A 72-week Randomized Clinical Trial Comparing the Safety and Efficacy of Three Initial Antiretroviral Regimens -GPO-VIR S (d4T/3TC/NVP) for 24 Weeks Followed by GPO-VIR Z (AZT/3TC/NVP) vs GPO-VIR Z vs TDF/FTC/NVP

Study Overview
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Brief Summary
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This protocol aims to determine the risk/benefits of this policy by comparing head-to-head a regimen of GPO-VIR Z or TDF/FTC/NVP for 18 months in ARV-naïve patients to a 6-month lead in with GPO-VIR S followed by 12 months of GPO-VIR Z. The primary outcomes to be assessed will be anemia, neuropathy, lipoatrophy and renal function.

Detailed Description
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GPO-VIR Z is a new combination antiretroviral (ARV) medication that substitutes zidovudine (AZT) for stavudine (d4T) from the original formulation of GPO-VIR S. This new combination should decrease rates of lipoatrophy and neuropathy which are side-effects strongly linked to the use of d4T. However, there is some risk that initiating therapy with an AZT- containing regimen may cause unacceptable rates of anemia. Many Thai physicians have adopted a practice of using 6 months of the stavudine-containing GPO-VIR S as a lead in before introducing AZT-containing GPO-VIR Z in an effort to balance the risks and benefits of these two medications. There are no definitive data, however, that can attest to the benefit of such an approach.

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP
* Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP
* Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented HIV-1 infection Age ≥ 18 years old. Subjects must be naïve to ARV. Individuals with past exposure to ARV associated with pregnancy will be allowed to enroll as long as the exposure is at least 3 months prior to entry. CD4 < 350 cells/mm3 Subject understands the study and is able to sign informed consent Exclusion Criteria: Evidence of symptomatic persistent symptoms of tingling or numbness of lower extremities and bilateral lower extremity neuropathy on exam at entry. Abnormal exam includes 1) Diminished (compared with the knee) or absent ankle reflexes OR 2) Diminution of either vibration sensation in the legs (defined as perception of vibration for < 10 seconds at the great toe with a tuning fork initially struck hard enough to be audible) OR 3) Diminution of pin or temperature sensation in lower extremities OR 4) Contact allodynia in the feet. Laboratory values 1) Absolute neutrophil count (ANC) < 750/mm3 2) Hemoglobin < 8.0 g/dL 3) ALT (SGPT) > 5 x ULN 4) Creatinine > 2 X ULN or < creatinine clearance < 30 cc per min by Cockroft-Gault formula Active AIDS-defining opportunistic infection (OI) within 30 days prior to entry. Subjects must be off all acute treatments for OI for at least 14 days prior to entry. Subjects on maintenance or prophylactic therapy for AIDS-related OIs will be eligible. Any immunomodulator, HIV vaccine or investigational therapy within 30 days of study entry Pregnancy or breast-feeding; intent to become pregnant during the course of the study. Presence of any active malignancy.

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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1. GPO-VIR S 1 pill orally every 12 hours<br> | Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP<br>* GPO-VIR S(D4T30mg+3TC150mg+NVP200mg)1 pill orally every 12 hours until week 24 and then switch to GPO-VIR Z<br>Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP<br>* GPO-VIR Z(AZT250mg+3TC150mg+NVP200mg) 1 pill orally every 12 hours until week 72<br>|
| Experimental: 2 GPO-VIR Z 1 pill orally every 12 hours<br> | Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP<br>* GPO-VIR S(D4T30mg+3TC150mg+NVP200mg)1 pill orally every 12 hours until week 24 and then switch to GPO-VIR Z<br>Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP<br>* GPO-VIR Z(AZT250mg+3TC150mg+NVP200mg) 1 pill orally every 12 hours until week 72<br>|
| Experimental: 3 Truvada 1 pill oral q 24 hr and NVP 1 pill oral q 12 hr<br> | Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP<br>* Truvada(FTC200mg+TDF300mg) every 24 hours + NVP 200 mg every 12 hours orally until week 72<br>Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP<br>* GPO-VIR S(D4T30mg+3TC150mg+NVP200mg)1 pill orally every 12 hours until week 24 and then switch to GPO-VIR Z<br>Drug: AZT/3TC/NVP, AZT/D4T/NVP, Truvada/NVP<br>* GPO-VIR Z(AZT250mg+3TC150mg+NVP200mg) 1 pill orally every 12 hours until week 72<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean hemoglobin at 24 weeks and 72 weeks |  | 72 weeks | 
| Proportion of participants with peripheral neuropathy at 24 weeks and 72 weeks |  | 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in body weight, limb fat, and lean body mass by DEXA scan at 24 weeks and 72 weeks |  | 72 weeks | 
| Change from baseline in serum creatinine at 24 weeks and 72 weeks |  | 72 weeks | 
| Proportion of participants with plasma HIV-1 RNA less than 50 copies/mL at 24 weeks and 72 weeks |  | 72 weeks | 
| Change from baseline in CD4 count at 24 weeks and 72 weeks |  | 72 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV/AIDS patients