Effect of HBV DNA Levels on HIV Infection and Response to ART in a HIV/HBV Co-infected Nigerian Cohort John Idoko 1 , Seema Meloni 2 , Mohammed Muazu 1 , Claudia Hawkins 3 , Bitrus Bidang 1 , Ladep Nimzing 1 , Phyllis Kanki 2 , Robert Murphy 3 , Ernest Ekong 4 , Chloe Thio 5 1 Jos University Teaching Hospital, Plateau State, Nigeria, 2 Harvard School of Public Health, Boston, MA, USA, 3 Northwestern University, Chicago, IL, USA, 4 Military Reference Hospital, Lagos, Nigeria, 5 Johns Hopkins Medical Institutions, Baltimore, MD, USA Abstract Background: In a Nigerian HIV-HBV co-infected cohort, we showed that hepatitis B was associated with lower CD4 counts and higher HIV RNA prior to antiretroviral therapy (ART). We hypothesized that high HBV DNA levels would influence pre-ART HIV stage and ART-related hepatotoxicity, but that it would not affect ART response. Methods: We tested our hypothesis in HIV+/HCV- patients who initiated ART through PEPFAR in Nigeria. We compared HIV parameters between a control group of HIV+/HBV-/HCV- (HIV only) patients and several HIV/HBV coinfected (HBsAg+) groups stratified according to HBV DNA levels (≥20,000 IU/ml) and HBeAg status. Comparisons were made at baseline and after months 3 and 6 of ART using nonparametric tests for continuous variables and Fisher’s exact tests for categorical variables. Hepatotoxicity was defined according to ACTG definitions. Results: There were 1,305 HIV only and 264 HIV/HBV patients, of which 263 (99.6%) and 226 (86%) were tested for HBeAg and HBV DNA, respectively. Median baseline CD4 count (cells/mm3) was lower in the HIV/HBV group with high HBV DNA (89) compared to the HIV only or the HIV/HBV with low HBV DNA (130 and 129, respectively; p=0.001). Stratification by HBeAg revealed that the median baseline CD4 count in the HBeAg-, low HBV DNA was similar to the HIV only group (129 and 130 cells, respectively); all other groups had lower median baseline counts. The median baseline HIV RNA was similar between the HIV/HBV groups with high and low HBV DNA (89,882 and 96,895 c/ml), which was significantly higher than the HIV only group (55,708 c/ml; p=0.01). After 6 months of ART, neither HBV DNA nor HBeAg status altered the percent with HIV RNA <400 c/ml. CD4 counts increased in all groups at 6 months, but those with high HBV DNA had lower median CD4 counts (216 vs 229 for low HBV DNA and 240 for HIV only, p=0.08). HBeAg status did not alter this relationship. The high HBV DNA group had significantly higher median baseline ALT (p=0.0002) and the greatest cumulative hepatotoxicity by month 6 (12.1% vs. 3.9-4.9%, P=0.01). Conclusions: In this HIV/HBV co-infected Nigerian cohort, high HBV DNA levels were associated with lower baseline CD4 counts and increased risk for hepatotoxicity on ART. High HBV DNA levels did not clearly impair immunological and virological responses with 6 months of ART, but CD4 counts remained lower in those with high HBV DNA. Further studies are needed to understand the impact of HBV on HIV therapy and management. Introduction and Hypothesis PEPFAR Provides drugs and clinical care to six sites Initial ARV regimen in “Branded” program (received Branded medications): Zerit®, Epivir®, Viramune® Laboratories: At baseline and every 6 months. Hepatitis B surface antigen (HBsAg) only at baseline. HIV-Hepatitis B virus (HBV) in PEPFAR in Nigeria 17.1% of HAART initiators in Nigerian PEPFAR are HBsAg+ (Idoko et al, CROI 2007) HBsAg+ associated with lower CD4 counts and higher HIV RNA levels pre-HAART. HBeAg+ had lower CD4 counts and higher HIV RNA levels compared to HBeAg-. HBsAg+ does not limit HAART response at 6 months. Hepatotoxicity low but highest in those who were HBsAg+ Hypothesis HBV DNA levels influence pre-ART HIV stage and ART-related hepatotoxicity but not response to ART. Contact information: Chloe Thio, MD 1503 E Jefferson Street Baltimore, MD 21231 cthio@jhmi.edu Study subjects Participants in Branded PEPFAR in site in Jos, Nigeria Initiated HAART HCV antibody negative Laboratory testing HBsAg, HBeAg, and HBV DNA at baseline CD4 count, HIV RNA, ALT, HBV at baseline, 6, and 12 months Outcomes HIV RNA- baseline and <200 copies/ml at 6 and 12 months CD4 cell count-baseline and 6 and 12 months, ↑ >50 cell/mm 3 at 6 and 12 months Hepatotoxicity-ALT >5x ULN or >3.5 baseline if abnormal at baseline Analysis: Stata, version 9 Stratified by high HBV DNA (≥ 20,000 IU/ml) Continuous variables were compared with the Fisher’s exact test Categorical variables were compared with the Wilcoxon test and the non- parametric K-sample test of equal medians Methods 1968 HAART initiators 264 HIV/HBV with sufficient f/u 1302 HIV+ only with sufficient f/u 226 (86%) tested for HBV DNA 402 insufficient f/u Results 0 50,000 100,000 HIV only HIV/high HBV DNA HIV/low HBV DNA Table 2: HIV RNA <200 copies/ml at 6 and 12 months HIV HIV/high HBV DNA 71 63 65 74 HIV/low HBV DNA 6 months (%)* 69 12 months (%)* 74 130 90 129 0 40 80 120 160 HIV HIV/high HBV DNA HIV/low HBV DNA Study cohort Figure 1: Flow chart of participants included in this study HIV RNA Figure 2: Median baseline HIV RNA levels do not differ based on HBV DNA CD4 cell count Figure 3: Median baseline CD4 cell count lower with high HBV DNA Table 3: CD4 cell count at 6 and 12 months on HAART HIV HIV/high HBV DNA HIV/low HBV DNA P Median month 6, (cells/mm 3 ) 240 216 229 0.08 247 76 291 78 Median month 12, (cells/mm 3 ) 282 0.22 ↑ >50 cells/mm 3 (%), month 12 80 NS 0 5 10 6 months 12 months Months % hepatotoxicity HIV only HIV/high HBV DNA HIV/low HBV DNA Hepatotoxicity Conclusions In HIV/HBV co-infected HAART initiators, High HBV DNA is associated with lower baseline CD4 counts, which continues up to 12 months HBV DNA does not affect baseline HIV RNA High HBV DNA trends towards lower frequency of HIV RNA <200 cp/ml at 6 and 12 months Hepatotoxicity rates are low up to 12 months Figure 4: Hepatotoxicity is low at all HBV DNA levels HIV RNA (copies/ml) HIV-HBV co-infected individuals had significantly higher baseline HIV RNA (P = 0.002), but HIV RNA did not differ based on HBV DNA. Higher HBV DNA was associated with lower CD4+ cell counts (P = 0.001). Stratification by HBeAg status revealed that the low HBV DNA/HBeAg- had CD4 counts similar to HIV only with all other groups being lower (P =0.0001). CD4 cell count (cells/mm 3 ) Acknowledgements: This work was supported by PEPFAR and a grant from NIAID. The authors would like to acknowledge the hard work and dedication of the clinical, data, and laboratory staff at Jos, Nigeria and the patients who participated in this study. HIV+ only N=1302 HIV/high HBV DNA N=106 34 34 61 46 25.9 66 CDC stage 3, entry (%)* 33 38 27.5 HIV/low HBV DNA N=120 Median age, years 34 Female gender, % 66 Median time on ARV, mos 26.5 Table 1: Demographics Poster 1031 *P = 0.01 *P> 0.05