Cyclosporine A in Combination With Abacavir Sulfate, Lamivudine, and Zidovudine and Lopinavir/Ritonavir in HIV

During the early stages of HIV infection, HIV replicates unchecked, massive numbers of
cluster of differentiation 4 (CD4) T cells are infected and destroyed, and other CD4 cells
become infected but enter a latent phase. This latent pool of infected CD4 cells poses a
difficult challenge in eliminating HIV infection during the early stages of infection because
the cells persist for long periods, even with highly active effective antiretroviral therapy,
and may later become active.

CsA is popularly used as a lifelong immunosuppressant for organ transplant patients. CsA
inhibits cellular activation, including CD4 cell activation and proliferation. By reducing
CD4 cell activation during acute HIV infection, fewer CD4 cells may be infected and die; more
importantly, there may be fewer latent cells with the potential to become active later in the
disease. However, CsA has many potential toxic effects, including renal damage, and may
affect neurologic, endocrine, and hepatic organ systems.

In a previous small study of adults with acute HIV infection, a short 8-week course of CsA
was well tolerated, and it is thought that a 4-week course of CsA may result in substantial
reduction in both viral load and T cell activation, outweighing any potential toxic effects
sustained during the one month treatment. This study will evaluate the safety of and immune
response to a 4-week course of CsA with ABC/3TC/AZT and LPV/r compared to ABC/3TC/AZT and
LPV/r alone in patients with acute HIV infection.

This 48-week study will randomly assign patients to one of two arms. During the first 4 weeks
of the study, Arm A will receive one tablet of ABC/3TC/AZT twice daily, 3 capsules or 2
tablets of LPV/r twice daily, and liquid CsA (dose determined by weight) twice daily. At Week
5, Arm A patients will stop CsA but continue both ABC/3TC/AZT and LPV/r. Arm B will receive
one tablet of ABC/3TC/AZT twice daily and 3 capsules or 2 tablets of LPV/r twice daily for
all 48 weeks. On a case-by-case basis, an investigator may wish to prescribe ABC/3TC rather
than ABC/3TC/AZT at initial therapy. Participants with ABC hypersensitivity will be given
3TC/AZT instead of ABC/3TC/AZT.

A complete physical exam and medical history assessment will occur at study entry and at Week
48. Study visits will occur every week until Week 4, then every 4 weeks until the end of the
study. Blood and urine collection and clinical assessments will occur at each study visit.
Additionally, patients in Arm A only will undergo CsA level monitoring at Day 3 and Weeks 1,
2, and 3; CsA dosage may be adjusted as necessary.

Inclusion Criteria:

- Acute HIV infection with HIV viral load of more than 50,000 copies/ml AND either
negative ELISA OR Western blot with 5 bands or less within 4 weeks prior to study
entry

- Hepatitis B surface antigen negative within 12 weeks prior to study entry

- Hepatitis C antibody negative within 12 weeks prior to study entry

- Willing to use acceptable methods of contraception

Exclusion Criteria:

- Prior antiretroviral therapy. A patient who has undergone Post Exposure Prophylaxis
(PEP) taken at least 6 months prior to study entry is not excluded.

- Allergy or hypersensitivity to any study medications or their components

- Require certain medications, including those that may alter CsA levels or cause renal
dysfunction. More information on this criterion can be found in the protocol.

- Any medical or psychiatric condition, including alcohol or drug abuse, that may
interfere with adherence to study requirements

- Weight less than 88 lbs (40 kg)

- Uncontrolled hypertension

- History of pancreatitis

- History of cancer. Participants with cancer in remission who have not had treatment
for at least 3 years may be eligible for this study.

- Pregnancy or breastfeeding