Influence of alternative thresholds for initiating HIV treatment on quality-adjusted life expectancy: a decision model.
BACKGROUND
The optimal threshold for initiating HIV treatment is unclear.


OBJECTIVE
To compare different thresholds for initiating HIV treatment.


METHODS
A validated computer simulation was used to weigh important harms from earlier initiation of antiretroviral therapy (toxicity, side effects, and resistance accumulation) against important benefits (decreased HIV-related mortality).


METHODS
Veterans Aging Cohort Study (5742 HIV-infected patients and 11 484 matched uninfected controls) and published reports.


METHODS
Individuals with newly diagnosed chronic HIV infection and varying viral loads (10,000, 30,000, 100,000, and 300,000 copies/mL) and ages (30, 40, and 50 years).


METHODS
Unlimited.


CONCLUSIONS
Societal.


METHODS
Alternative thresholds for initiating antiretroviral therapy (CD4 counts of 200, 350, and 500 cells/mm3).


METHODS
Life-years and quality-adjusted life-years (QALYs).


RESULTS
Although the simulation was biased against earlier treatment initiation because it used an upper-bound assumption for therapy-related toxicity, earlier treatment increased life expectancy and QALYs at age 30 years regardless of viral load (life expectancies with CD4 initiation thresholds of 500, 350, and 200 cells/mm3 were 18.2 years, 17.6 years, and 17.2 years, respectively, for a viral load of 10,000 copies/mL and 17.3 years, 15.9 years, and 14.5 years, respectively, for a viral load of 300,000 copies/mL), and increased life expectancies at age 40 years if viral loads were greater than 30 000 copies/mL (life expectancies were 12.5 years, 12.0 years, and 11.4 years, respectively, for a viral load of 300,000 copies/mL).


RESULTS
Findings favoring early treatment were generally robust.


CONCLUSIONS
Results favoring later treatment may not be valid. The findings may not be generalizable to women.


CONCLUSIONS
This simulation suggests that earlier initiation of combination antiretroviral therapy is often favored compared with current recommendations.
Braithwaite
R Scott
RS
Yale University and Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut 06516, USA. Ronald.Braithwaite@va.gov
Roberts
Mark S
MS
Chang
Chung Chou H
CC
Goetz
Matthew Bidwell
MB
Gibert
Cynthia L
CL
Rodriguez-Barradas
Maria C
MC
Shechter
Steven
S
Schaefer
Andrew
A
Nucifora
Kimberly
K
Koppenhaver
Robert
R
Justice
Amy C
AC
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D003198:Computer Simulation; D003661:Decision Support Techniques; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D006801:Humans; D008017:Life Expectancy; D009154:Mutation; D019057:Quality-Adjusted Life Years; D012680:Sensitivity and Specificity; D013997:Time Factors; D019562:Viral Load
D019380:Anti-HIV Agents