A Novel Regimen to Prevent Malaria and STI in Pregnant Women With HIV
Condition: HIV; Pregnancy Malaria; Sexually Transmitted Infection
MeSH terms: Infections; Malaria; Sexually Transmitted Diseases
Study type: Interventional
Phase: Phase 2

Summary: 
      More than 3 billion people worldwide are at risk of acquiring malaria and pregnant women
      living with HIV in Africa are at particular risk. An effective prophylaxis regimen capable of
      preventing malaria and other common perinatal infections would have great potential to
      improve adverse birth outcomes. The purpose of this randomized controlled trial is to
      evaluate a new combination prophylaxis regimen in pregnant women with HIV in Cameroon to
      determine its efficacy and safety.
    

Detailed description: 
      The World Health Organization (WHO) recommends malaria prophylaxis for all pregnant women
      living in endemic areas in order to reduce maternal anemia, low birth weight and perinatal
      mortality by 25-45%. The most commonly used regimen is intermittently dosed
      sulfadoxine-pyrimethamine (SP).Unfortunately, SP prophylaxis is contraindicated for
      HIV-infected pregnant women since co-administration with TMPS (trimethoprim-sulfamethoxazole)
      causes serious adverse events. TMPS (Bactrim or Cotrimoxazole) is an effective,
      well-tolerated, low-cost antibiotic that is used as prophylaxis in HIV-patients with low CD4
      counts. It has anti-malarial activity with prophylactic efficacy that is comparable to SP
      (30-90%). Daily TMPS is recommended as malaria prophylaxis in pregnant women with HIV in many
      African countries (including Cameroon) but malaria infection rates are high even when
      medication compliance is excellent; thus, new and improved options are urgently needed.
      Azithromycin (AZ) is a macrolide antibiotic with activity against malaria, a good safety
      profile in pregnancy and proven utility as a part of combination malaria prevention regimens
      (such as SP-AZ). It also has activity against sexually transmitted infections (STI) and
      perinatal pathogens, including chlamydia (CT), gonorrhea (GC), syphilis and GBS
      (Streptococcus agalactiae or Group B Streptococcus), a potential but understudied contributor
      to high rates of newborn sepsis and death in Africa. SP-AZ prophylaxis in HIV-uninfected
      pregnant women has been reported to reduce prevalence of low birth weight (RR 0.74, 95%
      confidence interval (CI) 0.6-0.9) and preterm delivery (RR 0.66, 95% CI 0.48-0.91) compared
      to SP alone.

      Thus, the central hypothesis is that a TMPS-AZ combination will be more effective than
      standard TMPS malaria prophylaxis in pregnant women with HIV, and that it will also decrease
      STI coinfection. Investigators plan a test-of-concept of the central hypothesis by conducting
      a double blinded, Phase II randomized controlled trial (RCT).
    

Intervention name(s): Azithromycin/TMPS; Placebo/TMPS
Intervention type(s): Drug; Drug
Intervention description(s): 2 tabs po daily x 3 days at enrollment and at each monthly follow up visit; 2 tabs po daily x 3 days at enrollment and at each monthly follow up visit
Other intervention name(s): Cotrimoxazole; Co-Trimoxazole
Intervention MeSH terms: Azithromycin; Trimethoprim, Sulfamethoxazole Drug Combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: STI Prevention; Cameroon; sub-Saharan Africa; HIV pregnancy; Malaria in pregnancy