The Impact and Cost-effectiveness of Safer Conception Strategies for HIV-discordant Couples (SAFER)

Study Overview
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Brief Summary
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This is a prospective, non-randomized, open-label study to look at the uptake, adherence to, and impact of pre-exposure prophylaxis (PrEP), antiretroviral therapy (ART), semen washing, and vaginal insemination to prevent HIV among HIV-discordant couples attempting conception in Zimbabwe.

Detailed Description
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The reproductive needs of HIV-discordant couples who desire pregnancy represent an urgent public health problem that has been neglected in HIV prevention research. In Zimbabwe , and across sub-Saharan Africa, the vast majority of HIV-infected individuals are adults of reproductive age. Pregnancy and the desire for children are common among HIV-infected individuals, and HIV-discordant couples face a difficult choice between attempting pregnancy and risking HIV transmission to their partners. Recent surveys have found that 30-50% of HIV-infected individuals in sub-Saharan Africa are involved in stable, HIV-discordant relationships, and HIV transmission within married, cohabitating HIV-discordant couples accounts for 44-60% of new HIV infections in some regions of sub-Saharan Africa. While knowledge of HIV discordance can lead to increased condom use, many discordant couples have unprotected intercourse often motivated by the desire to conceive. Currently, HIV discordant couples who attempt to conceive place themselves at considerable risk of transmission. This research study aims to help promote couples' rights to conceive while at the same time decreasing the risk of HIV transmission.

Official Title
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The Impact and Cost-effectiveness of Safer Conception Strategies for HIV-discordant Couples

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: PrEP (Truvada)
* Drug: Antiretrovirals
* Procedure: Semen washing
* Procedure: Artificial vaginal insemination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all couples: Couple expresses a desire to conceive Sexually active (defined as having vaginal sex with one another at least 6 times in the past 3 months Willing to enter the study as a couple and intending to remain as a couple and have a sexual relationship for the next 12 months Willing to use at least one safer conception strategy For men, age ≥18 years. For women, age 18 - 35 years; Able and willing to provide written informed consent For HIV-uninfected members of the couple HIV-negative based on parallel negative HIV rapid tests, both at study screening and enrollment visit Adequate renal function, defined by normal creatinine levels and estimated creatinine clearance ≥60 mL/min For HIV-infected members of the couple HIV-positive based on parallel positive HIV rapid tests, based on national algorithm No current AIDS-defining illness Exclusion Criteria: Amenorrheic Currently pregnant Active and serious infections, including active tuberculosis infection; active clinically significant medical problems including cardiac disease, pulmonary disease, and previously diagnosed malignancy expected to require further treatment. History of infertility defined as a year or more of regular unprotected intercourse with current partner without pregnancy, or otherwise medically diagnosed infertility Currently on any concomitant medication that requires the participant to avoid use of PrEP

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV+male/HIV-female<br>discordant couple given the choice of using at least one of the following: Antiretrovirals, PrEP (Truvada), or semen washing | Drug: PrEP (Truvada)<br>* oral, daily Truvada for HIV-negative participants<br>* Other names: emtricitabine/tenofovir disoproxil fumarate;Drug: Antiretrovirals<br>* oral daily antiretrovirals and frequent viral load monitoring for HIV-positive participant<br>* Other names: ART;Procedure: Semen washing<br>* collection of semen from an HIV-positive man, processing semen to remove HIV, followed by intrauterine insemination<br>|
| HIV+female/HIV-male<br>discordant couple given the choice of using at least one of the following: Antiretrovirals, PrEP (Truvada), or artificial vaginal insemination | Drug: PrEP (Truvada)<br>* oral, daily Truvada for HIV-negative participants<br>* Other names: emtricitabine/tenofovir disoproxil fumarate;Drug: Antiretrovirals<br>* oral daily antiretrovirals and frequent viral load monitoring for HIV-positive participant<br>* Other names: ART;Procedure: Artificial vaginal insemination<br>* collection of semen from an HIV-negative man, followed by intravaginal insemination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uptake of safer conception strategies | proportion of couples choosing the strategy | 12 months | 
| Acceptability of safer conception strategies | proportion of couples remaining on strategy; reports of satisfaction | 12 months | 
| Adherence to safer conception strategies | proportion of couples with high adherence to strategy | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of safer conception strategies on HIV prevention | incidence of HIV | 12 months | 
| Effectiveness of safer conception strategies on achieving pregnancy | incidence of pregnancy | 12 months | 
| costs of providing safer conception services | costs | 12 months | 
| cost-effectiveness of safer conception strategies | model the cost effectiveness of various combinations of safer conception strategies | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-discordant couple, ART, PrEP, semen washing, artificial vaginal insemination, safer conception, pregnancy