HIV InfectionsNCT00351442
Examining Factors That May Influence Resistance to HIV-1 Infection
An observational study of HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in 2 countries.
Trial summary
Some people who are exposed to the HIV-1 virus are capable of either controlling or completely preventing viral infection. Multiple genetic factors may contribute to preventing or controlling HIV-1 infection. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- How many people
- 522 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Feb 2007to Sep 2010
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Community sample, including HIV infected individuals and their uninfected partners.
Who may be able to join
- Willing to provide adequate location information
- Planning to remain in the area for the duration of the study
- HIV-1 antibody positive AND nucleic acid test (NAT) or p24 antigen negative
- Report unprotected receptive or insertive vaginal, oral, or anal intercourse with Group 2 partner on at least 12 occasions (St. Mary's cohort) or 25 occasions (MRC/UVRI Uganda cohort) during the 12 months prior to screening; the first sexual exposure with Group 2 partner must have occurred at least 10 months prior to screening
- HIV-1 infected at screening, as determined by enzyme immunoassay and western blot
- Documentation of HIV-1 infection for at least 12 months prior to screening, as determined by enzyme immunoassay and western blot
Show all 19Show fewer
- Willing to provide clinical information about HIV-1 RNA and CD4 cell count
- Report unprotected receptive or insertive vaginal, oral, or anal intercourse with Group 1 partner on at least 12 occasions during the 12 months prior to screening; the first sexual exposure with Group 1 partner must have occurred at least 10 months prior to screening
- HIV-1 infected, as determined by enzyme immunoassay and western blot
- Report unprotected receptive or insertive vaginal, oral, or anal intercourse with Group 1 partner on at least 25 occasions during the 12 months prior to screening; the first sexual exposure with Group 1 partner must have occurred at least 10 months prior to screening
- HIV-1 infected for at least 12 months prior to screening, as determined by one of the following criteria:
- Report a past medical history indicating Herpes zoster infection within the prior 5 years or report a medical history indicating WHO Clinical Staging Criteria for HIV/AIDS of III or IV within the prior 5 years, OR
- CD4 cell count no greater than 450/mm3 for females or no greater than 400/mm3 for males
- Report no prior HIV testing, test HIV-1 seropositive at screening, and meet one of the following criteria:
- Report a past medical history indicating Herpes zoster infection within the prior 5 years or report a past medical history indicating WHO Clinical Staging Criteria for HIV/AIDS of III or IV in the prior 5 years, OR
- CD4 cell count no greater than 450/mm3 for females or no greater than 400/mm3 for males
- HIV-1 antibody negative AND nucleic acid test (NAT) or p24 antigen negative
- Test negative for Neisseria gonorrhoeae, syphilis, Chlamydia trachomatis, and trichomoniasis (MRC/UVRI Uganda cohort only)
- Report a monogamous relationship of at least 12 months duration prior to screening
Who cannot join
- Injection drug use in the 5 years prior to screening
- Any condition that, in the opinion of the investigator, would be unsafe or interfere with the study
- Any obligations that may require long absences from the area
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United Kingdom2 sites
King's College Hosp., Caldecot Ctr. CHAVI CRS
London
St. Mary's Hosp. of London, Imperial College School of Medicine, Clinical Trials Ctr. CHAVI CRS
London
Uganda1 site
Uganda Virus Research Institute, MRC/UVRI Uganda Research Unit on AIDS CHAVI CRS
Entebbe
About this study
Official title: Prospective Study of the Determinants of Host Resistance to HIV-1 Infection
Some people who are exposed to the HIV-1 virus are capable of either controlling or completely preventing viral infection. Multiple genetic factors may contribute to preventing or controlling HIV-1 infection. The purpose of this study is to analyze the immune system responses of individuals who are exposed to HIV-1 but remain uninfected.
Read the detailed description
Even with repeated exposure to HIV-1, some individuals appear to be resistant to infection. The exact mechanism of this resistance, however, remains unknown. The relative risk of HIV-1 infection appears to depend on various factors: route of transmission, viral load of the infected donor, nature and extent of exposure, presence of sexually transmitted infections (STIs), and genetic and immunological status of the exposed individual. This last factor may explain the inherent ability of some people to remain uninfected despite repeated exposure to HIV-1.
Immune response in HIV-1 exposed uninfected individuals is sometimes characterized by specific cytotoxic CD8 T cell response without antibody response, suggesting that resistance may, in part, be mediated by HIV-1 specific T cells. Exposed uninfected individuals may also be genetically protected, in which case key genes-possibly linked to immune responses-may lead to resistance to HIV-1. A clearer understanding of the role of an individual's genetic and immune-mediated resistance to HIV-1 infection is needed and will provide important information for advancing preventive HIV vaccine design. The purpose of this study is to examine the immune responses of individuals who have been exposed to HIV-1, but who remain uninfected. Through the use of highly sensitive technology, low level immune responses and viral levels will be evaluated. The study will also compare genetic profiles, exposure characteristics, donor viral load, STIs, and sexual behaviors among all participants. In the infected member of a serodiscordant couple, the HIV-1 virus will be examined and sequenced.
This observational study will last approximately 24 months. Screening will involve at least one visit and will occur at least 8 weeks prior to study entry. Eligible participants will fall into one of three groups:
- Group 1 will include individuals who have been exposed to HIV-1 but who remain uninfected.
- Group 2 will include HIV infected regular sexual partners of Group 1 members.
- Group 3 will include HIV uninfected individuals or couples who have not been exposed to HIV-1.
Study visits will occur every 3 months for a total of 8 visits. At all visits, participants will verify address location, complete standardized questionnaires about sexual behaviors, and receive HIV safe sex counseling and free condoms. Blood and urine will be collected to test for HIV, STIs, and pregnancy. All participants will undergo a review of their medical history and a physical examination, including a genital exam for both males and females and a pelvic exam for females. At selected visits, participants may opt to provide additional samples of urine, saliva, genital secretions, breastmilk, and feces for research purposes. Groups 1 and 3 will have HIV testing at all but the first study visit; Group 2 will have no HIV testing, but will be assessed for CD4 cell count at all study visits. Participants requiring clinical care for the management of HIV or STIs will be either treated at the study site or referred for appropriate care.
- Conditions
- HIV Infections
- Keywords
- Host Resistance
- Medical subject headings
- HIV Infections
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 |
|---|---|---|
| 1 | Inidividuals who have been exposed to HIV but remain uninfected. | |
| 2 | HIV infected regular sexual partners of Group 1 participants. | |
| 3 | HIV uninfected individuals or couples who have not been exposed to HIV. |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2006 (estimated)
- Study startFeb 2007
- Primary completionSep 2010
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies 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-control
- Time perspective
- Prospective
- Enrolment
- 522 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Center for HIV/AIDS Vaccine Immunology
- Responsible party
- Sponsor
- Investigators
- Andrew J. McMichael, MD, PhD, Study chair, University of Oxford, Weatherall Institute of Molecular Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00351442
- Sponsor's protocol ID
- CHAVI 002
- Other IDs
- 10464
- Status last verified
- Apr 2014
- First submitted
- 11 Jul 2006
- Last updated
- 9 Apr 2014
- Results posted
- No
Publications
An P, Bleiber G, Duggal P, Nelson G, May M, Mangeat B, Alobwede I, Trono D, Vlahov D, Donfield S, Goedert JJ, Phair J, Buchbinder S, O'Brien SJ, Telenti A, Winkler CA. APOBEC3G genetic variants and their influence on the progression to AIDS. J Virol. 2004 Oct;78(20):11070-6. doi: 10.1128/JVI.78.20.11070-11076.2004.
PubMed 15452227Kebba A, Kaleebu P, Rowland S, Ingram R, Whitworth J, Imami N, Gotch F. Distinct patterns of peripheral HIV-1-specific interferon- gamma responses in exposed HIV-1-seronegative individuals. J Infect Dis. 2004 May 1;189(9):1705-13. doi: 10.1086/383227. Epub 2004 Apr 19.
PubMed 15116309Kebba A, Kaleebu P, Serwanga J, Rowland S, Yirrell D, Downing R, Gilmour J, Imami N, Gotch F, Whitworth J. HIV type 1 antigen-responsive CD4+ T-lymphocytes in exposed yet HIV Type 1 seronegative Ugandans. AIDS Res Hum Retroviruses. 2004 Jan;20(1):67-75. doi: 10.1089/088922204322749512.
PubMed 15000700Missale G, Papagno L, Penna A, Pilli M, Zerbini A, Vitali P, Pieroni G, Urbani S, Uggeri J, Pinheiro S, Rowland-Jones S, Ferrari C. Parenteral exposure to high HIV viremia leads to virus-specific T cell priming without evidence of infection. Eur J Immunol. 2004 Nov;34(11):3208-15. doi: 10.1002/eji.200424889.
PubMed 15459901O'Brien SJ, Nelson GW. Human genes that limit AIDS. Nat Genet. 2004 Jun;36(6):565-74. doi: 10.1038/ng1369.
PubMed 15167933
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study of the Determinants of Host Resistance to HIV-1 Infection
- ClinicalTrials.gov ID
- NCT00351442
- Acronym / sponsor ID
- CHAVI 002
- Conditions
- HIV Infections
- Keywords
- Host Resistance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 522 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Center for HIV/AIDS Vaccine Immunology
- Study start
- Feb 2007
- Primary completion
- Sep 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 12 Jul 2006 (estimated)
- 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.
Some people who are exposed to the HIV-1 virus are capable of either controlling or completely preventing viral infection. Multiple genetic factors may contribute to preventing or controlling HIV-1 infection. The purpose of this study is to analyze the immune system responses of individuals who are exposed to HIV-1 but remain uninfected.
Detailed description
Even with repeated exposure to HIV-1, some individuals appear to be resistant to infection. The exact mechanism of this resistance, however, remains unknown. The relative risk of HIV-1 infection appears to depend on various factors: route of transmission, viral load of the infected donor, nature and extent of exposure, presence of sexually transmitted infections (STIs), and genetic and immunological status of the exposed individual. This last factor may explain the inherent ability of some people to remain uninfected despite repeated exposure to HIV-1.
Immune response in HIV-1 exposed uninfected individuals is sometimes characterized by specific cytotoxic CD8 T cell response without antibody response, suggesting that resistance may, in part, be mediated by HIV-1 specific T cells. Exposed uninfected individuals may also be genetically protected, in which case key genes-possibly linked to immune responses-may lead to resistance to HIV-1. A clearer understanding of the role of an individual's genetic and immune-mediated resistance to HIV-1 infection is needed and will provide important information for advancing preventive HIV vaccine design. The purpose of this study is to examine the immune responses of individuals who have been exposed to HIV-1, but who remain uninfected. Through the use of highly sensitive technology, low level immune responses and viral levels will be evaluated. The study will also compare genetic profiles, exposure characteristics, donor viral load, STIs, and sexual behaviors among all participants. In the infected member of a serodiscordant couple, the HIV-1 virus will be examined and sequenced.
This observational study will last approximately 24 months. Screening will involve at least one visit and will occur at least 8 weeks prior to study entry. Eligible participants will fall into one of three groups:
- Group 1 will include individuals who have been exposed to HIV-1 but who remain uninfected.
- Group 2 will include HIV infected regular sexual partners of Group 1 members.
- Group 3 will include HIV uninfected individuals or couples who have not been exposed to HIV-1.
Study visits will occur every 3 months for a total of 8 visits. At all visits, participants will verify address location, complete standardized questionnaires about sexual behaviors, and receive HIV safe sex counseling and free condoms. Blood and urine will be collected to test for HIV, STIs, and pregnancy. All participants will undergo a review of their medical history and a physical examination, including a genital exam for both males and females and a pelvic exam for females. At selected visits, participants may opt to provide additional samples of urine, saliva, genital secretions, breastmilk, and feces for research purposes. Groups 1 and 3 will have HIV testing at all but the first study visit; Group 2 will have no HIV testing, but will be assessed for CD4 cell count at all study visits. Participants requiring clinical care for the management of HIV or STIs will be either treated at the study site or referred for appropriate care.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Inidividuals who have been exposed to HIV but remain uninfected. |
| 2 | – | –HIV infected regular sexual partners of Group 1 participants. |
| 3 | – | –HIV uninfected individuals or couples who have not been exposed to HIV. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Community sample, including HIV infected individuals and their uninfected partners.
Key inclusion criteria (19 listed)
- Willing to provide adequate location information
- Planning to remain in the area for the duration of the study
- HIV-1 antibody positive AND nucleic acid test (NAT) or p24 antigen negative
- Report unprotected receptive or insertive vaginal, oral, or anal intercourse with Group 2 partner on at least 12 occasions (St. Mary's cohort) or 25 occasions (MRC/UVRI Uganda cohort) during the 12 months prior to screening; the first sexual exposure with Group 2 partner must have occurred at least 10 months prior to screening
- HIV-1 infected at screening, as determined by enzyme immunoassay and western blot
Key exclusion criteria (3 listed)
- Injection drug use in the 5 years prior to screening
- Any condition that, in the opinion of the investigator, would be unsafe or interfere with the study
- Any obligations that may require long absences from the area
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
Not reported in the source record.
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 9 Apr 2014.
- Background: PubMed 15452227An P, Bleiber G, Duggal P, Nelson G, May M, Mangeat B, Alobwede I, Trono D, Vlahov D, Donfield S, Goedert JJ, Phair J, Buchbinder S, O'Brien SJ, Telenti A, Winkler CA. APOBEC3G genetic variants and their influence on the progression to AIDS. J Virol. 2004 Oct;78(20):11070-6. doi: 10.1128/JVI.78.20.11070-11076.2004.
- Background: PubMed 15116309Kebba A, Kaleebu P, Rowland S, Ingram R, Whitworth J, Imami N, Gotch F. Distinct patterns of peripheral HIV-1-specific interferon- gamma responses in exposed HIV-1-seronegative individuals. J Infect Dis. 2004 May 1;189(9):1705-13. doi: 10.1086/383227. Epub 2004 Apr 19.
- Background: PubMed 15000700Kebba A, Kaleebu P, Serwanga J, Rowland S, Yirrell D, Downing R, Gilmour J, Imami N, Gotch F, Whitworth J. HIV type 1 antigen-responsive CD4+ T-lymphocytes in exposed yet HIV Type 1 seronegative Ugandans. AIDS Res Hum Retroviruses. 2004 Jan;20(1):67-75. doi: 10.1089/088922204322749512.
- Background: PubMed 15459901Missale G, Papagno L, Penna A, Pilli M, Zerbini A, Vitali P, Pieroni G, Urbani S, Uggeri J, Pinheiro S, Rowland-Jones S, Ferrari C. Parenteral exposure to high HIV viremia leads to virus-specific T cell priming without evidence of infection. Eur J Immunol. 2004 Nov;34(11):3208-15. doi: 10.1002/eji.200424889.
- Background: PubMed 15167933O'Brien SJ, Nelson GW. Human genes that limit AIDS. Nat Genet. 2004 Jun;36(6):565-74. doi: 10.1038/ng1369.
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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.
Andrew J. McMichael, MD, PhD study chair
University of Oxford, Weatherall Institute of Molecular Medicine
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 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 19 inclusion and 3 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 9 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom, 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00351442, which also lists 5 linked publications.
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 9 Apr 2014.