The CHARISMA Expansion Study is a two-arm, randomized (1:1), controlled study of a behavioral intervention-the Community Health clinic model for Agency in Relationships and Safer Microbicide Adherence (CHARISMA)-to reduce social harms (SHs) and intimate partner violence (IPV), increase healthy relationship dynamics and oral PrEP (pre-exposure prophylaxis) TDF/FTC (tenofovir disoproxil fumarate/emtricitabine), hereafter called PrEP, adherence among enrolled women. This study is an expansion of the CHARISMA intervention pilot study which was appended to the Microbicide Trials Network (MTN)-025 HOPE (HIV Open Label Prevention Extension) study.

CHARISMA is defined by the use of a tool, called the CHARISMA HEAlthy Relationship Assessment Tool (HEART) used in combination with three counselling modules:

• Module A: General Partner Communication and Relationship Skills
• Module B: Partner Disclosure and Communication around PrEP Use
• Module C: Responding to Intimate Partner Violence and Safety Planning

The CHARISMA Expansion Study is a two-arm, randomized (1:1), controlled study of a behavioral intervention-the Community Health clinic model for Agency in Relationships and Safer Microbicide Adherence (CHARISMA)-which aims to reduce social harms (SHs) and intimate partner violence (IPV), increase healthy relationship dynamics and oral PrEP TDF/FTC (hereafter called PrEP) adherence among enrolled women. This study is an expansion of the CHARISMA intervention pilot study which was appended to the Microbicide Trials Network (MTN)-025 HOPE study and will conclude in 2018.

CHARISMA is defined by the use of a tool, called the CHARISMA HEAlthy Relationship Assessment Tool (HEART) used in combination with three counselling modules:

• Module A: General Partner Communication and Relationship Skills
• Module B: Partner Disclosure and Communication around PrEP Use
• Module C: Responding to Intimate Partner Violence and Safety Planning

The HEART will be used to assess the status of women's relationships and experience of IPV in the intervention arm. The HEART, previously piloted in HOPE, is a tool used to facilitate assessment of, and response to, the range of positive and negative effects of HIV prevention product use experienced by women in intimate partner relationships.

In September 2015, the World Health Organization issued guidelines recommending PrEP be offered to all persons at substantial HIV risk (defined as HIV incidence rate above 3%) worldwide. In sub-Saharan Africa, women account for 58% of the total number of people living with HIV. Given the high HIV incidence and evidence for high potential effectiveness of PrEP when adherence to product use is high, PrEP delivery, adherence, and associated male partner dynamics should be evaluated among a broad age range of women.

This study will enroll sexually active, HIV-uninfected women, who are trial naïve, non-pregnant and aged 18-45 years (inclusive). PrEP, delivered according to national guidelines, IPV screening using the WHO Violence Against Women Survey (VAWS) and referrals for care will be offered to all eligible participants as Standard of Care (SOC) in the control arm. CHARISMA intervention arm participants will receive in-person counselling as part of the CHARISMA intervention to help them assess and build support for PrEP use within their relationships. SHs, IPV, relationship dynamics (e.g. communication, support) and PrEP adherence will be compared across the two arms. Social harms are defined as non-clinical trial related adverse events that result in psychosocial, social, or physical harm among women.

Design: Two-arm, randomized (1:1), controlled study of a behavioral intervention to increase adherence to daily oral PrEP, improve partner relationships (communication and support) and reduce SH and IPV.

A PrEP delivery project will be established in accordance with national guidelines in South African Department of Health (DoH) PrEP guidelines supplemented by the addition of the CHARISMA intervention. Participants presenting for enrolment will be randomized to one of two study arms below:

1. Control: Standard of care (SOC) HIV prevention services in line with the South African DoH PrEP rollout program that include daily oral TDF/FTC. In addition, risk reduction counseling, IPV screening using the VAWS with referrals for counseling, medical care, or shelter assistance, among other care options if needed and an informational packet regarding HIV prevention services for themselves and male partners will be offered;

2. CHARISMA Intervention: SOC per control arm plus provider-administration of HEART and provider-administration of CHARISMA counseling modules, as applicable:

   • Module A: General Partner Communication and Relationship Skills
   • Module B: Partner Disclosure and Communication around PrEP Use
   • Module C: Responding to Intimate Partner Violence and Safety Planning

Population: Approximately four hundred sexually active, HIV-uninfected women who are trial naïve, non-pregnant, and not planning to be pregnant for the next six months, non-breastfeeding, aged 18 to 45 years of age (inclusive)

Study Site(s): Wits RHI (Reproductive Health and HIV Institute) Clinical Research Site, Johannesburg, South Africa Other site(s) to be determined

Approach: This project will offer a PrEP delivery package within two arms of a controlled, randomized study of women to evaluate the impact of the CHARISMA intervention when paired with PrEP delivery.

Study Duration: Accrual will require approximately 12 months. Each participant presenting for PrEP education and services will be enrolled and followed for 6 months. Participants in both study arms will participate in scheduled visits for screening, enrollment, and months 1, 3, and 6 of follow-up. A subset of participants will be asked to participate in a qualitative interview at month 6, and/or month 9.

Primary Objectives:

1. To determine the effectiveness of the CHARISMA intervention in increasing PrEP adherence/persistence at month 6;

2. To determine the effectiveness of the CHARISMA intervention in reducing reported experiences of social harms while on PrEP;

3. To determine the effectiveness of the CHARISMA intervention in reducing reported experiences of IPV (irrespective of time on PrEP);

4. To determine the effectiveness of CHARISMA on participant's reported relationship dynamics, including disclosure of PrEP use, support for product use, and communication;

   Secondary Objective:

5. To explore the acceptability and feasibility of the CHARISMA intervention; and

Exploratory Objective:

7) To assess the sensitivity and specificity of a brief IPV screening tool compared to a longer validated tool in identifying cases of IPV.

Inclusion Criteria:

• Able and willing to provide written informed consent and locator information
• Reports having a current male primary partner,
• Sexually active, defined by vaginal intercourse with a male at least 4 times per month in the past 3 months and plan to be sexually active during the study duration
• Not pregnant (defined by urine pregnancy testing) and not breastfeeding
• Not planning on becoming pregnant in the next 6 months
• English or Zulu speaking
• HIV negative based on negative HIV rapid tests, at the time of enrollment

Exclusion Criteria:

• Previously participated in a clinical trial or a longitudinal HIV prevention research study
• Unwilling to use daily oral PrEP
• Has any significant medical condition or other condition that, in the opinion of the Principal Investigator (PI)/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.