination, or screening laboratory studies.
History of significant opportunistic infection or HIV-associated malignancy.
Patient must not ever have had a total CD4 count of less than or equal to 150 cells/cubic
millimeter during the year prior to enrollment. At least 2 measurements, possibly including
the measurement during the screening visit and/or H&P visit, must be available.
Due to a possible increased risk of a hypersensitivity reaction, patients on an
abacavir-containing regimen will not be eligible for treatment interruption.
Patients with chronic hepatitis B infection receiving treatment with 3TC (lamivudine),
adefovir, or tenofovir for suppresion are not eligible for this study.