PIs and Adipogenesis - PowerPoint PPT Presentation

1 / 1
About This Presentation
Title:

PIs and Adipogenesis

Description:

... London NHS Trust, London: Chloe Orkin, Kevin Jones, Rachel Thomas, James Hand; ... Jane Anderson, Selina Gann, Kevin Jones; Edinburgh: Clifford Leen, Alan Wilson; ... – PowerPoint PPT presentation

Number of Views:222
Avg rating:3.0/5.0
Slides: 2
Provided by: liea5
Category:

less

Transcript and Presenter's Notes

Title: PIs and Adipogenesis


1
IS OLDER AGE A RISK FACTOR FOR ANTIRETROVIRAL-TOXI
CITIES?
CA SABIN, CJ SMITH, T HILL, AN PHILLIPS FOR THE
UK COLLABORATIVE HIV COHORT (CHIC) STUDY, ROYAL
FREE CENTRE FOR HIV MEDICINE, LONDON UK
Correspondence Professor Caroline
Sabin, Department of Primary Care and Population
Sciences, Royal Free UC Medical School, Rowland
Hill Street, London, UK, NW3 2PF. Tel 44
207830 2239 ext 34752. Fax 44 207 794 1224.
E-mail c.sabin_at_pcps.ucl.ac.uk
BACKGROUND
RESULTS (cont.)
  • Unadjusted for other factors, older individuals
    had an increased hazard of TRTD (HR 1.23, 95 CI
    1.05-1.45, p0.01). Whilst the hazard of TRTD
    was similar in older and younger individuals in
    the first year after starting HAART, hazards
    diverged thereafter (first year 1.09
    0.83-1.42, p0.55 year two onwards 1.33
    1.09-1.62, p0.005)
  • After adjustment for potential confounders, both
    relationships became non-significant, although
    the effect remained stronger from the second year
    onwards (Table 2)
  • Whilst most antiretroviral drugs are associated
    with the development of toxicities, the
    relationship between older age and the risk of
    toxicities has not been described
  • Such a relationship would be biologically
    plausible for at least two reasons
  • 1) As an individual ages, s/he may develop other
    conditions typical of aging these conditions
    and/or the medications used to treat them may
    interact with antiretroviral drugs, thus placing
    these individuals at higher risk of toxicity
  • 2) As older individuals are thought to have a
    greater adherence to therapy, the incidence of
    toxicities may be higher because exposure to drug
    is greater
  • We aimed to assess the relationship between older
    age and a) the time to toxicity-related treatment
    discontinuation (TRTD) and b) the incidence of
    laboratory-defined toxicities, among a large
    cohort of antiretroviral-naïve patients starting
    HAART

TABLE 2 RESULTS FROM MULTIVARIABLE COX
PROPORTIONAL HAZARDS REGRESSION MODEL OF FACTORS
ASSOCIATED WITH TRTD
METHODS
  • All antiretroviral-naïve patients starting HAART
    in the UK CHIC Study were included for the
    purposes of these analyses, HAART was defined as
    any treatment combination that included at least
    one PI, NNRTI, abacavir, tenofovir, or
    enfuvirtide
  • Older age was defined as gt50 years although age
    was also considered as a continuous covariate in
    some analyses

Statistical methods i) Analyses of TRTD
Time to first discontinuation of the third drug
in the regimen was calculated. Discontinuations
were defined as toxicity-related if they occurred
whilst the viral load was lt50 copies/ml.
Patients included in this analysis therefore had
to have viral loads measured both pre-HAART and,
if they discontinued treatment, post-HAART but
pre-discontinuation. Time to TRTD was described
using Kaplan-Meier and Cox proportional hazards
regression methods. Treatment discontinuation
with viral failure was treated as a competing
risk, thus follow-up on all patients who did not
experience a TRTD was censored on the date of the
patients last available viral load measurement.
Other potential confounders included sex, risk
group, ethnicity, calendar year, type of HAART
regimen and the CD4 count and HIV viral load at
the time of starting HAART
  • Older individuals had significantly higher
    pre-HAART TG (p0.0001), TC (p0.0001) and ALT
    (p0.001) and lower Hb (p0.0002) than younger
    individuals
  • In univariable analyses (Figure 1), abnormal TG,
    TC and Hb were all more common in those aged gt50
    years than in younger individuals. After
    adjusting for patient demographics, the
    relationship between age and abnormal TG levels
    became non-significant (Table 3). Further
    adjustment for pre-HAART TG levels removed the
    relationship between older age and abnormal TG
    levels. Only abnormal Hb levels remained more
    common in older individuals than younger
    individuals after adjusting for patient
    demographics and pre-HAART levels

ii) Analyses of laboratory-defined toxicities
The incidence of laboratory-defined toxicities in
the first year after starting HAART was
calculated, ignoring treatment discontinuations/sw
itches. Abnormal laboratory markers were defined
as follows Triglycerides (TG) gt2.3 mmol/L total
cholesterol (TC) gt6.2 mmol/L haemoglobin (Hb)
lt11.5 g/l bilirubin gt17 mmol/L ALT gt40 IU/L.
The incidence of abnormal laboratory markers in
older and younger individuals was compared using
univariable and multivariable logistic regression
analyses, after controlling for the potential
confounders above. Eligible patients had to have
at least one post-HAART measurement of each
marker although those with missing pre-HAART
measurements were not excluded, patients were
excluded if they were known to have an abnormal
pre-HAART value
FIGURE 1 INCIDENCE OF ABNORMAL LABORATORY
MEASUREMENTS IN OLDER AND YOUNGER INDIVIDUALS IN
THE FIRST YEAR OF HAART
P-values TG 0.02 TC 0.0001 Hb 0.007 Bili
1.00 ALT 0.55 Any 0.03
RESULTS
  • Overall, 7932 antiretroviral-naïve patients
    started HAART in the UK CHIC Study of these, 693
    (8.7) were aged gt50 years
  • Older individuals were more likely to be male,
    homosexual, of white ethnicity, and had lower CD4
    counts and higher HIV RNA levels at the time of
    starting HAART (Table 1), but there were no
    differences in the type of initial HAART regimen,
    the specific drugs received nor the year of
    starting HAART between the two age groups
  • Overall, 4794 patients with follow-up viral loads
    discontinued the third drug in their regimen
    of these, 1703 were classified as TRTD.
    Kaplan-Meier estimates of the proportion of
    patients with TRTD were 4.4, 9.7, 14.4 and
    17.9 by months 6, 12, 18 and 24 respectively in
    younger individuals, and 4.4, 10.7, 17.7 and
    22.0 among older individuals (p0.01, log-rank
    test).

TABLE 3 ODDS RATIOS FOR ABNORMAL LABORATORY
MEASUREMENTS ASSOCIATED WITH OLDER AGE,
UNADJUSTED AND ADJUSTED FOR BASELINE DEMOGRAPHICS
AND PRE-TREATMENT VALUES
TABLE 1 CHARACTERISTICS OF OLDER AND YOUNGER
INDIVIDUALS STARTING HAART IN THE UK CHIC STUDY
CONCLUSIONS
  • Whilst older individuals do appear to have a
    higher rate of TRTD and a higher incidence of
    laboratory-defined toxicities in the first year
    of HAART, these findings are largely explained by
    the demographic profiles and pre-existing
    age-related changes in these individuals prior to
    starting HAART
  • Our definition of TRTD will over-estimate the
    incidence of this phenomenon, as it does not
    exclude the possibility that patients may have
    discontinued their drugs for other reasons
    although UK CHIC does collect information on
    reasons for treatment discontinuation, these data
    may be incomplete, particularly in the early
    HAART era

United Kingdom Collaborative HIV Cohort (UK
CHIC) Medical Research Council Clinical Trials
Unit (MRC CTU), London Abdel Babiker, David
Dunn, Esther Fearnhill, Kholoud Porter HIV
Epidemiology and Biostatistics Unit, Department
of Primary Care Population Sciences, Royal Free
and University College Medical School (RFUCMS)
Caroline Sabin, Teresa Hill, Loveleen Bansi,
Andrew Phillips Kings College Hospital, London
Philippa Easterbrook, Stephen Duffell, Eghosa
Bazuaye, Emma Macfarlane Brighton and Sussex
University Hospitals NHS Trust Martin Fisher,
Duncan Churchill, Wendy Harris, Nicky Perry,
Anthony Pullin Chelsea and Westminster NHS
Trust, London Brian Gazzard, Steve Bulbeck,
Jemima Clarke, Sundhiya Mandalia Mortimer Market
Centre, RFUCMS Richard Gilson, Julie Dodds, Andy
Rider, Ian Williams Health Protection Agency
-Communicable Disease Surveillance Centre
(HPA-CDSC), London Valerie Delpech Royal Free
NHS Trust Margaret Johnson, Clinton Chaloner,
Helen Gumley, Fiona Lampe, Dewi Ismajani
Puradiredja, Colette Smith, Mike Youle St.
Marys Hospital, London John Walsh, Christian
Kemble, Jonathan Weber Barts and the London NHS
Trust, London Chloe Orkin, Kevin Jones, Rachel
Thomas, James Hand Homerton Hospital, London
Jane Anderson, Selina Gann, Kevin Jones
Edinburgh Clifford Leen, Alan Wilson North
Middlesex Hospital Achim Schwenk, Jonathan
Ainsworth.
Write a Comment
User Comments (0)
About PowerShow.com