Pilot Study of the Impact of Adding Raltegravir (MK-0518) to Antiretroviral Therapy in Patients With Undetectable Plasma Virus

This is a non-randomized, non-comparative, single center trial of antiretroviral therapy
intensification using the investigational integrase inhibitor MK-0518 and an investigational
viral load assay to measure response to additional antiviral therapy. Eighteen patients will
receive open-label MK-0518 400 mg P.O. every 12 hours for 28 days in addition to their
prescribed antiretroviral therapy. Patients will take their doses of MK-0518 without regard
to food. The study will enroll patients on antiretroviral therapy regimens with CD4 counts
greater than 200 cells/ul, HIV-1 RNA levels <50 copies RNA/ml plasma using a commercial
assay(conventional Amplicor) and with detectable plasma virus (viral loads ≥ 1 copies RNA/ml
plasma, SCA assay). Acceptable antiretroviral regimens will include those on NRTIs + PI,
NRTIs + NNRTI + PI, or NRTIs + NNRTI-containing regimens. Patients cannot have prior
evidence of resistance to antiretroviral drugs. Patients will be screened for
intensification by history, physical exam, and laboratory evaluations (see below). Patients
who are eligible and who agree to participate will intensify their antiretroviral therapy
for 28 days with MK-0518 400 mg by mouth twice a day. During the 28- day drug addition,
patients will have samples drawn for SCA assay at entry and on days 7, 14, 21, and 28 (+/- 1
d), with the last day of intensification as day 28. Patients will have additional phlebotomy
after intensification on days 29, 30, 35, 42, 49 and 58 (+/- 1 day). The intensification
period is followed by a post- intensification period to determine whether removal of the
drug resulted in viral RNA changes.

Inclusion Criteria:

- HIV-1 infection documented by positive HIV-1 ELISA and positive

- Male or female at least 18 years of age, and able to provide written, informed
consent

- Current antiretroviral therapy with DHHS-recommended regimen: NRTIs + PI, NRTIs +
NNRTI + PI, or NRTIs + NNRTI

- Screening CD4 > 200 cells/ µl and CD4%> 14%; does not require prophylaxis for
opportunistic infections

- Receiving a stable antiretroviral regimen for 4 months prior to screening

- HIV-1 RNA level below the limit of detection by commercial HIV-1 RNA determination
assays for at least 12 months prior to screening.

- HIV RNA ≥ 0.6 copy RNA/ml plasma by SCA(single copy assay)

- Hgb ≥ 9.0 mg/dl, absolute neutrophil count > 1000/mm3, platelet count > 100,000/mm3

- Alkaline phosphatase, AST and ALT < 2.0 x upper limit of normal

- Willing to take MK-0518 for 28 days in addition to ongoing antiretroviral therapy

- Be considered clinically stable, in the opinion of the investigator, at the time of
entry into the study; i.e., clinical status and all chronic medications should be
unchanged for at least two weeks prior to entry.

Exclusion Criteria:

- Prior participation in an MK-0518 or other integrase inhibitor trial

- Requires prohibited medications noted in the protocol

- Requires cytotoxic agents including hydroxyurea or vaccinations during the study
period

- Received immunosuppressive therapy including steroids within one month prior to
treatment in this study

- Used any investigational agents within a month prior to treatment in this study

- Documented resistance to any drug in each of the 4 classes of licensed antiretroviral
agents by genotype or phenotype

- Any febrile illness (T>38oC) in the 3 weeks prior to enrollment

- Any vaccination in the 6 weeks prior to enrollment

- Diagnosis of acute hepatitis due to any cause

- Positive Hepatitis B surface antigen

- Severe renal insufficiency defined as a calculated creatinine clearance at time of
screening as < 30 ml/min, based on the Cockcroft-Gault equation.

- Condition (including but not limited to alcohol or other substance use) which in the
opinion of the investigator would interfere with patient compliance or safety