A Pilot Study Of the Effects of Highly Active Antiretroviral Therapy on Kaposi's Sarcoma in Zimbabwe

Study Overview
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Brief Summary
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Open-label study of a regimen of antiretrovirals for the treatment of AIDS-KS. This study will be conducted at a single site, the Parirenyatwa Hospital KS Clinic. Step 1 was conducted to determine the extent of clinical resolution of AIDS-KS disease in response to treatment with antiretroviral therapy and to investigate whether clinical resolution of KS is associated with suppression of KSHV replication. Step 2 was developed to then evaluate the clinical, immunological, and virological effects of a switch from a twice-daily all-nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral regimen to a once-daily regimen of 2 NRTIs plus a ritonavir-boosted protease inhibitor in persons with AIDS-KS and good virologic suppression an all NRTI regimen. Step 3 was included to evaluate the clinical, immunological, and virological effects of intensification with a ritonavir-boosted protease inhibitor in persons with AIDS-KS who have virological failure on an all NRTI regimen.

Detailed Description
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To identify factors associated with successful treatment of KS with antiretroviral therapy and to determine if highly active antiretroviral therapy improves survival and quality of life for persons with AIDS-KS in Zimbabwe. A secondary objective is to investigate the durability of HIV-1 suppression by the combination of ABC/3TC/ZDV in persons infected with HIV-1 subtype C and to evaluate the timing and characteristics of mutations in HIV-1 reverse transcriptase in subjects who fail to achieve, or to maintain suppression of HIV-1 replication during treatment with ABC/3TC/ZDV. An important objective is to assess adherence to a simplified antiretroviral regimen in a resource-limited setting. The study will evaluate the clinical, immunological, and virological effects of a switch from a twice-daily all-nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral regimen to a once-daily regimen of 2 NRTIs plus a ritonavir-boosted protease inhibitor in persons with AIDS-KS and good virologic suppression on ABC/3TC/ZDV (see above).

Official Title
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A Pilot Study Of the Effects of Highly Active Antiretroviral Therapy on Kaposi's Sarcoma in Zimbabwe

Conditions
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AIDS-related Kaposi's Sarcoma

Intervention / Treatment
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* Drug: abacavir/3TC/zidovudine
* Drug: abacavir /3TC plus ritonavir boosted lopinavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Completion of at least 96 weeks of treatment with ABC/3TC/ZDV on protocol Step 1. Currently receiving ABC/3TC/ZDV on Step 1/initial open-label allNRTI phase of study. Plasma HIV-1 RNA < 400 copies/mL on the most recent plasma HIV-1 RNA performed within 4 weeks of Step 2 entry. Willing to potentially switch to a new antiretroviral regimen. In the opinion of the site investigator currently has clinical evidence of active KS disease. Exclusion Criteria None

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2A<br>co-formulated abacavir 300mg/3TC 150mg/zidovudine 300mg po(Trizivir)one tablet twice daily(BID)for 96 weeks | Drug: abacavir/3TC/zidovudine<br>* continued use of oral co-formulated abacavir 300mg/3TC 150mg/zidovudine 300mg for 96 weeks<br>* Other names: Trizivir;|
| Active Comparator: 2B<br>co-formulated abacavir 600mg/3TC 300mg orally (as Kivexa) one tablet daily plus fixed dose lopinavir 133.3mg/ritonavir 33.3mg orally (as Aluvia) four tablets daily for 96 weeks | Drug: abacavir /3TC plus ritonavir boosted lopinavir<br>* fixed dose abacavir 600mg/3TC 300mg one tablet po QD for 96 weeks plus fixed dose ritonavir 33.3mg/lopinavir 133.3mg four tablets po QD for 96 weeks<br>* Other names: Aluvia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare effects of twice-daily all-(NRTI) antiretroviral regimen to a once-daily regimen of 2 NRTIs plus a protease inhibitor AIDS-KS subjects with good virologic suppression on all-NRTI regimen. |  | 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AIDS-related Kaposi's sarcoma, antiretroviral therapy