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

Condition(s) targeted: HIV Infections

Intervention: 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 (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: South East Asia Research Collaboration with Hawaii

Official(s) and/or principal investigator(s):
Jintanat - Ananworanich, M.D., Principal Investigator, Affiliation: SEARCH Thailand
Jintanat - Ananworanich, M.D., Ph.D, Principal Investigator, Affiliation: SEARCH Thailand
Jintanat - Ananworanich, M.D., Principal Investigator, Affiliation: SEARCH Thailand

Overall contact:
Jintanat - Ananwaoranich, M.D., Phone: 662-254-2566, Ext: 1, Email: jintanat.a@searchthailand.org

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.

Study design: Treatment, Randomized, Open Label, Factorial Assignment, Safety/Efficacy Study

Primary outcome:

Compared to the d4T switch and TDF arms, AZT will have a lower Hgb

At baseline, the rates of peripheral neuropathy (presumably HIV-induced) will be comparable among the 3 arms

Secondary outcome:

The overall toxicity profile, as assessed by NIAID Division of AIDS Toxicity Grading Scale, will be less in the AZT and TDF arms compared to the d4T arm

All arms will have similar virologic/immunologic outcomes and adherence.

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Documented HIV-1 infection

2. Age ≥ 18 years old.

3. 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.

4. CD4 < 350 cells/mm3

5. Subject understands the study and is able to sign informed consent

Exclusion Criteria:

1. 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.

2. 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

3. 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.

4. Any immunomodulator, HIV vaccine or investigational therapy within 30 days of study entry

5. Pregnancy or breast-feeding; intent to become pregnant during the course of the study.

6. Presence of any active malignancy.

Jintanat - Ananwaoranich, M.D., Phone: 662-254-2566, Ext: 1, Email: jintanat.a@searchthailand.org

SEARCH Thailand, Bangkok, - 10330, Thailand; Recruiting
Nitiya - Chomchey, RN. B.Sc., Phone: 66-2254-2566, Ext: 2, Email: nitiya.c@searchthailand.org

Starting date: April 2008
Last updated: July 28, 2009