Secondary Cervical Cancer Prevention of Vulnerable Women With HPV and HIV Co-infection in India

In this 5-year parallel-group RCT, the investigators will conduct a RCT to assess the efficacy of our six-month SAKHI HPV intervention, featuring: 1) eight in-depth group education sessions by nurses, OB/GYN and HIV physicians, psychologists, and nutrition experts on HPV/HIV, CC, and nutrition; 2) peer counselor supported 1:1 sessions and community referrals; and 3) selected life skills training by expert artisans as compared to an Enhanced Standard of Care (SOC+) program, featuring 3 group sessions: wellness, basic nutrition and HIV/HPV information and referrals. The primary outcome is HR-HPV persistence (consecutive positivity for same HR-HPV type, separated by 12-18 months).

Secondary outcomes include improved: 1) HIV-related indices (HIV viral load and CD4 count); 2) Nutritional indices (serum albumin) measured at 6, 12, and 18 mos.

The investigators will conduct a two-arm parallel-group RCT among 348 W-Co-V who are cared for at the Belgaum District ART centers. Participants recruited in Karnataka will be individually randomized in a 1:1 ratio to the SAKHI and SOC+ study arms prior to enrollment. A cohort of 16 women (8 per group) will be enrolled every month. Primary outcome, HR-HPV persistence (positivity for same HR-HPV type, separated by 12-18 months), will be compared to enhanced standard of care (SOC+) control group that is above and beyond what is typically offered to WLH treated in the health facility. Persistent HR-HPV is a widely used outcome for HPV vaccine and other CC prevention interventions, due to its critical role in HPV-related cervical oncogenesis. Secondary outcomes will focus on improvement in: 1) HIV related indices (HIV viral load and CD4 count); and 2) Nutritional index, serum albumin levels - a marker for protein consumption).

Setting: Karnataka is selected as our key site for the study as rates of HPV have remained second highest in the country. The W-Co-V are being recruited from underserved ART centers in the Bangalore and its surrounding districts. In the next several months, the team will be in Districts outside Bangalore including Tumkur, and Kolar, while additional sites will be conducted in Northern Karnataka to include Belgaum, Athani, Chikooi, Gokak, Raibagh and Saudatti.

The KSAPS (Karnataka State acquired immunodeficiency syndrome (AIDS) Program Society) has approved these sites to participate in our study. To enroll 348 W-Co-V, a total of 3480 WLH will be screened; thus, ongoing screening of our staff will be conducted in all ART centers. First-line ART is offered free by the government to all eligible PLWH and all newly diagnosed are referred to the ART centers. Thus, the investigators anticipate the 6 ART Centers will provide a sufficient number of eligible women.

Screening and Enrollment Procedure: The interviewers are informing the WLH about the study with flyers posted in the lobbies of the ART centers. Interested WLH approach the interviewer, stationed in the lobby, and retreat to a private room for further information. After the study is discussed, and all questions answered, the initial informed consent form (ICF) for screening is signed by the WLH. Immediately thereafter, the interviewer administers a brief 5-minute screening assessing age, prior HPV screening/treatment for HPV, abnormal cytology/CC, and HIV and ART status. Those who found not eligible are thanked for their time, provided the screening compensation and provided any immediately needed referrals in the community. Among those eligible, HPV status is assessed by requesting the women to perform a self-sample vaginal swab collection in the clinic restroom, wherein trained peer counselors are available to assist. The samples are collected and sent to a selected lab for processing. At the lab, the samples are processed for presence of oncogenic HPV, and genotyping.

For this step, participants will be offered two options based on their preference:

1. Undergo the self-swab HPV test followed by VIA on the same day. Participants will be notified of their eligibility after the test results are available. 2. Undergo the self-swab HPV test and wait for the results. If the result of the HPV test is positive, participants will be notified and asked to return on a different day for VIA. Eligibility will be determined based on the results of both the self-swab test and VIA.

Typically, in India, nurses are trained to do VIAs; a good substitute for CC screening in low resource areas. Results will be provided confidentially to the woman by the nurse under the guidance of protocols developed by our gynecologist. If found to be VIA negative, the W-CoV will be referred to the interviewer for consideration of enrollment into the study, and a second ICF for participating in the RCT will be discussed and signed. Women found to be VIA positive are immediately referred to a gynecologist. Eligible and consenting women will be individually randomized in a 1:1 ratio to either the SAKHI or SOC+ programs prior to study initiation.

Based on World Health Organization (WHO) guidelines, WLH found to be HPV positive should be rescreened for HPV in the next 12 months, along with VIA. If found to be VIA negative, screening can be resumed every 3 years. The interview staff are not involved in the delivery of the intervention and thus are blinded to condition for all assessments. Providers at the ART centers will also be blinded to study conditions.

Study Procedure: The investigators will recruit and enroll 348 eligible women living with HIV who test positive for HPV (WLHIV-HPV+) into one of two study arms: the SAKHI intervention arm or the Enhanced Standard of Care (SOC+) control arm. Participants will be recruited from ART centers across Karnataka, including KC General Hospital, Chikkaballapur, Kolar, Tumkur, Ramanagara, and Belagavi. Recruitment will occur in small groups of approximately 8 women per arm to facilitate intervention delivery and group-based activities. Following screening and informed consent procedures, eligible participants complete HPV self-swab testing and VIA screening. Women who are HPV-positive and VIA-negative proceed to baseline enrollment and randomization. Follow-up assessments occur at baseline, 6 months, 12 months, and 18 months.

At baseline and follow-up assessments, blinded interviewers administer questionnaire-based assessments using REDCap on tablet computers. Assessments include demographic information, HIV and HPV treatment barriers, stigma, emotional well-being, food security, substance use, physical activity, ART adherence, and psychosocial functioning. Dietary assessments are conducted using a two-day 24-hour dietary recall through the NINA-DISH application. Blood samples are collected to assess nutrition markers, Serum Albumin, Iron, Vitamin B12, Vitamin A, Vitamin D, CD4 count, and HIV viral load. Bioelectrical Impedance Analysis (BIA) and Body Mass Index (BMI) assessments are conducted during assessment visits. In addition to scheduled assessments, peer counselors maintain regular contact with participants through weekly visits, ongoing support, group sessions, and referral coordination as outlined in the intervention protocol. Group sessions focus on HPV education, HIV wellness, nutrition, mental health, resilience, behavioral activation, self-care, and employability skill-building. For implementation of the intervention, seven peer counselors have been trained, with five assigned to the SAKHI intervention arm and two assigned to the SOC+ arm. Peer counselors have undergone rigorous training conducted by the study investigators, project coordinator, and co-investigators. Training includes protocol orientation, mock sessions, counseling techniques, module-guided intervention delivery, confidentiality procedures, documentation practices, and mobile phone-based field reporting. Quarterly quality assurance assessments and booster training are conducted to maintain intervention fidelity and data quality. To minimize self-selection bias and improve participant comfort, interviewers and peer counselors receive training on confidentiality, stigma reduction, culturally sensitive communication, and disclosure avoidance. Recruitment will occur across multiple ART centers and at varying times to ensure representation of a broad and diverse participant population.

SAKHI Intervention: After completing their training, peer counselors are assigned to participants within the SAKHI intervention or SOC+ control arms to provide individualized support and follow-up, with each peer counselor effectively managing approximately 6-7 participants to ensure continuity and quality of engagement. To minimize contamination, we allot randomized participant lists and organize peer counselors into two working teams to support participant engagement in a structured manner with protocol-driven, with arm-specific modules, schedules, and content implemented according to participant assignment. The peer counselors are supervised by the nurse supervisor, the Project Coordinator, and investigators. Peer counselors maintain regular weekly contact with SAKHI participants and once every alternative month over the six month intervention period to assess participant needs, provide support, reinforce intervention content, monitor participation, and document activities according to the study protocol.

Based on initial interactions with participants, peer counselors and supervising staff identify barriers to intervention participation, follow-up care, ART adherence, screening attendance, and overall engagement. This information helps tailor support strategies to individual participant needs while ensuring that all core intervention components are consistently delivered.

The SAKHI intervention includes:

1. Six monthly group sessions led by trained intervention staff and supported by experts such as physicians, nutritionists, psychologists, and counselors. Sessions cover topics including HPV and cervical cancer education, HIV wellness, nutrition, mental health, resilience, behavioral activation, self-care, and skill-building. 2. Weekly individual peer counselor support and follow-up visits. 3. Referral to grant-supported employability and life skills training programs, including sewing, embroidery, computer training, and other participant-identified skill programs delivered by trained experts.

The specific classes relevant to our targeted W-Co-V were assessed in our CAB/focus group discussions, and include selling vegetables, sewing, weaving, embroidery, etc. These classes will provide economic sustainability, as accomplished by 80% of the WLH in our ASHA-Nutrition study. In the 8 group sessions, based on the comprehensive health seeking and coping paradigm (CHSCP), the nurse and content experts in Nursing, Medicine, Psychology and Nutrition address distinct barriers to ongoing engagement in care by educating the cohort about health promotion, HPV/HIV, coping with stigma, improving depressive symptoms, seeking trusted support, and keeping mentally healthy. The peer counselors who care for these women also attend, listen to the program, and support the team. The assigned peer counselors contact the women weekly and focus on providing 1:1 support to the W-Co-V in accessing and/or adhering to ART as well as reinforcing education received in group sessions, assisting with transportation, offering to accompany them to appointments, providing counseling, promote healthy lifestyle choices, and links with community resources. This weekly peer counselors support will occur over the six-month intervention. Records of time spent will be carefully monitored on the tablets. As lack of job skills has been previously identified as a source of stress, the peer counselors will assess job skills of interest for each woman and arrange selected training sessions weekly over the six-month period with skilled artisans.

The 8 (1.5 hours) group sessions will be held bimonthly over the first four months in a s

• HIV Viral Load [Срок оценки: Baseline and month 6, 12, and 18]
• CD4 Count [Срок оценки: Baseline and month 6, 12, and 18]
• Serum-based Albumin [Срок оценки: Baseline and month 6, 12, and 18]