Reducing the Burden of Malaria in HIV-Infected Pregnant Women and Their HIV-Exposed Children (PROMOTE-BC2)
Condition: Malaria; Human Immunodeficiency Virus
MeSH terms: Malaria; Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes
Intervention: Monthly dihydroartemisinin-piperaquine (DP) + daily trimethoprim/sulfamethoxazole (TS); Monthly placebo + daily trimethoprim/sulfamethoxazole (TS)
Intervention MeSH terms: Piperaquine; Trimethoprim; Artenimol; Sulfamethoxazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 200.0
Sex: Female
Minimum age: 16 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Chemoprevention; Malaria; Uganda; Dihydroartemisinin-piperaquine; Trimethoprim-sulfamethoxazole; Human Immunodeficiency Virus

Summary:

      This is a double-blinded, randomized controlled trial of 200 HIV-infected pregnant women
      living in Tororo, Uganda, an area of high malaria transmission. HIV-infected pregnant women
      between 12 and 28 weeks gestation will be randomized to receive enhanced malaria
      chemoprevention with monthly dihydroartemisinin-piperaquine (DP) versus monthly DP placebo.
      Their HIV-exposed children will receive the same prevention regimen from 2 to 24 months of
      age to which the mothers were randomized. All women will receive daily
      trimethoprim-sulfamethoxazole (TS) throughout the study per Uganda Ministry of Health
      guidelines. Children will also receive daily TS from 6 weeks to 24 months of age. TS will be
      considered a study drug only in infants and children beginning 6 weeks after cessation of
      breastfeeding and upon exclusion of HIV infection. Women and their children will be followed
      for 36 months after delivery. In a subset of the study population, the investigators will
      conduct an intensive pharmacokinetic study that will evaluate pharmacokinetic exposure of DP
      and EFV. The investigators will also measure HIV-related outcomes among the women enrolled in
      the study. The investigators will test the hypothesis that for HIV-infected mothers and
      HIV-exposed infants, that enhanced versus standard malaria chemoprevention in HIV-infected
      pregnant women and their children will reduce the incidence of malaria among children from 0
      to 24 months of age and improve the development of naturally acquired antimalarial immunity.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Intrauterine pregnancy confirmed by ultrasound

          2. Estimated gestational age between 12-28 weeks

          3. Confirmed to be HIV-infected by Uganda country standard rapid HIV test

          4. 16 years of age or older

          5. Residency within 30 km of the study clinic

          6. Provision of informed consent

          7. Agreement to come to the study clinic for any febrile episode or other illness and
             avoid medications given outside the study protocol

          8. Plan to deliver in the hospital

        Exclusion Criteria:

          1. History of serious adverse event to TS or DP

          2. Refusal to take cART during pregnancy or as part of routine HIV care

          3. Active medical problem requiring inpatient evaluation at the time of screening

          4. Intention of moving more than 30 km from the study clinic

          5. Active WHO stage 4 condition not stable under treatment

          6. Signs or symptoms of early or active labor

          7. Currently on ritonavir

          8. Currently taking drugs associated with known risk of Torsades de pointes

          9. Currently taking CYP3A inhibitor medications which potentially inhibit the metabolism
             of piperaquine

         10. History of cardiac problems or fainting