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 theefficacy of our six‐month SAKHI HPV intervention, featuring: 1) eight in‐depth groupeducation sessions by nurses, OB/GYN and HIV physicians, psychologists, and nutritionexperts on HPV/HIV, CC, and nutrition; 2) ASHA supported 1:1 sessions and communityreferrals; and 3) selected life skills training by expert artisans as compared to anEnhanced Standard of Care (SOC+) program, featuring 3 group sessions: wellness, basicnutrition and HIV/HPV information and referrals. The primary outcome is HR‐HPVpersistence (consecutive positivity for same HR‐HPV type, separated by 12‐18 months).Secondary outcomes include improved: 1) HIV‐related indices (HIV viral load and CD4count); 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 arecared for at the Belgaum District ART centers. Participants from 24 villages in Karnatakawill be individually randomized in a 1:1 ratio to the SAKHI and SOC+ study arms prior toenrollment. A cohort of 16 women (8 per group) will be enrolled every month. Primaryoutcome, 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 andbeyond what is typically offered to WLH treated in the health facility. Persistent HR‐HPVis a widely used outcome for HPV vaccine and other CC prevention interventions, due toits critical role in HPV‐related cervical oncogenesis. Secondary outcomes will focus onimprovement in: 1) HIV related indices (HIV viral load and CD4 count); and 2) Nutritionalindex, serum albumin levels ‐ a marker for protein consumption).Setting: Karnataka is selected as our key site for the study as rates of HPV haveremained second highest in the country. The W‐Co‐V are being recruited from underservedART 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, whileadditional 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) hasapproved these sites to participate in our study. To enroll 348 W‐Co‐V, a total of 4200WLH will be screened; thus, ongoing screening of our staff will be conducted in all ARTcenters. First‐line ART is offered free by the government to all eligible PLWH and allnewly diagnosed are referred to the ART centers. Thus, the investigators anticipate the 6ART Centers will provide a sufficient number of eligible women.Screening and Enrollment Procedure: The interviewers are informing the WLH about thestudy with flyers posted in the lobbies of the ART centers. Interested WLH approach theinterviewer, stationed in the lobby, and retreat to a private room for furtherinformation. After the study is discussed, and all questions answered, the initialinformed consent form (ICF) for screening is signed by the WLH. Immediately thereafter,the interviewer administers a brief 5‐minute screening assessing age, prior HPVscreening/treatment for HPV, abnormal cytology/CC, and HIV and ART status. Those whofound not eligible are thanked for their time, provided the screening compensation andprovided any immediately needed referrals in the community. Among those eligible, HPVstatus is assessed by requesting the women to perform a self‐sample vaginal swabcollection in the clinic restroom, wherein trained ASHA are available to assist. Thesamples are collected and sent to a selected lab for processing. At the lab, the samplesare processed for presence of oncogenic HPV, and genotyping. If oncogenic type HPV isfound, a visual inspection of the cervix with application of acetic acid is scheduled andconducted by our trained nurse. The decision to have the VIA immediately after theself‐swab is also an option.Typically, in India, nurses are trained to do VIAs; a good substitute for CC screening inlow resource areas. Results will be provided confidentially to the woman by the nurseunder the guidance of protocols developed by our gynecologist. If found to be VIAnegative, the W‐CoV will be referred to the interviewer for consideration of enrollmentinto the study, and a second ICF for participating in the RCT will be discussed andsigned. 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 eitherthe SAKHI or SOC+ programs prior to study initiation. Once assigned, the PC delivers theassignment to the appropriate study nurse and ASHA. Based on World Health Organization(WHO) guidelines, WLH found to be HPV positive should be rescreened for HPV in the next12 months, along with VIA. If found to be VIA negative, screening can be resumed every 3years. The interview staff are not involved in the delivery of the intervention and thusare blinded to condition for all assessments. Providers at the ART centers will also beblinded to study conditions.Study Procedure: The investigators will recruit and enroll 348 eligible women living withHIV who test positive for HPV (WLHIV‐HPV+) into one of two study arms: the SAKHIintervention arm or the Enhanced Standard of Care (SOC+) control arm. Participants willbe recruited from ART centers across Karnataka, including KC General Hospital,Chikkaballapur, Kolar, Tumkur, Ramanagara, and Belagavi. Recruitment will occur in smallgroups of approximately 8 women per arm to facilitate intervention delivery andgroup‐based activities. Following screening and informed consent procedures, eligibleparticipants complete HPV self‐swab testing and VIA screening. Women who are HPV‐positiveand VIA‐negative proceed to baseline enrollment and randomization. Follow‐up assessmentsoccur at baseline, 6 months, 12 months, and 18 months.At baseline and follow‐up assessments, blinded interviewers administerquestionnaire‐based assessments using REDCap on tablet computers. Assessments includedemographic information, HIV and HPV treatment barriers, stigma, emotional well‐being,food security, substance use, physical activity, ART adherence, and psychosocialfunctioning. Dietary assessments are conducted using a two‐day 24‐hour dietary recallthrough the NINA‐DISH application. Blood samples are collected to assess nutritionmarkers, Serum Albumin, Iron, Vitamin B12, Vitamin A, Vitamin D, CD4 count, and HIV viralload. Bioelectrical Impedance Analysis (BIA) and Body Mass Index (BMI) assessments areconducted during assessment visits. In addition to scheduled assessments, peer counselorsmaintain regular contact with participants through weekly visits, ongoing support, groupsessions, and referral coordination as outlined in the intervention protocol. Groupsessions focus on HPV education, HIV wellness, nutrition, mental health, resilience,behavioral activation, self‐care, and employability skill‐building. For implementation ofthe intervention, seven peer counselors have been trained, with five assigned to theSAKHI intervention arm and two assigned to the SOC+ arm. Peer counselors have undergonerigorous training conducted by the study investigators, project coordinator, andco‐investigators. Training includes protocol orientation, mock sessions, counselingtechniques, module‐guided intervention delivery, confidentiality procedures,documentation practices, and mobile phone‐based field reporting. Quarterly qualityassurance assessments and booster training are conducted to maintain interventionfidelity and data quality. To minimize self‐selection bias and improve participantcomfort, interviewers and peer counselors receive training on confidentiality, stigmareduction, culturally sensitive communication, and disclosure avoidance. Recruitment willoccur across multiple ART centers and at varying times to ensure representation of abroad and diverse participant population.SAKHI Intervention: After completing their training, peer counselors are assigned toparticipants within the SAKHI intervention or SOC+ control arms to provide individualizedsupport and follow‐up, with each peer counselor effectively managing approximately 6‐7participants to ensure continuity and quality of engagement. To minimize contamination,we allot randomized participant lists and organize peer counselors into two working teamsto support participant engagement in a structured manner with protocol‐driven, witharm‐specific modules, schedules, and content implemented according to participantassignment. The peer counselors are supervised by the nurse supervisor, the ProjectCoordinator, and investigators. Peer counselors maintain regular weekly contact withSAKHI participants and once every alternative month over the six month interventionperiod 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 staffidentify barriers to intervention participation, follow‐up care, ART adherence, screeningattendance, and overall engagement. This information helps tailor support strategies toindividual participant needs while ensuring that all core intervention components areconsistently delivered.The SAKHI intervention includes: 1. Six monthly group sessions led by trained intervention staff and supported byexperts such as physicians, nutritionists, psychologists, and counselors. Sessionscover 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‐identifiedskill programs delivered by trained experts.The specific classes relevant to our targeted W‐Co‐V were assessed in our CAB/focus groupdiscussions, and include selling vegetables, sewing, weaving, embroidery, etc. Theseclasses will provide economic sustainability, as accomplished by 80% of the WLH in ourASHA‐Nutrition study. In the 8 group sessions, based on the comprehensive health seekingand coping paradigm (CHSCP), the nurse and content experts in Nursing, Medicine,Psychology and Nutrition address distinct barriers to ongoing engagement in care byeducating the cohort about health promotion, HPV/HIV, coping with stigma, improvingdepressive symptoms, seeking trusted support, and keeping mentally healthy. The peercounselors who care for these women also attend, listen to the program, and support theteam. The assigned peer counselors contact the women weekly and focus on providing 1:1support to the W‐Co‐V in accessing and/or adhering to ART as well as reinforcingeducation received in group sessions, assisting with transportation, offering toaccompany them to appointments, providing counseling, promote healthy lifestyle choices,and links with community resources. This weekly peer counselors support will occur overthe six‐month intervention. Records of time spent will be carefully monitored on thetablets. As lack of job skills has been previously identified as a source of stress, thepeer counselors will assess job skills of interest for each woman and arrange selectedtraining 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 aspace the research team will rent that is central to all villages, based on the needsidentified by prior WLH, and updated by the planned community advisory board (CAB), focusgroup (FG) meetings, and needs assessment. In months 5 and 6 of the program, the peercounselors will hold role play sessions once a month where the cohort will come together,and role play what they have learned in group sessions and how they are implementing it.Module 1 (sessions 1 & 2) begins with relaxation/grounding exercises, provide generalinformation on HPV on how it spreads, recognizing the link between HPV and cervicalcancer, the importance of seeking support from peer counselors, healthcare providers andtrusted family/friends; importance of routine HPV screening, and know about the HPVvaccine and where to access care. Module 2 (sessions 3 & 4) focuses on caring for selfand family, and begin with relaxation/ grounding exercises, discussions on HIV and howthe virus is transmitted; and how the immune system is activated; and information aboutART. There also is the beginning of Life Skills offered by experts on ways to enhancecoping, including legal and spiritual; and beginning life skills vocational classes.Finally, a discussion about HIV and cervical cancer and information on alcohol and druguse. In Module 3 (sessions 5 & 6), the focus will be on emotional health and well‐being.Participants will learn more in depth about relaxation techniques, and skills building,strategies to improve coping, stigma and problem solving, all of which will buildresilience. They will learn to set goals and commit to uplifting activities; andcontinued life skills. They will also receive a handout of local mental health resources.Module 4 (sessions 7 & 8) will focus on providing education about which foods are theleast expensive, easily accessible, and highly nutritious and immune supportive; andsharing recipes and enjoying cooking classes. Our nutrition experts will guide foodselections using the Dietary Guidelines for Indians and food availability in the localregion. Finally, ASHA will provide monthly food supplements that will consist of highprotein foods (i.e. Dal lentils), while attending to minimal saturated fat, fiber(soluble fiber), and the cholesterol content of the foods. Food will be distributed basedon family size with enough food for each family member to ensure the participant receivesthe intervention. In addition, to accommodate women who are unable to make group‐assignedclasses, additional flexible dates will be offered. If successful, this intervention canbe easily scaled up by integrating ASHA training into the current Health Mission of Indiastrategies.Enhanced Standard of Care (SOC+): In India, screening services are lacking at most ARTcenters. Since it would be unethical to withhold potentially lifesaving information aboutHPV, the investigators offer an enhanced standard of care to include usual care + three(1.5 hour) group sessions on wellness, basic nutrition, coping with mental health issues,importance of HPV screening and treatment as needed, and ART adherence, and similarlydelivered by the nurse and content experts over the six‐month intervention. Womenassigned to the SOC+ program are HPV screened at baseline as well and l meet as a groupthree times to meet their distinct SOC+ nurse and peer counselor at the research site.The SOC+ nurse and peer counselor, who follow distinct program protocols, provideinformation on resources in the community, including nutritious and low‐cost foods, aswell as referral to ART and other services as needed, and remind the participants byphone of upcoming appointments. However, peer counselors do not visit the women in theirhomes, nor do they receive the other modules or food supplements. Each of the SOC+ peercounselors follow their cohort of 8 participants every month over the six‐month period.The SOC+ nurse guide their peer counselor and answer medical questions for theirparticipants.