Enhancing HIV/HBV and HIV/HCV Co-Infection Management: Key Updates and Strategies
Globally, 7.4% of people living with HIV (PLWH) also have chronic hepatitis B virus (HBV) infection, and 6.2% have evidence of hepatitis C virus (HCV) exposure—translating to 2.3 million PLWH with HCV markers out of 36.7 million total. These co-infections raise the risk of liver damage, cancer, and early death—but new research from Zhan-Lian Huang, Da-Biao Chen, Zhi-Liang Gao, and Bing-Liang Lin offers critical steps to improve care. The team from the Department of Infectious Diseases at The Third Affiliated Hospital of Sun Yat-sen University in Guangzhou, China, outlined their findings in a 2020 correspondence published in the Chinese Medical Journal.
One of the biggest gaps in care is under-screening. While PLWH routinely get HBV/HCV tests before starting antiretroviral therapy (ART), the reverse is rarely true: people diagnosed with HBV or HCV often don’t get HIV screening. This is risky. Drugs like entecavir—used to treat HBV—have weak anti-HIV activity. If a patient has undiagnosed HIV, using entecavir alone can lead to HIV resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), a key class of ART. Routine HIV screening for all new HBV/HCV patients could catch infections earlier and prevent resistance, the authors emphasize. The World Health Organization (WHO) supports this, noting overlapping transmission routes (like unprotected sex or injection drug use) make co-infections common.
Tenofovir alafenamide (TAF), a newer NRTI, is changing the game for PLWH with HBV. Unlike its predecessor tenofovir disoproxil fumarate (TDF), TAF is a prodrug that delivers tenofovir directly to immune cells and liver cells. This means lower doses and fewer side effects (like kidney or bone toxicity). A study found that PLWH with stable HBV co-infection who switched from TDF to TAF kept their HBV under control with fewer safety concerns. As TAF becomes more widely available, researchers are eager to see if it will improve long-term outcomes—like reducing liver damage—over time.
To find the best ART regimen for HIV/HBV co-infection, Hasifa Nampala and colleagues (2018) created a mathematical model to test common combinations. They looked at NRTI backbones (emtricitabine/FTC, lamivudine/3TC, TDF) paired with either non-nucleoside reverse transcriptase inhibitors (NNRTIs like efavirenz/EFV or nevirapine/NVP) or boosted protease inhibitors (PIs like atazanavir or lopinavir). The model found that FTC + TDF + EFV was optimal—it balanced strong viral suppression with minimal toxicity, a key guide for doctors choosing first-line therapy for co-infected patients.
Direct-acting antivirals (DAAs) revolutionized HCV treatment, curing over 95% of patients—including those with advanced cirrhosis. For HIV/HCV co-infected patients, modern guidelines now recommend the same DAA regimens as HCV-monoinfected patients. But a 2020 study by Mathieu Chalouni and team found a critical caveat: while co-infected patients had similar liver outcomes post-DAAs, they faced higher risks of all-cause mortality, non-liver deaths, and non-liver cancers. The cause? Chronic inflammation from HIV, plus high-risk behaviors like smoking or alcohol use common in this group. Even after curing HCV, co-infected patients need ongoing care for these non-liver risks.
Integrase strand transfer inhibitors (INSTIs)—like raltegravir—are first-line ART for most PLWH. A 2014 study by Maria del Mar Gutierrez and colleagues found that raltegravir had a better hepatic safety profile than PIs or NNRTIs in PLWH with HCV. However, HCV co-infection was linked to mild liver enzyme elevations. Another study (the SAILING trial) noted that PLWH with HBV/HCV co-infection sometimes experience “immune reconstitution inflammatory syndrome”—temporary liver flares—when starting INSTIs, especially if HBV therapy isn’t given alongside. Close monitoring is key for these patients.
Despite ART advances, PLWH with HBV/HCV co-infection still face high rates of end-stage liver disease (ESLD), like liver failure or cancer. A 2016 study by Michael B. Klein and team looked at 15 years of data and found no clear reduction in ESLD risk—even as ART use increased. The problem? For years, there were no effective treatments for HBV/HCV. Now, with DAAs for HCV and tenofovir-based regimens for HBV, expanding access to these drugs is critical to lowering ESLD rates, the authors stress.
Safety is another priority. Some ART drugs—like nevirapine (NVP), efavirenz (EFV), and boosted PIs—are toxic to the liver. The authors warn against using these in co-infected patients with advanced liver disease. INSTIs are safer, but there’s limited data on their use in decompensated cirrhosis (severe liver damage). Doctors should monitor these patients closely if they use INSTIs.
Progress in HIV, HBV, and HCV treatment has drastically improved outcomes for co-infected patients. But gaps remain: non-liver mortality in HIV/HCV patients, long-term TAF benefits, and ESLD prevention. The authors urge continued research—and vigilance. Even after viral suppression (for HIV/HBV) or cure (for HCV), co-infected patients need regular check-ups to catch liver damage or other health issues early.
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