Multicenter AIDS Cohort Study Dossier November 2004

1
Multicenter AIDS Cohort StudyDossierNovember
2004

• Prepared by CAMACS
• Fax [phone]
• Web site http//statepi.jhsph.edu/macs/macs.html

November 2004
2
MACS Sites andPrincipal Investigators

• Sites
• Baltimore, MD (J. Margolick)
• Chicago, IL (J. Phair)
• Los Angeles, CA (R. Detels, B. Visscher)
• Pittsburgh (C. Rinaldo, L. Kingsley)
• Data Coordinating Center (CAMACS)
• Baltimore, MD (L. Jacobson, A. Muñoz)

November 2004
3
MACS Working Groups - Chairs

• Behavioral - D. Ostrow
• Clinical - F. Palella
• Core Laboratory - C. Rinaldo J. Margolick
• Data - L. Jacobson
• Malignancy/Pathology - O. Martinez-Maza
• Metabolic/Cardiovascular - L. Kingsley
• Neuropsychology - E. Miller
• Viral Hepatitis - C. Thio

November 2004
4
Semiannual Visit

• Medications
• Antiretrovirals, specific for OIs, Adherence
• Physical Examination / Lipodystrophy
• Specimens and Labs
• Plasma, Serum, Cells
• T-cells, HIV RNA, HBV HCV serology, lipids
• B-cell lines, National Repository
• Questionnaire / ACASI
• Medical History, Health Services, Behavior
• Demographics / Psychosocial
• Quality of Life
• Neuropsychological Screening

November 2004
5
Continuous Outcome Ascertainment

• Seroconversion
• Clinical Outcomes (medical records confirmation)
• AIDS diagnoses
• Non-AIDS diagnoses
• Cardiovascular disease
• Cerebrovascular disease
• Kidney disease
• Liver disease
• Lung infection, bacterima, septicemia
• Malignancies
• Neurologic
• Mortality

November 2004
6
Administrative Forms

• Data Set Transmission
• Study Investigator Registration for using MACS
  Specimens
• Restricted Use of MACS Specimens

May 2000
7
Data Collection Forms

• Drug Form 1 (anti-virals) 2 (non-antivirals)
• Antiretroviral Medication Adherence
• Section 2 (demographics, psychosocial)
• Physical Exam / Lipodystrophy Exam
• Section 4 (behavior, medical history, health
  services)
• Quality of Life
• Neuropsychological
• PWA
• Seroconversion
• Clinical Outcomes

Administered using Audio Computer Assisted
Structured Interview (ACASI)
October 2002
8
CAMACS

• Planning and design of studies
• Coordination of data acquisition
• Form development
• Codebooks
• Data transfer
• Standardization and data management
• Edits and updates
• Data security
• Data analysis, statistical computing and
  methodological research

September 1995
9
MACS Database(as of October 2004)
Publications 925 Participants
6,973 Person-Years 66,995 Variables
7,496 Repository aliquots 800,961
(plasma, serum, cells)
HIV HIV- Person-Visits 43,784
58,755 CD4 Measurements 40,876 45,208 HIV RNA
Measurements 22,323 1,138
November 2004
10
MACS Cohort
Created 9/04
6973
Inactive 4/03
Seroprevalent 2884 (41.4)
Seronegative 4089 (58.6)
Seroconverter 615 (15.0)
Seronegative 3474 (85.0)
AIDS 1533 (53.2)
AIDS-Free 1351 (46.8)
AIDS 299 (48.6)
AIDS-Free 316 (51.4)
2245 seronegative men had been administratively
censored, follow-up is expected of 981
seronegative men from the pre-2001 cohort and 647
seronegatives from the 2001-3 recruits for a
total denominator of 1628 seronegative men

November 2004
11
Composition Size of Cohort
Participants (thousands)
Visit (Calendar year)
1665 (95 of 1758) have been administratively
censored
November 2004
12
Total of CD4 and HIV RNAMeasurements by
Serostatus
November 2004
13
Incidence of Seroconversion in the MACS by Center
Kingsley, Zhou, . . ., Muñoz - AJE 1991
(update)
Baltimore Chicago Pittsburgh Los Angeles
Incidence of seroconverters per 1,000
person-semesters
September 1995
14
Decline in CD4 Count per Year by Plasma HIV-1 RNA
June 1997
15
Likelihood of Developing AIDS in Three Years
Mellors, Muñoz, . . ., Rinaldo - Ann Int Med
1997
June 1997
16
Use of Antiretroviral Therapy by Seropositive
MACS Participants with Clinical AIDS
Detels, Tarwater, . . ., Muñoz - AIDS 2001
(update)

Receiving Therapy
Calendar Year
November 2004
17
Use of Antiretroviral Therapy and Effectiveness
at the Population Level
Tarwater, Mellors, . . ., Muñoz - AJE
2001 Detels, Muñoz, . . ., Phair - JAMA 1998
(update)
100
Relative Hazard of AIDS at equal infection
duration
1.52
1
0.91
0.30
Relative Hazard of AIDS at equal CD4 cell count
and HIV RNA
80
1.52
1
1.03
0.31
60
Receiving Therapy
40
20
0
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999

May 2001
18
MACS Subgroups of Particular Interest

• Long-term seropositive individuals with minimal
  declines in CD4 levels
• Seropositive individuals with rapid declines in
  CD4 levels
• Long-term survivors with low CD4 levels
• Seroconverters
• High-risk seronegatives

19
Estimated Long Term AIDS-Free ProportionsPrior
to Potent Antiretroviral Therapies
October 1998
20
Number of Participants withSpecimens Available
in the National RepositoryRelative to the Time
of Seroconversion
Pre-2001 Cohort
Specimen Type Plasma Serum Cells
Last Seronegative Visit 440 469 410
First Seropositive Visit 462 473 397
2 or more tubes A total of 573 participants
have a known seroconversion date
November 2004
21
Number of Participants withSpecimens Available
in the National RepositoryRelative to the
Development of AIDS
Pre-2001 Cohort
Specimen Type Plasma Serum Cells
Within 1 Year Pre-AIDS 1200 1187 783
After 6 Months Post AIDS 576 552 323
Within 6 Months Post AIDS 594 561 273
2 or more tubes A total of 1832 participants
have developed AIDS
November 2004
22
Number of Participants withSpecimens Available
in the National RepositoryRelative to HAART Use
Pre-2001 Cohort
Specimen Type Plasma Serum Cells
Within 1 Year Prior to HAART 563 551 443
After 6 Months Post HAART 622 620 588
Within 6 Months Post HAART 436 426 358
All 3 355 339 248
A total of 773 participants have initiated HAART
November 2004
23
Number of Participants withSpecimens Available
in the National RepositoryRelative to the Time
of Seroconversion
Pre-2001 Cohort
Specimen Type Plasma Serum Cells
Last Seronegative Visit 440 469 410
First Seropositive Visit 462 473 397
2 or more tubes A total of 573 participants
have a known seroconversion date
November 2004
24
Key Factors in the Success of the MACS

• The commitment and sacrifice of the participants
• The staff members of the MACS
• Strong laboratory support

25
UCLA MACS Staff

• John Oishi, Study Coordinator
• Max Hechter
• Claudia Endler
• Kevin Barrett
• Georgina Castle

26
MACS Staff

• Dennis Miles, LA Mens Study Site Manager
• May Htike, Staff Physician

27
MACS Laboratory Support

• Beth Jamieson
• John Fahey
• Anthony Butch
• Steve Young