1030
Chronic HBV/HIV Co-infection and HIV Suppression, CD4 Recovery, Mortality, and Hepatotoxicity in an African ART Cohort
Christopher Hoffmann*1, S Charalambous2, D Martin3, K Fielding4, A Moss3, G Churchyard2, R Chaisson1, A Grant4, and C Thio1
1Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 2Aurum Inst for Hlth Res; 3Toga Labs, Zambia; and 4London Sch of Hygiene and Tropical Med, UK
Background: In parts of Africa and Asia, chronic hepatitis
B (HBV) co-infection occurs among 10 to 20% of HIV-infected individuals. Thus, it
is important to determine if HBV affects HIV outcomes in persons receiving ART.
We evaluated the effect of chronic HBV on HIV virologic response, CD4 rise,
hepatotoxicity, and mortality among subjects in an African ART cohort with a
high prevalence of HBV/HIV co-infection.
Methods: We prospectively studied the first 72 weeks of ART
of zidovudine, lamivudine, and efavirenz in a multi-site workplace ART cohort
in South Africa. HBV surface antigen (HBsAg) and HBV DNA levels were tested on
samples acquired pre-ART. Subjects were stratified as HBsAg–, HBV
DNA £104 copies/mL, and HBV
DNA >104 copies/mL. Median pre-ART alanine aminotransferase (ALT),
HIV RNA, and CD4 were compared using the Kruskal-Wallis method. HIV RNA suppression
was modeled using generalized estimating equations, CD4 rise was modeled using
mixed linear models. The incidence of severe hepatotoxicity (modified AIDS
Clinical Trials Group [ACTG] criteria) was determined by Poisson regression and
death by Cox proportional hazards.
Results: The 536 subjects with 559 person-year follow-up included
were primarily men (95%) with a median age of 41 years of whom 106 (20%) had
detectable HBsAg, and of those 62 had HBV DNA £104
copies/mL (~2000 IU/mL) and 44 had HBV DNA >104 copies/mL. Median
pre-ART HIV RNA level was similar for each group (range: log10
4.8-5.0 copies/mL, p = 0.34) and HBV status did not predict HIV RNA
suppression on ART (p = 0.65). Median pre-ART CD4 counts were lowest
among the group with HBV DNA £104
but not significantly different across strata (p = 0.10). HBV status was
not associated with CD4 response (p = 0.33). Baseline ALT was highest among
those with HBV DNA >104 copies/mL (58 IU/L, p = 0.003) and
there was a trend toward more severe hepatotoxic events in those with HBV DNA
>104 copies/mL than in either other category (rate 12/100 person-years
vs 6 for HBsAg– and 2 for HBV DNA £104,
p = 0.08). Furthermore, hepatotoxicity occurring after the first 12
weeks occurred more frequently among those with HBV DNA >104 (75%
of episodes). In multivariate modeling HBV status was not associated with death
on ART (p = 0.36).
Conclusions: In this study, set in South Africa, there was no evidence that HBV affected the clinical response to ART. In
addition, while hepatotoxicity is known to be increased in HBV/HIV co-infection,
HBV was not associated with higher mortality.
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