Impact of Hepatitis C, HIV, or Both on Survival in Veterans in Care Before and After the Introduction of HAART (1996) SL Fultz, MD, MPH CH Chang, PhD AA Butt, MD M Skanderson, MSW D Rimland, MD MO Rigsby, MD AC Justice, MD, PhD

Background HIV and hepatitis C (HCV) coinfection common Mortality in HIV+ decreased due to HAART Management of comorbid conditions important

Background Studies have reported conflicting results HCV infection More aggressive in HIV+ patients Leads to faster HIV progression HCV coinfection has no effect on survival No study compared HCV monoinfection with HIV/HCV coinfection 1st – decreased time to HCC 2nd – increased mortality

Objective To determine: Whether a survival difference exists between patients diagnosed with HCV, HIV or both compared to general medical controls Whether these differences were affected by the introduction of HAART in 1996

Methods Adapted algorithm used by Fasciano, et al (1998) Search based on ICD-9 codes: AIDS (042-044) Asymptomatic HIV (044.9 and V08) Inconclusive HIV test results (795.8) Diagnostic Related Group codes (488-490) Found to be sensitive (93%) for HIV+ state Only inpatient codes before FY 1997

Methods Identified HIV- controls matched for: Age Race VISN FY of HIV diagnosis End of FY 1996 marker for introduction of HAART Could cross over from pre- to post-1996 period and be analyzed in both Censored at end of pre-1996 period if match did not cross over into post-1996 period

Methods HCV-related ICD-9 codes Hepatitis C virus (070.41, 070.44, 070.51, and 070.54) Hepatitis C carrier (V02.62) Period of Service (POS) categorized as ‘Vietnam era and before’ versus ‘Post-Vietnam’ Used as surrogate for time of HCV infection Same codes as used by HCV ICR As being a Vietnam-era veteran is associated with HCV infection in the VA system

Methods Death information obtained from: VA inpatient administrative data BIRLS (Beneficiary Identification and Records Locator System) As complete as National Death Index (NDI)

Methods Kaplan-Meier curves stratified pre-, post-1996 Cox proportional hazards regression Model 1: HIV, HCV, HIV/HCV, age, race, POS, stratified pre and post-1996 Model 2: HIV, HCV, 1996 time period, POS, and interaction terms Explain why interaction terms

Results - Demographics Pre-1996 Post-1996 HIV+ HIV- N 15,685 16,161 26,521* 25,482** Age (mean) 43.7 43.8 47.7 48.2 Race White 40.5 41.8 42.6 44.9 African-American 49.6 48.0 45.7 Other 9.9 10.2 9.4 Observation Time (median years) 1.39 2.76 3.96 4.54 Deaths (#) 6696 1131 4837 1987 Deaths/100 person-years 24.7 2.6 5.0 1.9 Hep C (%) 18.4 10.7 23.6 9.1 Mention that no p values because even small differences were statistically significant *Includes 6245 crossovers **Includes 6732 crossovers

Mention sample size is large, and walk through each line.

Cox – Stratified Model* Pre-1996 Post-1996 HR 95% CI HIV Infection 10.2 9.58 – 10.91 2.7 2.53 – 2.84 HCV Infection 0.3 0.22 – 0.42 1.2 1.05 – 1.39 HIV/HCV Coinfection 2.2 1.93 – 2.43 2.6 2.43 – 2.82 Post-Vietnam** 0.8 0.71 – 0.79 0.6 0.56 – 0.64 *Model also controls for age and race.

Cox – Model with Interactions HR 95% CI HIV Infection 10.4 9.75 – 11.09 HCV Infection 0.3 0.20 – 0.38 Post-1996 0.7 0.66 – 0.77 HIV, Post-1996 Interaction 0.24 – 0.28 HCV, Post-1996 Interaction 4.0 2.83 – 5.64 HIV, HCV Interaction 0.50 – 0.97 HIV, HCV, Post-1996 Interaction 1.2 0.84 – 1.73 Post-Vietnam* 0.6 0.55 – 0.59 *Baseline is ‘Vietnam era or before’

Conclusions HIV monoinfection HCV monoinfection HIV/HCV coinfection Lower survival in both time periods HCV monoinfection “Protective” pre-1996 Increased risk of mortality post-1996 period HIV/HCV coinfection Similar risk of mortality as HIV monoinfection State which analysis for each

Limitations Administrative data No lab or pharmacy data Only inpatient codes before FY 1997 No information on non-VA visits Retrospective study Relatively short follow-up

Future Work Perform analysis while examining impact of: Lab data ALT/AST HCV Screening CD4, HIV-1 viral load Hemoglobin HCV genotype Pharmacy data Drug and alcohol use Medical comorbidities Why is HCV protective? Pharmacy data – HAART, toxicity, HCV treatment

Questions?