Progesterone Supplementation for HIV-positive Pregnant Women on Anti-Retrovirals

Study Overview
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Brief Summary
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In pregnancy, cART is considered optimal for maternal health and for preventing the emergence of resistance that could compromise further care. In Canada, the majority of HIV-positive pregnant women receive a PI-based cART regimen. In the past, therapy was generally deferred until after the first trimester (if not required for maternal health) to minimize any unknown risk of teratogenicity. However, as treatment is now started earlier in HIV infection and as perinatal transmission rates are lowest in those with prolonged suppression of viral load during pregnancy, women are increasingly commencing cART either before conception or earlier in pregnancy. Multiple reports and cohort studies provided data suggesting an association between PI-based cART use and preterm birth, low birth weight, and small for gestational age (SGA) babies, although conflicting data exist. In the general population progesterone supplementation is widely used, is well tolerated, is considered safe, and is beneficial to prevent recurrent pre-term birth and increase birth weight. The investigators experimental findings suggest that PI use during pregnancy is associated with declines in progesterone levels that correlate with fetal growth, and that progesterone supplementation can improve PI-induced fetal growth restriction. The investigators preliminary findings in HIV+ pregnant women suggest that PI-use is associated with declines in progesterone levels, which correlate with birth weight percentile. Since HIV-positive women have higher rates of pre-term delivery and low birth weight that may be magnified by the use of PIs, then progesterone supplementation could be of benefit to neonatal health in the context of HIV-positive pregnancy.

Official Title
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Progesterone Supplementation for HIV-positive Pregnant Women on Anti-Retrovirals

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: Prometrium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented HIV-1 infection On (stable) or initiating a cART regimen containing either ritonavir-boosted lopinavir (LPV/r), atazanavir (ATZ/r) or darunavir (DRV/r) Pregnant up to 24 weeks gestational age Singleton pregnancy 18 years or older Ability to give informed consent Exclusion Criteria: Hypersensitivity or allergy to soya or peanut (non-active ingredient supplement in Prometrium) Contraindications to intravaginal progesterone use including: documented hypersensitivity to Prometrium active or history of breast cancer, active or history of arterial thromboembolitic disease (e.g. stroke, myocardial infarction, coronary heart disease) active or history of venous thromboembolism (e.g. deep venous thrombosis or pulmonary embolism) or active thrombophlebitis any prior neoplasia, except for skin abnormal vaginal bleeding Known lethal fetal anomaly Any contraindication to continuation of pregnancy Inability to communicate in English Prior participation in this trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prometrium<br>Prometrium (progesterone capsules) intervention | Drug: Prometrium<br> <br> * Other names: progesterone capsules;|
| No Intervention: No treatment<br>no treatment arm | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total enrollment / eligible population per year | Qualitative information on the reasons to decline participation will be collected and summarized. Reasons for non-enrolling questionnaire will be used. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of progesterone supplementation during pregnancy for HIV-positive women. | The number of Grade 3 or 4 AE in the ITT vs. comparator group. The number of Grade 1 or 2 AE in the ITT vs. comparator group. AE questionnaire. | 40 weeks | 
| Acceptability of progesterone supplementation during pregnancy for HIV+ women. | Assessed in the ITT group. Acceptability based on experience with medication questionnaire. Screening questionnaire (acceptability of being recruited to no treatment arm) | 40 weeks | 
| Compliance of progesterone supplementation. Assessed in the ITT group. | Number of missed doses / total prescribed doses per patient. Compliance questionnaire | 40 weeks | 
| Barriers to adherence to progesterone supplementation. Assessed in the ITT group | Reasons for missed dose questionnaire. Reasons for missed appointment questionnaire | 40 weeks |