HIV JO Slide Template

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COMPLICATIONS of ART and HIV
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Complications

• Serious Non-AIDS Events
• Heart Attacks MI
• Lipodystrophy
• Hepatitis C
• Starting Antiretrovirals during TB or crypto
  meningitis

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Serious Non-AIDS events

• More attention to other types of problems people
  living with HIV are experiencing
• Liver disease
• Heart Disease
• Kidney Disease
• These are related to level of CD4 as well as
  other factors
• Risk factors for these events include age,
  SMOKING, high blood pressure
• Need to focus on reducing risk for these problems
  too.

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Heart Attacks and HIV

• In general, people with HIV seem to be at a
  higher risk of heart attacks than others the same
  age
• Overall, the rate of MI is low
• Maybe due to higher rates of smoking in large
  groups of HIV people
• Could be related to blood lipids increasing with
  HIV treatment
• Risk may be higher if HIV is not treated or if
  treatment is stopped
• Big question is Do different medicines used for
  HIV treatment differ in their association with
  risk for MI???

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DAD Study

• Combination of different ongoing studies that was
  designed to look at rates of MI in people
  receiving HIV treatment.
• Includes over 30,000 people US, Europe, Australia
• Previously showed that with increasing time on
  ART- risk of MI slowly rises ( partly due to
  aging) but seemed to be higher in those on
  Protease inhibitors
• What about individual drugs?
• Limitation of this type of study cannot control
  for all the other factors that may contribute to
  risk for MI, but may be the best info for now.

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2 Studies Investigating ART Exposure and Risk of
MI

• Updated analysis of DAD Study1 (N 33,308
  from 11 cohorts)
• Earlier analyses of DAD study found increased
  risk of MI associated with cumulative exposure to
  PIs and recent exposure to ABC or ddI
• Case-control study within French Hospital
  Database on HIV (FHDH) ANRS CO42
• HIV-infected patients enrolled in FHDH with first
  documented MI between January 2000 and December
  2006 (N 1173)
• Controls HIV-infected patients with no history
  of MI matched with MI case for timing of
  follow-up, age, sex, and treatment center
• Study undertaken to determine association between
  risk for MI and cumulative, recent, and past
  exposure to individual NRTIs, and cumulative
  exposure to individual PIs

1. Lundgren JD, et al. CROI 2009. Abstract
44LB.2. Lang S, et al. CROI 2009. Abstract 43LB.
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DAD Recent and/or Cumulative Antiretroviral
Exposure and Risk of MI
RR of cumulative exposure/year95CI
NRTI
RR of recent exposureyes/no95CI
1.9
1.9
1.5
1.5
1.2
1.2
1.0
1.0
0.8
0.8
0.6
0.6
ZDV
ddC
d4T
3TC
ABC
TDF
ddI
PYFU 138,109 74,407
29,676 95,320 152,009
53,300 39,157 MI 523 331 148 40
554 221
139
NNRTI
PI
FV
Current or within last 6 months. Approximate
test for heterogeneity P 0.02
Lundgren JD, et al. CROI 2009. Abstract 44LB.
Graphics reproduced with permission.
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DAD Recent and/or Cumulative Antiretroviral
Exposure and Risk of MI
RR of cumulative exposure/year95CI
NRTI
RR of recent exposureyes/no95CI
1.9
1.9
1.5
1.5
1.2
1.2
1.0
1.0
0.8
0.8
0.6
0.6
ZDV
ddI
ddC
d4T
3TC
ABC
TDF
PYFU 138,109 74,407
29,676 95,320 152,009
53,300 39,157 MI 523 331 148 40
554 221
139
RR of cumulative exposure/year95CI
NNRTI
PI
1.2
1.13
1.1
1.0
0.9
IDV
NFV
LPV/RTV
SQV
NVP
EFV
PYFU 68,469 56,529
37,136 44,657
61,855 58,946 MI 298 197
150 221
228 221
Current or within last 6 months. Approximate
test for heterogeneity P 0.02
Lundgren JD, et al. CROI 2009. Abstract 44LB.
Graphics reproduced with permission.
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French Study Cumulative Exposure to Certain
PIs, but Not ABC, Increased Risk of MI

• Current or recent exposure to ABC for lt 1 yr
  associated with increased risk for MI among
  HIV-infected patients (OR 1.97 95 CI 1.09 -
  3.56 P .025)
• In contrast to DAD, current or recent exposure
  to ABC for gt 1 yr not associated with MI (OR
  1.05 95 CI 0.65-1.69 P .844)
• No association with exposure and risk for MI
  found for other NRTIs analyzed

Lang S, et al. CROI 2009. Abstract 43LB.
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Summary of Clinical Trial and Cohort Analyses of
ABC Use and CVD Risk
All or majority of patients antiretroviral-experie
nced at ABC initiation
All or majority of patients antiretroviral-naive
at ABC initiation
1. Lundgren JD, et al. CROI 2009. Abstract 44LB.
2. Lang S, et al. CROI 2009. Abstract 43LB. 3.
SMART. AIDS. 200822F17-F24. 4. Carr A, et al.
CROI 2009. Abstract 576. 5. Cutrell A, et al. IAC
2008. Abstract WEAB0106. 6. Benson C, et al. CROI
2009. Abstract 721. Thanks to Peter Reiss, MD,
PhD, for permission to reproduce the table.
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What does this mean if you are on one of these
medications?
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Rosiglitazone Improves Lipoatrophy in Previous
ZDV or d4T Recipients

• Patients with clinical lipoatrophy, 12 mos
  cumulative exposure to d4T or ZDV, discontinued
  d4T or ZDV from current HAART regimen for 24
  wks prior to study
• Randomized to receive rosiglitazone 4 mg BID (n
  34) or placebo (n 37) in addition to current
  regimen

Rosiglitazone
1000
P lt .001
Placebo
800
P .018
600
Change in Limb Fatat Wk 48 (g)
400
P .03
200
n
29
32
0
Rosiglitazone
Placebo
Intragroup comparison. Intergroup comparison.
El-Bajjani D, et al. CROI 2009. Abstract 42LB.
Graphic reproduced with permission.
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Outcomes in HIV/HCV-Coinfected Patients

• EuroSIDA1 HIV/HCV-coinfected patients with high
  HCV RNA (gt 500,000 IU/mL) had significantly
  increased incidence of all-cause death and
  liver-related death
• Regardless of response, HCV treatment did not
  affect survival or hepatic decompensation in
  HIV/HCV-coinfected patients with cirrhosis2
• Suggests clinical utility of early intervention
  to prevent cirrhosis
• Genotype of Hep C also important- better outcomes
  in genotype 2 and 3.

1. Rockstroh J, et al. CROI 2009. Abstract 101.
2. Montes ML, et al. CROI 2009. Abstract 106.
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Acute Hepatitis C- sexual transmission

• Fierer and colleagues evaluated risk factors and
  outcomes of 31 HIV-infected patients identified
  with acute HCV infection in New York City
  (Abstract 802).
• In a case-control study
• unprotected receptive anal intercourse
• unprotected oral sex
• use of drugs
• were risk factors for acquiring HCV infection.
  HCV spontaneously cleared in 13 of patients
• Importance of screening for acute hep C and
  prevention messages around this issue

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SAPiT Optimal Time to Initiate ART in
HIV/TB-Coinfected Patients
Early ART ART initiated during intensive or
continuation phase of TB therapy (n 429)
HIV-infected patients diagnosed with TB and CD4
cell count lt 500 cells/mm3 (N 642)
Sequential ART ART initiated after TB therapy
completed (n 213)
Primary endpoint all-cause mortality
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Early ART Decreases Survival in HIV Patients
With Cryptococcal Meningitis

• HIV-infected African patients diagnosed with
  cryptococcal meningitis randomized to receive 10
  wks of fluconazole 800 mg QD ART (n 26) or
  fluconazole alone (n 28)
• After 10 wks, all patients received fluconazole
  200 mg QD ART

1.00
Delayed ART
0.75
Early ART
Survival
0.50
0.25
P .028
0.00
0
600
800
200
400
Time to Death (in Days)

• After 2 yrs of follow-up 23 deaths in early ART
  group (87 mortality rate) vs 9 deaths in delayed
  ART group (37 mortality rate) (P .002)
• Median survival, early ART vs delayed ART 35 vs
  274 days (P .028)

Makadzange AT, et al. CROI 2009. Abstract 36cLB.
Graphic reproduced with permission.