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ART Reinitiation and HBV Rebound among HIV/HBV-co-infected Patients following ART Interruption in the Strategies for the Management of ART Study
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Frequent HBV DNA rebound following ART interruption may be associated with accelerated immune deficiency. Therefore, maintenance of HBV viral control should be recommended in the setting of ART interruption.
Reported by Jules Levin CROI 2009 Feb 8-12
Vincent Soriano and for the SMART/INSIGHT Study Group
Hosp Carlos III, Madrid, Spain
Background: The SMART study demonstrated that ART interruption increased morbidity and mortality among HIV-infected patients when compared to continuous ART.. We hypothesized that interruption of ART among HIV/hepatitis B virus (HBV)-co-infected patients in SMART would lead to HBV viral rebound and influence HIV immunopathogenesis.
Methods: The SMART study randomized HIV patients with a CD4 count above 350 cells/μL to a drug conservation (interrupt ART until CD4 <250 cells/μL) versus viral suppression (continued use of ART) group. Participants were classified at entry as HBV+ if HBV surface antigen (HBsAg) positive for >6 months. Plasma HBV DNA was measured on all HBV+ participants at baseline, and at months 1, 2, 4, 6, 8, 10, and 12. Time to ART reinitiation was examined by Kaplan Meier analysis.
Results: Among 5472 participants, 930 (17%) were hepatitis co-infected (HBV+ [n = 120, 2.2%]; HCV+ [n = 796, 14.5%]; HBV+ and HCV+ [n = 14, 0.3%]). Among HBV+ participants in the drug conservation and viral suppression arms, HBV DNA rebound of >1 log from baseline was seen in 31 to 33% and 3 to 4%, respectively, at months 1 to 4 (p = 0.017 to 0.003). Of the HBV+ participants, 13 had HBV DNA rebound of >3 log, including 12 in the drug conservation arm, of which 8 were on tenofovir (TDF)-containing regimens. Factors independently associated with HBV DNA rebound were: drug conservation arm (p <0.0001), non-detectable HBV DNA at baseline (p = 0.008), black race (p = 0.03), and baseline tenofovir (TDF)-containing ART regimen (p = 0.04). Median time to ART reinitiation was shorter (7.5, 15.6, 17.8 months, p <0.0001) and proportion reinitiating greater (62.5, 46.5, 39.7%, p = 0.0002) among HBV+ participants compared to HCV+ and non-HBV/HCV participants in the drug conservation arm. Over the initial 4 months follow-up in the drug conservation arm, the median CD4 decline (slope) per month was 70.9 cells/mm3, 50.6 cells/mm3, and 53.0 cells/mm3, for HBV+, HCV+, and non-HBV/HCV groups. The median CD4 count (cells/mm3) at ART re-initiation was 240, 241, and 233 for HBV+, HCV+, and non-HBV/HCV groups; and reasons for ART reinitiation were similar across the groups. HBV DNA rebound was correlated to both HIV RNA increase and CD4 decline.
Conclusions: Frequent HBV DNA rebound following ART interruption may be associated with accelerated immune deficiency. Therefore, maintenance of HBV viral control should be recommended in the setting of ART interruption.
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