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Impact of Chronic HCV Co-infection
  on HIV Clinical Outcomes in the
       District of Columbia
               Sarah Willis, MPH
   Department of Epidemiology and Biostatistics
    School of Public Health and Health Services
        The George Washington University

     2011 National HIV Prevention Conference
A Public Health/Academic Partnership
                  between the
  District of Columbia Department of Health
                      and
The George Washington University School of
      Public Health and Health Services
Department of Epidemiology and Biostatistics

    Contract Number POHC-2006-C-0030
Background
• An estimated 1/4 of those infected with HIV are
  also infected with hepatitis C virus (HCV)
• Estimates of HIV/HCV co-infection range from 50-
  90% among certain sub-populations
• Supporting evidence that HIV negatively impacts
  HCV disease progression and reduces the
  effectiveness of available treatments
Background (2)
• Less research has been conducted regarding
  role of HCV co-infection on HIV disease and
  existing studies have conflicting results
  – Association between HCV/HIV co-infection and
    worsening liver disease and higher mortality
    when compared to those with HIV or HCV
    monoinfection (Merriman et al)
  – HCV co-infection associated with blunted CD4
    cell recovery after initiating HAART yet no effect
    on virologic response or mortality (Carmo et al)
Objectives
Utilize routinely reported surveillance data to:
  1. Determine the extent of HIV/HCV co-infection
     in the District of Columbia between 2000-2009
  2. Describe potential factors that may be
     associated with HIV/HCV co-infection
  3. Determine the impact that HIV/HCV co-
     infection has on HIV clinical outcomes and
     mortality
Methods
• Identified name-based HIV/AIDS cases diagnosed
  and reported to the DCDOH between 2000 – 2009
  (n=10,215)
• Identified chronic HCV cases reported to DCDOH
  during the same time period (n=16,235)
• Used Link Plus Probability matching program to
  match cases by:
  –   First and last name
  –   Date of birth
  –   Sex
  –   Race
• Reviewed potential matches for accuracy
Methods (2)
• Performed bivariate analyses to detect differences
  among HIV/HCV co-infected and HIV mono-infected
  individuals based on:
   – Demographics
   – Entrance into HIV Care (time between HIV/AIDS diagnosis
     and first VL or CD4 test reported to DCDOH)
   – Engagement in HIV Care
      • Continuous Care - evidence (e.g. HIV-related lab test) of at least 2
        visits to an HIV medical provider 10-14 weeks apart
      • Sporadic care - one visit to a provider or 2 visits but more than 14
        weeks apart
   – Viral load and CD4 count (at time of diagnosis and most
     recent results)
   – Mortality
Methods (3)
• Assessed timing of HIV/HCV co-infection
• Association between HIV/HCV co-infection
  and mortality (time to death) examined
  through:
  – Kaplan-Meier log rank test/log rank survival plots
  – Cox proportional hazard ratio model
Demographics of Co-Infected
                   and Monoinfected Cases
        11.3% of reported HIV cases were HCV co-infected
                             HIV/HCV                 HIV
                                                                        Chi-square
                           Co-infected           Monoinfected
                                                                         p-value
                            (n=1,151)             (n=9,017)
Sex
 Male                         67.2%                   70.5%               0.0189
 Female                       32.8%                   29.5%
Race/ethnicity
 White                        4.5%                    14.4%
 Black                        90.4%                   77.5%              <0.0001
 Hispanic                     3.1%                    5.8%
 Other*                       2.0%                    2.3%
*Other race includes Asian, Alaska Native, American Indian, Native Hawaiian,
Pacific Islander, and Mixed and Unknown race
Age and Vital Status of
          Co-Infected and Monoinfected Cases
                               HIV/HCV         HIV
                                                          Chi-square
                             Co-infected   Monoinfected
                                                           p-value
                              (n=1,151)     (n=9,017)
Age at HIV diagnosis
 13-19                         0.2%           3.1%
 20-29                         3.7%           20.6%
 30-39                         13.9%          32.4%        <0.0001
 40-49                         48.1%          28.1%
 50-59                         28.8%          11.8%
 ≥60                           5.3%           4.1%
Vital Status*
 Alive                         80.5%          88.5%        <0.0001
 Dead                          19.5%          11.5%
*as of December 31st, 2009
HIV Mode of Transmission
                                45.0%
                                                        40.3%
                                40.0%
                                                36.4%
Proportion of Diagnosed Cases




                                35.0%
                                                                                                    31.6%
                                30.0%

                                25.0%                                                       23.5%

                                20.0%   17.6%                                                                       17.2%
                                15.0%                        12.1%                                          13.8%

                                10.0%
                                                                        4.6%
                                 5.0%                                          2.6%
                                 0.0%
                                           MSM             IDU           MSM/IDU            Heterosexual      Risk Not
                                                                                                             Identified
                                                           HIV/HCV Co-infected        HIV
Timing of HIV/HCV Infection
                     Concurrent
                      Infections
                     (< 3 months
                        apart)
                        27.1%


HCV Infection
 3+ months
 prior to HIV
    58.7%             HIV Infection
                       3+ months
                      prior to HCV
                         14.2%
HIV Care Seeking Behavior
                       HIV/HCV         HIV
                                                  Chi-square
                     Co-infected   Monoinfected
                                                   p-value
                      (n=1,151)     (n=9,017)
Entrance into Care
 < 3 months            56.9%          59.9%
 3 – 6 months          5.7%           4.6%
                                                   <0.0001
 6 – 12 months         6.3%           5.6%
 > 1 year              25.0%          20.4%
 Not in care           6.0%           9.5%
Engagement in Care
 No care               6.0%           9.5%
                                                   <0.0001
 Sporadic Care         57.7%          61.4%
 Continuous Care       36.3%          29.1%
HIV Viral Load at Time of HIV Diagnosis
                                 100,000
                                  90,000
Median Viral Load at Diagnosis




                                  80,000
                                  70,000
        (copies/mL)




                                  60,000
                                  50,000
                                  40,000
                                  30,000
                                  20,000
                                                                                     16,406
                                  10,000              10,551
                                      0
                                           HIV/HCV Co-infection                 HIV only
                                                        Kruskal Wallis; p = 0.3031
Most Recent Viral Load Results
3,500

3,000

2,500

2,000

1,500

1,000

 500

   0               74                                  74
        HIV/HCV coinfection                      HIV only
                          Kruskal Wallis; p = 0.0119
CD4 Count at HIV Diagnosis
                                500
                                450
Median CD4 Count at Diagnosis




                                400
                                350
                                300
         (cells/µL)




                                250
                                200                                                    192
                                                 185
                                150
                                100
                                50
                                 0
                                      HIV/HCV coinfection                         HIV only

                                               Kruskal Wallis; p-value = 0.3986
Most Recent CD4 Results
                              700

                              600
Median CD4 Count (cells/µL)




                              500
                                                                                     445
                              400                389
                              300

                              200

                              100

                               0
                                      HIV/HCV coinfection                       HIV only

                                                 Kruskal Wallis; p-value = 0.0002
Survival Among
HIV/HCV and HIV only cases

                              HIV only cases



                     HIV/HCV co-infected cases



 Log-rank = 47.35
 p-value = <0.0001
Adjusted Hazard Ratio for
    Mortality among HIV/HCV Co-infected Cases

                         Adjusted Hazard         95% Confidence
                              Ratio†                Interval
HCV/HIV vs. HIV only           1.20                1.02, 1.40
†Adjusted for sex, race/ethnicity, age, engagement in care, HIV mode
of transmission, and progression to AIDS
Conclusions
• More than half of HIV/HCV co-infections were
  infected with HCV first
• In comparison to HIV monoinfected cases, HIV/HCV
  co-infected cases in DC were more likely to be:
  – Black
  – Over 40 years of age
  – IDU
• HIV/HCV co-infected cases in DC may have poorer
  HIV clinical outcomes over time
  – Lower CD4 counts among HIV/HCV co-infected cases at
    most recent test
  – Increased mortality among HIV/HCV co-infected cases
Limitations
• May have underestimated HIV/HCV co-
  infections due to errors in data entry, name
  changes or incorrect spelling
• Large proportion of cases with missing CD4
  and viral load data at diagnosis and at follow-
  up (25%-75%) in eHARS, could not assess their
  clinical outcomes
Recommendations
• Subsequent studies should be conducted to better
  understand the impact of HCV co-infection on HIV
  disease
• Studies utilizing surveillance data for this purpose
  should:
   – Improve completeness of VL and CD4 test results data
   – Obtain data on ART utilization
• Prevention and treatment interventions should be
  developed for sub-populations with high rates of
  HCV/HIV co-infection, such as IDUs
Acknowledgments
DC DOH HIV/AIDS,            George Washington
Hepatitis, STD, TB          University School of
Administration              Public Health and Health
   –   Angelique Griffin*   Services
   –   Yujiang Jia             – Amanda D. Castel*
   –   Gregory Pappas          – Irene Kuo*
   –   Rowena Samala           – Alan Greenberg
   –   Tiffany West*


  *Co-authors

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  • 1. Impact of Chronic HCV Co-infection on HIV Clinical Outcomes in the District of Columbia Sarah Willis, MPH Department of Epidemiology and Biostatistics School of Public Health and Health Services The George Washington University 2011 National HIV Prevention Conference
  • 2. A Public Health/Academic Partnership between the District of Columbia Department of Health and The George Washington University School of Public Health and Health Services Department of Epidemiology and Biostatistics Contract Number POHC-2006-C-0030
  • 3. Background • An estimated 1/4 of those infected with HIV are also infected with hepatitis C virus (HCV) • Estimates of HIV/HCV co-infection range from 50- 90% among certain sub-populations • Supporting evidence that HIV negatively impacts HCV disease progression and reduces the effectiveness of available treatments
  • 4. Background (2) • Less research has been conducted regarding role of HCV co-infection on HIV disease and existing studies have conflicting results – Association between HCV/HIV co-infection and worsening liver disease and higher mortality when compared to those with HIV or HCV monoinfection (Merriman et al) – HCV co-infection associated with blunted CD4 cell recovery after initiating HAART yet no effect on virologic response or mortality (Carmo et al)
  • 5. Objectives Utilize routinely reported surveillance data to: 1. Determine the extent of HIV/HCV co-infection in the District of Columbia between 2000-2009 2. Describe potential factors that may be associated with HIV/HCV co-infection 3. Determine the impact that HIV/HCV co- infection has on HIV clinical outcomes and mortality
  • 6. Methods • Identified name-based HIV/AIDS cases diagnosed and reported to the DCDOH between 2000 – 2009 (n=10,215) • Identified chronic HCV cases reported to DCDOH during the same time period (n=16,235) • Used Link Plus Probability matching program to match cases by: – First and last name – Date of birth – Sex – Race • Reviewed potential matches for accuracy
  • 7. Methods (2) • Performed bivariate analyses to detect differences among HIV/HCV co-infected and HIV mono-infected individuals based on: – Demographics – Entrance into HIV Care (time between HIV/AIDS diagnosis and first VL or CD4 test reported to DCDOH) – Engagement in HIV Care • Continuous Care - evidence (e.g. HIV-related lab test) of at least 2 visits to an HIV medical provider 10-14 weeks apart • Sporadic care - one visit to a provider or 2 visits but more than 14 weeks apart – Viral load and CD4 count (at time of diagnosis and most recent results) – Mortality
  • 8. Methods (3) • Assessed timing of HIV/HCV co-infection • Association between HIV/HCV co-infection and mortality (time to death) examined through: – Kaplan-Meier log rank test/log rank survival plots – Cox proportional hazard ratio model
  • 9. Demographics of Co-Infected and Monoinfected Cases 11.3% of reported HIV cases were HCV co-infected HIV/HCV HIV Chi-square Co-infected Monoinfected p-value (n=1,151) (n=9,017) Sex Male 67.2% 70.5% 0.0189 Female 32.8% 29.5% Race/ethnicity White 4.5% 14.4% Black 90.4% 77.5% <0.0001 Hispanic 3.1% 5.8% Other* 2.0% 2.3% *Other race includes Asian, Alaska Native, American Indian, Native Hawaiian, Pacific Islander, and Mixed and Unknown race
  • 10. Age and Vital Status of Co-Infected and Monoinfected Cases HIV/HCV HIV Chi-square Co-infected Monoinfected p-value (n=1,151) (n=9,017) Age at HIV diagnosis 13-19 0.2% 3.1% 20-29 3.7% 20.6% 30-39 13.9% 32.4% <0.0001 40-49 48.1% 28.1% 50-59 28.8% 11.8% ≥60 5.3% 4.1% Vital Status* Alive 80.5% 88.5% <0.0001 Dead 19.5% 11.5% *as of December 31st, 2009
  • 11. HIV Mode of Transmission 45.0% 40.3% 40.0% 36.4% Proportion of Diagnosed Cases 35.0% 31.6% 30.0% 25.0% 23.5% 20.0% 17.6% 17.2% 15.0% 12.1% 13.8% 10.0% 4.6% 5.0% 2.6% 0.0% MSM IDU MSM/IDU Heterosexual Risk Not Identified HIV/HCV Co-infected HIV
  • 12. Timing of HIV/HCV Infection Concurrent Infections (< 3 months apart) 27.1% HCV Infection 3+ months prior to HIV 58.7% HIV Infection 3+ months prior to HCV 14.2%
  • 13. HIV Care Seeking Behavior HIV/HCV HIV Chi-square Co-infected Monoinfected p-value (n=1,151) (n=9,017) Entrance into Care < 3 months 56.9% 59.9% 3 – 6 months 5.7% 4.6% <0.0001 6 – 12 months 6.3% 5.6% > 1 year 25.0% 20.4% Not in care 6.0% 9.5% Engagement in Care No care 6.0% 9.5% <0.0001 Sporadic Care 57.7% 61.4% Continuous Care 36.3% 29.1%
  • 14. HIV Viral Load at Time of HIV Diagnosis 100,000 90,000 Median Viral Load at Diagnosis 80,000 70,000 (copies/mL) 60,000 50,000 40,000 30,000 20,000 16,406 10,000 10,551 0 HIV/HCV Co-infection HIV only Kruskal Wallis; p = 0.3031
  • 15. Most Recent Viral Load Results 3,500 3,000 2,500 2,000 1,500 1,000 500 0 74 74 HIV/HCV coinfection HIV only Kruskal Wallis; p = 0.0119
  • 16. CD4 Count at HIV Diagnosis 500 450 Median CD4 Count at Diagnosis 400 350 300 (cells/µL) 250 200 192 185 150 100 50 0 HIV/HCV coinfection HIV only Kruskal Wallis; p-value = 0.3986
  • 17. Most Recent CD4 Results 700 600 Median CD4 Count (cells/µL) 500 445 400 389 300 200 100 0 HIV/HCV coinfection HIV only Kruskal Wallis; p-value = 0.0002
  • 18. Survival Among HIV/HCV and HIV only cases HIV only cases HIV/HCV co-infected cases Log-rank = 47.35 p-value = <0.0001
  • 19. Adjusted Hazard Ratio for Mortality among HIV/HCV Co-infected Cases Adjusted Hazard 95% Confidence Ratio† Interval HCV/HIV vs. HIV only 1.20 1.02, 1.40 †Adjusted for sex, race/ethnicity, age, engagement in care, HIV mode of transmission, and progression to AIDS
  • 20. Conclusions • More than half of HIV/HCV co-infections were infected with HCV first • In comparison to HIV monoinfected cases, HIV/HCV co-infected cases in DC were more likely to be: – Black – Over 40 years of age – IDU • HIV/HCV co-infected cases in DC may have poorer HIV clinical outcomes over time – Lower CD4 counts among HIV/HCV co-infected cases at most recent test – Increased mortality among HIV/HCV co-infected cases
  • 21. Limitations • May have underestimated HIV/HCV co- infections due to errors in data entry, name changes or incorrect spelling • Large proportion of cases with missing CD4 and viral load data at diagnosis and at follow- up (25%-75%) in eHARS, could not assess their clinical outcomes
  • 22. Recommendations • Subsequent studies should be conducted to better understand the impact of HCV co-infection on HIV disease • Studies utilizing surveillance data for this purpose should: – Improve completeness of VL and CD4 test results data – Obtain data on ART utilization • Prevention and treatment interventions should be developed for sub-populations with high rates of HCV/HIV co-infection, such as IDUs
  • 23. Acknowledgments DC DOH HIV/AIDS, George Washington Hepatitis, STD, TB University School of Administration Public Health and Health – Angelique Griffin* Services – Yujiang Jia – Amanda D. Castel* – Gregory Pappas – Irene Kuo* – Rowena Samala – Alan Greenberg – Tiffany West* *Co-authors