Prevalence and Burden of HBV Co-infection Among People Living With HIV

A Global Systematic Review and Meta-analysis

Lucy Platt; Clare E. French; Catherine R. McGowan; Keith Sabin; Erin Gower; Adam Trickey; Bethan McDonald; Jason Ong; Jack Stone; Philippa Easterbrook; Peter Vickerman

Disclosures

J Viral Hepat. 2020;27(3):294-315. 

In This Article

Abstract and Introduction

Abstract

Globally, in 2017 35 million people were living with HIV (PLHIV) and 257 million had chronic HBV infection (HBsAg positive). The extent of HIV-HBsAg co-infection is unknown. We undertook a systematic review to estimate the global burden of HBsAg co-infection in PLHIV. We searched MEDLINE, Embase and other databases for published studies (2002–2018) measuring prevalence of HBsAg among PLHIV. The review was registered with PROSPERO (#CRD42019123388). Populations were categorized by HIV-exposure category. The global burden of co-infection was estimated by applying regional co-infection prevalence estimates to UNAIDS estimates of PLHIV. We conducted a meta-analysis to estimate the odds of HBsAg among PLHIV compared to HIV-negative individuals. We identified 506 estimates (475 studies) of HIV-HBsAg co-infection prevalence from 80/195 (41.0%) countries. Globally, the prevalence of HIV-HBsAg co-infection is 7.6% (IQR 5.6%-12.1%) in PLHIV, or 2.7 million HIV-HBsAg co-infections (IQR 2.0–4.2). The greatest burden (69% of cases; 1.9 million) is in sub-Saharan Africa. Globally, there was little difference in prevalence of HIV-HBsAg co-infection by population group (approximately 6%-7%), but it was slightly higher among people who inject drugs (11.8% IQR 6.0%-16.9%). Odds of HBsAg infection were 1.4 times higher among PLHIV compared to HIV-negative individuals. There is therefore, a high global burden of HIV-HBsAg co-infection, especially in sub-Saharan Africa. Key prevention strategies include infant HBV vaccination, including a timely birth-dose. Findings also highlight the importance of targeting PLHIV, especially high-risk groups for testing, catch-up HBV vaccination and other preventative interventions. The global scale-up of antiretroviral therapy (ART) for PLHIV using a tenofovir-based ART regimen provides an opportunity to simultaneously treat those with HBV co-infection, and in pregnant women to also reduce mother-to-child transmission of HBV alongside HIV.

Introduction

Chronic hepatitis B (CHB) infection, defined as persistence of hepatitis B surface antigen (HBsAg), is a major public health problem resulting in an estimated 900 000 deaths in 2015.[1–4] Although HBV can be prevented with vaccination, in 2015, there were an estimated 257 million persons chronically infected.[4] Between 20 and 30% of those with chronic infection develop complications, mainly cirrhosis and hepatocellular carcinoma (HCC).[5] CHB accounts for 43% of cases of HCC and 40% of cirrhosis, with much higher proportions in lower middle-income countries,[4] and 5%-10% of liver transplants in high-income countries.[6] Age is a key determinant of the risk of chronic infection: chronicity is common following acute infection in neonates (around 90%) and young children under the age of 5 years (20–60%), but occurs rarely (<5%) when infection is acquired in adulthood.7,8 Worldwide, most persons with CHB were infected at birth or in early childhood.[9] The highest prevalence of HBsAg (>5%) is in sub-Saharan Africa, East Asia, parts of Balkans, the Pacific Islands and the Amazon Basin.[10] Regional variation exists in the epidemiology of HBV: perinatal or horizontal transmission predominates in sub-Saharan Africa and Asia, whereas in high-income countries transmission is predominantly via injection drug use and high-risk sexual behaviours.[9,11]

As PLHIV live longer due to increased access to antiretroviral therapies, liver disease has emerged as a leading cause of death in PLHIV co-infected with HBV or HCV.[12,13] Among people with HBsAg, co-infection with HIV results in higher rates of chronicity and occult HBV (HBV-DNA positivity in the absence of HBsAg), accelerated liver disease progression, higher liver-related mortality and decreased treatment response.[14–17] Co-infection with CHB also increases risk of hepatotoxicity from antiretroviral therapy (ART) three- to five-fold,[18,19] and cross-resistance between HIV and HBV drugs is common.[20,21] Fortunately, tenofovir, a drug commonly included in ART regimens, is also the most effective drug for long-term treatment of HBV, leading to long-term HBV viral suppression, reversal of cirrhosis and fibrosis, and reduction in HBV-related mortality.[22]

There is a need to establish the global burden of HBsAg co-infection among PLHIV, to characterize the most affected populations and geographical regions, and to inform national and regional screening programmes and clinical management. However, to date, no review has estimated the global burden of HBV co-infection among PLHIV. Existing estimates suggest approximately 10% of PLHIV have chronic hepatitis B or 2–4 million people, but were based on small numbers of studies with unclear methodology.[17,23,24] Other reviews have focussed on specific regions[25] or people who inject drugs (PWID).[11,26] We therefore undertook a global systematic review of the prevalence and burden of HBsAg in PLHIV.

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