Clinical trial NCT02889094: French HIV-HBV Cohort
Official title: Multi-center Study Evaluating Persistence of Hepatitis B Virus Replication, Long-term Prognostic Indicators and Their Clinical Relevance in Patients Co-infected With the Human Immunodeficiency Virus and Chronic Hepatitis B
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatitis B
HIV
Liver Cirrhosis
End Stage Liver Disease
Lead sponsor: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
Sponsor class: OTHER
Collaborators: name: ANRS, Emerging Infectious Diseases
name: Sidaction
First posted: 2016-09-05
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-infected patients with chronic hepatitis B.

Brief summary: The overarching purpose of this study is to further understand the reasons for and clinical implications of persistent HBV infection in patients co-infected with HIV and HBV in the era of highly effective antiviral treatment against both viruses.

Detailed description: The French HIV-HBV Cohort is an observational, non-interventional study including 308 HIV-infected patients with chronic HBV infection (HBsAg-positive serology \>6 months) in seven clinical centers. Patients were recruited in 2002-2003 and followed prospectively every three to twelve months, during two phases, until 2010-2011. Extensive information on a variety of HIV- and HBV-related parameters were collected during these study visits.

This particular study aims to extend follow-up of the French HIV-HBV Cohort using a different type of design. Patients who completed at least one study phase of the French HIV-HBV Cohort are selected for participation. Patients continuing follow-up at a participating clinical center are asked to undergo their routine clinical visit, during which time medical data from the years since last cohort visit until their routine visit are extracted. For those who died, information from the years since last cohort visit until death will be collected.

The primary objective for this cohort extension is to further understand the reasons for and clinical implications of persistent HBV infection in patients co-infected with HIV and HBV in the era of highly effective antiviral treatment against both viruses.

The following secondary objectives are as follows:

* To establish the extent of persistent viremia (PV) of HBV, quantified either in serum or within the hepatocyte
* To understand whether this persistence effects clinically-relevant serological outcomes (i.e. HBeAg and HBsAg seroclearance and seroconversion along with HBsAg quantification) after prolonged follow-up
* To quantify the evolution of liver fibrosis using non-invasive methods and, in a small subset of patients, liver biopsies, while investigating the virological and immunological factors associated with its progression and regression
* To describe the causes of liver-related and non-liver-related morbidity and mortality and the direct effect of persistent HBV DNA replication on these outcomes

Eligibility criteria: Inclusion Criteria:

* HBsAg seropositivity for \>6 months (at initial cohort inclusion)
* HIV-positive serology confirmed with Western blot (at initial cohort inclusion)
* Karnofsky score \>70 (at initial cohort inclusion)
* Age ≥18 years old (at initial cohort inclusion)
* Completed follow-up in at least one previous study phase of the French HIV-HBV Cohort
* Obtained signed written informed consent

Exclusion Criteria:

* Refusal to participate
* Any severe physical, clinical or mental condition preventing participation

Primary outcomes:
measure: HBV DNA replication
timeFrame: 14 years
measure: HBeAg-seroclearance
timeFrame: 14 years
measure: HBsAg-seroclearance
timeFrame: 14 years
measure: Liver fibrosis (FibroTest)
timeFrame: 14 years
measure: Liver fibrosis (FibroScan)
timeFrame: 14 years
Secondary outcomes:
measure: Liver-related morbidity
timeFrame: 14 years
measure: Liver-related mortality
timeFrame: 14 years
Other outcomes:
Locations:
city: Lyon
country: France
facility: Centre hospitalier universitaire de Lyon
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hôpital Tenon
Study officials:
affiliation: INSERM UMR S 1136
name: Anders Boyd, MPH, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: INSERM UMR S 1136
name: Karine Lacombe, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Boyd A, Gozlan J, Miailhes P, Lascoux-Combe C, Cam MS, Rougier H, Zoulim F, Girard PM, Lacombe K. Rates and determinants of hepatitis B 'e' antigen and hepatitis B surface antigen seroclearance during long-term follow-up of patients coinfected with HIV and hepatitis B virus. AIDS. 2015 Sep 24;29(15):1963-73. doi: 10.1097/QAD.0000000000000795.
citation: Boyd A, Gozlan J, Maylin S, Delaugerre C, Peytavin G, Girard PM, Zoulim F, Lacombe K. Persistent viremia in human immunodeficiency virus/hepatitis B coinfected patients undergoing long-term tenofovir: virological and clinical implications. Hepatology. 2014 Aug;60(2):497-507. doi: 10.1002/hep.27182. Epub 2014 Jun 20.
citation: Lacombe K, Massari V, Girard PM, Serfaty L, Gozlan J, Pialoux G, Mialhes P, Molina JM, Lascoux-Combe C, Wendum D, Carrat F, Zoulim F. Major role of hepatitis B genotypes in liver fibrosis during coinfection with HIV. AIDS. 2006 Feb 14;20(3):419-27. doi: 10.1097/01.aids.0000200537.86984.0e.