Differences Between Stavudine and Tenofovir Each Combined With Lamivudine and Efavirenz in SA HIV-infected Patients

• Status: Terminated
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Even with the benefits of HIV therapy, there is a possibility that HIV-infected individuals develop metabolic complications once they initiate treatment, which may also ultimately put them at a risk for impending heart disease in the next decades.

The main mechanism through which the main HIV drugs are thought to cause these metabolic changes and organ toxicities is mitochondrial toxicity. Most of studies that have been done, have taken place in the West, but few, if any, have been done in South Africa.

The purpose of this study is to prospectively identify early changes between the two different drugs, Stavudine and Tenofovir, to assess their virological response, molecular, biochemical and clinical picture, and the possible associated change in cardiovascular risk factors, this, in the South African setting, and make recommendations to modify the current National AIDS role out programme

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Witwatersrand, South Africa
• Treatments: Efavirenz; Lamivudine; Stavudine; Tenofovir

Criteria

Inclusion Criteria:

1. HIV-1 infection, documented by a rapid HIV test or any licensed ELISA test kit, and confirmed by either a second rapid HIV test or an ELISA consistent with the Themba Lethu Clinic guidelines.

2. Age >/= 18 years,

3. CD4+ cell count < 200 cells/mm3.

4. The following laboratory values obtained within 45 days prior to study entry:

• Absolute neutrophil count (ANC) ≥ 750/mm3

• Hemoglobin ≥ 7.0 g/dL

• Platelet count ≥ 50,000/mm3

• AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 2.5 x ULN

• Total bilirubin ≤ 2.5 x ULN

5. Evidence of normal renal function within 45 days prior to study entry as determined by an estimated creatinine clearance of ≥60 mL/min using the Cockcroft-Gault formula:

{[140 - age (yr)] x [weight (kg)] ÷ [72 x serum Cr (mg/dL)]} (X 0.85 in females.)

6. Participants of reproductive age (defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months, i.e. who have had menses within the preceding 24 months), or who have not undergone surgical sterilization (e.g. hysterectomy, or bilateral oophorectomy or salpingotomy) must have a negative serum or urine pregnancy test within 45 days prior to study entry.

7. Participants of reproductive potential, must be willing to abstain from participation in a conception process (e.g. active attempt to become pregnant or in vitro fertilization). If participants are sexual active, that could lead to pregnancy, they must use at least one reliable form of contraception listed below while receiving protocol-specified medications and for 6 weeks after stopping the medication.

• Male or female condoms with or without a spermicidal agent (condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV transmission).

• Diaphragm or cervical cap with spermicide

• IUD

• Hormonal-based contraception

• Possible interactions of study drugs with estrogen-based contraceptives: LPV/RTV decrease plasma levels of ethinyl estradiol; therefore, estrogen-based contraceptives are not reliable for women receiving LPV/RTV and an alternative contraception method must be used.

• NOTE: Participants who are not of reproductive potential (girls who have not reached menarche, women who have been post-menopausal for at least 24 consecutive months) girls and women who are not participating in sexual activity that could lead to pregnancy, or women who have undergone surgical sterilization, (e.g. hysterectomy, or bilateral oophorectomy or salpingotomy) are eligible without requiring the use of contraception.

8. Ability and willingness of participant

9. Intent to remain in current geographical area of residence for the duration of study.

10. Willingness to attend study visits as required by the study.

Exclusion Criteria:

1. Receipt of any antiretrovirals (including for purposes of occupational or sexual post exposure prophylaxis), except for SD Nevirapine taken within six months.

2. Use of systemic cancer chemotherapy, systemic investigational agents, immunomodulators (growth factors, systemic corticosteroids, HIV vaccines, immune globulin, interleukins, interferons) or rifampin within 30 days prior to study entry.

3. Breastfeeding or pregnancy.

4. Allergy to study drugs.

5. Any condition, including active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.

6. Any serious illness requiring systemic treatment and/or hospitalization until participant either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 30 days prior to study entry.

7. Involuntary incarceration in a correctional facility, for legal reasons or in a medical facility for treatment of either a psychiatric or physical (e.g., infectious disease) illness.