HIV infected people often must take anti-HIV drugs for long periods, leading to long-term drug exposure and toxicity. Interruptions in anti-HIV therapy, also known as structured treatment interruptions (STIs), may have few negative health effects and may be helpful to the overall long-term health of HIV infected people. The purpose of this study is to determine if consecutive STIs are of benefit to HIV infected people who have not previously taken anti-HIV drugs.

Study hypothesis: Immune response to repeated cycles of 2 to 8 weeks off anti-HIV therapy followed by 16 weeks of therapy is not worse than continuous therapy over the same treatment period.

Condition	Treatment or Intervention
HIV Infections	Behavior: Structured treatment interruption  Drug: Lamivudine  Drug: Lopinavir/ritonavir  Drug: Stavudine  Vaccine: Rabies de novo antigen

Further Study Details: 

Primary Outcomes: Delay of viral load setpoint of greater than 30,000 copies/ml
Expected Total Enrollment:  90

Long-term toxicity and the high cost of medications are two problems faced by HIV infected people taking antiretroviral therapy (ART). Previous studies in HIV infected patients suggest that ART with STIs may decrease drug exposure and lessen long-term drug toxicity, while not sacrificing viral suppression and patient health. This study will determine if ART with STIs can maintain the same level of immune function in HIV infected people as continuous ART. This study will recruit patients in South Africa.

This study will last 3.5 years. At study entry, all participants will begin daily ART consisting of lamivudine, lopinavir/ritonavir, and stavudine. At Month 6, only participants who have responded well to ART (CD4 count greater than 250 cells/mm3 and viral load less than 50 copies/ml at Month 6) will be randomly assigned to one of two groups. Group 1 participants will participate in STIs during therapy, and Group 2 participants will receive continuous therapy. People in Group 1 will have treatment interruptions of 2, 4, 8, 8, and 8 weeks of duration in between 12-week periods of ART. People in Group 2 will continue taking ART throughout the study.

At screening, participants will undergo medical history assessment, a physical exam, and magnetic resonance imaging (MRI) and dual energy x-ray absorptiometry (DEXA) scans. There will be at least 27 study visits occurring approximately every 8 weeks, each lasting 45 to 60 minutes. At each study visit, participants will be asked about their quality of life. Blood collection will occur at selected visits. Participants will receive rabies vaccinations at Weeks 40, 41, and 46. A visit at Week 164 will include MRI and DEXA scans, and participants will receive a rabies vaccine booster.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• HIV infected
• CD4 count of 200 to 350 cells/mm3 within 60 days of starting study treatment
• Antiretroviral naive. Participants who have received antiretrovirals through postexposure prophylaxis or short course therapy to prevent mother-to-child transmission are eligible for this study.
• Willing to adhere to study treatment
• Willing to be followed for the duration of this study

Exclusion Criteria:

• History of AIDS-defining illness (CDC category C). Patients with a history of pulmonary tuberculosis are not excluded.
• Newly diagnosed AIDS-defining opportunistic infection or other condition requiring acute therapy at study entry
• Previous therapy with agents with significant myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic, or cytotoxic potential within 30 days prior to study entry
• History of immunomodulatory therapy within 4 weeks prior to screening, or cannot abstain from immunomodulators during the study
• Previously received rabies vaccine
• Current alcohol or drug abuse that, in the opinion of the investigator, may interfere with the study
• Diarrhea (more than 6 stools per day for 7 consecutive days) within 30 days prior to study entry
• Active or suspected acute hepatitis within 30 days of study entry
• Bilateral peripheral neuropathy of Grade 2 or higher at screening
• Inability to tolerate oral medication
• Any clinical condition that, in the opinion of the investigator, would interfere with the study
• Pregnancy or breastfeeding

Luis J. Montaner, DVM, MSci, DPhil      215-898-3934    montaner@wistar.upenn.edu

South Africa
      University of the Witwatersrand, Johannesburg,  South Africa

Study chairs or principal investigators

Luis J. Montaner, DVM, MSci, DPhil,  Principal Investigator,  The Wistar Institute   
Ian M. Sanne, MBBCH, FCP(SA), DTM&H,  Principal Investigator,  University of the Witwatersrand   

Study ID Numbers:  1 R01 AI051986-01A2; R01 AI 51986; Protocol 2411209
Record last reviewed:  January 2005
Last Updated:  January 4, 2005
Record first received:  January 4, 2005
ClinicalTrials.gov Identifier:  NCT00100646
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08