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  AIDS 2022
July 29 - Aug 2
24th Intl AIDS Conference
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Low CD4 Count Linked to DAA Failure in People With HIV
  AIDS 2022, July 29-August 2, Montreal
Mark Mascolini
CD4 count between 200 and 349, versus a higher count, emerged as the only variable that predicted failure of direct-acting antiviral (DAA) therapy for HCV infection in people with HIV [1]. But this 3945-person international study could not determine whether the low CD4s reflected poor adherence to antiretroviral therapy (ART) or suppressive ART’s failure to boost CD4s.
DAAs cure HCV infection in 90% to 95% of people with HIV, who had been considered hard to treat successfully in the pre-DAA era. Prior smaller studies found evidence linking DAA failure in HIV-positive people to cirrhosis, mental illness, frequent drug injection, and low CD4 count. Researchers working with the International Collaboration of Hepatitis C Elimination in HIV Cohorts (InCHEHC) decided to address the question of DAA failure in a large and diverse group.
Six countries participated in the study: Australia, Canada, France, the Netherlands, Spain, and Switzerland. The researchers focused on HCV/HIV-coinfected people treated with a noninterferon regimen in 2014-2019. Participants had to have an HCV RNA test 12 or more weeks after finishing DAA therapy to determine whether treatment induced a sustained virologic response (SVR12). The researchers defined unsuccessful treatment as detectable HCV RNA on the first RNA test 12 or more weeks after treatment ended. They defined relapse as detectable HCV RNA after a negative RNA test following the end of treatment. Nonresponse meant never having undetectable HCV RNA during treatment.
The research team used mixed-effects logistic regression to identify factors associated with lack of SVR12 testing and unsuccessful treatment. They used multinomial mixed-effects logistic regression to spot factors linked to unsuccessful treatment due to relapse or nonresponse.
The analysis included 4510 people with DAA treatment data, 81% of them male, 46% men who have sex with men, and 36% with a history of injecting drugs. Median age stood at 51 (range 21 to 85). Of the initial 4510 treated people, 3945 (87%) had an HCV RNA test for SVR and got included in further analysis. Among those 3945 people, 217 (5.5%) were unsuccessfully treated, of whom 146 (67%) had a relapse.
Only one variable, previous HCV treatment, predicted not having an SVR12 test, lowering the odds of no testing by one third (adjusted odds ratio [aOR] 0.67, 95% confidence interval [CI] 0.52 to 0.87). Variables that did not affect chances of no SVR12 testing were age, HIV/HCV risk group, CD4 count, years since HIV diagnosis, and HIV load.
In the analysis of unsuccessful treatment, a CD4 count between 200 and 349 (versus 350 or higher) boosted odds of unsuccessful treatment 40% (aOR 1.40, 95% CI 1.03 to 1.93). But a CD4 count below 200 did not affect chances of unsuccessful treatment. Variables not associated with unsuccessful treatment were HIV/HCV risk group, age, and cirrhosis. A CD4 count between 200 and 349 (versus 350 or higher) was specifically associated with relapse, raising odds 46% (aOR 1.46, 95% CI 1.02 to 2.09).
The researchers noted recent proposals for less on-treatment and post-treatment monitoring because of the high cure rate with DAAs. They believe their findings suggest this advice may be premature for people with HIV and a lower CD4 count.
1. Harney BL, Sacks-Davis R, van Santen DK, et al. Understanding unsuccessful direct-acting antiviral hepatitis C treatment among people living with HIV from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). AIDS 2022, July 29-August 2, Montreal. Abstract EPB051.