Study type

Study topic

Disease /health condition
Human medicinal product

Study type

Non-interventional study

Scope of the study

Other
Safety study (incl. comparative)

If ‘other’, further details on the scope of the study

Retrospective analysis of prospectively collected data

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Other

Non-interventional study design, other

Retrospective analysis of prospectively collected data from the D:A:D study
Study drug and medical condition

Study drug International non-proprietary name (INN) or common name

ABACAVIR
FOSAMPRENAVIR
LAMIVUDINE
MARAVIROC
ZIDOVUDINE

Medical condition to be studied

HIV infection
Population studied

Short description of the study population

All D:A:D participants who have evidence of co-infection with hepatitis B virus (HBV)/ hepatitis C virus (HCV) and/or chronic liver enzyme elevations (CLEEs) at the time of initiating one of the three treatments/combinations will be included. D:A:D collects data on alanine transaminase (ALT), AST, total bilirubin, platelet counts, albumin, creatinine, and haemoglobin and a host of other laboratory testing. Participants from cohorts that do not provide information on ALT levels will be excluded and CLEEs will be defined as in the recent D:A:D paper by Kovari et al. (1). The study population will therefore be split into three groups at the time of initiation of each treatment/combination: (i) those with HCV and/or HBV infection and no CLEE; (ii) those with no HCV and/or HBV but with CLEE; and (iii) those with HCV and/or HBV and CLEE. Due to the estimated small number of study participants with chronic hepatic impairment and/or CLEE, and the possibility that the antiretroviral drugs may themselves induce hepatic impairment or liver enzyme elevation, the groups will be defined at the time of first exposure to the treatment/combination and will not be updated if an individual’s status changes (e.g. if his/her ALT levels fall or if the individual subsequently becomes co-infected with HCV/HBV). Participants whose first ALT level in the dataset post-dates the start of the treatment/combination will be excluded. Where possible, dosing levels will be captured for the hepatically-impaired individuals for the relevant products.
Aim 2: All D:A:D participants without a prior cancer at D:A:D study enrolment who are enrolled from cohorts that provide data on cancer incidence will be included. Individuals who have died or are lost-to-follow-up before the cohort-specific baseline date for cancer analyses (2004 onwards) will be excluded.
Aims 3 and 4: All D:A:D participants without liver impairment (hepatotoxicity includes end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), and CLEE) or without a prior myocardial infarction (MI) at D:A:D study entry. Analyses of liver impairment will additionally exclude those from cohorts that do not provide data on ALT levels.

Age groups

Adults (18 to < 46 years)
Adults (46 to < 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Special population of interest

Immunocompromised

Estimated number of subjects

0
Study design details

Main study objective

To describe any safety issues that arise among hepatically-impaired individuals exposed to abacavir (ABC) containing products or fosamprenavir, to determine the risk of carcinogenicity following exposure to ABC containing products and lamivudine/zidovudine, and to determine the risk of hepatotoxicity and ischaemic cardiac events following exposure to maraviroc and fosamprenavir.

Outcomes

Safety events, cancer events, hepatotoxicity and ischaemic cardiac events

Data analysis plan

Descriptive statistics will be used to summarize event rates as the numbers are expected to be small. If the number of events is sufficient, Poisson regression can be performed to calculate relative rates for different exposure categories.
Documents
Study results

viiv-206247-clinical-study-report-redact

English (8.05 MB - PDF)View document