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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: PrEP (Truvada); Drug: Antiretrovirals; Procedure: Semen washing; Procedure: Artificial vaginal insemination

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 46

Contacts and Locations

Study Locations

• Zimbabwe
  • Harare, Zimbabwe
    • UZCHS-UCSF CTRC Zengeza Clinical Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV-discordant couples in Harare, Zimbabwe who are trying to get pregnant

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute of Mental Health (NIMH); Gilead Sciences; UZ-UCSF Collaborative Research Programme
• Investigators: Principal Investigator: Joelle M Brown, PhD, MPH, University of California, San Francisco; Principal Investigator: Felix Mhlanga, MBChB, MMed, UZ-UCSF Collaborative Research Programme

Publications and helpful links

General Publications

• Hughes CS, Brown J, Murombedzi C, Chirenda T, Chareka G, Mhlanga F, Mateveke B, Gitome S, Makurumure T, Matubu A, Mgodi N, Chirenje Z, Kahn JG. Estimated costs for the delivery of safer conception strategies for HIV-discordant couples in Zimbabwe: a cost analysis. BMC Health Serv Res. 2020 Oct 12;20(1):940. doi: 10.1186/s12913-020-05784-4.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2017
• Primary Completion (Actual): June 3, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: February 7, 2017
• First Submitted That Met QC Criteria: February 7, 2017
• First Posted (Estimate): February 9, 2017

Study Record Updates

• Last Update Posted (Actual): September 30, 2019
• Last Update Submitted That Met QC Criteria: September 27, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: PrEP; pregnancy; ART; safer conception; HIV-discordant couple; semen washing; artificial vaginal insemination
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Anti-Retroviral Agents
• Other Study ID Numbers: A126763; K01MH100994 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be made available at the end of the study on an online repository.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No