HIV-accelerated Liver Disease in persons of African

High Risk of Liver Fibrosis and Cirrhosis Among HIV/HBV Co-Infected Persons in Rakai, Uganda Lara Stabinski1, Gregory D. Kirk2, Steve J Reynolds1, Ponsiano Ocama3, Francis Bbosa4, Melissa Saulynas2, V. Kiggundu4, Dave Thomas2, Ron Gray2, Tom Quinn1 & Chloe Thio2 (1) NIH/LIR Bethesda, Maryland, and the NIH ICER Rakai, Uganda (2) Johns Hopkins University, Baltimore, Maryland (3) Makerere University, Kampala, Uganda, (4) Rakai Health Sciences Program, Rakai, Uganda

Background • Liver disease is a leading cause of death among HIV-infected persons in western cohorts, especially among those coinfected with hepatitis B or C viruses (HBV, HCV) • Data regarding the effects of HIV, hepatitis B and HAART on liver disease in Africa remain extremely sparse • Estimates of hepatotoxicity among HIV-infected persons based on liver enzyme elevation are low in Africa • Evidence that liver enzyme elevation may have substantial limitations as a marker of liver disease in HIV + persons •

Biopsy studies to ascertain liver disease are invasive and often difficult to conduct in resource-limited settings

Methods: A non-invasive, cross sectional study in Uganda • Transient elastography (TE) (FibroScan®) used to estimate fibrosis • Population prevalence of HIV/HBV co-infection 5% • Participants – 61 HBV/HIV co-infected Rakai Health Sciences Program (RHSP) ART program – 51HBV mono-infected RHSP population cohort – All included participants had valid TE scans, available HBV DNA

Methods • After consent, participants underwent a structured interview, collection of biological samples, and transient elastography to obtain liver stiffness measurements (LSM) for quantitation of liver fibrosis. • LSM cutoffs (in kilopascals, kPa) – Significant fibrosis (equivalent to Metavir F ≥2, LSM ≥9.3) – Cirrhosis (Metavir F>4, LSM ≥12.3).

• Correlates of liver fibrosis were identified using modified Poisson regression to estimate prevalence rate ratios (PRR) with 95% confidence intervals (CI).

Results: Demographics HIV/HBV Co-infected

HBV Mono-infected

27 (44)

24 (47)

37 (32-57)

30 (25-46)

Use Liquor

12 (20)

5 (10)

On HAART

33 (54)

-

21 (11-48)

-

406 (179-1152)

-

22(36)

-

Male Gender †Median Age (IQR)

Median HAART Duration, months (IQR) Median CD4 count (cells/mm3) Nadir CD4 100 IU/ml

2.6 (1.0-6.5)

0.040

HIV positive, No HAART

2.4 (1.0-5.3)

0.039

HIV positive on HAART

1.8 (0.7-4.7)

0.257

† Numbers of participants were insufficient to further characterize risks with other categorizations of HBV DNA above 100 IU/ml ‡ adjusted for age, gender and liquor use

Notable Predictors of Liver Disease in HIV/HBV co-infected Population •HAART associated with a 60% reduction in fibrosis; PRR 0.4 (95% CI 0.1-1.0), adjusted for age, gender and nadir CD4