Clinical trial NCT00669487: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV/AIDS patients
Lead sponsor: SEARCH Research Foundation
Sponsor class: OTHER
Collaborators: name: Queen Savang Vadhana Memorial Hospital, Thailand
name: Thai Red Cross AIDS Research Centre
name: University of Hawaii
First posted: 2008-04-30
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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.

Primary outcomes:
measure: Change from baseline in mean hemoglobin at 24 weeks and 72 weeks
timeFrame: 72 weeks
measure: Proportion of participants with peripheral neuropathy at 24 weeks and 72 weeks
timeFrame: 72 weeks
Secondary outcomes:
measure: Changes from baseline in body weight, limb fat, and lean body mass by DEXA scan at 24 weeks and 72 weeks
timeFrame: 72 weeks
measure: Change from baseline in serum creatinine at 24 weeks and 72 weeks
timeFrame: 72 weeks
measure: Proportion of participants with plasma HIV-1 RNA less than 50 copies/mL at 24 weeks and 72 weeks
timeFrame: 72 weeks
measure: Change from baseline in CD4 count at 24 weeks and 72 weeks
timeFrame: 72 weeks
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: SEARCH Thailand
Study officials:
affiliation: SEARCH Thailand
name: Jintanat - Ananworanich, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: SEARCH Thailand
name: Jintanat - Ananworanich, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: