Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women
Condition: Malaria; HIV Infections
MeSH terms: Malaria
Intervention: Lopinavir/ritonavir; Efavirenz; Zidovudine; Lamivudine
Intervention description: LPV 200mg/r 50mg; 600mg; Zidovudine 300 mg; Lamivudine 150 mg
Intervention MeSH terms: Ritonavir; Lopinavir; Lamivudine; Zidovudine; Efavirenz
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 389.0
Sex: Female
Minimum age: 16 Years
Healthy volunteers: No
Keywords: HIV; Placental Malaria; Pregnancy; Uganda; Protease inhibitors; Trimethoprim-sulfamethoxazole; Treatment experienced

Summary:

      This study is an open-label, single site, randomized controlled trial comparing protease
      inhibitor (PI)-based antiretroviral therapy (ART) to non-PI based ART for HIV-infected
      pregnant and breastfeeding women of all CD4 cell counts at high risk of malaria. The study is
      designed to test the hypothesis that pregnant women receiving a PI-based ART regimen will
      have lower risk of placental malaria compared to pregnant women receiving a non-PI based ART
      regimen. The primary study endpoint of the study is placental malaria. This study also
      enrolls the infants of these women at the time of delivery.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age > 16 years (if <18 years old, living independently from parents)

          2. Documentation of HIV status must come from two assays. Assays include DNA PCR, HIV
             RNA, Western blot, or rapid HIV antibody test

          3. Confirmed pregnancy by positive serum or urine pregnancy test or ultrasound

          4. Estimated gestational age between 12 and 28 weeks (based on first day of last
             menstrual period with physical exam confirmation and ultrasound confirmation) at time
             of enrollment

          5. Residency within 30 km of the study site

          6. Willing to provide informed consent

        Exclusion Criteria:

          1. Current or prior use of HAART

          2. Exposure to single-dose NVP (alone or with zidovudine or zidovudine/lamivudine or
             other abbreviated monotherapy or dual therapy for PMTCT) less than 24 months prior to
             enrollment

          3. Prior dose-limited toxicity to TS within 14 days of study enrollment

          4. Receipt of any contraindicated medications within 14 days of study enrollment (See
             Appendix III.)

          5. Active tuberculosis or other WHO Stage 4 diseases

          6. Screening laboratory values:

               1. Hemoglobin: <7.5 g/dL (Note: Women found to have a hemoglobin <7.5 at screening
                  may receive iron and folic acid and/or a blood transfusion at the physician's
                  discretion. If a repeat hemoglobin is ≥7.5 g/dL, the woman may be considered for
                  study inclusion.)

               2. Absolute neutrophil count (ANC): <750/mm3

               3. Platelet count: <50,000/mm3

               4. ALT: >225 U/L (>5.0x ULN)

               5. AST: >225 U/L (>5.0x ULN)

               6. Bilirubin (total): > 2.5x ULN

               7. Creatinine: > 1.8x ULN

          7. Known cardiac conduction abnormalities or structural heart defect

        NOTE: A woman will be excluded from study participation during the current pregnancy if she
        goes into labor, experiences ruptured membranes or develops active tuberculosis or a WHO
        stage 4 condition following study enrollment but prior to study drug initiation.