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

NCT07209917 | Recruiting

• 2 other identifiers: 2988-29621R01CA285063-01
• Study Type: interventional
• Target: 420
• Locations: 1 country
• Sites: 1

Brief Summary

Cervical cancer (CC) remains one of the most common malignancies among women in India, with nearly 100,000 women diagnosed annually and over 60,000 preventable deaths annually. With high-risk human papillomavirus (HR-HPV) as the causative agent for CC, one risk factor that places women at high risk for CC is human immunodeficiency virus (HIV), as impaired immune response against Human papillomavirus (HPV) may result in persistent HR-HPV infection, a critical risk factor for progression of HPV-related cervical oncogenesis. Progression of precancerous lesions among women living with HIV (WLH) is also associated with: 1) lack of HPV screening; 2) high levels of depressive symptoms and stigma; and 3) malnutrition, which negatively impacts the activation and proliferation of immune cells. Yet programs that offer WLH with comprehensive services focused on HPV screening and psychological and nutritional support are almost non-existent, and the gap is critical. Nutrition plays an integral role in relationship to HPV/HIV co-infection, as demonstrated by an increased risk of HR-HPV associated with poor nutrition; nutritional deficiencies are likewise linked to cervical intra-epithelial neoplasia. The immunological effect of malnutrition may also be exacerbated among WLH due to elevated energy demands of chronic immune activation; worsened with HPV/HIV co-infection. Further, depressive symptoms (aka depression for brevity) partially mediate the effect of food insecurity on HIV viral suppression. In our completed ASHA-Nutrition R01 study of antiretroviral (ART) adherence, the investigators trained lay community health workers, named Accredited Social Health Activist (ASHA), to improve the health of 600 rural WLH by providing emotional support, skill-building, nutrition education, and/or protein-enriched food supplements. In that study, our intervention, co-delivered by our trained ASHA, and guided by nurses, led to increased CD4+ T cell recovery and improved anthropometric and psychosocial outcomes. The investigators found that ASHA support plus protein supplements and nutritional education were significantly associated with improved CD4 counts and increased lean mass at 18 months (P \< 0.001), as well as significant improvements in depression, ART adherence, social support and internalized stigma. In our sub study, CC screening of 598 of these WLH revealed that 13% were found to have abnormal cervical lesions and 4 (1%) had squamous CC. Preliminary evidence also revealed that nutritional supplements may be associated with a 40% reduction in the risk of abnormal cervical lesions (adjusted odds ratio \[aOR\] = 0.60), with an association between serum albumin and reduced risk of abnormal lesions (aOR= 0.39). With a focus on secondary prevention of CC, the investigators hope to mitigate the link between HR-HPV persistence and risk of CC as well as improve the health of women co-infected with HPV/HIV (W-Co-V). Our stellar team plans to build upon our prior ASHA-Nutrition intervention, using formative research to refine a nurse-led, ASHA co-delivered, nutrition-enhanced ASHA-Health HPV intervention, adapted for W-Co-V. This will be followed by a randomized controlled trial (RCT), assessing the efficacy of our refined comprehensive, multifaceted ASHA-Health HPV intervention, as compared with an enhanced Standard of Care (SOC+) (usual care + 3 sessions \[wellness, basic nutrition and HPV/HIV health promotion\]) among 420 high-risk co-infected women to prevent CC while remaining engaged in the HIV treatment cascade, and managing nutritional health. Participants, recruited from a total of 24 villages, will be individually randomized in a 1:1 ratio into the two study arms. Our Primary outcome is HR-HPV persistence (2 positive tests for the same HR-HPV type, separated by 12-18 months). The two aims incorporating RCT interventions are as follows: Aim 2. To evaluate the efficacy of ASHA-Health HPV intervention among 420 W-Co-V on the primary outcome (HR-HPV persistence) as compared to the Enhanced Standard of Care (SOC+) program. H2: Compared to the SOC+ participants, ASHA-Health participants will have lower rates of HR-HPV persistence. Aim 3. Assess the impact of the ASHA-Health program secondarily on: 1) HIV indices (HIV viral load; CD4 count); 2) Nutritional index (serum albumin) at 6-, 12-, and 18-months.

Conditions

Cervical Cancer; Human Papillomavirus (HPV) Infection; Human Immunodeficiency Virus (HIV) Infection

Keywords

Cervical Cancer Prevention; HPV-HIV Co-Infection; ASHA-Nutrition

Outcome Measures

Primary Outcomes (1)

• HR-HPV Detection

  HR- HPV test will detect 14 oncogenic HR-HPV genotypes (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). HR-HPV persistence is defined as the presence of the same genotype over at least 12 months.

  Baseline and month 6, 12 and 18 month follow-ups

Secondary Outcomes (3)

• HIV Viral Load

  Baseline and month 6, 12, and 18

• CD4 Count

  Baseline and month 6, 12, and 18

• Serum-based Albumin

  Baseline and month 6, 12, and 18

Study Arms (2)

ASHA-Health

EXPERIMENTAL

The ASHA-Health program will include: 1) 8 group sessions, led by the nurse, and inclusive of other experts (such as HPV/HIV physician, nutritionist, psychologist) to provide the group classes for each cohort of 42 W-Co-V in the program, covering content about staying healthy, taking care of self/family, skills building, and eating healthy; 2) Individual 1:1 weekly ASHA support; and 3) referral to grant-supported life skills classes taught by experts.

Behavioral: ASHA-Health HPV Intervention

SOC+

OTHER

The investigators will 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 (similar to Modules for ASHA-Health), and similarly delivered by the nurse and content experts over the six-month intervention.

Behavioral: Enhanced Standard of Care (SOC+)

Interventions

ASHA-Health HPV Intervention BEHAVIORAL

The ASHA-Health HPV program will include three components: 1) Individual 1:1 weekly ASHA support; 2) 8 group sessions for the 42 W-Co-V in the ASHAHealth cohort, covering content in Modules 1-4; and 3) referral to life skills classes. The assigned ASHA will provide services to support the W-Co- V in accessing and/or adhering to HPV and ART appointments (arrange transportation, provide counseling, promote healthy lifestyle choices, and link with community resources). ASHA will also promote positive coping, social support, and aid in dealing with stigma. The 8 group sessions will be held over the six months, based on the needs identified by the women. Overall, the intervention content targets the provision of emotional support, skill building, HPV/ HIV and nutrition education, and protein-enriched food supplements, and ways to deal with stress, stigma, and the importance of engagement and retention in care. Food selections will be guided by our nutrition experts.

ASHA-Health

Enhanced Standard of Care (SOC+) BEHAVIORAL

Selecting our base at the Belgaum ART Centers will provide the most up to date services for the SOC+ group. Yet, there is no typical standard of care in India as it relates to HPV screening for W-Co-V and stigma associated with both diseases is high. Further, in India, screening services are lacking at most ART centers. Since it would be unethical to withhold potentially lifesaving information about HPV, the investigators will offer an enhanced standard of care to include usual care + 3 (1.5 hour) group sessions on wellness, basic nutrition, coping with mental health issues, and HIV/ HPV information. Thus, women will meet as a group three times over the six-month period. In addition, the women have access to our SOC+ nurse and ASHA to respond to questions.

SOC+

Eligibility Criteria

• Age: 25 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• WLH, 25 - 50 years of age; based on HIV-based guidelines;
• Receiving ART for \> 12 months to ensure medication stabilization, and ensure any impact on the cervical cancer outcomes will not be attributed solely to recent ART initiation, as validated by an ART card given to all ART patients;
• Screened as HPV positive by RT-PCR (Reverse Transcription Polymerase Chain Reaction) for oncogenic genes; and assessed to be VIA negative;
• Have not participated in Phase I Formative Study.

You may not qualify if:

• Pregnant or lactating women due to hormonal and dietary guideline differences;
• Women older than age 50. These women will be immediately referred to a gynecology specialist.

Sponsors & Collaborators

• University of California, Irvine: lead
• National Cancer Institute (NCI): collaborator
• University of California, San Francisco: collaborator
• National Institute of Mental Health and Neuro Sciences (NIMHANS): collaborator

Study Sites (1)

KC General Hospital

Bangalore, Karnataka, India

RECRUITING

Related Publications (4)

• Nyamathi A, Hanson AY, Salem BE, Sinha S, Ganguly KK, Leake B, Yadav K, Marfisee M. Impact of a rural village women (Asha) intervention on adherence to antiretroviral therapy in southern India. Nurs Res. 2012 Sep-Oct;61(5):353-62. doi: 10.1097/NNR.0b013e31825fe3ef.

  PMID: 22872107 BACKGROUND

• Nyamathi A, Ekstrand M, Salem BE, Sinha S, Ganguly KK, Leake B. Impact of Asha intervention on stigma among rural Indian women with AIDS. West J Nurs Res. 2013 Aug;35(7):867-83. doi: 10.1177/0193945913482050. Epub 2013 Mar 27.

  PMID: 23539322 BACKGROUND

• Garfin DR, Shin SS, Ekstrand ML, Yadav K, Carpenter CL, Sinha S, Nyamathi AM. Depression, social support, and stigma as predictors of quality of life over time: results from an Asha-based HIV/AIDS intervention in India. AIDS Care. 2019 May;31(5):563-571. doi: 10.1080/09540121.2018.1563281. Epub 2019 Feb 3.

  PMID: 30714386 BACKGROUND

• Nyamathi A, Ekstrand M, Srivastava N, Carpenter CL, Salem BE, Al-Harrasi S, Ramakrishnan P, Sinha S. ASHA-Life Intervention Perspectives Voiced by Rural Indian Women Living With AIDS. Health Care Women Int. 2016;37(4):412-25. doi: 10.1080/07399332.2015.1066790. Epub 2015 Jul 6.

  PMID: 26147930 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Papillomavirus Infections; Infections; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; HIV Infections; Blood-Borne Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Slow Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Adey Nyamathi, ANP, PhD, FAAN

  UCI Sue & Bill Gross School of Nursing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Veena Satyanarayana

CONTACT

91-80-26995180/5877; veena.a.s@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Distinguished Professor

Model Details: In Phase 2 (mos 12 - 41) + follow-ups, the investigators will conduct a two-arm parallel-group RCT among 420 W-Co-V who are cared for at ART centers in Bangalore and northern Karnataka. Participants will be allocated to the ASHA-Health and SOC+ study arms through individual randomization in a 1:1 ratio prior to study enrollment. A cohort of 84 women (42 per group) will be enrolled every six months.

Study Record Dates

• First Submitted: September 29, 2025
• First Posted: October 7, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): July 31, 2030
• Last Updated: February 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)