Safer Conception Intervention for HIV-1 Serodiscordant Couples
Condition: HIV Seropositivity; Pregnancy, High-Risk
MeSH terms: HIV Seropositivity
Study type: Observational

Summary: 
      The greatest burden of the HIV-1 epidemic lies in sub-Saharan Africa, where a substantial
      proportion of infections occur in long-term heterosexual HIV-1 serodiscordant partnerships.
      Such couples face a difficult dilemma when considering their desire to have children: forego
      condom use, attempt to conceive and risk HIV-1 transmission or continue condom use and
      relinquish their childbearing desires. Based on evidence from rigorous clinical trials
      demonstrating the strong efficacy of individual interventions for HIV-1 prevention and
      formative work with HIV-1 serodiscordant couples and clinicians with expertise in HIV-1
      prevention and reproductive health in the Kenyan context, this study pilots a safer
      conception intervention that focuses on antiretrovirals (as antiretroviral therapy [ART]
      taken by the HIV-1 infected partner and pre-exposure prophylaxis [PrEP] taken by the HIV-1
      uninfected partner) and timed condomless sex. Additional strategies for couples include
      diagnosis and treatment of STIs and male circumcision.

      mHealth tools, including SMS and mobile applications are novel and very popular among Kenyans
      to ease the burden of addressing health problems. This safer conception intervention
      incorporates mHealth tools to improve couples' experiences tracking fertility indicators and
      communicating with providers about their readiness to practice safer conception. SMS surveys
      to collect daily information from women about their fertility signs and SMS messages are used
      to reinforce HIV-1 prevention, including condom use for couples during periods that do not
      have a high likelihood of fertility. An in-clinic mobile application is used to improve
      clinician-patient counseling and assessments of couple readiness to practice safer
      conception. To inform future engagement of mHealth tools, the investigators will
      prospectively evaluate clinician and patient experiences using SMS surveys and the tablet
      application. Couples with immediate fertility intentions will be followed longitudinally,
      allowing careful tracking of pregnancy and HIV-1 incidence. The study takes place in Thika,
      Kenya.
    

Detailed description: 
      Overall Design This is an open-label, prospective cohort pilot study of HIV-1 serodiscordant
      couples with immediate fertility desires. The overall goal is to determine uptake and
      sustained use of safer conception strategies, strategies for HIV-1 risk reduction during
      periods when couples attempt to conceive a child. The study offers PrEP (daily oral TDF or
      FTC/TDF) to the HIV-1 uninfected member of the couple, ART to the HIV-1 infected member of
      the couple, teach women about tracking fertility indicators and predicting upcoming periods
      of peak fertility, and work with couples to establish their readiness to practice timed
      condomless sex. mHealth tools will be integrated to capture fertility indicators, sexual
      behavior, improve patient-provider communication, and remind couples about their upcoming
      periods with peak fertility. The investigators will conduct mixed-methods work to understand
      couples experiences practicing safer conception and couples and providers experiences using
      the mHealth tools.

      AIMS

        1. To determine uptake (and adherence, when applicable) of each component of an integrated
           safer conception intervention among HIV-1 serodiscordant couples, including:

             1. Use of PrEP by the HIV-1 uninfected partner

             2. Use of ART by the HIV-1 infected partner

             3. Menstrual cycle monitoring

             4. Patterns of condom use

             5. STI treatment

             6. Medical male circumcision, and

             7. Vaginal self-insemination

        2. To determine rates of pregnancy and HIV-1 incidence among HIV-1 serodiscordant couples
           participating in a safer conception intervention pilot

        3. To determine which fertility indicators - including onset of menses, basal body
           temperature, vaginal mucus characteristics, results from luteinizing hormone tests - are
           most feasible for Kenyan women in HIV-1 serodiscordant partnerships to monitor via SMS

        4. To obtain user feedback about mHealth tools designed to improve patient experience with
           safer conception including:

             1. Women's experiences tracking fertility signs through SMS and

             2. Couples' and provider's experiences using a clinic-based tablet application that
                encompasses clinical, laboratory and fertility data to improve patient-provider
                communication about safer conception readiness

             3. Women and men's experiences receiving SMS messages with personalized safer
                conception reminders

        5. To assess participant experiences with an mHealth-enhanced safer conception intervention

      Study procedures:

      Clinic visits will take place at screening and enrollment, monthly prior to pregnancy and
      quarterly during pregnancy, for up to 12 months or the end of pregnancy, whichever comes
      later. Couples will move from a preparatory period into a peri-conception period once they
      decide to practice timed condomless sex, based on discussions with study clinicians and
      counselors. They will move from peri-conception to pregnancy once pregnancy occurs or from
      peri-conception to study exit if pregnancy does not occur within 12 months of study
      enrollment. During the preparatory and peri-conception periods, women will receive daily SMS
      surveys.

      Screening:

      At screening, both members of couples will undergo HIV-1 testing to verify HIV-1
      serodiscordancy and women will have a pregnancy test. Demographic, behavioral and medical
      information will be collected, along with additional laboratory results to establish
      eligibility (for HIV-1 uninfected partners - serum creatinine, hepatitis B surface antigen).
      Couples' fertility desires will be assessed and medical history will include information
      about current use of contraceptives and menstrual cycle regularity.

      Enrollment:

      At enrollment, members of couples will separately complete interviewer-administered
      questionnaires to assess their pre-intervention knowledge, perceptions of, and barriers to
      safer conception strategies and gather data on their demographic and medical characteristics,
      sexual behavior and any current contraception and/or antiretroviral use. Both partners will
      undergo diagnostic testing and treatment of genital infections, including gonorrhea,
      chlamydia, trichomonas, and bacterial vaginosis (BV, if there are symptoms). HIV-1 uninfected
      partners will be re-tested to verify their HIV-1 status and assessed for acute HIV-1
      infection. Women will be tested for pregnancy. HIV-1 infected partners will have specimen
      collected for CD4 and plasma viral load quantification. Physical exams will be conducted for
      both partners. Social harm will also be assessed in a culturally appropriate manner and
      captured on validated case report forms. Safer conception behavioral counseling will be in
      addition to couples counseling for HIV-1 prevention that fosters an understanding of HIV-1
      serodiscordancy and negotiation of safer sex.

      Daily SMS surveys:

      The day after enrollment, women will begin to receive daily SMS surveys to assess fertility
      signs and sexual behavior.

      Follow up visits:

      Participants will complete follow up visits to track their compliance with the intervention
      strategies and study procedures. Participants will be scheduled for monthly study visits
      during the preparatory and peri-conception periods and quarterly during pregnancy.
      Participants can move from the preparatory period to peri-conception based on their own
      desires and counseling from a clinician.

      Exit:

      Following the end of pregnancy or 12 months after study enrollment (whichever is later),
      couples will be exited from the study. At study exit, couples will be counseled about their
      current fertility goals (which may have changed throughout the course of follow up,
      especially for couples who become pregnant and have a child during the study period) and
      offered contraception and referrals for ongoing services, as appropriate.

      Qualitative interviews:

      To gain a deeper understanding of how participants perceive the integrated safer conception
      intervention and the mHealth components that are part of the intervention, we will conduct
      in-depth interviews with up to 40 couples. Interview topics will include: identification of
      factors influencing individuals' preferences for safer conception strategies, their
      experience with safer conception strategies, and their intentions for continued use of these
      strategies should they desire pregnancy again and user satisfaction with the mHealth tools
      and suggestions for improvement.
    

Intervention name(s): PrEP; Counseling on timed condomless sex, ART and PrEP adherence
Intervention type(s): Drug; Behavioral
Intervention description(s): An integrated, phased safer conception intervention that focuses on ART use by the HIV-1 infected partner, PrEP use by the HIV-1 uninfected partner, and timed condomless sex during the peri-conception period.; An integrated, phased safer conception intervention that focuses on ART use by the HIV-1 infected partner, PrEP use by the HIV-1 uninfected partner, and timed condomless sex
Other intervention name(s): Truvada
Intervention MeSH terms: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Heterosexual HIV-1 serodiscordant couples in Thika, Kenya with immediate fertility desires,
        who did not participate in a previous study "Partners PrEP Study or the Partners
        Demonstration Project" at the site, and study clinicians and counselors delivering the
        intervention.
      
Biospecimen description: 
      Plasma
    
Keywords: Pre-Exposure Prophylaxis; Fertility; mHealth; Pregnancy