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Herpesviruses Reactivation In Hiv-Infected Women Initiating ART (HERA)

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ClinicalTrials.gov Identifier: NCT03092505
Recruitment Status : Recruiting
First Posted : March 28, 2017
Last Update Posted : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:

Background:

Herpes virus can cause sores on the body. It can cause flu-like symptoms like fever and muscle aches, and even a type of cancer. Many people with HIV also have infections with herpes virus. When these people start taking HIV medicines, their herpes virus symptoms can suddenly start or become worse. Researchers want to find out more about how often this happens and why.

Objective:

To study the effects of HIV treatment in women who may have herpes virus infections.

Eligibility:

Women age 18 years and older who have been diagnosed with HIV infection.

Design:

Participants will be screened with a physical exam, medical history, and blood and urine tests.

Participants will have about 8 study visits. Each will take about 1-2 hours.

Participants will return to the clinic 1-2 weeks after the screening visit to receive their antiretroviral (ART) medicine. They will get instructions for taking it.

Participants will have 6 more study visits over 1 year.

During study visits, participants will have blood and urine tests, vaginal fluid collected, and an oral swab. They may have an external genital exam. They will get their next supply of ART medicine.

Some participants may have a chest x-ray.

Participants may have leukapheresis. Blood will be removed through a needle in an arm. It will be run through a machine that separates out the white blood cells. The rest of the blood will be returned through a needle in the other arm.

The total time participants will be in the study is about 1 year.


Condition or disease
Herpesvirus

Detailed Description:

Initiation of antiretroviral therapy (ART) can lead to a short-term increase of herpes virus-related illnesses including genital herpes flares, higher likelihood of varicella zoster virus (VZV), cytomegalovirus (CMV) uveitis or other end-organ disease, and herpes simplex virus (HSV) associated encephalitis. Herpesvirus reactivation upon ART initiation may be related to immune restoration disease of immune reconstitution inflammatory syndrome (IRIS), but the etiology is unclear. We hypothesize that ART initiation can induce herpesvirus reactivation causing increased cellular, systemic, and localized immune activation and that alterations of interferon (IFN) pathways during initial HIV viral suppression are involved in this reactivation.

To investigate these mechanisms, we propose to document the incidence of clinical herpetic disease and viral shedding in vaginal and oral secretions from HIV-positive women initiating ART and to assess the associations between viral shedding or clinical disease and cellular, mucosal, and systemic immune activation. We will determine the role of IFN pathway in herpesvirus reactivation following initiation of ART. We will also evaluate the potential impact of herpesvirus reactivation on HIV cellular reservoirs by comparing residual HIV plasma viral replication and cell-associated virus prior to and 52 weeks after ART initiation.

We propose to recruit up to 200 HIV-infected women initiating ART at the NIH Clinical Center (n=30 to 40) and the Rakai Health Sciences Program (RHSP) site in Kalisizo, Uganda and Kalisizo Hospital ARV clinic (n=160 to 170). Women will be recruited regardless of CD4+ T-cell count, presence of opportunistic infections and co-infection status. Pregnant women will be excluded. During 8 study visits to occur over a 12-month period, participants will receive standard-of-care treatment for HIV and opportunistic infections. Blood, vaginal fluid and oral swabs collected at study visits will be tested for viral levels of HIV and various herpesviruses. Vaginal samples will also be used to study differences in vaginal microbiota between women with and without herpetic disease prior and after ART. Plasma samples will be tested for antibody levels (IgG) specific for different herpesviruses to examine changes in anti-herpetic humoral responses. ART adherence will be monitored in plasma using high-resolution mass spectrometry.


Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Herpesviruses Reactivation In Hiv-Infected Women Initiating ART (HERA)
Estimated Study Start Date : June 22, 2018
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : February 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Group/Cohort
Females
Females participants who are about to start first line antiretroviral therapy.



Primary Outcome Measures :
  1. Compare the prevalence of herpetic disease, demonstrated by viral shedding of HSV-1 and 2 in the vaginal secretions of HIV-positive women prior to and 4 and 8 weeks after ART initiation. [ Time Frame: 8 weeks post enrollment ]

Secondary Outcome Measures :
  1. To estimate the associations of viral shedding or clinical herpetic disease post-ART at weeks 4 or 8 with concurrent and baselinemeasurement of systemic inflammation (IL-6, CRP, TNF or sCD14). [ Time Frame: 8 weeks post enrollment ]
  2. To estimate the associations of viral shedding or clinical herpetic disease post-ART at weeks 4 or 8 with concurrent and baselinemeasurements of cellular activation (CD4 and CD8 T cells expressing HLA-DR/CD38). [ Time Frame: 8 weeks post enrollment ]
  3. To estimate the associations of viral shedding or clinical herpetic disease in genital area post-ART at weeks 4 or 8 with concurrent and baseline measurements of cytokine levels in vaginal secretions. [ Time Frame: 8 weeks post enrollment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Potential participants will be recruited from primary HIV care cliniics in Kalisizo town which provide antiretorviral treatment.
Criteria
  • INCLUSION CRITERIA:

    1. At least 18 years of age
    2. Female
    3. Weight >40 kilograms
    4. A diagnosis of HIV infection as documented by any positive serological test (ELISA, HIV rapid test, or Western Blot)
    5. Participants in Uganda must be eligible for ART by current clinical guidelines in Uganda
    6. Willingness to begin ART
    7. Will allow storage of biological sample

EXCLUSION CRITERIA:

  1. Previous exposure to ART (participants with a brief exposure (<3 months) that occurred greater thatn or equal to 6 months prior to screening will be eligible to enroll if, the opinion of the investigator, the ART usage will not impact the scientific validity of the protocol)
  2. On acyclovir, valacyclovir, valganciclovir, or ganciclovir treatment
  3. Pregnancy or intent to become pregnant during the study period
  4. Intrauterine device (IUD) use
  5. Inability to follow study instructions, according to the investigator's judgment
  6. Active, serious infections other than HIV infection that may interfere with study participation (eg, severe cerebral toxoplasmosis or cryptococcal meningitis) during the 2 weeks prior to enrollment
  7. Malignancies requiring chemotherapy
  8. Therapy with systemic corticosteroids, immunosuppressants or immunomodulating agents
  9. Any condition that, in the investigator s opinion, may put the participant at undue risk or compromise the study's scientific objectives

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03092505


Contacts
Contact: Yolanda Mejia (240) 669-2877 yolanda.mejia@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Steven J Reynolds, M.D. National Institute of Allergy and Infectious Diseases (NIAID)