Herpes Virus-Related IllnessesNCT03092505
Herpesviruses Reactivation In Hiv-Infected Women Initiating ART (HERA)
An observational study of Herpes Virus-Related Illnesses, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years, women only
- Conditions the study is for
- Herpes Virus-Related Illnesses
- How many people
- 190 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 15 Jun 2018to 4 Feb 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Approximately 200 women initiating ART as part of standard HIV care will be recruited at four sites, the NIH Clinical Center (approximately 30-40), the RHSP/ICER , the Villa Maria Hospital and the Kalisizo sites in Uganda (approximately 160-170). Women will be recruited regardless of CD4+ T-cell count, presence of opportunistic infections and co-infection status. Participants taking antibiotics for co-infections and prophylaxis will be able to participate in the study and antibiotic use will be captured in study data. Participants may co-enroll in other non-interventional studies. Pregnant women will be excluded.
Who may be able to join
- At least 18 years of age
- Female
- Weight >40 kilograms
- A diagnosis of HIV infection as documented by any positive serological test (ELISA, HIV rapid test, or Western Blot)
- Participants in Uganda must be eligible for ART by current clinical guidelines in Uganda
- Willingness to begin ART
- Will allow storage of biological sample
Who cannot join
- 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)
- On acyclovir, valacyclovir, valganciclovir, or ganciclovir treatment
- Pregnancy or intent to become pregnant during the study period
- Intrauterine device (IUD) use
- Inability to follow study instructions, according to the investigator's judgment
- 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
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- Malignancies requiring chemotherapy
- Therapy with systemic corticosteroids, immunosuppressants or immunomodulating agents
- Any condition that, in the investigator s opinion, may put the participant at undue risk or compromise the study's scientific objectives
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the 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 enroll up to 200 HIV-infected women initiating ART at the NIH Clinical Center (n=30 to 40) and between the Villa Maria Hospital, 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.
- Conditions
- Herpes Virus-Related Illnesses
- Keywords
- HSV, Uganda, Sample, Natural History
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Females | Females participants who are about to start first line antiretroviral therapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
viral shedding of HSV-1 and 2
Measured: prior to and at 4 and 8 weeks after inititian of antiretroviral treatment
Secondary outcomes (1)
1. To estimate the associations of viral shedding or clinical herpetic disease post-ART at weeks 4 or 8 with concurrent and baseline measurement of systemic inflammation (IL-6, CRP, TNF or sCD14). [ Time Frame: 8 weeks post enrollment ]
Measured: at week 4 and at week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2017
- Study start15 Jun 2018
- Primary completion1 Feb 2021
- Study completion4 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Herpes Virus-Related IllnessesStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 190 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Steven J Reynolds, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03092505
- Sponsor's protocol ID
- 170072
- Other IDs
- 17-I-0072
- Status last verified
- 28 Jul 2026
- First submitted
- 22 Mar 2017
- Last updated
- 22 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Schaftenaar E, Verjans GM, Getu S, McIntyre JA, Struthers HE, Osterhaus AD, Peters RP. High seroprevalence of human herpesviruses in HIV-infected individuals attending primary healthcare facilities in rural South Africa. PLoS One. 2014 Jun 10;9(6):e99243. doi: 10.1371/journal.pone.0099243. eCollection 2014.
PubMed 24914671
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Herpesviruses Reactivation In Hiv-Infected Women Initiating ART (HERA)
- ClinicalTrials.gov ID
- NCT03092505
- Acronym / sponsor ID
- 170072
- Conditions
- Herpes Virus-Related Illnesses
- Keywords
- HSV, Uganda, Sample, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 190 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 15 Jun 2018 (actual)
- Primary completion
- 1 Feb 2021 (actual)
- Study completion
- 4 Feb 2021 (actual)
- First posted
- 28 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 enroll up to 200 HIV-infected women initiating ART at the NIH Clinical Center (n=30 to 40) and between the Villa Maria Hospital, 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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Females | – | –Females participants who are about to start first line antiretroviral therapy. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Approximately 200 women initiating ART as part of standard HIV care will be recruited at four sites, the NIH Clinical Center (approximately 30-40), the RHSP/ICER , the Villa Maria Hospital and the Kalisizo sites in Uganda (approximately 160-170). Women will be recruited regardless of CD4+ T-cell count, presence of opportunistic infections and co-infection status. Participants taking antibiotics for co-infections and prophylaxis will be able to participate in the study and antibiotic use will be captured in study data. Participants may co-enroll in other non-interventional studies. Pregnant women will be excluded.
Key inclusion criteria (7 listed)
Key exclusion criteria (9 listed)
- 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)
- On acyclovir, valacyclovir, valganciclovir, or ganciclovir treatment
- Pregnancy or intent to become pregnant during the study period
- Intrauterine device (IUD) use
- Inability to follow study instructions, according to the investigator's judgment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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: prior to and at 4 and 8 weeks after inititian of antiretroviral treatment
viral shedding of HSV-1 and 2
1 secondary outcome
1. To estimate the associations of viral shedding or clinical herpetic disease post-ART at weeks 4 or 8 with concurrent and baseline measurement of systemic inflammation (IL-6, CRP, TNF or sCD14). [ Time Frame: 8 weeks post enrollment ]
Time frame: at week 4 and at week 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Background: PubMed 24914671Schaftenaar E, Verjans GM, Getu S, McIntyre JA, Struthers HE, Osterhaus AD, Peters RP. High seroprevalence of human herpesviruses in HIV-infected individuals attending primary healthcare facilities in rural South Africa. PLoS One. 2014 Jun 10;9(6):e99243. doi: 10.1371/journal.pone.0099243. eCollection 2014.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven J Reynolds, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Herpes Virus-Related Illnesses, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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: prior to and at 4 and 8 weeks after inititian of antiretroviral treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03092505, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.